GAB3

protein-coding

GRB2 associated binding protein 3, the group of Pleckstrin homology domain containing

Gene summary

This gene is a member of the GRB2-associated binding protein gene family. These proteins are scaffolding/docking proteins that are involved in several growth factor and cytokine signaling pathways, and they contain a pleckstrin homology domain, and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. The protein encoded by this gene facilitates macrophage differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

MANE transcript

NM_001081573.3

Inheritance

—

ClinVar variants

U:154B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chrX:154,675,249-154,751,583

External References & Databases

Ensembl (ENSG00000160219)

Transcript & Mutation Effects

hg38 • Region Span ~76.3 kb

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GenCC 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 GAB3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 59

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001081573.3. 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			16 clinvar		1 clinvar	17
missense			111 clinvar	1 clinvar	1 clinvar	113
nonsense			10 clinvar			10
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			17 clinvar			17
Total	0	0	154	1	2	157

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001081573.3	RefSeq	NP_001075042.1	10	MANE Select
ENST00000424127.3	Ensembl	ENSP00000399588.2	10	MANE Select
NM_001282283.2	RefSeq	NP_001269212.1	9	Standard
NM_080612.4	RefSeq	NP_542179.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

macrophage differentiation

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000424127
Coding exons: 10
Length: 76330
Individuals with no LoFs: 125325
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125327
p: 0.00000798

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	161	223	0.723	0.0000174	3830
Missense (PolyPhen)		41	67.061	0.61139		1120
Synonymous	0.850	76	86.0	0.883	0.00000670	1165
Loss of Function	3.55	2	18.5	0.108	0.00000144	318

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.000014	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.102

Intolerance Scores

RVIS EVS: -0.05
RVIS percentile EVS: 50.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.734

Gene Damage Prediction

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