WBP11

Chr 12AD

WW domain binding protein 11

Also known as: BUG13, NPWBP, PPP1R165, SIPP1, VCTERL, VCTRL, WBP-11

The protein activates pre-mRNA splicing and may inhibit PP1 phosphatase activity, functioning as a component of nuclear mRNA processing machinery. Mutations cause vertebral, cardiac, tracheoesophageal, renal, and limb defects with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.148), indicating intolerance to protein disruption.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Vertebral, cardiac, tracheoesophageal, renal, and limb defectsMIM #619227
AD
0
Active trials
6
Pubs (1 yr)
67
P/LP submissions
0%
P/LP missense
0.15
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryWBP11
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
60 unique Pathogenic / Likely Pathogenic· 113 VUS of 202 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 5.09
OE 0.03 (0.010.15)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.98Z-score
OE missense 0.56 (0.500.63)
205 obs / 365.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.03 (0.010.15)
00.351.4
Missense OE0.56 (0.500.63)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 1 / 32.1Missense obs/exp: 205 / 365.3Syn Z: 1.43
DN
0.2598th %ile
GOF
0.2099th %ile
LOF
0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 22% of P/LP variants are LoF · LOEUF 0.15

Literature Evidence

LOFImportantly, Wbp11 heterozygous null mice are small and exhibit defects in axial skeleton, kidneys and esophagus, similar to the affected individuals, supporting the role of WBP11 haploinsufficiency in the development of congenital malformations in humans.PMID:33276377

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

202 submitted variants in ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic13
VUS113
Likely Benign3
Benign1
Conflicting3
47
Pathogenic
13
Likely Pathogenic
113
VUS
3
Likely Benign
1
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
42
0
47
Likely Pathogenic
8
0
5
0
13
VUS
5
97
11
0
113
Likely Benign
0
3
0
0
3
Benign
0
0
1
0
1
Conflicting
3
Total18100590180

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

View in ClinVar →

Protein Context — Lollipop Plot

WBP11 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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