WDR75

Chr 2

WD repeat domain 75

Also known as: NET16, UTP17

NCBI Gene: 84128 ENSG00000115368 UniProt: Q8IWA0

WDR75 encodes a ribosome biogenesis factor that is part of the small subunit processome and involved in nucleolar processing of pre-18S ribosomal RNA and optimal pre-ribosomal RNA transcription by RNA polymerase I. The gene is highly constrained against loss-of-function variants (LOEUF 0.541), but no definitive disease associations have been established for this gene. Clinical correlation is required when interpreting variants in WDR75.

ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Involved in positive regulation of rRNA processing; positive regulation of transcription by RNA polymerase I; and ribosomal small subunit biogenesis. Located in nucleolus. Part of small-subunit processome. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 0.54

Clinical Summary— WDR75

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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

2 unique Pathogenic / Likely Pathogenic· 81 VUS of 114 total submissions

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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?

0.54LOEUF

pLI 0.000

Z-score 4.07

OE 0.36 (0.25–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.21Z-score

OE missense 0.83 (0.76–0.91)

353 obs / 423.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.25–0.54)

0≤0.351.4

Missense OE?0.83 (0.76–0.91)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 17 / 47.2Missense obs/exp: 353 / 423.1Syn Z: -0.35

ClinVar Variant Classifications

114 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS81

Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	2	2
Likely Pathogenic	0	0	0	0
VUS	1	80	0	81
Likely Benign	0	0	0	0
Benign	0	0	0	0
Total	1	80	2	83

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap WDR75 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →