PDS5B

Chr 13

PDS5 cohesin associated factor B

Also known as: APRIN, AS3, CG008

NCBI Gene: 23047 ENSG00000083642 UniProt: Q9NTI5

The PDS5B protein regulates sister chromatid cohesion during mitosis by stabilizing the cohesin complex's association with chromatin, ensuring accurate chromosome segregation. Mutations cause Cornelia de Lange syndrome with autosomal dominant inheritance, characterized by intellectual disability, growth restriction, limb malformations, and distinctive facial features. This gene is highly constrained against loss-of-function variants, reflecting its essential role in chromosome biology.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein that interacts with the conserved protein complex termed cohesin. The cohesin complex holds together sister chromatids and facilitates accurate chromosome segregation during mitosis and meiosis. This protein is also a negative regulator of cell proliferation and may be a tumor-suppressor gene. [provided by RefSeq, Jul 2015]

ResearchGenerating clinical summary…

Clinical highlights

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.18

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.18LOEUF

pLI 1.000

Z-score 7.47

OE 0.10 (0.06–0.18)

Highly constrained

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

Missense Constraint?

4.39Z-score

OE missense 0.55 (0.50–0.59)

404 obs / 740.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.10 (0.06–0.18)

0≤0.351.4

Missense OE?0.55 (0.50–0.59)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 8 / 80.2Missense obs/exp: 404 / 740.4Syn Z: -0.23

Background carrier burden — how many people carry a rare variant somewhere in PDS5B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 71

1,259 rare PASS variants

Rare truncating (LoF)

1 in 450

130 rare PASS variants

Rare synonymous (reference)

1 in 55

609 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PDS5B. 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 87	1 in 460
South Asian	~43k	1 in 86	1 in 390
Remaining (unassigned)	~30k	1 in 64	1 in 610
European (Finnish)	~27k	1 in 190	1 in 1,100
Admixed American	~22k	1 in 76	1 in 460
African / African American	~21k	1 in 71	1 in 440
East Asian	~20k	1 in 78	1 in 590
Ashkenazi Jewish	~13k	1 in 490	1 in 390
Middle Eastern	~2,884	1 in 76	1 in 560

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 34 coding exons well covered in gnomAD exomes; exons 2, 4, 5, 6, 7 and 17 more marginal. Genomes: all 34.? see exons ↓