PRDM16

Chr 1AD

PR/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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 1LLMIM #615373
AD
Left ventricular noncompaction 8MIM #615373
AD
1
Active trials
113
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.19
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryPRDM16
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Gene-Disease Validity (ClinGen)
dilated cardiomyopathy · ADStrong

Strong evidence — appropriate for clinical testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — PRDM16
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 5.95
OE 0.08 (0.040.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.35Z-score
OE missense 0.87 (0.820.93)
745 obs / 855.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.040.19)
00.351.4
Missense OE0.87 (0.820.93)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 4 / 48.9Missense obs/exp: 745 / 855.9Syn Z: -1.64
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPRDM16-related dilated cardiomyopathyOTHERAD
DN
0.3395th %ile
GOF
0.2696th %ile
LOF
0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.19

Literature Evidence

LOFSimilarly, haploinsufficiency of PRDM16-a gene which was recently shown to be sufficient to cause the left ventricular noncompaction-SKI, PRKCZ, RERE, UBE4B and MASP2 may contribute to the development of cardiomyopathy.PMID:24454898

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

0 submitted variants 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.

Clinical Literature
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