WDR45

Chr XXLD

WD repeat domain 45

Also known as: JM5, NBIA4, NBIA5, WDRX1, WIPI-4, WIPI4

NCBI Gene: 11152ENSG00000196998UniProt: Q9Y484OMIM: 300526

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodegeneration with brain iron accumulation 5MIM #300894
XLD

Clinical highlights

Gene-disease validity (ClinGen)
X-linked complex neurodevelopmental disorder · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
38
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.21
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — WDR45
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.21LOEUF
pLI 0.991
Z-score 3.50
OE 0.00 (0.00–0.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.02Z-score
OE missense 0.56 (0.47–0.66)
92 obs / 164.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.21)
0≤0.351.4
Missense OE?0.56 (0.47–0.66)
0≤0.61.4
Synonymous OE?0.72
0≤1.21.6
LoF obs/exp: 0 / 14.3Missense obs/exp: 92 / 164.8Syn Z: 1.78

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

WDR45 · protein map & ClinVar variants

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

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients