GAB1
protein-codingGRB2 associated binding protein 1, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes
Gene summary
The protein encoded by this gene is a member of the IRS1-like multisubstrate docking protein family. It is an important mediator of branching tubulogenesis and plays a central role in cellular growth response, transformation and apoptosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
- DFNB26
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~137.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0011553
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic
Intervention: Audiologic/Otolaryngologic
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development
Comments: Individuals with heterozygous variants in METTL13 may not develop deafness
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GAB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002039.4. 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 | 7 | 1 | 8 | |||
| missense | 1 | 1 | 80 | 1 | 83 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 1 | 80 | 8 | 1 | 91 |
Highest pathogenic variant AF is 0.000026046868
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002030.2 | 10 | MANE Select | |
| Ensembl | ENSP00000262994.4 | 10 | MANE Select | |
| RefSeq | NP_997006.1 | 11 | Standard | |
| Ensembl | ENSP00000262995.4 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gab1 | Danio rerio | Structure: embryo development Quality: arrested abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gastric cancer - Homo sapiens (human)
- Renal cell carcinoma - Homo sapiens (human)
- Neurotrophin signaling pathway - Homo sapiens (human)
- ErbB signaling pathway - Homo sapiens (human)
- Hepatocellular carcinoma - Homo sapiens (human)
Biological Process
- angiogenesis
- epidermal growth factor receptor signaling pathway
- axon guidance
- cell population proliferation
- insulin receptor signaling pathway
Molecular Function
- SH3/SH2 adaptor activity
- protein binding
- 1-phosphatidylinositol-3-kinase activity
- phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262995
- Coding exons
- 11
- Length
- 137807
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125748
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.56 | 311 | 399 | 0.780 | 0.0000209 | 4746 |
| Missense (PolyPhen) | 100 | 168.92 | 0.59199 | 1921 | ||
| Synonymous | 0.661 | 132 | 142 | 0.929 | 0.00000766 | 1416 |
| Loss of Function | 4.02 | 8 | 32.8 | 0.244 | 0.00000201 | 382 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000091 | 0.000088 | rare |
| South Asian | 0.00012 | 0.000098 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adapter protein that plays a role in intracellular signaling cascades triggered by activated receptor-type kinases. Plays a role in FGFR1 signaling. Probably involved in signaling by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR). Involved in the MET/HGF-signaling pathway (PubMed:29408807). {ECO:0000269|PubMed:29408807}.;
- Disease
- DISEASE: Deafness, autosomal recessive, 26 (DFNB26) [MIM:605428]: A form of non-syndromic sensorineural deafness characterized by prelingual, severe to profound hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:29408807}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.138
Intolerance Scores
- LoFtool
- 0.582
- RVIS EVS
- 0
- RVIS percentile EVS
- 53.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |