This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10) domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded preproprotein is proteolytically processed to generate the ma... See more...

Aliases for SORL1 Gene

Aliases for SORL1 Gene

  • Sortilin Related Receptor 1 2 3 5
  • LDLR Relative With 11 Ligand-Binding Repeats 2 3 4
  • Low-Density Lipoprotein Receptor Relative With 11 Ligand-Binding Repeats 3 4
  • Sorting Protein-Related Receptor Containing LDLR Class A Repeats 3 4
  • Sortilin-Related Receptor 3 4
  • C11orf32 3 4
  • SorLA-1 3 4
  • LR11 3 4
  • Sortilin-Related Receptor, L(DLR Class) A Repeats Containing 3
  • Sortilin-Related Receptor, L(DLR Class) A Repeats-Containing 2
  • Chromosome 11 Open Reading Frame 32 2
  • Mosaic Protein LR11 3
  • SORLA 3
  • Gp250 3
  • SorLA 4
  • LRP9 3

External Ids for SORL1 Gene

Previous HGNC Symbols for SORL1 Gene

  • C11orf32

Previous GeneCards Identifiers for SORL1 Gene

  • GC11P123323
  • GC11P122835
  • GC11P121356
  • GC11P120860
  • GC11P120828
  • GC11P117266

Summaries for SORL1 Gene

Entrez Gene Summary for SORL1 Gene

  • This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10) domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded preproprotein is proteolytically processed to generate the mature receptor, which likely plays roles in endocytosis and sorting. Mutations in this gene may be associated with Alzheimer's disease. [provided by RefSeq, Feb 2016]

GeneCards Summary for SORL1 Gene

SORL1 (Sortilin Related Receptor 1) is a Protein Coding gene. Diseases associated with SORL1 include Early-Onset, Autosomal Dominant Alzheimer Disease and Alzheimer Disease. Among its related pathways are Neuroscience and Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3. Gene Ontology (GO) annotations related to this gene include transmembrane signaling receptor activity and low-density lipoprotein particle binding. An important paralog of this gene is SORCS2.

UniProtKB/Swiss-Prot Summary for SORL1 Gene

  • Sorting receptor that directs several proteins to their correct location within the cell (Probable). Along with AP-1 complex, involved Golgi apparatus - endosome sorting (PubMed:17646382). Sorting receptor for APP, regulating its intracellular trafficking and processing into amyloidogenic-beta peptides. Retains APP in the trans-Golgi network, hence preventing its transit through late endosomes where amyloid beta peptides Abeta40 and Abeta42 are generated (PubMed:16174740, PubMed:16407538, PubMed:17855360, PubMed:24523320). May also sort newly produced amyloid-beta peptides to lysosomes for catabolism (PubMed:24523320). Does not affect APP trafficking from the endoplasmic reticulum to Golgi compartments (PubMed:17855360). Sorting receptor for the BDNF receptor NTRK2/TRKB that facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling by controlling the intracellular location of its receptor (PubMed:23977241). Sorting receptor for GDNF that promotes GDNF regulated, but not constitutive secretion (PubMed:21994944). Sorting receptor for the GDNF-GFRA1 complex, directing it from the cell surface to endosomes. GDNF is then targeted to lysosomes and degraded, while its receptor GFRA1 recycles back to the cell membrane, resulting in a GDNF clearance pathway. The SORL1-GFRA1 complex further targets RET for endocytosis, but not for degradation, affecting GDNF-induced neurotrophic activities (PubMed:23333276). Sorting receptor for ERBB2/HER2. Regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulating phosphoinositide 3-kinase (PI3K)-dependent ERBB2 signaling. In ERBB2-dependent cancer cells, promotes cell proliferation (PubMed:31138794). Sorting receptor for lipoprotein lipase LPL. Promotes LPL localization to endosomes and later to the lysosomes, leading to degradation of newly synthesized LPL (PubMed:21385844). Potential sorting receptor for APOA5, inducing APOA5 internalization to early endosomes, then to late endosomes, wherefrom a portion is sent to lysosomes and degradation, another portion is sorted to the trans-Golgi network (PubMed:18603531). Sorting receptor for the insulin receptor INSR. Promotes recycling of internalized INSR via the Golgi apparatus back to the cell surface, thereby preventing lysosomal INSR catabolism, increasing INSR cell surface expression and strengthening insulin signal reception in adipose tissue. Does not affect INSR internalization (PubMed:27322061). Plays a role in renal ion homeostasis, controlling the phospho-regulation of SLC12A1/NKCC2 by STK39/SPAK kinase and PPP3CB/calcineurin A beta phosphatase, possibly through intracellular sorting of STK39 and PPP3CB (By similarity). Stimulates, via the N-terminal ectodomain, the proliferation and migration of smooth muscle cells, possibly by increasing cell surface expression of the urokinase receptor uPAR/PLAUR. This may promote extracellular matrix proteolysis and hence facilitate cell migration (PubMed:14764453). By acting on the migration of intimal smooth muscle cells, may accelerate intimal thickening following vascular injury (PubMed:14764453). Promotes adhesion of monocytes (PubMed:23486467). Stimulates proliferation and migration of monocytes/macrophages (By similarity). Through its action on intimal smooth muscle cells and macrophages, may accelerate intimal thickening and macrophage foam cell formation in the process of atherosclerosis (By similarity). Regulates hypoxia-enhanced adhesion of hematopoietic stem and progenitor cells to the bone marrow stromal cells via a PLAUR-mediated pathway. This function is mediated by the N-terminal ectodomain (PubMed:23486467). Metabolic regulator, which functions to maintain the adequate balance between lipid storage and oxidation in response to changing environmental conditions, such as temperature and diet. The N-terminal ectodomain negatively regulates adipose tissue energy expenditure, acting through the inhibition the BMP/Smad pathway (By similarity). May regulate signaling by the heterodimeric neurotrophic cytokine CLCF1-CRLF1 bound to the CNTFR receptor by promoting the endocytosis of the tripartite complex CLCF1-CRLF1-CNTFR and lysosomal degradation (PubMed:26858303). May regulate IL6 signaling, decreasing cis signaling, possibly by interfering with IL6-binding to membrane-bound IL6R, while up-regulating trans signaling via soluble IL6R (PubMed:28265003).

Additional gene information for SORL1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SORL1 Gene

Genomics for SORL1 Gene

GeneHancer (GH) Regulatory Elements for SORL1 Gene

Promoters and enhancers for SORL1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J121446 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 527.5 +0.3 291 11.3 CTCF SIN3A USF1 POLR2G SP1 NCOR1 TEAD4 EP300 ZIC2 KDM6A SORL1 ENSG00000246790 LOC105369536 TBCEL SC5D
GH11J121416 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 34.5 -34.0 -34038 2.7 SP1 EP300 ZIC2 RELA TRIM22 ZNF341 BCL11A TCF12 ZNF316 CBFB SORL1 ENSG00000246790 ENSG00000271022 lnc-BLID-8 lnc-SORL1-3
GH11J121493 Enhancer 1.2 FANTOM5 Ensembl ENCODE dbSUPER 18 +42.5 42498 3.8 MEF2C POLR2A MEF2B TCF12 ELF1 POU2F2 IKZF1 NFATC3 MAZ ATF2 piR-48759-046 SORL1 ENSG00000246790 SC5D TECTA piR-48759-045
GH11J121481 Enhancer 1.4 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 13.8 +31.5 31488 5 EP300 RELA POLR2A NFYB MEF2B SPI1 ELF1 FOS EBF1 IKZF1 LOC105369535 SORL1 ENSG00000246790 piR-48759-045
GH11J121571 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 13.1 +127.6 127582 16.4 EP300 SP1 FOS FOXA2 BCL11A NR2F2 TCF12 ZNF316 SMC3 CBFB SORL1 ENSG00000246790 lnc-BLID-6 piR-48759-046
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SORL1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SORL1

Top Transcription factor binding sites by QIAGEN in the SORL1 gene promoter:
  • COUP
  • COUP-TF
  • COUP-TF1
  • CUTL1
  • GATA-3
  • HNF-4alpha1
  • HNF-4alpha2
  • HSF2
  • POU2F1
  • POU2F1a

Genomic Locations for SORL1 Gene

Genomic Locations for SORL1 Gene
chr11:121,452,203-121,633,763
(GRCh38/hg38)
Size:
181,561 bases
Orientation:
Plus strand
chr11:121,322,912-121,504,471
(GRCh37/hg19)
Size:
181,560 bases
Orientation:
Plus strand

Genomic View for SORL1 Gene

Genes around SORL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SORL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SORL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SORL1 Gene

Proteins for SORL1 Gene

  • Protein details for SORL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q92673-SORL_HUMAN
    Recommended name:
    Sortilin-related receptor
    Protein Accession:
    Q92673
    Secondary Accessions:
    • B2RNX7
    • Q92856

    Protein attributes for SORL1 Gene

    Size:
    2214 amino acids
    Molecular mass:
    248426 Da
    Quaternary structure:
    • After maturation cleavage, interacts (via N-terminus) with its own propeptide; this interaction prevents interaction with other ligands, including CRLF1, GDNF, GFRA1, IL6 and IL6R (PubMed:11294867, PubMed:12530537, PubMed:15364913, PubMed:23333276, PubMed:24523320). Interacts (via N-terminal ectodomain) with APP, forming a 1:1 stoichiometric complex, including with isoforms APP695, APP751 and APP770; this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides (PubMed:16174740, PubMed:16407538, PubMed:17855360, PubMed:24523320). Also interacts with APP C-terminal fragment C99 and with Abeta40 (PubMed:16407538). Interacts with beta-secretase BACE1/BACE; this interaction may affect BACE1-binding to APP and hence reduce BACE1-dependent APP cleavage (PubMed:16407538). Interacts with LRPAP1/RAP (PubMed:8940146, PubMed:11294867, PubMed:12530537, PubMed:15053742, PubMed:14764453, PubMed:15364913, PubMed:26858303). Interacts (via C-terminal cytosolic domain) with GGA1 and GGA2 (via N-terminal VHS domain) (PubMed:11821067, PubMed:17855360, PubMed:30679749, PubMed:20015111). Interacts with PACS1 (PubMed:17855360, PubMed:17646382). May interact (via the N-terminal ectodomain) with the morphogenetic neuropeptide, also called head activator or HA; this interaction is impaired in the presence of propeptide (PubMed:11082041, PubMed:11294867, PubMed:12530537). Interacts with neurotensin/NTS (PubMed:11294867). Interacts (via the N-terminal ectodomain) with PDGFB homodimer (PubMed:15053742, PubMed:16393139). Interacts (via N-terminal ectodomain) with the uPA receptor PLAUR; this interaction decreases PLAUR internalization (PubMed:14764453, PubMed:23486467). Interacts (via N-terminal ectodomain) with uPA/PLAU and PAI1/SERPINE1, either individually or in complex with each other, leading to endocytosis; this interaction is abolished in the presence of LRPAP1 (PubMed:15053742). Also interacts with the ternary complex composed of PLAUR-PLAU-PAI1 (PubMed:15053742). Also interacts with tPA/PLAT either alone or in complex with SERPINE1 (PubMed:15053742). Interacts (via C-terminus) with AP-1 and AP-2 complexes (PubMed:17646382). Interacts with BMPR1A and BMPR1B (By similarity). Interacts with lipoprotein lipase LPL; this interaction is optimal in slightly acidic conditions (PubMed:21385844). Interacts (via N-terminal ectodomain) with GDNF (via propeptide) and GDNF receptor alpha-1/GFRA1, either individually or in complex with each other (PubMed:15364913, PubMed:21994944, PubMed:23333276). The interaction with GDNF occurs mostly intracellularly (PubMed:21994944). Also interacts with other GDNF receptor alpha family members, including GFRA2, GFRA3 and GFRA4 (PubMed:23333276). Interacts with the insulin receptor INSR; this interaction strongly increases the surface exposure of INSR (PubMed:27322061). Interacts (via cytosolic C-terminus) with STK39/SPAK (PubMed:20385770). Interacts (via N-terminal ectodomain) with the heterodimeric complex CRLF1-CLC; within this complex, the interaction is mediated predominantly by the CRLF1 moiety (PubMed:26858303). Interacts with CNTFR, as well as with the tripartite signaling complex formed by CRLF1, CLC and CNTFR (PubMed:26858303). Interacts (via N-terminal ectodomain) with IL6; this interaction leads to IL6 internalization and lysosomal degradation (PubMed:28265003). Binding of SOLRL1 secreted N-terminal ectodomain to IL6 may increase IL6 trans signaling (PubMed:28265003). Interacts with secreted IL6R; this interaction leads to IL6R internalization (PubMed:28265003). Also interacts with transmembrane IL6R; this interaction does not affect IL6R subcellular location (PubMed:28265003). Interacts with APOE (PubMed:30448281). Interacts with apolipoprotein E-rich beta-VLDL (By similarity). Interacts with APOA5; this interaction leads to APOA5 internalization and is abolished by heparin (PubMed:17326667, PubMed:18603531). Interaction with APOA5 results in enhanced binding to chylomicrons (PubMed:17326667). Interacts with ROCK2 (PubMed:21147781). Interacts (via cytosolic C-terminus) with PPP3CB/calcineurin A beta (By similarity). Interacts with NTRK2/TRKB; this interaction facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling (By similarity). Interacts (via cytosolic C-terminus) with HSPA12A in an ADP-dependent manner; this interaction affects SORL1 internalization and subcellular localization (PubMed:30679749). Interacts (via N-terminal ectodomain) with ERBB2/HER2 (PubMed:31138794).
    Miscellaneous:
    • There may be a positive correlation of body mass index with levels of SORL1 transcript and SORLA protein in visceral adipose tissue.

    Three dimensional structures from OCA and Proteopedia for SORL1 Gene

neXtProt entry for SORL1 Gene

Post-translational modifications for SORL1 Gene

  • Within the Golgi apparatus, the propeptide may be cleaved off by FURIN or a furin-like protease (Probable). After cleavage, the propeptide interacts with the mature protein N-terminus, preventing the association with other ligands (PubMed:11294867). At the cell surface, partially subjected to proteolytic shedding that releases the ectodomain in the extracellular milieu (PubMed:11082041, PubMed:16393139, PubMed:16531402, PubMed:28265003). The shedding may be catalyzed by ADAM17/TACE (PubMed:16393139, PubMed:16531402). Following shedding, PSEN1/presenilin-1 cleaves the remaining transmembrane fragment and catalyzes the release of a C-terminal fragment in the cytosol and of a soluble N-terminal beta fragment in the extracellular milieu. The C-terminal cytosolic fragment localizes to the nucleus (PubMed:16531402).
  • Phosphorylation at Ser-2206 facilitates the interaction with GGA1.
  • Glycosylation at Asn99, Asn158, Asn368, Asn430, Asn616, Asn674, Asn818, Asn871, Asn1035, Asn1068, Asn1164, Asn1191, Asn1246, Asn1367, Asn1458, Thr1508, Asn1608, Asn1706, Asn1733, Asn1809, Asn1854, Asn1894, Asn1986, Asn2010, Asn2054, Asn2069, Asn2076, and Asn2092
  • Ubiquitination at Lys730
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for SORL1 Gene

No data available for DME Specific Peptides for SORL1 Gene

Domains & Families for SORL1 Gene

Gene Families for SORL1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for SORL1 Gene

Blocks:
  • Type I EGF
  • Low density lipoprotein-receptor, class A
  • Fibronectin type III repeat signature
  • Low-density lipoprotein receptor, YWTD repeat
  • VPS10
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for SORL1 Gene

GenScript: Design optimal peptide antigens:
  • Sorting protein-related receptor containing LDLR class A repeats (SORL_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q92673

UniProtKB/Swiss-Prot:

SORL_HUMAN :
  • Belongs to the VPS10-related sortilin family. SORL1 subfamily.
Family:
  • Belongs to the VPS10-related sortilin family. SORL1 subfamily.
genes like me logo Genes that share domains with SORL1: view

Function for SORL1 Gene

Molecular function for SORL1 Gene

UniProtKB/Swiss-Prot Function:
Sorting receptor that directs several proteins to their correct location within the cell (Probable). Along with AP-1 complex, involved Golgi apparatus - endosome sorting (PubMed:17646382). Sorting receptor for APP, regulating its intracellular trafficking and processing into amyloidogenic-beta peptides. Retains APP in the trans-Golgi network, hence preventing its transit through late endosomes where amyloid beta peptides Abeta40 and Abeta42 are generated (PubMed:16174740, PubMed:16407538, PubMed:17855360, PubMed:24523320). May also sort newly produced amyloid-beta peptides to lysosomes for catabolism (PubMed:24523320). Does not affect APP trafficking from the endoplasmic reticulum to Golgi compartments (PubMed:17855360). Sorting receptor for the BDNF receptor NTRK2/TRKB that facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling by controlling the intracellular location of its receptor (PubMed:23977241). Sorting receptor for GDNF that promotes GDNF regulated, but not constitutive secretion (PubMed:21994944). Sorting receptor for the GDNF-GFRA1 complex, directing it from the cell surface to endosomes. GDNF is then targeted to lysosomes and degraded, while its receptor GFRA1 recycles back to the cell membrane, resulting in a GDNF clearance pathway. The SORL1-GFRA1 complex further targets RET for endocytosis, but not for degradation, affecting GDNF-induced neurotrophic activities (PubMed:23333276). Sorting receptor for ERBB2/HER2. Regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulating phosphoinositide 3-kinase (PI3K)-dependent ERBB2 signaling. In ERBB2-dependent cancer cells, promotes cell proliferation (PubMed:31138794). Sorting receptor for lipoprotein lipase LPL. Promotes LPL localization to endosomes and later to the lysosomes, leading to degradation of newly synthesized LPL (PubMed:21385844). Potential sorting receptor for APOA5, inducing APOA5 internalization to early endosomes, then to late endosomes, wherefrom a portion is sent to lysosomes and degradation, another portion is sorted to the trans-Golgi network (PubMed:18603531). Sorting receptor for the insulin receptor INSR. Promotes recycling of internalized INSR via the Golgi apparatus back to the cell surface, thereby preventing lysosomal INSR catabolism, increasing INSR cell surface expression and strengthening insulin signal reception in adipose tissue. Does not affect INSR internalization (PubMed:27322061). Plays a role in renal ion homeostasis, controlling the phospho-regulation of SLC12A1/NKCC2 by STK39/SPAK kinase and PPP3CB/calcineurin A beta phosphatase, possibly through intracellular sorting of STK39 and PPP3CB (By similarity). Stimulates, via the N-terminal ectodomain, the proliferation and migration of smooth muscle cells, possibly by increasing cell surface expression of the urokinase receptor uPAR/PLAUR. This may promote extracellular matrix proteolysis and hence facilitate cell migration (PubMed:14764453). By acting on the migration of intimal smooth muscle cells, may accelerate intimal thickening following vascular injury (PubMed:14764453). Promotes adhesion of monocytes (PubMed:23486467). Stimulates proliferation and migration of monocytes/macrophages (By similarity). Through its action on intimal smooth muscle cells and macrophages, may accelerate intimal thickening and macrophage foam cell formation in the process of atherosclerosis (By similarity). Regulates hypoxia-enhanced adhesion of hematopoietic stem and progenitor cells to the bone marrow stromal cells via a PLAUR-mediated pathway. This function is mediated by the N-terminal ectodomain (PubMed:23486467). Metabolic regulator, which functions to maintain the adequate balance between lipid storage and oxidation in response to changing environmental conditions, such as temperature and diet. The N-terminal ectodomain negatively regulates adipose tissue energy expenditure, acting through the inhibition the BMP/Smad pathway (By similarity). May regulate signaling by the heterodimeric neurotrophic cytokine CLCF1-CRLF1 bound to the CNTFR receptor by promoting the endocytosis of the tripartite complex CLCF1-CRLF1-CNTFR and lysosomal degradation (PubMed:26858303). May regulate IL6 signaling, decreasing cis signaling, possibly by interfering with IL6-binding to membrane-bound IL6R, while up-regulating trans signaling via soluble IL6R (PubMed:28265003).
UniProtKB/Swiss-Prot Induction:
Up-regulated by morphogenetic neuropeptide, also called head activator or HA (PubMed:11082041). Up-regulated under hypoxic conditions in hematopoietic stem and progenitor cells, a physiological condition encountered by these cells in the endosteum. This up-regulation may be mediated by HIF1A-induced transcription (PubMed:23486467).

Phenotypes From GWAS Catalog for SORL1 Gene

Gene Ontology (GO) - Molecular Function for SORL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001540 amyloid-beta binding IPI 16407538
GO:0004888 transmembrane signaling receptor activity TAS 9157966
GO:0005041 low-density lipoprotein particle receptor activity TAS 20005821
GO:0005515 protein binding IEA,IPI 11821067
GO:0030169 low-density lipoprotein particle binding IPI 17326667
genes like me logo Genes that share ontologies with SORL1: view
genes like me logo Genes that share phenotypes with SORL1: view

Human Phenotype Ontology for SORL1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SORL1 Gene

MGI Knock Outs for SORL1:

Animal Model Products

  • Taconic Biosciences Mouse Models for SORL1

CRISPR Products

miRNA for SORL1 Gene

miRTarBase miRNAs that target SORL1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SORL1 Gene

Localization for SORL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SORL1 Gene

Golgi apparatus membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein. Early endosome membrane; Single-pass type I membrane protein. Recycling endosome membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome, multivesicular body membrane; Single-pass type I membrane protein. Cell membrane; Single-pass type I membrane protein. Cytoplasmic vesicle, secretory vesicle membrane; Single-pass type I membrane protein. Secreted. Note=Mostly intracellular, predominantly in the trans-Golgi network (TGN) and in endosome, as well as in endosome-to-TGN retrograde vesicles; found at low levels on the plasma membrane (PubMed:11294867, PubMed:15053742, PubMed:17855360, PubMed:21994944, PubMed:21385844, PubMed:31138794). At the cell surface, partially subjected to proteolytic shedding that releases the ectodomain (also called soluble SORLA, solLR11 or sLR11) in the extracellular milieu (PubMed:11082041, PubMed:16393139, PubMed:16531402). The shedding may be catalyzed by ADAM17/TACE (PubMed:16393139). Following shedding, PSEN1/presenilin-1 cleaves the remaining transmembrane fragment and catalyzes the release of a C-terminal fragment in the cytosol and of a soluble N-terminal beta fragment in the extracellular milieu. The C-terminal cytosolic fragment localizes to the nucleus (PubMed:16531402). At the cell surface, the full-length protein undergoes partial clathrin-dependent endocytosis guided by clathrin adapter protein 2 (AP-2) (PubMed:11294867, PubMed:15053742, PubMed:17646382). {ECO:0000269 PubMed:11082041, ECO:0000269 PubMed:11294867, ECO:0000269 PubMed:15053742, ECO:0000269 PubMed:16393139, ECO:0000269 PubMed:16531402, ECO:0000269 PubMed:17646382, ECO:0000269 PubMed:17855360, ECO:0000269 PubMed:21385844, ECO:0000269 PubMed:21994944, ECO:0000269 PubMed:31138794}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SORL1 gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 5
endoplasmic reticulum 5
endosome 5
golgi apparatus 5
cytosol 3
cytoskeleton 2
mitochondrion 2
lysosome 2
peroxisome 1

Gene Ontology (GO) - Cellular Components for SORL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IDA 14764453
GO:0005623 cell IEA --
GO:0005641 nuclear envelope lumen IDA,IEA 17855360
genes like me logo Genes that share ontologies with SORL1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SORL1 Gene

Pathways & Interactions for SORL1 Gene

genes like me logo Genes that share pathways with SORL1: view

Pathways by source for SORL1 Gene

2 Reactome pathways for SORL1 Gene
1 Cell Signaling Technology pathway for SORL1 Gene

SIGNOR curated interactions for SORL1 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for SORL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002024 diet induced thermogenesis ISS,IEA --
GO:0006605 protein targeting IMP,IEA 16174740
GO:0006622 protein targeting to lysosome IDA 24523320
GO:0006892 post-Golgi vesicle-mediated transport IDA 17855360
GO:0006897 endocytosis IEA --
genes like me logo Genes that share ontologies with SORL1: view

Drugs & Compounds for SORL1 Gene

No Compound Related Data Available

Transcripts for SORL1 Gene

mRNA/cDNA for SORL1 Gene

1 REFSEQ mRNAs :
19 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SORL1 Gene

No ASD Table

Relevant External Links for SORL1 Gene

GeneLoc Exon Structure for
SORL1

Expression for SORL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SORL1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SORL1 Gene

This gene is overexpressed in Whole Blood (x13.9).

Protein differential expression in normal tissues from HIPED for SORL1 Gene

This gene is overexpressed in Bone marrow stromal cell (13.2) and Peripheral blood mononuclear cells (11.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SORL1 Gene



Protein tissue co-expression partners for SORL1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SORL1

SOURCE GeneReport for Unigene cluster for SORL1 Gene:

Hs.368592

mRNA Expression by UniProt/SwissProt for SORL1 Gene:

Q92673-SORL_HUMAN
Tissue specificity: Highly expressed in brain (at protein level) (PubMed:9157966, PubMed:16174740, PubMed:21147781). Most abundant in the cerebellum, cerebral cortex and occipital pole; low levels in the putamen and thalamus (PubMed:9157966, PubMed:16174740). Expression is significantly reduced in the frontal cortex of patients suffering from Alzheimer disease (PubMed:16174740). Also expressed in spinal cord, spleen, testis, prostate, ovary, tyroid and lymph nodes (PubMed:9157966, PubMed:8940146).

Evidence on tissue expression from TISSUES for SORL1 Gene

  • Nervous system(4.9)
  • Blood(4.5)
  • Liver(4.4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SORL1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cerebellum
  • head
  • mouth
  • pharynx
Thorax:
  • esophagus
Abdomen:
  • stomach
Limb:
  • foot
  • lower limb
  • upper limb
General:
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
  • spinal cord
genes like me logo Genes that share expression patterns with SORL1: view

Orthologs for SORL1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for SORL1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SORL1 31 30
  • 98.52 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SORL1 31 30
  • 89.41 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SORL1 31 30
  • 88.09 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Sorl1 17 31 30
  • 87.59 (n)
rat
(Rattus norvegicus)
Mammalia Sorl1 30
  • 87.23 (n)
oppossum
(Monodelphis domestica)
Mammalia SORL1 31
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SORL1 31
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves SORL1 31 30
  • 75.79 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SORL1 31
  • 76 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sorl1 30
  • 68.27 (n)
zebrafish
(Danio rerio)
Actinopterygii sorl1 31 30
  • 64.76 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010896 30
  • 49.39 (n)
worm
(Caenorhabditis elegans)
Secernentea R01H2.3 32
  • 29 (a)
B0244.8 32
  • 28 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 31
  • 24 (a)
ManyToMany
-- 31
  • 21 (a)
ManyToMany
-- 31
  • 16 (a)
ManyToMany
VTH1 31
  • 16 (a)
ManyToMany
PEP1 31
  • 16 (a)
ManyToMany
VTH2 31
  • 16 (a)
ManyToMany
-- 31
  • 16 (a)
ManyToMany
-- 31
  • 15 (a)
ManyToMany
-- 33
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 38 (a)
OneToOne
Species where no ortholog for SORL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SORL1 Gene

ENSEMBL:
Gene Tree for SORL1 (if available)
TreeFam:
Gene Tree for SORL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SORL1: view image

Paralogs for SORL1 Gene

Paralogs for SORL1 Gene

(4) SIMAP similar genes for SORL1 Gene using alignment to 6 proteins:

  • SORL_HUMAN
  • E9PKB0_HUMAN
  • E9PP43_HUMAN
  • E9PPB3_HUMAN
  • E9PS32_HUMAN
  • L8EA23_HUMAN
genes like me logo Genes that share paralogs with SORL1: view

Variants for SORL1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SORL1 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs146353234 Likely Benign: not specified 121,591,090(+) A/T MISSENSE_VARIANT
rs377498269 Alzheimer disease (AD) [MIM:104300] p.Asn924Ser
rs747306346 Alzheimer disease (AD) [MIM:104300] p.Asn1358Ser
rs762365011 Uncertain Significance: not provided 121,554,071(+) T/C MISSENSE_VARIANT
rs766895956 A colorectal cancer sample p.Leu1972Val

Additional dbSNP identifiers (rs#s) for SORL1 Gene

Structural Variations from Database of Genomic Variants (DGV) for SORL1 Gene

Variant ID Type Subtype PubMed ID
esv1624966 CNV insertion 17803354
esv24898 CNV loss 19812545
esv2566564 CNV deletion 19546169
esv2665043 CNV deletion 23128226
esv2674399 CNV deletion 23128226
esv2677977 CNV deletion 23128226
esv2745152 CNV deletion 23290073
esv27517 CNV loss 19812545
esv2759866 CNV gain 17122850
esv3334676 CNV duplication 20981092
esv3427283 CNV duplication 20981092
esv34768 CNV gain 17911159
esv3627922 CNV loss 21293372
nsv1141204 CNV duplication 24896259
nsv512242 CNV loss 21212237
nsv522474 CNV loss 19592680
nsv526 CNV insertion 18451855
nsv527072 CNV loss 19592680
nsv7225 OTHER inversion 18451855
nsv818867 CNV gain 17921354
nsv8875 CNV gain 18304495

Variation tolerance for SORL1 Gene

Residual Variation Intolerance Score: 25.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.37; 81.68% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SORL1 Gene

Human Gene Mutation Database (HGMD)
SORL1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SORL1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SORL1 Gene

Disorders for SORL1 Gene

MalaCards: The human disease database

(12) MalaCards diseases for SORL1 Gene - From: Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
early-onset, autosomal dominant alzheimer disease
  • early-onset autosomal dominant alzheimer disease
alzheimer disease
  • ad
dementia
  • dementias
atrial septal defect 8
  • asd8
frontotemporal dementia
  • ftd
- elite association - COSMIC cancer census association via MalaCards
Search SORL1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SORL_HUMAN
  • Alzheimer disease (AD) [MIM:104300]: Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269 PubMed:21220680, ECO:0000269 PubMed:22472873, ECO:0000269 PubMed:23565137, ECO:0000269 PubMed:24523320}. Note=The gene represented in this entry may be involved in disease pathogenesis.

Additional Disease Information for SORL1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SORL1: view

No data available for Genatlas for SORL1 Gene

Publications for SORL1 Gene

  1. A novel mosaic protein containing LDL receptor elements is highly conserved in humans and chickens. (PMID: 9157966) Mörwald S … Saito Y (Arteriosclerosis, thrombosis, and vascular biology 1997) 2 3 4 23 54
  2. Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein. (PMID: 8940146) Jacobsen L … Petersen CM (The Journal of biological chemistry 1996) 2 3 4 23 54
  3. Meta-analysis of the association between variants in SORL1 and Alzheimer disease. (PMID: 21220680) Reitz C … Genetic and Environmental Risk in Alzheimer Disease 1 Consortium (Archives of neurology 2011) 3 4 41 54
  4. SORL1 is genetically associated with Alzheimer disease in a Japanese population. (PMID: 19539718) Kimura R … Takeda M (Neuroscience letters 2009) 3 23 41 54
  5. Implication of sex and SORL1 variants in italian patients with Alzheimer disease. (PMID: 19822782) Cellini E … Nacmias B (Archives of neurology 2009) 3 23 41 54

Products for SORL1 Gene

Sources for SORL1 Gene