PRDM13

Chr 6AR

PR/SET domain 13

Also known as: CDIDHH, MU-MB-20.220, PCH17, PFM10

NCBI Gene: 59336ENSG00000112238UniProt: Q9H4Q3

Predicted to enable histone methyltransferase activity. Predicted to be involved in regulation of gene expression. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II and neurogenesis. Predicted to be active in nucleus. Implicated in pontocerebellar hypoplasia. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadismMIM #619761
AR
Pontocerebellar hypoplasia, type 17MIM #619909
AR
500
ClinVar variants
5
Pathogenic / LP
0.56
pLI score
0
Active trials
Clinical Summary— PRDM13
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.56) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 338 VUS of 500 total submissions
Some data sources returned errors (1)

clinvar: 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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.42Z-score
OE missense 0.94 (0.86–1.02)
353 obs / 376.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.20 (0.10–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.86–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 4 / 19.9Missense obs/exp: 353 / 376.1Syn Z: -1.04

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
VUS338
Likely Benign143
Benign11
Conflicting3
5
Pathogenic
338
VUS
143
Likely Benign
11
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
4
0
5
Likely Pathogenic
0
0
0
0
0
VUS
9
299
29
1
338
Likely Benign
0
13
16
114
143
Benign
0
3
2
6
11
Conflicting
—3
Total1031551121500

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRDM13 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PRDM13-related olivopentocerebellar hypoplasia syndrome

moderate
ARUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗

PRDM13-related North Carolina macular dystrophy

definitive
ADUndeterminedIncreased Gene Product Level
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism

MIM #619761

Molecular basis of disorder known

Autosomal recessive

Pontocerebellar hypoplasia, type 17

MIM #619909

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PRDM13
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families.
Al-Kasbi G et al.·Sci Rep
2022
A novel PRDM13 gene duplication causing congenital North Carolina macular dystrophy phenotype in a Mexican family.
Chacon-Camacho OF et al.·Mol Vis
2024
CONGENITAL POSTERIOR POLAR CHORIORETINAL HYPOPLASIA: Expansion of the Clinical Spectrum, Mutation, and Its Association With PRDM13.
Small KW et al.·Retina
2022
Recessive PRDM13 mutations cause fatal perinatal brainstem dysfunction with cerebellar hypoplasia and disrupt Purkinje cell differentiation.
Coolen M et al.·Am J Hum Genet
2022
A novel duplication involving PRDM13 in a Turkish family supports its role in North Carolina macular dystrophy (NCMD/MCDR1).
Small KW et al.·Mol Vis
2021
A novel tandem duplication of PRDM13 in a Chinese family with North Carolina macular dystrophy.
Wu S et al.·Graefes Arch Clin Exp Ophthalmol
2022
North Carolina macular dystrophy (MCDR1) caused by a novel tandem duplication of the PRDM13 gene.
Bowne SJ et al.·Mol Vis
2016
A novel duplication of PRMD13 causes North Carolina macular dystrophy: overexpression of PRDM13 orthologue in drosophila eye reproduces the human phenotype.
Manes G et al.·Hum Mol Genet
2017
A unique PRDM13-associated variant in a Georgian Jewish family with probable North Carolina macular dystrophy and the possible contribution of a unique CFH variant.
Namburi P et al.·Mol Vis
2020Case report
North Carolina Macular Dystrophy: Phenotypic Variability and Computational Analysis of Disease-Associated Noncoding Variants.
Green DJ et al.·Invest Ophthalmol Vis Sci
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools