WNT11

Chr 11

Wnt family member 11

WNT11 encodes a secreted signaling protein that acts as a ligand for frizzled receptors and functions as a developmental signaling molecule affecting tissue patterning over short distances, particularly in skeleton, kidney, and lung development. Mutations in WNT11 cause robinow syndrome, an autosomal recessive disorder characterized by distinctive facial features, short stature, and skeletal abnormalities including mesomelic limb shortening and genital hypoplasia. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in associated disease.

ResearchSummary from RefSeq, UniProt

Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.81

LOEUF

Mechanism· predicted

Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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?

0.81LOEUF

pLI 0.006

Z-score 2.08

OE 0.41 (0.22–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.41Z-score

OE missense 0.74 (0.65–0.84)

169 obs / 228.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.22–0.81)

0≤0.351.4

Missense OE?0.74 (0.65–0.84)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 6 / 14.6Missense obs/exp: 169 / 228.9Syn Z: 0.70

Background carrier burden — how many people carry a rare variant somewhere in WNT11?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

491 rare PASS variants

Rare truncating (LoF)

1 in 4,900

41 rare PASS variants

Rare synonymous (reference)

1 in 110

206 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for WNT11. 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 170	1 in 6,500
South Asian	~43k	1 in 130	1 in 8,400
Remaining (unassigned)	~30k	1 in 95	≈ 1 in 7,400
European (Finnish)	~27k	1 in 340	1 in 3,900
Admixed American	~22k	1 in 130	≈ 1 in 7,600
African / African American	~21k	1 in 120	≈ 1 in 4,800
East Asian	~20k	1 in 97	1 in 1,600
Ashkenazi Jewish	~13k	1 in 850	none seen
Middle Eastern	~2,884	1 in 170	≈ 1 in 2,900

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): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 5.? see exons ↓