SORBS3
protein-codingsorbin and SH3 domain containing 3
Gene summary
This gene encodes an SH3 domain-containing adaptor protein. The presence of SH3 domains play a role in this protein's ability to bind other cytoplasmic molecules and contribute to cystoskeletal organization, cell adhesion and migration, signaling, and gene expression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.8 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 SORBS3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005775.5. 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 | 4 | 4 | 3 | 11 | ||
| missense | 151 | 10 | 6 | 167 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 159 | 14 | 9 | 182 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005766.3 | 20 | MANE Select | |
| Ensembl | ENSP00000240123.7 | 20 | MANE Select | |
| RefSeq | NP_001018003.1 | 9 | Standard | |
| Ensembl | ENSP00000429723.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sorbs3 | Danio rerio | Structure: dorsal root ganglion Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Smooth Muscle Contraction
- Muscle contraction
Biological Process
- negative regulation of transcription by RNA polymerase II
- muscle contraction
- actin filament organization
- cell adhesion
- cell-substrate adhesion
Molecular Function
- structural constituent of cytoskeleton
- protein binding
- transcription factor binding
- vinculin binding
Cellular Component
- nucleus
- cytosol
- cytoskeleton
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000240123
- Coding exons
- 20
- Length
- 30803
- Individuals with no LoFs
- 125650
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 98
- Defined
- 125748
- p
- 0.000390
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.924 | 476 | 423 | 1.13 | 0.0000264 | 4299 |
| Missense (PolyPhen) | 164 | 168.72 | 0.97203 | 1724 | ||
| Synonymous | -0.216 | 172 | 168 | 1.02 | 0.0000108 | 1362 |
| Loss of Function | 2.61 | 25 | 43.6 | 0.574 | 0.00000232 | 446 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00031 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.0012 | 0.0012 | notable |
| European (Non-Finnish) | 0.00041 | 0.00039 | rare |
| South Asian | 0.00040 | 0.00039 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Vinexin alpha isoform promotes up-regulation of actin stress fiber formation. Vinexin beta isoform plays a role in cell spreading and enhances the activation of JNK/SAPK in response to EGF stimulation by using its third SH3 domain.;
Recessive Scores
- pRec
- 0.163
Intolerance Scores
- LoFtool
- 0.905
- RVIS EVS
- 0.26
- RVIS percentile EVS
- 69.72
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.906
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |