GRB14

Chr 2

growth factor receptor bound protein 14

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. This protein likely has an inhibitory effect on receptor tyrosine kinase signaling and, in particular, on insulin receptor signaling. This gene may play a role in signaling pathways that regulate growth and metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 0.50
Clinical SummaryGRB14
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
87 VUS of 106 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.50LOEUF
pLI 0.053
Z-score 3.63
OE 0.27 (0.160.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
-0.04Z-score
OE missense 1.01 (0.911.12)
265 obs / 262.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.27 (0.160.50)
00.351.4
Missense OE?1.01 (0.911.12)
00.61.4
Synonymous OE?1.11
01.21.6
LoF obs/exp: 8 / 29.1Missense obs/exp: 265 / 262.9Syn Z: -0.81

This gene — mechanism propensity

DN
0.6358th %ile
GOF
0.6248th %ile
LOF
0.4135th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

106 submitted variants in ClinVar

Classification Summary

VUS87
Likely Benign2
Benign1
87
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
87
0
0
87
Likely Benign
0
1
0
1
2
Benign
0
0
0
1
1
Total0880290

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap GRB14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

GRB14 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →