PRDM14

Chr 8

PR/SET domain 14

Also known as: PFM11

NCBI Gene: 63978ENSG00000147596UniProt: Q9GZV8

The protein is a transcription factor that maintains embryonic stem cell identity and pluripotency by regulating the expression of differentiation and pluripotency genes, including direct upregulation of POU5F1. Mutations cause autosomal recessive primary ovarian insufficiency and disorders of sex development affecting gonadal function. The gene shows moderate constraint against loss-of-function variants, reflecting its specialized role in germ cell development and reproductive function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
14
Pubs (1 yr)
32
P/LP submissions
0%
P/LP missense
0.60
LOEUF
DN
Mechanism· predicted
Clinical Summary— PRDM14
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 50 VUS of 89 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.60LOEUF
pLI 0.019
Z-score 2.95
OE 0.32 (0.18–0.60)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.88Z-score
OE missense 0.70 (0.63–0.79)
226 obs / 321.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.18–0.60)
0≤0.351.4
Missense OE0.70 (0.63–0.79)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 7 / 21.9Missense obs/exp: 226 / 321.0Syn Z: 1.18
DN
0.6840th %ile
GOF
0.4974th %ile
LOF
0.4528th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

89 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic1
VUS50
Likely Benign3
31
Pathogenic
1
Likely Pathogenic
50
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
1
0
1
VUS
0
49
1
0
50
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total05233085

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

View in ClinVar →

Protein Context — Lollipop Plot

PRDM14 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients