GRAPL

Chr 17

GRB2 related adaptor protein like

Also known as: GRAPLDR

NCBI Gene: 400581 ENSG00000189152 UniProt: Q8TC17

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

Predicted to enable receptor tyrosine kinase binding activity and signaling adaptor activity. Predicted to be involved in cell migration and enzyme-linked receptor protein signaling pathway. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.87

Clinical Summary— GRAPL

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.87LOEUF

pLI 0.309

Z-score 0.47

OE 0.00 (0.00–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.65Z-score

OE missense 0.00 (0.00–0.90)

0 obs / 3.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.87)

0≤0.351.4

Missense OE?0.00 (0.00–0.90)

0≤0.61.4

Synonymous OE?0.69

0≤1.21.6

LoF obs/exp: 0 / 0.3Missense obs/exp: 0 / 3.3Syn Z: 0.30

This gene — mechanism propensity

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.