SH2B1

Chr 16

SH2B adaptor protein 1

Also known as: PSM, SH2B

NCBI Gene: 25970ENSG00000178188UniProt: Q9NRF2

This gene encodes a member of the SH2-domain containing mediators family. The encoded protein mediates activation of various kinases and may function in cytokine and growth factor receptor signaling and cellular transformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

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.
5
Active trials
26
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.32
LOEUF· LoF intol.
LOF
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.32LOEUF
pLI 0.969
Z-score 4.24
OE 0.14 (0.07–0.32)
Highly constrained

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

Missense Constraint?
0.69Z-score
OE missense 0.91 (0.84–0.99)
415 obs / 456.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.14 (0.07–0.32)
0≤0.351.4
Missense OE?0.91 (0.84–0.99)
0≤0.61.4
Synonymous OE?0.97
0≤1.21.6
LoF obs/exp: 4 / 28.4Missense obs/exp: 415 / 456.5Syn Z: 0.29

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SH2B1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients