WDR45B

Chr 17AR

WD repeat domain 45B

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

NCBI Gene: 56270ENSG00000141580UniProt: Q5MNZ6

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]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizuresMIM #617977
AR
97
ClinVar variants
26
Pathogenic / LP
0.16
pLI score
0
Active trials
Clinical Summary— WDR45B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 58 VUS of 97 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.01Z-score
OE missense 0.79 (0.69–0.91)
150 obs / 189.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.26 (0.14–0.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.69–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 5 / 19.1Missense obs/exp: 150 / 189.2Syn Z: -0.86

ClinVar Variant Classifications

97 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic7
VUS58
Likely Benign8
Benign4
Conflicting1
19
Pathogenic
7
Likely Pathogenic
58
VUS
8
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
7
0
7
VUS
0
30
28
0
58
Likely Benign
0
1
0
7
8
Benign
0
0
3
1
4
Conflicting
—1
Total03157897

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.

Gene2Phenotype Curations

WDR45B-related intellectual developmental disorder

moderate
ARUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures

MIM #617977

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — WDR45B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrative single-cell transcriptomic analyses reveal the cellular ontological and functional heterogeneities of primary and metastatic liver tumors.
Gui M et al.·J Transl Med
2024Functional
A homozygous variant of WDR45B results in global developmental delay: Additional case and literature review.
Zhang J et al.·Mol Genet Genomic Med
2022Review
El-Hattab-Alkuraya syndrome caused by biallelic WDR45B pathogenic variants: Further delineation of the phenotype and genotype.
Almannai M et al.·Clin Genet
2022
WDR45B-related intellectual disability, spastic quadriplegia, epilepsy, and cerebral hypoplasia: A consistent neurodevelopmental syndrome.
Suleiman J et al.·Clin Genet
2018
Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.
Anazi S et al.·Mol Psychiatry
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools