WDR45B

Chr 17

WD repeat domain 45B

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

NCBI Gene: 56270 ENSG00000141580 UniProt: Q5MNZ6

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the WIPI or SVP1 family of WD40 repeat-containing proteins. The protein contains seven WD40 repeats that are thought to fold into a beta-propeller structure that mediates protein-protein interactions, and a conserved motif for interaction with phospholipids. The human genome contains several pseudogenes of this gene. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

LOEUF 0.55

Clinical Summary— WDR45B

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 31 VUS of 62 total submissions

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GeneReview available — WDR45B

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.55LOEUF

pLI 0.156

Z-score 2.99

OE 0.26 (0.14–0.55)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.01Z-score

OE missense 0.79 (0.69–0.91)

150 obs / 189.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.14–0.55)

0≤0.351.4

Missense OE?0.79 (0.69–0.91)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 5 / 19.1Missense obs/exp: 150 / 189.2Syn Z: -0.86

ClinVar Variant Classifications

62 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic2

VUS31

Likely Benign8

Benign4

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	2	0	0	0	2
VUS	0	31	0	0	31
Likely Benign	0	1	0	7	8
Benign	0	0	3	1	4
Conflicting	—				1
Total	3	32	3	8	47

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 52) ClinVar copy-number / structural variants overlap WDR45B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →