GIPC1
Chr 19ADGIPC PDZ domain containing family member 1
Also known as: C19orf3, GIPC, GLUT1CBP, Hs.6454, IIP-1, NIP, OPDM2, RGS19IP1
GIPC1 encodes a scaffolding protein that regulates cell surface receptor expression and trafficking. Mutations cause oculopharyngodistal myopathy 2, a neuromuscular disorder affecting the eyes, pharynx, and distal muscles, with autosomal dominant inheritance. The gene shows low constraint to loss-of-function variants, suggesting tolerance to protein truncation.
Primary Disease Associations & Inheritance
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 (dominant-negative, gain-of-function and loss-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. 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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
94 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 | 14 | 0 | 14 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 58 | 5 | 0 | 63 |
Likely Benign | 0 | 2 | 1 | 2 | 5 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 60 | 22 | 2 | 84 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GIPC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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 →External Resources
Links to major genomics databases and tools