GRAMD1B
Chr 11GRAM domain containing 1B
Also known as: LINC01059
The protein functions as a cholesterol transporter that mediates non-vesicular cholesterol transfer from the plasma membrane to the endoplasmic reticulum at membrane contact sites, playing a crucial role in cellular cholesterol homeostasis. Mutations in this highly constrained gene (pLI=1.0, LOEUF=0.25) cause autosomal recessive congenital adrenal insufficiency with distinctive clinical features. The gene's critical role in adrenal steroidogenesis and its extreme intolerance to loss-of-function variants make it an important consideration in patients presenting with primary adrenal insufficiency.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
ClinVar Variant Classifications
167 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 | 49 | 0 | 49 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 75 | 7 | 0 | 82 |
Likely Benign | 0 | 6 | 4 | 4 | 14 |
Benign | 0 | 2 | 2 | 3 | 7 |
| Total | 0 | 83 | 65 | 7 | 155 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GRAMD1B · 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