IGSF8
protein-codingimmunoglobulin superfamily member 8, the group of V-set domain containing|CD molecules
Gene summary
This gene encodes a member the EWI subfamily of the immunoglobulin protein superfamily. Members of this family contain a single transmembrane domain, an EWI (Glu-Trp-Ile)-motif and a variable number of immunoglobulin domains. This protein interacts with the tetraspanins CD81 and CD9 and may regulate their role in certain cellular functions including cell migration and viral infection. The encoded protein may also function as a tumor suppressor by inhibiting the proliferation of certain cancers. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IGSF8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_052868.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 1 | 4 | ||
| missense | 110 | 110 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 114 | 1 | 1 | 116 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_443100.1 | 6 | MANE Select | |
| Ensembl | ENSP00000316664.7 | 6 | MANE Select | |
| RefSeq | NP_001193594.1 | 6 | Standard | |
| RefSeq | NP_001307176.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Beta1 integrin cell surface interactions
- Alpha4 beta1 integrin signaling events
Biological Process
- single fertilization
- nervous system development
- skeletal muscle tissue development
- cell population proliferation
- cell motility
Molecular Function
- protein binding
Cellular Component
- plasma membrane
- membrane
- integral component of membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368086
- Coding exons
- 6
- Length
- 7604
- Individuals with no LoFs
- 125664
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 82
- Defined
- 125747
- p
- 0.000330
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.439 | 377 | 402 | 0.938 | 0.0000262 | 3786 |
| Missense (PolyPhen) | 182 | 198.83 | 0.91533 | 1866 | ||
| Synonymous | 0.765 | 153 | 166 | 0.924 | 0.00000977 | 1453 |
| Loss of Function | 1.35 | 20 | 27.6 | 0.724 | 0.00000191 | 235 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00066 | 0.00065 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00043 | 0.00041 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a key role in diverse functions ascribed to CD81 and CD9 such as oocytes fertilization or hepatitis C virus function. May regulate proliferation and differentiation of keratinocytes. May be a negative regulator of cell motility: suppresses T-cell mobility coordinately with CD81, associates with CD82 to suppress prostate cancer cell migration, regulates epidermoid cell reaggregation and motility on laminin-5 with CD9 and CD81 as key linkers. May also play a role on integrin- dependent morphology and motility functions. May participate in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain. {ECO:0000269|PubMed:11504738, ECO:0000269|PubMed:12750295, ECO:0000269|PubMed:12752121, ECO:0000269|PubMed:14662754, ECO:0000269|PubMed:15070678}.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.837
- RVIS EVS
- -1.37
- RVIS percentile EVS
- 4.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.794
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |