PRDM12

Chr 9AR

PR/SET domain 12

Also known as: HSAN8, PFM9

This gene encodes a transcriptional regulator that is essential for the development and function of nociceptive (pain-sensing) neurons, activating pro-neuronal transcription factors like NEUROD1 and ISL1 specifically within pain neurons. Mutations cause hereditary sensory and autonomic neuropathy type VIII, characterized by congenital insensitivity to pain due to impaired peripheral sensory neuron development and function. The condition follows autosomal recessive inheritance, and the gene is highly constrained against loss-of-function variants (pLI 0.93, LOEUF 0.37).

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.371 OMIM phenotype
Clinical SummaryPRDM12
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
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GeneReview available — PRDM12
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
0.37LOEUF
pLI 0.930
Z-score 3.07
OE 0.08 (0.030.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.67Z-score
OE missense 0.66 (0.570.76)
123 obs / 187.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.030.37)
00.351.4
Missense OE0.66 (0.570.76)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 1 / 12.9Missense obs/exp: 123 / 187.4Syn Z: -0.29
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePRDM12-related hereditary sensory and autonomic neuropathyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4289th %ile
GOF
0.4678th %ile
LOF
0.73top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

PRDM12 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
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