WDR45B

Chr 17AR

WD repeat domain 45B

Also known as: NEDSBAS, WDR45L, WIPI-3, WIPI3

The protein contains seven WD40 repeats that form a beta-propeller structure mediating protein-protein interactions and contains a conserved motif for phospholipid interaction, functioning in preautophagosomal structures. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures. The pathogenic mechanism likely involves disrupted autophagy processes due to impaired preautophagosomal structure formation.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.551 OMIM phenotype
Clinical SummaryWDR45B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 59 VUS of 113 total submissions
📖
GeneReview available — WDR45B
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.156
Z-score 2.99
OE 0.26 (0.140.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.01Z-score
OE missense 0.79 (0.690.91)
150 obs / 189.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.140.55)
00.351.4
Missense OE0.79 (0.690.91)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 5 / 19.1Missense obs/exp: 150 / 189.2Syn Z: -0.86

ClinVar Variant Classifications

113 submitted variants in ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic7
VUS59
Likely Benign8
Benign4
Conflicting1
19
Pathogenic
7
Likely Pathogenic
59
VUS
8
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
18
0
19
Likely Pathogenic
2
0
5
0
7
VUS
0
31
28
0
59
Likely Benign
0
1
0
7
8
Benign
0
0
3
1
4
Conflicting
1
Total33254898

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

View in ClinVar →

Protein Context — Lollipop Plot

WDR45B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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