DRG1

Chr 22AR

N-myc downstream regulated 1

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

NCBI Gene: 10397ENSG00000185721UniProt: 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

Tan-Almurshedi syndromeMIM #620641
AR
UniProtCharcot-Marie-Tooth disease, demyelinating, type 4D
53
ClinVar variants
23
Pathogenic / LP
0.33
pLI score
0
Active trials
Clinical Summary— DRG1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 23 VUS of 53 total submissions

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.
0.53LOEUF
pLI 0.329
Z-score 2.96
OE 0.23 (0.11–0.53)
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.
2.21Z-score
OE missense 0.56 (0.48–0.66)
114 obs / 202.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.23 (0.11–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.56 (0.48–0.66)
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.1.05
0≤1.21.6
LoF obs/exp: 4 / 17.3Missense obs/exp: 114 / 202.4Syn Z: -0.33

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic6
VUS23
17
Pathogenic
6
Likely Pathogenic
23
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
1
5
0
6
VUS
1
19
3
0
23
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total12025046

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DRG1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

DRG1-related neurodevelopmental disorder with microcephaly and dysmorphic facial features (Tan-Almurshedi syndrome)

moderate
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
stop gainedmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Tan-Almurshedi syndrome

MIM #620641

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families.
Al-Kasbi G et al.·Sci Rep
2022
Inactivation of DRG1, encoding a translation factor GTPase, causes a recessive neurodevelopmental disorder.
Westrip CAE et al.·Genet Med
2023
Drg1 expression in 131 colorectal liver metastases: correlation with clinical variables and patient outcomes.
Shah MA et al.·Clin Cancer Res
2005
m6A-dependent up-regulation of DRG1 by METTL3 and ELAVL1 promotes growth, migration, and colony formation in osteosarcoma.
Ling Z et al.·Biosci Rep
2020
Preclinical and clinical studies of novel breast cancer drugs targeting molecules involved in protein kinase C signaling, the putative metastasis-suppressor gene Cap43 and the Y-box binding protein-1.
Fujii T et al.·Curr Med Chem
2008Review
A meta-analysis of gene expression-based biomarkers predicting outcome after tamoxifen treatment in breast cancer.
Mihály Z et al.·Breast Cancer Res Treat
2013Meta-analysis
A phase I clinical trial of the sequential combination of irinotecan followed by flavopiridol.
Shah MA et al.·Clin Cancer Res
2005Clinical trial
Metastasis suppressors in human benign prostate, intraepithelial neoplasia, and invasive cancer: their prospects as therapeutic agents.
Khamis ZI et al.·Med Res Rev
2012Review
Reanalysis of exome sequencing data of intellectual disability samples: Yields and benefits.
Al-Nabhani M et al.·Clin Genet
2018
Hla-DR2-restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice.
Kawamura K et al.·J Clin Invest
2000
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