GRIPAP1

Chr X

GRIP1 associated protein 1

Also known as: GRASP-1

The protein functions as a guanine nucleotide exchange factor that regulates AMPA receptor recycling to dendritic membranes and is required for synaptic plasticity and long-term potentiation. Mutations cause autosomal recessive intellectual disability with seizures and behavioral abnormalities. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.16
Clinical SummaryGRIPAP1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
61 unique Pathogenic / Likely Pathogenic· 56 VUS of 220 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 5.53
OE 0.05 (0.020.16)
Highly constrained

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

Missense Constraint
2.62Z-score
OE missense 0.60 (0.540.67)
204 obs / 339.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.020.16)
00.351.4
Missense OE0.60 (0.540.67)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 2 / 39.5Missense obs/exp: 204 / 339.7Syn Z: 1.61
DN
0.4884th %ile
GOF
0.4183th %ile
LOF
0.66top 25%

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

LOFprediction above median · LOEUF 0.16

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

220 submitted variants in ClinVar

Classification Summary

Pathogenic59
Likely Pathogenic2
VUS56
Likely Benign3
Benign7
Conflicting1
59
Pathogenic
2
Likely Pathogenic
56
VUS
3
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
59
0
59
Likely Pathogenic
0
0
2
0
2
VUS
0
49
7
0
56
Likely Benign
0
2
0
1
3
Benign
0
1
2
4
7
Conflicting
1
Total052705128

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

View in ClinVar →

Protein Context — Lollipop Plot

GRIPAP1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC