NDRG1

Chr 8AR

N-myc downstream regulated 1

Also known as: CAP43, CMT4D, DRG-1, DRG1, GC4, HMSNL, NDR1, NMSL

NCBI Gene: 10397ENSG00000104419UniProt: Q92597

This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation. The encoded protein is necessary for p53-mediated caspase activation and apoptosis. Mutations in this gene are a cause of Charcot-Marie-Tooth disease type 4D, and expression of this gene may be a prognostic indicator for several types of cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, type 4DMIM #601455
AR
565
ClinVar variants
46
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— NDRG1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 162 VUS of 565 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.58LOEUF
pLI 0.011
Z-score 3.14
OE 0.32 (0.19–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.65Z-score
OE missense 0.89 (0.79–0.99)
226 obs / 255.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.32 (0.19–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.79–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 8 / 24.9Missense obs/exp: 226 / 255.3Syn Z: -0.66

ClinVar Variant Classifications

565 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic15
VUS162
Likely Benign326
Benign31
31
Pathogenic
15
Likely Pathogenic
162
VUS
326
Likely Benign
31
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
21
0
31
Likely Pathogenic
13
0
2
0
15
VUS
4
126
27
5
162
Likely Benign
1
4
175
146
326
Benign
0
0
31
0
31
Total28130256151565

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Charcot-Marie-Tooth disease, type 4D

MIM #601455

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — NDRG1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PIM1 instigates endothelial-to-mesenchymal transition to aggravate atherosclerosis.
Xue Z et al.·Theranostics
2025
NSUN6-mediated 5-methylcytosine modification of NDRG1 mRNA promotes radioresistance in cervical cancer.
Yu M et al.·Mol Cancer
2024
NDRG1 enhances the sensitivity to Cetuximab by promoting Stat1 ubiquitylation in colorectal cancer.
Yang G et al.·J Adv Res
2025
NDRG1-Driven Lactate Accumulation Promotes Lung Adenocarcinoma Progression Through the Induction of an Immunosuppressive Microenvironment.
Wu G et al.·Adv Sci (Weinh)
2025
NDRG1 and its family members: More than just metastasis suppressor proteins and targets of thiosemicarbazones.
Azad MG et al.·J Biol Chem
2025Review
Metabolic effects of RUBCN/Rubicon deficiency in kidney proximal tubular epithelial cells.
Matsuda J et al.·Autophagy
2020
NDRG1 regulates Filopodia-induced Colorectal Cancer invasiveness via modulating CDC42 activity.
Aikemu B et al.·Int J Biol Sci
2021
NDRG1 alleviates Erastin-induced ferroptosis of hepatocellular carcinoma.
Li L et al.·BMC Cancer
2025
Metixene is an incomplete autophagy inducer in preclinical models of metastatic cancer and brain metastases.
Fares J et al.·J Clin Invest
2023Functional
Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy.
Frank D et al.·Blood
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools