PRDM5

Chr 4AR

PR/SET domain 5

Also known as: BCS2, PFM2

NCBI Gene: 11107 ENSG00000138738 UniProt: Q9NQX1 OMIM: 614161

PRDM5 encodes a transcription factor that represses gene expression through recruitment of histone methyltransferases and deacetylases, and regulates expression of extracellular matrix proteins including fibrillar collagens. Mutations cause brittle cornea syndrome 2, an autosomal recessive connective tissue disorder characterized by fragile corneas and associated ocular abnormalities. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a transcription factor of the PR-domain protein family. It contains a PR-domain and multiple zinc finger motifs. Transcription factors of the PR-domain family are known to be involved in cell differentiation and tumorigenesis. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Brittle cornea syndrome 2MIM #614170

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Brittle cornea syndrome 2; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.84

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — PRDM5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.32

OE 0.58 (0.41–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.70Z-score

OE missense 0.89 (0.81–0.98)

305 obs / 341.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.41–0.84)

0≤0.351.4

Missense OE?0.89 (0.81–0.98)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 21 / 36.1Missense obs/exp: 305 / 341.3Syn Z: -1.29

Background carrier burden — how many people carry a rare variant somewhere in PRDM5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

781 rare PASS variants

Rare truncating (LoF)

1 in 1,100

118 rare PASS variants

Rare synonymous (reference)

1 in 140

277 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRDM5. 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 140	1 in 1,200
South Asian	~43k	1 in 88	1 in 2,400
Remaining (unassigned)	~30k	1 in 80	1 in 1,900
European (Finnish)	~27k	1 in 320	1 in 3,000
Admixed American	~22k	1 in 69	1 in 660
African / African American	~21k	1 in 63	1 in 940
East Asian	~20k	1 in 110	1 in 1,900
Ashkenazi Jewish	~13k	1 in 380	none seen
Middle Eastern	~2,884	1 in 76	≈ 1 in 1,400

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): 15 of 16 coding exons well covered in gnomAD exomes; exon 8 marginal. Genomes: all 16.? see exons ↓