PRDM2

Chr 1

PR/SET domain 2

Also known as: HUMHOXY1, KMT8, KMT8A, MTB-ZF, RIZ, RIZ1, RIZ2

NCBI Gene: 7799 ENSG00000116731 UniProt: Q13029 OMIM: 601196

The protein is a histone methyltransferase that specifically methylates lysine-9 of histone H3 and functions as a DNA-binding transcription factor involved in transcriptional regulation during neuronal differentiation. Mutations cause intellectual disability and developmental delay with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants, indicating critical importance for normal development.

OMIM ResearchSummary from RefSeq, UniProt

This tumor suppressor gene is a member of a nuclear histone/protein methyltransferase superfamily. It encodes a zinc finger protein that can bind to retinoblastoma protein, estrogen receptor, and the TPA-responsive element (MTE) of the heme-oxygenase-1 gene. Although the functions of this protein have not been fully characterized, it may (1) play a role in transcriptional regulation during neuronal differentiation and pathogenesis of retinoblastoma, (2) act as a transcriptional activator of the heme-oxygenase-1 gene, and (3) be a specific effector of estrogen action. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.22

Clinical Summary— PRDM2

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 1.000

Z-score 6.29

OE 0.12 (0.07–0.22)

Highly constrained

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

Missense Constraint?

1.08Z-score

OE missense 0.90 (0.85–0.95)

845 obs / 938.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.12 (0.07–0.22)

0≤0.351.4

Missense OE?0.90 (0.85–0.95)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 7 / 59.2Missense obs/exp: 845 / 938.4Syn Z: -2.06

This gene — mechanism propensity

0.2997th %ile

GOF

0.1999th %ile

LOF

0.81top 5%

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

LOFprediction above median · LOEUF 0.22

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