WNT7A

Chr 3AR

Wnt family member 7A

Also known as: SANTOS, Wnt-7a

WNT7A encodes a secreted signaling protein that functions as a ligand in the canonical Wnt/beta-catenin pathway and is essential for limb development, skeleton formation, urogenital tract development, and CNS angiogenesis. Autosomal recessive mutations cause severe limb malformation syndromes including Fuhrmann syndrome, Santos syndrome, and absence of ulna and fibula with severe limb deficiency. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.71), consistent with its critical role in early embryonic development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.713 OMIM phenotypes
Clinical SummaryWNT7A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 59 VUS of 158 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.71LOEUF
pLI 0.036
Z-score 2.36
OE 0.34 (0.170.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.34Z-score
OE missense 0.76 (0.670.86)
186 obs / 245.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.170.71)
00.351.4
Missense OE0.76 (0.670.86)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 5 / 14.8Missense obs/exp: 186 / 245.2Syn Z: -0.77
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveWNT7A- related skeletal malformations syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6647th %ile
GOF
0.3094th %ile
LOF
0.3261th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

158 submitted variants in ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic5
VUS59
Likely Benign39
Benign17
Conflicting6
30
Pathogenic
5
Likely Pathogenic
59
VUS
39
Likely Benign
17
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
4
25
0
30
Likely Pathogenic
2
2
1
0
5
VUS
1
56
2
0
59
Likely Benign
0
1
17
21
39
Benign
0
0
11
6
17
Conflicting
6
Total4635627156

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

View in ClinVar →

Protein Context — Lollipop Plot

WNT7A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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