This gene encodes a member of the SPFH domain-containing family of lipid raft-associated proteins. The encoded protein is localized to lipid rafts of the endoplasmic reticulum and plays a critical role in inositol 1,4,5-trisphosphate (IP3) signaling by mediating ER-associated degradation of activated IP3 receptors. Mutations in this gene are a cause of spastic paraplegia-18 (SP... See more...

Aliases for ERLIN2 Gene

Aliases for ERLIN2 Gene

  • ER Lipid Raft Associated 2 2 3 5
  • Erlin-2 3 3 4
  • Stomatin-Prohibitin-Flotillin-HflC/K Domain-Containing Protein 2 3 4
  • Endoplasmic Reticulum Lipid Raft-Associated Protein 2 3 4
  • Spastic Paraplegia 18 (Autosomal Dominant) 2 3
  • SPFH Domain Family, Member 2 2 3
  • C8orf2 3 4
  • SPFH2 3 4
  • Epididymis Secretory Sperm Binding Protein 3
  • Chromosome 8 Open Reading Frame 2 2
  • SPFH Domain-Containing Protein 2 4
  • NET32 3
  • SPG18 3

External Ids for ERLIN2 Gene

Previous HGNC Symbols for ERLIN2 Gene

  • C8orf2
  • SPFH2
  • SPG18

Previous GeneCards Identifiers for ERLIN2 Gene

  • GC08P037715
  • GC08P037594
  • GC08P036128

Summaries for ERLIN2 Gene

Entrez Gene Summary for ERLIN2 Gene

  • This gene encodes a member of the SPFH domain-containing family of lipid raft-associated proteins. The encoded protein is localized to lipid rafts of the endoplasmic reticulum and plays a critical role in inositol 1,4,5-trisphosphate (IP3) signaling by mediating ER-associated degradation of activated IP3 receptors. Mutations in this gene are a cause of spastic paraplegia-18 (SPG18). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

GeneCards Summary for ERLIN2 Gene

ERLIN2 (ER Lipid Raft Associated 2) is a Protein Coding gene. Diseases associated with ERLIN2 include Spastic Paraplegia 18, Autosomal Recessive and Recessive Intellectual Disability-Motor Dysfunction-Multiple Joint Contractures Syndrome. Among its related pathways are FGFR1 mutant receptor activation and CDK-mediated phosphorylation and removal of Cdc6. An important paralog of this gene is ERLIN1.

UniProtKB/Swiss-Prot Summary for ERLIN2 Gene

  • Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1 (PubMed:19240031, PubMed:17502376). Promotes sterol-accelerated ERAD of HMGCR probably implicating an AMFR/gp78-containing ubiquitin ligase complex (PubMed:21343306). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. May promote ER retention of the SCAP-SREBF complex (PubMed:24217618).

Gene Wiki entry for ERLIN2 Gene

Additional gene information for ERLIN2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ERLIN2 Gene

Genomics for ERLIN2 Gene

GeneHancer (GH) Regulatory Elements for ERLIN2 Gene

Promoters and enhancers for ERLIN2 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 ERLIN2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ERLIN2

Top Transcription factor binding sites by QIAGEN in the ERLIN2 gene promoter:
  • AhR
  • C/EBPalpha
  • COMP1
  • Pbx1a
  • STAT5A

Genomic Locations for ERLIN2 Gene

Genomic Locations for ERLIN2 Gene
chr8:37,736,579-37,758,422
(GRCh38/hg38)
Size:
21,844 bases
Orientation:
Plus strand
chr8:37,594,097-37,616,619
(GRCh37/hg19)
Size:
22,523 bases
Orientation:
Plus strand

Genomic View for ERLIN2 Gene

Genes around ERLIN2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ERLIN2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ERLIN2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ERLIN2 Gene

Proteins for ERLIN2 Gene

  • Protein details for ERLIN2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O94905-ERLN2_HUMAN
    Recommended name:
    Erlin-2
    Protein Accession:
    O94905
    Secondary Accessions:
    • A0JLQ1
    • A8K5S9
    • B4DM38
    • D3DSW0
    • Q6NW21
    • Q86VS6
    • Q86W49

    Protein attributes for ERLIN2 Gene

    Size:
    339 amino acids
    Molecular mass:
    37840 Da
    Quaternary structure:
    • Forms a heteromeric complex with ERLIN1. In complex with ERLIN1, interacts with RNF170 (PubMed:19240031, PubMed:21610068). Interacts with activated ITPR1, independently of the degree of ITPR1 polyubiquitination (By similarity). Interacts with SCAP, INSIG1, SREBF1 and SREBF2 under cholesterol sufficiency conditions; indicative for an association with the SCAP-SREBP-INSIG complex (PubMed:24217618). Probably part of an AMFR/gp78 and INSIG1-containing ubiquitin ligase complex involved in ERAD of HMGCR. Interacts with TMUB1; TMUB1 bridges the association with AMFR. Interacts with SYVN1 and RNF139 (PubMed:21343306). Interacts with TMEM259 (By similarity).
    SequenceCaution:
    • Sequence=AAH50611.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for ERLIN2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ERLIN2 Gene

Post-translational modifications for ERLIN2 Gene

  • Glycosylation at Asn106, Thr334, and Thr336
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • ERLN2_HUMAN (1222)

No data available for DME Specific Peptides for ERLIN2 Gene

Domains & Families for ERLIN2 Gene

Gene Families for ERLIN2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Potential drug targets
  • Predicted intracellular proteins
  • Transporters

Protein Domains for ERLIN2 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for ERLIN2 Gene

GenScript: Design optimal peptide antigens:
  • Stomatin-prohibitin-flotillin-HflC/K domain-containing protein 2 (ERLN2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O94905

UniProtKB/Swiss-Prot:

ERLN2_HUMAN :
  • Belongs to the band 7/mec-2 family.
Family:
  • Belongs to the band 7/mec-2 family.
genes like me logo Genes that share domains with ERLIN2: view

Function for ERLIN2 Gene

Molecular function for ERLIN2 Gene

UniProtKB/Swiss-Prot Function:
Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1 (PubMed:19240031, PubMed:17502376). Promotes sterol-accelerated ERAD of HMGCR probably implicating an AMFR/gp78-containing ubiquitin ligase complex (PubMed:21343306). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. May promote ER retention of the SCAP-SREBF complex (PubMed:24217618).

Phenotypes From GWAS Catalog for ERLIN2 Gene

Gene Ontology (GO) - Molecular Function for ERLIN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 19240031
GO:0015485 cholesterol binding IBA 21873635
GO:0031625 ubiquitin protein ligase binding IPI 24019521
genes like me logo Genes that share ontologies with ERLIN2: view
genes like me logo Genes that share phenotypes with ERLIN2: view

Human Phenotype Ontology for ERLIN2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ERLIN2 Gene

MGI Knock Outs for ERLIN2:
  • Erlin2 Erlin2<tm1a(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for ERLIN2 Gene

Localization for ERLIN2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ERLIN2 Gene

Endoplasmic reticulum membrane; Single-pass type II membrane protein. Note=Associated with lipid raft-like domains of the endoplasmic reticulum membrane.

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 ERLIN2 gene
Compartment Confidence
endoplasmic reticulum 5
plasma membrane 4
cytosol 4
extracellular 2
mitochondrion 2
cytoskeleton 1
peroxisome 1
nucleus 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ERLIN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IEA,IDA --
GO:0005789 endoplasmic reticulum membrane TAS --
GO:0005829 cytosol IDA --
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with ERLIN2: view

Pathways & Interactions for ERLIN2 Gene

genes like me logo Genes that share pathways with ERLIN2: view

Pathways by source for ERLIN2 Gene

Gene Ontology (GO) - Biological Process for ERLIN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006629 lipid metabolic process IEA --
GO:0008202 steroid metabolic process IEA --
GO:0008203 cholesterol metabolic process IEA --
GO:0030433 ubiquitin-dependent ERAD pathway IEA,IDA 19240031
GO:0032933 SREBP signaling pathway IBA,IMP 24217618
genes like me logo Genes that share ontologies with ERLIN2: view

No data available for SIGNOR curated interactions for ERLIN2 Gene

Drugs & Compounds for ERLIN2 Gene

No Compound Related Data Available

Transcripts for ERLIN2 Gene

mRNA/cDNA for ERLIN2 Gene

5 REFSEQ mRNAs :
22 NCBI additional mRNA sequence :
11 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 ERLIN2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13 ^ 14
SP1:
SP2:
SP3:
SP4: -

Relevant External Links for ERLIN2 Gene

GeneLoc Exon Structure for
ERLIN2

Expression for ERLIN2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ERLIN2 Gene

Protein differential expression in normal tissues from HIPED for ERLIN2 Gene

This gene is overexpressed in Nasal epithelium (29.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ERLIN2 Gene



Protein tissue co-expression partners for ERLIN2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ERLIN2

SOURCE GeneReport for Unigene cluster for ERLIN2 Gene:

Hs.705490

mRNA Expression by UniProt/SwissProt for ERLIN2 Gene:

O94905-ERLN2_HUMAN
Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for ERLIN2 Gene

  • Liver(4.4)
  • Nervous system(4.4)
  • Intestine(4.2)
  • Lymph node(4.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ERLIN2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • eye
  • face
  • head
  • jaw
  • lip
  • mouth
  • pharynx
  • skull
  • tongue
Thorax:
  • esophagus
  • lung
  • rib
  • rib cage
Abdomen:
  • stomach
Pelvis:
  • pelvis
Limb:
  • foot
  • lower limb
  • upper limb
General:
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with ERLIN2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for ERLIN2 Gene

Orthologs for ERLIN2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for ERLIN2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ERLIN2 31 30
  • 100 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ERLIN2 31
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ERLIN2 31 30
  • 91.49 (n)
OneToOne
cow
(Bos Taurus)
Mammalia ERLIN2 31 30
  • 90.53 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ERLIN2 31
  • 90 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Erlin2 30
  • 89.97 (n)
mouse
(Mus musculus)
Mammalia Erlin2 17 31 30
  • 89.28 (n)
chicken
(Gallus gallus)
Aves ERLIN2 31 30
  • 79.15 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ERLIN2 31
  • 78 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia erlin2 30
  • 75.96 (n)
Str.17534 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.31380 30
zebrafish
(Danio rerio)
Actinopterygii ERLIN2 31
  • 79 (a)
OneToMany
erlin2 31 30
  • 72.7 (n)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea erl-1 31 30
  • 60.77 (n)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G03510 30
  • 59.93 (n)
rice
(Oryza sativa)
Liliopsida Os03g0421400 30
  • 62.15 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.11132 31
  • 64 (a)
OneToMany
Species where no ortholog for ERLIN2 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)
  • baker's yeast (Saccharomyces cerevisiae)
  • 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 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)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ERLIN2 Gene

ENSEMBL:
Gene Tree for ERLIN2 (if available)
TreeFam:
Gene Tree for ERLIN2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ERLIN2: view image

Paralogs for ERLIN2 Gene

Paralogs for ERLIN2 Gene

(2) SIMAP similar genes for ERLIN2 Gene using alignment to 3 proteins:

  • ERLN2_HUMAN
  • E5RHW4_HUMAN
  • E5RJ09_HUMAN
genes like me logo Genes that share paralogs with ERLIN2: view

Variants for ERLIN2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ERLIN2 Gene

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
639125 Pathogenic: Spastic paraplegia 37,737,964(+) CT/C FRAMESHIFT_VARIANT
679568 Likely Benign: not provided 37,749,445(+) C/T INTRON_VARIANT
682602 Likely Benign: not provided 37,744,335(+) G/A INTRON_VARIANT
697353 Likely Benign: not provided 37,749,862(+) C/T INTRON_VARIANT
697384 Likely Benign: not provided 37,753,481(+) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for ERLIN2 Gene

Structural Variations from Database of Genomic Variants (DGV) for ERLIN2 Gene

Variant ID Type Subtype PubMed ID
nsv1075549 CNV deletion 25765185

Variation tolerance for ERLIN2 Gene

Residual Variation Intolerance Score: 15.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.40; 8.81% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ERLIN2 Gene

Human Gene Mutation Database (HGMD)
ERLIN2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ERLIN2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ERLIN2 Gene

Disorders for ERLIN2 Gene

MalaCards: The human disease database

(21) MalaCards diseases for ERLIN2 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
spastic paraplegia 18, autosomal recessive
  • spg18
recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome
  • spastic paraplegia 18, autosomal recessive
spastic paraplegia 18
  • spastic paraplegia 18, autosomal recessive
primary lateral sclerosis, juvenile
  • plsj
paraplegia
  • paraplegia, lower
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

ERLN2_HUMAN
  • Spastic paraplegia 18, autosomal recessive (SPG18) [MIM:611225]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG18 is a severe form with onset in early childhood. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures. {ECO:0000269 PubMed:21330303}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for ERLIN2

genes like me logo Genes that share disorders with ERLIN2: view

No data available for Genatlas for ERLIN2 Gene

Publications for ERLIN2 Gene

  1. Erlin-1 and erlin-2 are novel members of the prohibitin family of proteins that define lipid-raft-like domains of the ER. (PMID: 16835267) Browman DT … Robbins SM (Journal of cell science 2006) 2 3 4 54
  2. Cloning and characterization of a novel gene (C8orf2), a human representative of a novel gene family with homology to C. elegans C42.C1.9. (PMID: 10449903) Ikegawa S … Nakamura Y (Cytogenetics and cell genetics 1999) 2 3 4 54
  3. Erlins restrict SREBP activation in the ER and regulate cellular cholesterol homeostasis. (PMID: 24217618) Huber MD … Gerace L (The Journal of cell biology 2013) 3 4 54
  4. Membrane-associated ubiquitin ligase complex containing gp78 mediates sterol-accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. (PMID: 21343306) Jo Y … DeBose-Boyd RA (The Journal of biological chemistry 2011) 3 4 54
  5. A nullimorphic ERLIN2 mutation defines a complicated hereditary spastic paraplegia locus (SPG18). (PMID: 21796390) Alazami AM … Alkuraya FS (Neurogenetics 2011) 2 3 54

Products for ERLIN2 Gene

Sources for ERLIN2 Gene