GAB2

Chr 11

GRB2 associated binding protein 2

NCBI Gene: 9846 ENSG00000033327 UniProt: Q9UQC2 OMIM: 606203

This gene is a member of the GRB2-associated binding protein (GAB) gene family. These proteins contain pleckstrin homology (PH) domain, and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. They act as adapters for transmitting various signals in response to stimuli through cytokine and growth factor receptors, and T- and B-cell antigen receptors. The protein encoded by this gene is the principal activator of phosphatidylinositol-3 kinase in response to activation of the high affinity IgE receptor. Two alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.983

Z-score 4.41

OE 0.13 (0.07–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

-0.62Z-score

OE missense 1.09 (1.00–1.18)

426 obs / 391.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.30)

0≤0.351.4

Missense OE?1.09 (1.00–1.18)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 4 / 30.1Missense obs/exp: 426 / 391.4Syn Z: 0.42

Background carrier burden — how many people carry a rare variant somewhere in GAB2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

939 rare PASS variants

Rare truncating (LoF)

1 in 450

124 rare PASS variants

Rare synonymous (reference)

1 in 110

341 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GAB2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 90	1 in 340
South Asian	~43k	1 in 46	1 in 2,100
Remaining (unassigned)	~30k	1 in 55	1 in 400
European (Finnish)	~27k	1 in 300	≈ 1 in 6,100
Admixed American	~22k	1 in 71	1 in 420
African / African American	~21k	1 in 48	1 in 380
East Asian	~20k	1 in 68	1 in 1,100
Ashkenazi Jewish	~13k	1 in 300	1 in 770
Middle Eastern	~2,884	1 in 69	≈ 1 in 1,200

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 10 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 10.? see exons ↓