GAB1

GRB2 associated binding protein 1, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 4:143336875-143474565

Previous symbols: [ "DFNB26" ]

Links

ENSG00000109458 ∙ NCBI:2549 ∙ OMIM:604439 ∙ HGNC:4066 ∙ Uniprot:Q13480 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 26 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 26	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	29408807
Individuals with heterozygous variants in METTL13 may not develop deafness

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GAB1 gene.

• Inborn genetic diseases (19 variants)
• not provided (9 variants)
• Autosomal recessive nonsyndromic hearing loss 26 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GAB1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense	1		18	1		20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					9	9
Total	1	0	18	1	9

Variants in GAB1

This is a list of pathogenic ClinVar variants found in the GAB1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-143336967-C-T			Benign (May 12, 2021)
4-143337239-G-C		GAB1-related disorder	Benign (Apr 24, 2019)
4-143415514-G-A		not specified	Uncertain significance (Sep 12, 2023)
4-143415579-A-G		not specified	Uncertain significance (May 09, 2022)
4-143415751-G-A		Autosomal recessive nonsyndromic hearing loss 26	Pathogenic (Oct 15, 2018)
4-143415931-T-TG			Benign (Jun 03, 2021)
4-143433599-C-A		not specified	Uncertain significance (Sep 22, 2023)
4-143433620-A-G		not specified	Likely benign (Mar 24, 2023)
4-143433625-C-A		not specified	Uncertain significance (Mar 12, 2024)
4-143433625-C-T		not specified	Uncertain significance (Apr 20, 2023)
4-143433704-C-G		not specified	Uncertain significance (Jun 06, 2023)
4-143433705-C-T		GAB1-related disorder	Likely benign (Apr 22, 2019)
4-143438001-C-T		not specified	Uncertain significance (Sep 27, 2022)
4-143438042-T-G		not specified	Uncertain significance (Mar 05, 2024)
4-143438159-G-T		not specified	Uncertain significance (Oct 20, 2021)
4-143438214-T-C		not specified	Uncertain significance (May 30, 2023)
4-143438235-G-A		not specified	Uncertain significance (Jul 20, 2021)
4-143438248-T-A		not specified	Uncertain significance (Dec 16, 2022)
4-143438286-C-T		not specified	Uncertain significance (Oct 20, 2023)
4-143438420-G-A		not specified	Uncertain significance (Dec 19, 2022)
4-143438452-T-C		GAB1-related disorder	Likely benign (May 28, 2019)
4-143438502-C-T		not specified	Uncertain significance (Dec 15, 2023)
4-143438558-A-G		not specified	Uncertain significance (Sep 06, 2022)
4-143439755-G-A			Benign (May 12, 2021)
4-143439882-C-A		not specified	Uncertain significance (Jul 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GAB1	protein_coding	protein_coding	ENST00000262995	11	137807

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.184	0.816	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.56	311	399	0.780	0.0000209	4746
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000914	0.0000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.000124	0.0000980
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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);Ras signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);EGF-Ncore;Signaling Pathways in Glioblastoma;Androgen Receptor Network in Prostate Cancer;B Cell Receptor Signaling Pathway;Alpha 6 Beta 4 signaling pathway;Signaling of Hepatocyte Growth Factor Receptor;IL-6 signaling pathway;BDNF-TrkB Signaling;VEGFA-VEGFR2 Signaling Pathway;ESC Pluripotency Pathways;MET in type 1 papillary renal cell carcinoma;Ras Signaling;EGF-EGFR Signaling Pathway;Insulin Signaling;ErbB Signaling Pathway;Developmental Biology;Signaling by FGFR2;PI-3K cascade:FGFR2;Downstream signaling of activated FGFR2;PI-3K cascade:FGFR4;PI-3K cascade:FGFR3;Downstream signaling of activated FGFR3;Disease;Signaling by FGFR3;Signal Transduction;Downstream signaling of activated FGFR4;Signaling by FGFR4;Signaling by FGFR;Alpha6Beta4Integrin;PI3K Cascade;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;HGF;FGF;Signaling by FGFR2 in disease;Fibroblast growth factor-1;MET activates RAP1 and RAC1;BCR;Signaling by EGFR;EGFR1;SHP2 signaling;ErbB1 downstream signaling;GAB1 signalosome;Signaling events mediated by TCPTP;PIP3 activates AKT signaling;Signaling events regulated by Ret tyrosine kinase;IL3;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Signaling by EGFRvIII in Cancer;Signaling by EGFR in Cancer;EPO signaling pathway;Signaling by FGFR3 point mutants in cancer;Signaling by FGFR4 in disease;RET signaling;Axon guidance;Signaling by FGFR3 fusions in cancer;Signaling by FGFR3 in disease;Signaling by FGFR in disease;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K events in ERBB2 signaling;Signaling by ERBB2;PI3K/AKT Signaling in Cancer;IL6;IRS-related events triggered by IGF1R;IGF1R signaling cascade;TNFalpha;MET activates PI3K/AKT signaling;MET promotes cell motility;Signaling by FGFR1 in disease;Signaling by MET;Constitutive Signaling by EGFRvIII;Signaling by Receptor Tyrosine Kinases;Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants;Signaling by Ligand-Responsive EGFR Variants in Cancer;MET activates PTPN11;Intracellular signaling by second messengers;Neurotrophic factor-mediated Trk receptor signaling;LPA receptor mediated events;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Signaling events mediated by Stem cell factor receptor (c-Kit);Trk receptor signaling mediated by PI3K and PLC-gamma;PDGFR-beta signaling pathway;Downstream signaling of activated FGFR1;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);IL6-mediated signaling events;FGF signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;PI-3K cascade:FGFR1;Signaling by FGFR1 (Consensus)

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.582
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.561
• hipred: Y
• hipred_score: 0.746
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.914

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gab1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: gab1
• Affected structure: embryo development
• Phenotype tag: abnormal
• Phenotype quality: arrested

Gene ontology

• Biological process: angiogenesis;epidermal growth factor receptor signaling pathway;axon guidance;cell population proliferation;insulin receptor signaling pathway;positive regulation of phosphatidylinositol 3-kinase signaling;actin cytoskeleton reorganization;response to hepatocyte growth factor;phosphatidylinositol-3-phosphate biosynthetic process;vascular endothelial growth factor signaling pathway;positive regulation of cell migration by vascular endothelial growth factor signaling pathway;ERBB2 signaling pathway;positive regulation of angiogenesis;phosphatidylinositol phosphorylation;positive regulation of protein kinase B signaling;endothelial cell chemotaxis to vascular endothelial growth factor
• Cellular component: cytosol
• Molecular function: SH3/SH2 adaptor activity;protein binding;1-phosphatidylinositol-3-kinase activity;phosphatidylinositol-4,5-bisphosphate 3-kinase activity