GORASP1
Chr 3golgi reassembly stacking protein 1
Also known as: GOLPH5, GRASP65, P65
The protein encoded by this gene is a key structural protein required for formation and maintenance of the Golgi apparatus ribbon structure and mediates docking of transport vesicles with Golgi membranes. Pathogenic variants in GORASP1 cause autosomal recessive genitopatellar syndrome, a rare developmental disorder characterized by genital anomalies, absent or hypoplastic patellae, intellectual disability, and distinctive facial features with early childhood onset. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.675), affecting multiple organ systems including skeletal, genitourinary, and neurological development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
98 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 8 | 0 | 8 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 1 | 66 | 0 | 0 | 67 |
Likely Benign | 0 | 4 | 0 | 0 | 4 |
Benign | 0 | 1 | 1 | 2 | 4 |
| Total | 1 | 71 | 10 | 2 | 84 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GORASP1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →No open access results found
External Resources
Links to major genomics databases and tools