DND1

Chr 5

DND microRNA-mediated repression inhibitor 1

Also known as: RBMS4

NCBI Gene: 373863ENSG00000256453UniProt: Q8IYX4

This gene encodes a protein that binds to microRNA-targeting sequences of mRNAs, inhibiting microRNA-mediated repression. Reduced expression of this gene has been implicated in tongue squamous cell carcinoma. Two pseudogenes of this gene are located on the long arm of chromosome 17. [provided by RefSeq, Dec 2010]

75
ClinVar variants
12
Pathogenic / LP
0.44
pLI score
0
Active trials
Clinical Summary— DND1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 61 VUS of 75 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.
0.55LOEUF
pLI 0.436
Z-score 2.74
OE 0.21 (0.10–0.55)
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.
2.22Z-score
OE missense 0.59 (0.51–0.68)
133 obs / 227.2 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.0.21 (0.10–0.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.51–0.68)
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.0.89
0≤1.21.6
LoF obs/exp: 3 / 14.1Missense obs/exp: 133 / 227.2Syn Z: 0.92

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
VUS61
Likely Benign2
12
Pathogenic
61
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
0
0
0
VUS
0
56
5
0
61
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total05718075

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

View in ClinVar →

Protein Context — Lollipop Plot

DND1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Multi-omics Analysis to Identify Key Immune Genes for Osteoporosis based on Machine Learning and Single-cell Analysis.
Zhang B et al.·Orthop Surg
2024
High DND1 Level Indicates a Poor Prognostic Factor in Prostate Cancer.
Xu G et al.·Dis Markers
2021
The RNA binding proteins RBM38 and DND1 are repressed in AML and have a novel function in APL differentiation.
Wampfler J et al.·Leuk Res
2016
Linking human Dead end 1 (DND1) variants to male infertility employing zebrafish embryos.
Westerich KJ et al.·Hum Reprod
2023Functional
A Tiered Approach to Exome Sequencing Analysis in Early-Onset Primary Ovarian Insufficiency.
McGlacken-Byrne SM et al.·J Clin Endocrinol Metab
2025
Circular RNA circFCHO2(hsa_circ_0002490) promotes the proliferation of melanoma by directly binding to DND1.
Yang Y et al.·Cell Biol Toxicol
2024
Predicting oncology drug-induced cardiotoxicity with donor-specific iPSC-CMs-a proof-of-concept study with doxorubicin.
Pang L et al.·Toxicol Sci
2024
Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors.
Linger R et al.·Genes Chromosomes Cancer
2008
Screening for germline DND1 mutations in testicular cancer patients.
Sijmons RH et al.·Fam Cancer
2010Cohort
Chromosome X modulates incidence of testicular germ cell tumors in Ter mice.
Hammond S et al.·Mamm Genome
2007
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