PRDM16

Chr 1

PR/SET domain 16

Also known as: CMD1LL, KMT8F, LVNC8, MEL1, PFM13

NCBI Gene: 63976 ENSG00000142611 UniProt: Q9HAZ2

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.

ResearchSummary from RefSeq, OMIM, UniProt

The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.19

Clinical Summary— PRDM16

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Gene-Disease Validity (ClinGen)

dilated cardiomyopathy · ADStrong

Strong evidence — appropriate for clinical testing

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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

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 5.95

OE 0.08 (0.04–0.19)

Highly constrained

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

Missense Constraint?

1.35Z-score

OE missense 0.87 (0.82–0.93)

745 obs / 855.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.19)

0≤0.351.4

Missense OE?0.87 (0.82–0.93)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 4 / 48.9Missense obs/exp: 745 / 855.9Syn Z: -1.64

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedPRDM16-related dilated cardiomyopathyOTHERAD

This gene — mechanism propensity

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.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References