GRAPL

Chr 17

GRB2 related adaptor protein like

Also known as: GRAPLDR

The protein is predicted to function as a signaling adaptor that binds receptor tyrosine kinases and participates in cell migration and enzyme-linked receptor signaling pathways. Mutations in GRAPL have been associated with neurodevelopmental disorders, though the specific phenotypic spectrum is still being characterized. The gene shows relatively low constraint to loss-of-function variation (pLI 0.31, LOEUF 1.87), and inheritance patterns for associated disorders require further clinical delineation.

ResearchSummary from RefSeq
GOFmechanismLOEUF 1.87
Clinical SummaryGRAPL
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.87LOEUF
pLI 0.309
Z-score 0.47
OE 0.00 (0.001.87)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.65Z-score
OE missense 0.00 (0.000.90)
0 obs / 3.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.001.87)
00.351.4
Missense OE0.00 (0.000.90)
00.61.4
Synonymous OE0.69
01.21.6
LoF obs/exp: 0 / 0.3Missense obs/exp: 0 / 3.3Syn Z: 0.30
DN
0.6065th %ile
GOF
0.6736th %ile
LOF
0.3649th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GRAPL · 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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