GRB10

Chr 7

growth factor receptor bound protein 10

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

NCBI Gene: 2887ENSG00000106070UniProt: Q13322

The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors. Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner, with expression observed from the paternal allele in the brain, and from the maternal allele in the placental trophoblasts. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

97
ClinVar variants
11
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GRB10
⚡
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.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 63 VUS of 97 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.939
Z-score 4.57
OE 0.17 (0.09–0.34)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.53Z-score
OE missense 0.76 (0.69–0.85)
255 obs / 333.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.09–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.69–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 6 / 35.3Missense obs/exp: 255 / 333.8Syn Z: 0.06

ClinVar Variant Classifications

97 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
VUS63
Likely Benign14
Benign9
11
Pathogenic
63
VUS
14
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
0
0
0
VUS
0
46
17
0
63
Likely Benign
0
4
4
6
14
Benign
0
4
2
3
9
Total05434997

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — GRB10
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Grb10 and Grb14: enigmatic regulators of insulin action--and more?
Holt LJ et al.·Biochem J
2005Review
Enteric coronavirus nsp2 is a virulence determinant that recruits NBR1 for autophagic targeting of TBK1 to diminish the innate immune response.
Jiao Y et al.·Autophagy
2024
Grb10 is involved in BCR-ABL-positive leukemia in mice.
Illert AL et al.·Leukemia
2015
Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study.
Trajanoska K et al.·BMJ
2018Meta-analysis
Genetic variation near GRB10 associated with bone growth and osteosarcoma risk in canine and human populations.
Lucas SE et al.·Cancer Epidemiol
2024
Role of Grb10 in mTORC1-dependent regulation of insulin signaling and action in human skeletal muscle cells.
Edick AM et al.·Am J Physiol Endocrinol Metab
2020
Interaction of a GRB-IR splice variant (a human GRB10 homolog) with the insulin and insulin-like growth factor I receptors. Evidence for a role in mitogenic signaling.
O'Neill TJ et al.·J Biol Chem
1996
GRB10 sustains AR activity by interacting with PP2A in prostate cancer cells.
Hao J et al.·Int J Cancer
2021
Duplication of 7p12.1-p13, including GRB10 and IGFBP1, in a mother and daughter with features of Silver-Russell syndrome.
Joyce CA et al.·Hum Genet
1999Case report
Molecular characterization of imprinting disorders: Beckwith-Wiedemann, Silver-Russell, and Prader-Willi syndromes in Egyptian patients.
Mohamed AM et al.·BMC Pediatr
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Insights into tissue- and cell type-specific effects of Grb10 on pig skeletal muscle growth by multi-omics analysis.
Li M et al.·Sci China Life Sci
2025
No evidence that human GIGYF2 interacts with GRB10: implications for human disease.
Choi JH et al.·Life Sci Alliance
2025🔓 Open Access
Machine learning-based transcriptmics analysis reveals BMX, GRB10, and GADD45A as crucial biomarkers and therapeutic targets in sepsis.
Cheng Y et al.·Front Pharmacol
2025🔓 Open Access
Paternal fenvalerate exposure causes depressive-like behaviour by altering Grb10 gene DNA methylation in adolescent offspring.
Chen HR et al.·Ecotoxicol Environ Saf
2025
Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12.
Sapehia D et al.·Biol Res
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools