GRB10

Chr 7

growth factor receptor bound protein 10

Also known as: GRB-IR, Grb-10, IRBP, MEG1, RSS

The GRB10 protein is an adapter protein that negatively regulates insulin and insulin-like growth factor receptor signaling by blocking downstream pathways and promoting receptor degradation. Mutations cause Silver-Russell syndrome, characterized by severe intrauterine and postnatal growth restriction, relative macrocephaly, and feeding difficulties typically apparent from birth. This gene shows parent-of-origin effects with brain-specific paternal expression and is highly intolerant to loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.34
Clinical SummaryGRB10
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.939
Z-score 4.57
OE 0.17 (0.090.34)
Highly constrained

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

Missense Constraint
1.53Z-score
OE missense 0.76 (0.690.85)
255 obs / 333.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.090.34)
00.351.4
Missense OE0.76 (0.690.85)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 6 / 35.3Missense obs/exp: 255 / 333.8Syn Z: 0.06
DN
0.4586th %ile
GOF
0.5366th %ile
LOF
0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.34

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GRB10 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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