PRDM16
Chr 1ADPR/SET domain 16
Also known as: CMD1LL, KMT8F, LVNC8, MEL1, PFM13
This gene encodes a transcription regulator that acts as both a histone methyltransferase and chromatin adapter, controlling brown adipocyte differentiation, regulatory T-cell development, and cardiac mitochondrial function. Mutations cause dilated cardiomyopathy and left ventricular noncompaction with autosomal dominant inheritance. The gene is highly constrained against loss-of-function mutations (pLI 0.9999, LOEUF 0.187), indicating that pathogenic variants are likely to have severe functional consequences.
Strong evidence — appropriate for clinical testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
1000 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 0 | 25 | 0 | 28 |
Likely Pathogenic | 5 | 0 | 1 | 0 | 6 |
VUS | 30 | 491 | 44 | 8 | 573 |
Likely Benign | 0 | 4 | 118 | 238 | 360 |
Benign | 0 | 0 | 11 | 1 | 12 |
Conflicting | — | 16 | |||
| Total | 38 | 495 | 199 | 247 | 995 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PRDM16 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools