FAT1
Chr 4FAT atypical cadherin 1
Also known as: CDHF7, CDHR8, FAT, ME5, hFat1
FAT1 encodes a large cadherin superfamily protein that functions as an adhesion molecule and signaling receptor essential for cellular polarization, directed cell migration, and modulating cell-cell contact. Mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) with autosomal dominant inheritance, affecting facial, shoulder, and upper arm muscles. The gene is highly constrained against loss-of-function variants, indicating that complete loss of function is likely incompatible with normal development.
Strong evidence — appropriate for clinical testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
FAT1 · 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
Clonal Hematopoiesis in Giant Cell Arteritis
NOT YET RECRUITINGA Phase 1 Clinical Study of NXP900 in Subjects With Advanced Cancers
RECRUITINGStudy of CP-383 in Patients With Advanced or Metastatic Solid Tumors
RECRUITINGNewer Therapeutic Targets in Head and Neck Cancers
RECRUITINGExternal Resources
Links to major genomics databases and tools