PRDM6

Chr 5AD

PR/SET domain 6

Also known as: KMT8C, PDA3, PRISM

NCBI Gene: 93166ENSG00000061455UniProt: Q9NQX0

The protein encoded by this gene is a transcriptional repressor and a member of the PRDM family. Family members contain a PR domain and multiple zinc-finger domains. The encoded protein is involved in regulation of vascular smooth muscle cells (VSMC) contractile proteins. Mutations in this gene result in patent ductus arteriosus 3 (PDA3). [provided by RefSeq, Apr 2017]

Primary Disease Associations & Inheritance

Patent ductus arteriosus 3MIM #617039
AD
171
ClinVar variants
24
Pathogenic / LP
0.61
pLI score
0
Active trials
Clinical Summary— PRDM6
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 124 VUS of 171 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.
0.42LOEUF
pLI 0.608
Z-score 3.68
OE 0.20 (0.10–0.42)
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.
1.13Z-score
OE missense 0.81 (0.73–0.90)
228 obs / 281.5 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.0.20 (0.10–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.73–0.90)
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: 5 / 24.8Missense obs/exp: 228 / 281.5Syn Z: -0.71

ClinVar Variant Classifications

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
VUS124
Likely Benign16
Benign7
24
Pathogenic
124
VUS
16
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
21
0
24
Likely Pathogenic
0
0
0
0
0
VUS
0
115
9
0
124
Likely Benign
0
4
4
8
16
Benign
1
2
2
2
7
Total11243610171

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

View in ClinVar →

Protein Context — Lollipop Plot

PRDM6 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PRDM6-related isolated nonsyndromic patent ductus arteriosus

limited
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Patent ductus arteriosus 3

MIM #617039

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The whole-genome landscape of medulloblastoma subtypes.
Northcott PA et al.·Nature
2017
Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility.
Zou M et al.·JCI Insight
2023
Molecular Stratification of Medulloblastoma: Clinical Outcomes and Therapeutic Interventions.
Sursal T et al.·Anticancer Res
2022Review
Defining molecular signatures of the solid/pseudopapillary and pseudoglandular patterns in so-called "solid-tubulocystic intrahepatic cholangiocarcinoma vs. NIPBL::NACC1 fusion hepatic carcinoma".
Bajpai P et al.·Pathol Res Pract
2025
A genome-wide association study of mammographic texture variation.
Liu Y et al.·Breast Cancer Res
2022
Single-cell transcriptional profiling reveals cellular and molecular divergence in human maternal-fetal interface.
Wang Q et al.·Sci Rep
2022
Genetic architecture of human thinness compared to severe obesity.
Riveros-McKay F et al.·PLoS Genet
2019
Patent ductus arteriosus and coarctation of the aorta in association with PRDM6 variants.
Stanley HM et al.·Am J Med Genet A
2024Case report
Genetic and Epigenetic Biomarkers in Hypertension Impact on the Effectiveness of Individualized Therapy: A Systematic Review.
Silva AMPD et al.·J Cardiovasc Pharmacol
2025Meta-analysis
A novel model incorporating chromatin regulatory factors for risk stratification, prognosis prediction, and characterization of the microenvironment in Wilms tumor.
Zhao X et al.·J Gene Med
2024Functional
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