GPRASP1

Chr X

G protein-coupled receptor associated sorting protein 1

Also known as: GASP, GASP-1, GASP1

The GPRASP1 protein modulates lysosomal sorting and targets G-protein coupled receptors (including dopamine, opioid, adrenergic, and cannabinoid receptors) for degradation in lysosomes. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. This gene is highly constrained against loss-of-function variation (LOEUF 0.416), indicating intolerance to protein-truncating mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
56
P/LP submissions
0%
P/LP missense
0.42
LOEUF
Mechanism
Clinical SummaryGPRASP1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 126 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.311
Z-score 4.20
OE 0.23 (0.130.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.73Z-score
OE missense 0.91 (0.840.98)
454 obs / 499.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.130.42)
00.351.4
Missense OE0.91 (0.840.98)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 8 / 34.7Missense obs/exp: 454 / 499.8Syn Z: 1.72

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic54
VUS126
Likely Benign17
Benign1
Conflicting2
54
Pathogenic
126
VUS
17
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
0
0
0
VUS
1
121
4
0
126
Likely Benign
0
13
0
4
17
Benign
0
0
0
1
1
Conflicting
2
Total1134585200

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

View in ClinVar →

Protein Context — Lollipop Plot

GPRASP1 · 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.

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Clinical Literature
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