WDR12

Chr 2

WD repeat domain 12

Also known as: YTM1

NCBI Gene: 55759 ENSG00000138442 UniProt: Q9GZL7 OMIM: 616620

WDR12 encodes a component of the PeBoW complex that is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome. Mutations cause Klippel-Feil syndrome 4 with neuropathy and developmental delay, which follows an autosomal recessive inheritance pattern. This gene is highly constrained against loss-of-function variants, indicating its critical role in cellular function.

OMIM ResearchSummary from RefSeq, UniProt

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 protein is highly similar to the mouse WD repeat domain 12 protein at the amino acid level. The protein encoded by this gene is a component of a nucleolar protein complex that affects maturation of the large ribosomal subunit.[provided by RefSeq, Dec 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.64

Clinical Summary— WDR12

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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

52 VUS of 72 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.05

OE 0.38 (0.24–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.48Z-score

OE missense 0.91 (0.81–1.02)

199 obs / 218.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.24–0.64)

0≤0.351.4

Missense OE?0.91 (0.81–1.02)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 11 / 28.6Missense obs/exp: 199 / 218.8Syn Z: 0.41

ClinVar Variant Classifications

72 submitted variants in ClinVar

ClinVar

Classification Summary

VUS52

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	52	52
Likely Benign	2	2
Benign	0	0
Total	54	54

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap WDR12 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →