SORT1 Gene (Protein Coding)

Sortilin 1

GC01M109310
GIFtS:
44
This gene encodes a member of the VPS10-related sortilin family of proteins. The encoded preproprotein is proteolytically processed by furin to generate the mature receptor. This receptor plays a role in the trafficking of different proteins to either the cell surface, or subcellular compartments such as lysosomes and endosomes. Expression levels of this gene may influence the ... See more...

Aliases for SORT1 Gene

Aliases for SORT1 Gene

  • Sortilin 1 2 3 5
  • Neurotensin Receptor 3 3 4
  • 100 KDa NT Receptor 3 4
  • Glycoprotein 95 3 4
  • Sortilin 3 4
  • Gp95 3 4
  • NTR3 3 4
  • NT3 3 4
  • LDLCQ6 3

External Ids for SORT1 Gene

Previous GeneCards Identifiers for SORT1 Gene

  • GC01M110335
  • GC01M108785
  • GC01M108957
  • GC01M109155
  • GC01M109568
  • GC01M109653
  • GC01M109852
  • GC01M107745

Summaries for SORT1 Gene

Entrez Gene Summary for SORT1 Gene

  • This gene encodes a member of the VPS10-related sortilin family of proteins. The encoded preproprotein is proteolytically processed by furin to generate the mature receptor. This receptor plays a role in the trafficking of different proteins to either the cell surface, or subcellular compartments such as lysosomes and endosomes. Expression levels of this gene may influence the risk of myocardial infarction in human patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

GeneCards Summary for SORT1 Gene

SORT1 (Sortilin 1) is a Protein Coding gene. Diseases associated with SORT1 include Low Density Lipoprotein Cholesterol Level Quantitative Trait Locus 6 and Myocardial Infarction. Among its related pathways are Vesicle-mediated transport and Clathrin derived vesicle budding. Gene Ontology (GO) annotations related to this gene include enzyme binding and nerve growth factor receptor activity. An important paralog of this gene is SORL1.

UniProtKB/Swiss-Prot Summary for SORT1 Gene

  • Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.

Gene Wiki entry for SORT1 Gene

Additional gene information for SORT1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SORT1 Gene

Genomics for SORT1 Gene

GeneHancer (GH) Regulatory Elements for SORT1 Gene

Promoters and enhancers for SORT1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SORT1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SORT1 gene promoter:
  • aMEF-2
  • AREB6
  • MEF-2A
  • NF-E2
  • NF-kappaB1
  • Nkx2-5
  • Pbx1a
  • TBP
  • TFIID

Genomic Locations for SORT1 Gene

Genomic Locations for SORT1 Gene
chr1:109,309,565-109,397,941
(GRCh38/hg38)
Size:
88,377 bases
Orientation:
Minus strand
chr1:109,852,187-109,940,573
(GRCh37/hg19)
Size:
88,387 bases
Orientation:
Minus strand

Genomic View for SORT1 Gene

Genes around SORT1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SORT1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SORT1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for SORT1 Gene

Proteins for SORT1 Gene

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  • Protein details for SORT1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99523-SORT_HUMAN
    Recommended name:
    Sortilin
    Protein Accession:
    Q99523
    Secondary Accessions:
    • B4DWI3
    • C0JYZ0
    • Q8IZ49

    Protein attributes for SORT1 Gene

    Size:
    831 amino acids
    Molecular mass:
    92068 Da
    Quaternary structure:
    • Interacts with LPL and SLC2A4 (By similarity). Interacts with the cytosolic adapter proteins GGA1 and GGA2 (PubMed:20015111). Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP, GM2A and NTS. Forms a complex with NGFR which binds specifically to the precursor forms of NGFB (proNGFB) and BDNF (proBDNF). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; may regulate their anterograde axonal transport and signaling. Interacts with CLN5 (PubMed:22431521). Interacts with PSAP (PubMed:22431521, PubMed:14657016). Interacts with GRN; this interaction mediates endocytosis and lysosome delivery of progranulin; interaction occurs at the neuronal cell surface in a stressed nervous system (PubMed:21092856).

    Three dimensional structures from OCA and Proteopedia for SORT1 Gene

    Alternative splice isoforms for SORT1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SORT1 Gene

Protein Expression for SORT1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for SORT1 Gene

  • The N-terminal propeptide is cleaved by furin and possibly other homologous proteases.
  • Phosphorylation at Ser-825 facilitates the interaction with GGA1.
  • Glycosylation at Asn162, Asn98, Asn274, Asn406, Asn582, and Asn684
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for SORT1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SORT1 Gene

Domains & Families for SORT1 Gene

Gene Families for SORT1 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for SORT1 Gene

Blocks:
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for SORT1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ50262, highly similar to Sortilin (B4DWI3_HUMAN)
  • Neurotensin receptor 3 (SORT_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99523

UniProtKB/Swiss-Prot:

SORT_HUMAN :
  • The N-terminal propeptide may facilitate precursor transport within the Golgi stack. Intrachain binding of the N-terminal propeptide and the extracellular domain may also inhibit premature ligand binding.
  • Belongs to the VPS10-related sortilin family. SORT1 subfamily.
Domain:
  • The N-terminal propeptide may facilitate precursor transport within the Golgi stack. Intrachain binding of the N-terminal propeptide and the extracellular domain may also inhibit premature ligand binding.
  • The extracellular domain may be shed following protease cleavage in some cell types.
Family:
  • Belongs to the VPS10-related sortilin family. SORT1 subfamily.
genes like me logo Genes that share domains with SORT1: view

Function for SORT1 Gene

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  2. CRISPR
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Molecular function for SORT1 Gene

UniProtKB/Swiss-Prot Function:
Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.
UniProtKB/Swiss-Prot Induction:
During osteoblast differentiation.

Phenotypes From GWAS Catalog for SORT1 Gene

Gene Ontology (GO) - Molecular Function for SORT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 10085125
GO:0010465 nerve growth factor receptor activity IDA 14985763
GO:0019899 enzyme binding IPI 10085125
GO:0030379 neurotensin receptor activity, non-G protein-coupled IDA 9756851
GO:0048406 nerve growth factor binding IPI 14985763
genes like me logo Genes that share ontologies with SORT1: view
genes like me logo Genes that share phenotypes with SORT1: view

Animal Models for SORT1 Gene

MGI Knock Outs for SORT1:

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids for SORT1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SORT1 Gene

Localization for SORT1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SORT1 Gene

Membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein. Golgi apparatus, Golgi stack membrane; Single-pass type I membrane protein. Nucleus membrane; Single-pass type I membrane protein. Cell membrane; Single-pass type I membrane protein; Extracellular side. Lysosome membrane; Single-pass type I membrane protein. Note=Localized to membranes of the endoplasmic reticulum, endosomes, Golgi stack, lysosomes and nucleus. A small fraction of the protein is also localized to the plasma membrane. May also be found in SLC2A4/GLUT4 storage vesicles (GSVs) in adipocytes. Localization to the plasma membrane in adipocytes may be enhanced by insulin.

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 SORT1 gene
Compartment Confidence
plasma membrane 5
lysosome 5
golgi apparatus 5
endosome 4
cytosol 4
nucleus 3
endoplasmic reticulum 3
extracellular 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Golgi apparatus (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SORT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005764 lysosome IEA,IDA 28541286
GO:0005765 lysosomal membrane IEA --
GO:0005768 endosome IEA --
GO:0005769 early endosome IDA 11331584
genes like me logo Genes that share ontologies with SORT1: view

Pathways & Interactions for SORT1 Gene

genes like me logo Genes that share pathways with SORT1: view

Gene Ontology (GO) - Biological Process for SORT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001503 ossification IEA --
GO:0006892 post-Golgi vesicle-mediated transport IBA 21873635
GO:0006895 Golgi to endosome transport IDA 11331584
GO:0006897 endocytosis IDA,IBA 11331584
GO:0007186 G protein-coupled receptor signaling pathway IMP 18258592
genes like me logo Genes that share ontologies with SORT1: view

No data available for SIGNOR curated interactions for SORT1 Gene

Drugs & Compounds for SORT1 Gene

Products:

  1. Drug

(2) Drugs for SORT1 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Mannose 6-phosphate Investigational Pharma 0

(1) Additional Compounds for SORT1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SORT1: view

Transcripts for SORT1 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
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mRNA/cDNA for SORT1 Gene

(2) REFSEQ mRNAs :
(23) Additional mRNA sequences :
(430) Selected AceView cDNA sequences:
(10) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for SORT1

Alternative Splicing Database (ASD) splice patterns (SP) for SORT1 Gene

No ASD Table

Relevant External Links for SORT1 Gene

GeneLoc Exon Structure for
SORT1
ECgene alternative splicing isoforms for
SORT1

Expression for SORT1 Gene

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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SORT1 Gene

mRNA expression in normal human tissues for SORT1 Gene
mRNA expression by GTEx for SORT1 GenemRNA expression by BioGPS for SORT1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SORT1 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (8.8), Amniocyte (8.4), and Spinal cord (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SORT1 Gene



NURSA nuclear receptor signaling pathways regulating expression of SORT1 Gene:

SORT1

SOURCE GeneReport for Unigene cluster for SORT1 Gene:

Hs.485195

mRNA Expression by UniProt/SwissProt for SORT1 Gene:

Q99523-SORT_HUMAN
Tissue specificity: Expressed in brain and prostate (at protein level). Expressed at high levels in brain, spinal cord, heart, skeletal muscle, thyroid, placenta and testis. Expressed at lower levels in lymphoid organs, kidney, colon and liver.

Evidence on tissue expression from TISSUES for SORT1 Gene

  • Nervous system(5)
  • Muscle(4.5)
  • Blood(4.4)
  • Lung(3.3)
  • Skin(2.5)
  • Heart(2.4)
  • Eye(2.2)
  • Kidney(2.2)
  • Liver(2.1)
  • Thyroid gland(2)
genes like me logo Genes that share expression patterns with SORT1: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SORT1 Gene

Orthologs for SORT1 Gene

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

Orthologs for SORT1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia SORT1 33 32
  • 99.84 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia SORT1 33 32
  • 91.58 (n)
 OneToOne
dog
(Canis familiaris)
 Mammalia SORT1 33 32
  • 91.24 (n)
 OneToOne
mouse
(Mus musculus)
 Mammalia Sort1 17 33 32
  • 87.76 (n)
rat
(Rattus norvegicus)
 Mammalia Sort1 32
  • 87.6 (n)
oppossum
(Monodelphis domestica)
 Mammalia SORT1 33
  • 83 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia SORT1 33
  • 74 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia SORT1 33
  • 68 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia sort1 32
  • 65.07 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.17947 32
zebrafish
(Danio rerio)
 Actinopterygii sort1a 33 32
  • 66.22 (n)
 OneToMany
sort1b 33
  • 60 (a)
 OneToMany
SORT1 (2 of 3) 33
  • 44 (a)
 OneToMany
baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes -- 33
  • 21 (a)
 ManyToMany
-- 33
  • 16 (a)
 ManyToMany
-- 33
  • 15 (a)
 ManyToMany
-- 33
  • 15 (a)
 ManyToMany
PEP1 33
  • 9 (a)
 ManyToMany
VTH2 35 33
  • 8 (a)
VTH1 33
  • 8 (a)
 ManyToMany
-- 33
  • 6 (a)
 ManyToMany
sea squirt
(Ciona savignyi)
 Ascidiacea CSA.4778 33
  • 32 (a)
 OneToOne
Species where no ortholog for SORT1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • chicken (Gallus gallus)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for SORT1 Gene

ENSEMBL:
Gene Tree for SORT1 (if available)
TreeFam:
Gene Tree for SORT1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SORT1: view image

Paralogs for SORT1 Gene

Paralogs for SORT1 Gene

genes like me logo Genes that share paralogs with SORT1: view

Variants for SORT1 Gene

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  1. SNP Genotyping and Copy Number Assay

Polymorphic Variants from UniProtKB/Swiss-Prot for SORT1 Gene

SORT_HUMAN-Q99523
Genetic variations in SORT1 influence low density lipoprotein cholesterol (LDL-C) variability and contribute to the low density lipoprotein cholesterol level quantitative trait locus 6 (LDLCQ6) [MIM:613589].

Sequence variations from dbSNP and Humsavar for SORT1 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs1000022847 -- 109,361,699(-) C/A/G intron_variant
rs1000059151 -- 109,313,680(-) A/C 3_prime_UTR_variant
rs1000078040 -- 109,355,387(-) C/A coding_sequence_variant, missense_variant
rs1000115090 -- 109,323,635(-) G/A intron_variant
rs1000246977 -- 109,373,285(-) C/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for SORT1 Gene

Variant ID Type Subtype PubMed ID
dgv252n100 CNV gain 25217958
esv3567303 CNV deletion 23714750
nsv1003653 CNV gain 25217958
nsv1118121 CNV deletion 24896259
nsv951390 CNV duplication 24416366

Variation tolerance for SORT1 Gene

Residual Variation Intolerance Score: 48.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.82; 47.73% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SORT1 Gene

Human Gene Mutation Database (HGMD)
SORT1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SORT1

SNP Genotyping and Copy Number Assay Products

Disorders for SORT1 Gene

MalaCards: The human disease database

(4) MalaCards diseases for SORT1 Gene - From: HGMD, OMIM, GTR, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
low density lipoprotein cholesterol level quantitative trait locus 6
  • ldlcq6
myocardial infarction
  • myocardial infarction, susceptibility to
inclusion-cell disease
  • mucolipidosis ii
frontotemporal dementia
  • ftd
- elite association - COSMIC cancer census association via MalaCards
Search SORT1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SORT_HUMAN
  • Note=A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.

Additional Disease Information for SORT1

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 SORT1: view

No data available for Genatlas for SORT1 Gene

Publications for SORT1 Gene

  1. Internalization and trafficking of neurotensin via NTS3 receptors in HT29 cells. (PMID: 15313463) Morinville A … Mazella J (The international journal of biochemistry & cell biology 2004) 3 4 23 56
  2. Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia. (PMID: 12598608) Martin S … Mazella J (The Journal of neuroscience : the official journal of the Society for Neuroscience 2003) 3 4 23 56
  3. Shedding of the luminal domain of the neurotensin receptor-3/sortilin in the HT29 cell line. (PMID: 12419319) Navarro V … Mazella J (Biochemical and biophysical research communications 2002) 3 4 23 56
  4. Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding. (PMID: 9927419) Munck Petersen C … Madsen P (The EMBO journal 1999) 3 4 23 56
  5. The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal sorting. (PMID: 22431521) Mamo A … Lefrancois S (Molecular and cellular biology 2012) 3 4 56

ExternalLinks

View latest publications for SORT1 gene in Mastermind

Products for SORT1 Gene

  • Addgene plasmids for SORT1

Sources for SORT1 Gene