PRDM13

Chr 6AR

PR/SET domain 13

ENSG00000112238 UniProt: Q9H4Q3 OMIM: 616741

PRDM13 encodes a histone methyltransferase that regulates transcription and is required for differentiation of hypothalamic KISS1-expressing neurons and GABAergic cell fate determination in the cerebellum. Mutations cause autosomal recessive pontocerebellar hypoplasia type 17, characterized by cerebellar dysfunction, intellectual disability, and hypogonadotropic hypogonadism. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.461), reflecting its critical role in cerebellar and hypothalamic development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

May be involved in transcriptional regulation. Is required for the differentiation of KISS1-expressing neurons in the arcuate (Arc) nucleus of the hypothalamus. Is a critical regulator of GABAergic cell fate in the cerebellum, required for normal postnatal cerebellar development (By similarity)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadismMIM #619761

Pontocerebellar hypoplasia, type 17MIM #619909

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism; Pontocerebellar hypoplasia, type 17; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.46

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.563

Z-score 3.30

OE 0.20 (0.10–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.42Z-score

OE missense 0.94 (0.86–1.02)

353 obs / 376.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.10–0.46)

0≤0.351.4

Missense OE?0.94 (0.86–1.02)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 4 / 19.9Missense obs/exp: 353 / 376.1Syn Z: -1.04

Background carrier burden — how many people carry a rare variant somewhere in PRDM13?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

1,105 rare PASS variants

Rare truncating (LoF)

1 in 2,800

86 rare PASS variants

Rare synonymous (reference)

1 in 140

564 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRDM13. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 88	1 in 3,400
South Asian	~43k	1 in 69	1 in 1,300
Remaining (unassigned)	~30k	1 in 51	1 in 900
European (Finnish)	~27k	1 in 280	1 in 3,000
Admixed American	~22k	1 in 65	1 in 1,100
African / African American	~21k	1 in 78	1 in 2,400
East Asian	~20k	1 in 54	1 in 1,700
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 60	≈ 1 in 1,100

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓