WDR74

Chr 11

WD repeat domain 74

Also known as: Nsa1

NCBI Gene: 54663 ENSG00000133316 UniProt: Q6RFH5

The WDR74 protein regulates the MTREX-exosome complex and participates in early pre-rRNA processing steps required for 60S ribosomal subunit synthesis. Mutations cause autosomal recessive Galloway-Mowat syndrome, characterized by early-onset nephrotic syndrome, microcephaly, developmental delay, and seizures. This gene is extremely intolerant to loss-of-function mutations, reflecting its essential role in ribosome biogenesis.

ResearchSummary from RefSeq, UniProt

Involved in rRNA processing and ribosomal large subunit biogenesis. Located in nuclear exosome (RNase complex) and nucleolus. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.12

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.12LOEUF

pLI 0.000

Z-score 1.13

OE 0.74 (0.50–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.92Z-score

OE missense 0.83 (0.73–0.93)

185 obs / 223.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.50–1.12)

0≤0.351.4

Missense OE?0.83 (0.73–0.93)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 16 / 21.7Missense obs/exp: 185 / 223.8Syn Z: 1.19

Background carrier burden — how many people carry a rare variant somewhere in WDR74?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

482 rare PASS variants

Rare truncating (LoF)

1 in 530

83 rare PASS variants

Rare synonymous (reference)

1 in 220

203 rare PASS variants

Rare missense and truncating variants are carried at similar rates in WDR74; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 840
South Asian	~43k	1 in 170	1 in 1,600
Remaining (unassigned)	~30k	1 in 180	1 in 560
European (Finnish)	~27k	1 in 930	1 in 550
Admixed American	~22k	1 in 150	1 in 700
African / African American	~21k	1 in 110	1 in 1,200
East Asian	~20k	1 in 140	1 in 2,200
Ashkenazi Jewish	~13k	1 in 570	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 99	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 11 coding exons well covered in gnomAD exomes. Genomes: 10 of 11 (exon 7 below).? see exons ↓