VSIG4
protein-codingV-set and immunoglobulin domain containing 4, the group of Complement system regulators and receptors|V-set domain containing
Gene summary
This gene encodes a v-set and immunoglobulin-domain containing protein that is structurally related to the B7 family of immune regulatory proteins. The encoded protein may be a negative regulator of T-cell responses. This protein is also a receptor for the complement component 3 fragments C3b and iC3b. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.4 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 VSIG4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007268.3. 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 | 13 | 3 | 16 | |||
| missense | 84 | 6 | 4 | 94 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 109 | 9 | 4 | 122 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009199.1 | 8 | MANE Select | |
| Ensembl | ENSP00000363869.4 | 8 | MANE Select | |
| RefSeq | NP_001093901.1 | 7 | Standard | |
| RefSeq | NP_001171759.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Complement and coagulation cascades - Homo sapiens (human)
- Human Complement System
Biological Process
- complement activation, alternative pathway
- negative regulation of interleukin-2 production
- negative regulation of T cell proliferation
- negative regulation of macrophage activation
Cellular Component
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374737
- Coding exons
- 8
- Length
- 18388
- Individuals with no LoFs
- 125587
- Homozygous LoFs
- 26
- Heterozygous LoFs
- 48
- Defined
- 125661
- p
- 0.000294
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.43 | 208 | 158 | 1.32 | 0.0000123 | 2584 |
| Missense (PolyPhen) | 43 | 42.333 | 1.0158 | 783 | ||
| Synonymous | -1.62 | 78 | 61.8 | 1.26 | 0.00000482 | 802 |
| Loss of Function | -0.263 | 13 | 12.0 | 1.08 | 8.45e-7 | 204 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000037 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00039 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00077 | 0.00054 | rare |
| South Asian | 0.00027 | 0.00016 | rare |
| Other | 0.00045 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Phagocytic receptor, strong negative regulator of T-cell proliferation and IL2 production. Potent inhibitor of the alternative complement pathway convertases. {ECO:0000269|PubMed:17016562, ECO:0000269|PubMed:17051150}.;
Recessive Scores
- pRec
- 0.0965
Intolerance Scores
- LoFtool
- 0.888
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.151
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |