NDRG1
Chr 8ARN-myc downstream regulated 1
Also known as: CAP43, CMT4D, DRG-1, DRG1, GC4, HMSNL, NDR1, NMSL
The protein encoded by NDRG1 is a cytoplasmic stress-responsive protein that regulates cell growth and differentiation, maintains peripheral nerve myelin sheaths in Schwann cells, and is necessary for p53-mediated caspase activation and apoptosis. Autosomal recessive mutations cause Charcot-Marie-Tooth disease type 4D through a predicted gain-of-function mechanism. The protein functions in cell trafficking, vesicular recycling, and microtubule dynamics, with disruption of these processes leading to peripheral neuropathy.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
200 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 | 6 | 0 | 7 | 0 | 13 |
Likely Pathogenic | 9 | 0 | 0 | 0 | 9 |
VUS | 0 | 31 | 7 | 0 | 38 |
Likely Benign | 1 | 3 | 94 | 41 | 139 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 16 | 34 | 109 | 41 | 200 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NDRG1 · 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 →External Resources
Links to major genomics databases and tools