WRAP73

Chr 1

WD repeat containing, antisense to TP73

Also known as: WDR8

NCBI Gene: 49856 ENSG00000116213 UniProt: Q9P2S5 OMIM: 606040

The protein regulates spindle anchoring at mitotic centrosomes, is required for centriole satellite protein targeting to centrosomes, and plays an essential role in ciliogenesis by facilitating ciliary vesicle docking at the basal body. Mutations cause autosomal recessive primary ciliary dyskinesia with early-onset respiratory symptoms, reflecting dysfunction of the ciliary machinery critical for airway clearance. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

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. Studies of the related mouse protein suggest that the encoded protein may play a role in the process of ossification. [provided by RefSeq, Mar 2009]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.80

Clinical Summary— WRAP73

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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

93 VUS of 114 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.38

OE 0.51 (0.34–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.01Z-score

OE missense 1.00 (0.91–1.10)

291 obs / 291.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.34–0.80)

0≤0.351.4

Missense OE?1.00 (0.91–1.10)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 14 / 27.4Missense obs/exp: 291 / 291.3Syn Z: -0.75

This gene — mechanism propensity

0.6840th %ile

GOF

0.5758th %ile

LOF

0.3549th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

114 submitted variants in ClinVar

ClinVar

Classification Summary

VUS93

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	93	0	93
Likely Benign	3	1	4
Benign	0	0	0
Total	96	1	97

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

View in ClinVar →

93 pathogenic / likely-pathogenic (of 109) ClinVar copy-number / structural variants overlap WRAP73 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →