SH3BP1
protein-codingSH3 domain binding protein 1, the group of AH/BAR family Rho GTPase activating proteins|N-BAR domain containing
Gene summary
This gene encodes a member of the Rho GTPase activating protein (RhoGAP) family. The encoded protein regulates Rac signaling and plays a role in cytoskeletal dynamics, cell motility and epithelial junction formation. This protein's association with the exocyst complex, which tethers secretory vesicles to the plasma membrane, has been demonstrated to be important in cell motility. In a distinct complex, this protein has been shown to regulate epithelial junction formation and morphogenesis. By interacting with the Plexin-D1 cell surface receptor, this protein mediates changes in the cytoskeleton in response to semaphorin binding. This protein may promote metastasis in human liver cancer cells and tissues. [provided by RefSeq, Mar 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.5 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 SH3BP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018957.6. 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 | 1 | 1 | 1 | 3 | ||
| missense | 123 | 2 | 125 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 129 | 3 | 1 | 133 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061830.3 | 18 | MANE Select | |
| Ensembl | ENSP00000497104.1 | 18 | MANE Select | |
| RefSeq | NP_001336984.1 | 18 | Standard | |
| Ensembl | ENSP00000411979.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- phagocytosis, engulfment
- actin filament organization
- cell migration
- regulation of actin filament depolymerization
- regulation of actin cytoskeleton organization
Molecular Function
- GTPase activator activity
- protein binding
- SH3 domain binding
- semaphorin receptor binding
- Rac GTPase binding
Cellular Component
- exocyst
- phagocytic cup
- nucleus
- cytosol
- adherens junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000357436
- Coding exons
- 18
- Length
- 32279
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125748
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.58 | 305 | 393 | 0.776 | 0.0000231 | 4425 |
| Missense (PolyPhen) | 107 | 157.99 | 0.67724 | 1818 | ||
| Synonymous | -0.244 | 172 | 168 | 1.02 | 0.0000106 | 1465 |
| Loss of Function | 3.45 | 9 | 29.1 | 0.310 | 0.00000123 | 361 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00014 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00010 | 0.000097 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: GTPase activating protein (GAP) which specifically converts GTP-bound Rho-type GTPases including RAC1 and CDC42 in their inactive GDP-bound form. By specifically inactivating RAC1 at the leading edge of migrating cells, it regulates the spatiotemporal organization of cell protrusions which is important for proper cell migration (PubMed:21658605). Also negatively regulates CDC42 in the process of actin remodeling and the formation of epithelial cell junctions (PubMed:22891260). Through its GAP activity toward RAC1 and/or CDC42 plays a specific role in phagocytosis of large particles. Specifically recruited by a PI3 kinase/PI3K-dependent mechanism to sites of large particles engagement, inactivates RAC1 and/or CDC42 allowing the reorganization of the underlying actin cytoskeleton required for engulfment (PubMed:26465210). It also plays a role in angiogenesis and the process of repulsive guidance as part of a semaphorin- plexin signaling pathway. Following the binding of PLXND1 to extracellular SEMA3E it dissociates from PLXND1 and inactivates RAC1, inducing the intracellular reorganization of the actin cytoskeleton and the collapse of cells (PubMed:24841563). {ECO:0000269|PubMed:21658605, ECO:0000269|PubMed:22891260, ECO:0000269|PubMed:24841563, ECO:0000269|PubMed:26465210}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.420
- RVIS EVS
- 0.47
- RVIS percentile EVS
- 78.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.758
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |