WDR5B

Chr 3

WD repeat domain 5B

NCBI Gene: 54554 ENSG00000196981 UniProt: Q86VZ2

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.

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]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.48

Clinical Summary— WDR5B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

37 VUS of 40 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

This gene — mechanism propensity

0.7326th %ile

GOF

0.4677th %ile

LOF

0.4136th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

40 submitted variants in ClinVar

ClinVar

Classification Summary

VUS37

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	37	37
Likely Benign	3	3
Benign	0	0
Total	40	40

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap WDR5B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →