FAT4
Chr 4ARFAT atypical cadherin 4
Also known as: CDHF14, CDHR11, FAT-J, FATJ, HKLLS2, NBLA00548, VMLDS2
FAT4 encodes a protocadherin that maintains planar cell polarity and regulates cell adhesion and proliferation. Mutations cause autosomal recessive Hennekam lymphangiectasia-lymphedema syndrome 2 and Van Maldergem syndrome 2, affecting lymphatic development, growth, and facial features. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.18), indicating strong selective pressure for proper function.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 0 | 0 | 1 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 2 | 25 | 1 | 0 | 28 |
Likely Benign | 0 | 0 | 10 | 60 | 70 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 3 | 25 | 11 | 60 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FAT4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools