WDR5B

Chr 3

WD repeat domain 5B

NCBI Gene: 54554 ENSG00000196981 UniProt: Q86VZ2 OMIM: 621240

The protein contains WD40 repeats and functions in retinal pigment epithelial cell proliferation, potentially serving as a substrate receptor for CUL4-DDB1 ubiquitin E3 ligase complex. This gene is extremely intolerant to loss-of-function mutations (pLI near 1.0), but specific disease associations and inheritance patterns have not yet been established in the literature. Clinical significance of variants in this gene remains to be determined.

OMIM ResearchSummary from RefSeq, UniProt

This intronless gene encodes a protein containing several WD40 repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, including a trp-asp at the C-terminal end. The encoded protein may mediate protein-protein interactions. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.48

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.48LOEUF

pLI 0.000

Z-score 0.50

OE 0.83 (0.48–1.48)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.45Z-score

OE missense 1.10 (0.97–1.24)

183 obs / 166.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.83 (0.48–1.48)

0≤0.351.4

Missense OE?1.10 (0.97–1.24)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 8 / 9.7Missense obs/exp: 183 / 166.6Syn Z: -0.50

Background carrier burden — how many people carry a rare variant somewhere in WDR5B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

400 rare PASS variants

Rare truncating (LoF)

1 in 400

90 rare PASS variants

Rare synonymous (reference)

1 in 230

156 rare PASS variants

Rare missense and truncating variants are carried at similar rates in WDR5B; this gene does not show strong loss-of-function constraint by this measure. 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 220	1 in 420
South Asian	~43k	1 in 170	1 in 390
Remaining (unassigned)	~30k	1 in 200	1 in 440
European (Finnish)	~27k	1 in 2,400	1 in 740
Admixed American	~22k	1 in 150	1 in 360
African / African American	~21k	1 in 100	1 in 530
East Asian	~20k	1 in 260	1 in 220
Ashkenazi Jewish	~13k	1 in 500	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 260	≈ 1 in 2,900

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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓