FAT2

Chr 5AD

FAT atypical cadherin 2

Also known as: CDHF8, CDHR9, HFAT2, MEGF1, SCA45

NCBI Gene: 2196ENSG00000086570UniProt: Q9NYQ8

This gene is the second identified human homolog of the Drosophila fat gene, which encodes a tumor suppressor essential for controlling cell proliferation during Drosophila development. The gene product is a member of the cadherin superfamily, a group of integral membrane proteins characterized by the presence of cadherin-type repeats. In addition to containing 34 tandem cadherin-type repeats, the gene product has two epidermal growth factor (EGF)-like repeats and one laminin G domain. This protein most likely functions as a cell adhesion molecule, controlling cell proliferation and playing an important role in cerebellum development. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia 45MIM #617769
AD
539
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FAT2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 380 VUS of 539 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.51LOEUF
pLI 0.000
Z-score 6.38
OE 0.40 (0.32–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.72Z-score
OE missense 0.96 (0.93–0.99)
2292 obs / 2390.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.32–0.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.93–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 54 / 133.6Missense obs/exp: 2292 / 2390.6Syn Z: -1.00

ClinVar Variant Classifications

539 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS380
Likely Benign118
Benign22
Conflicting9
9
Pathogenic
1
Likely Pathogenic
380
VUS
118
Likely Benign
22
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
1
0
0
1
VUS
3
365
11
1
380
Likely Benign
0
32
9
77
118
Benign
0
12
1
9
22
Conflicting
—9
Total34103087539

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

View in ClinVar →

Protein Context — Lollipop Plot

FAT2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinocerebellar ataxia 45

MIM #617769

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autosomal dominant cerebellar ataxias: new genes and progress towards treatments.
Coarelli G et al.·Lancet Neurol
2023Review
Hereditary ataxias and paraparesias: clinical and genetic update.
Parodi L et al.·Curr Opin Neurol
2018Review
ΔNp63α induces the expression of FAT2 and Slug to promote tumor invasion.
Dang TT et al.·Oncotarget
2016
Genetic Variation Analysis of Essential Tremor: Insights from the China Essential Tremor Alliance Cohort.
Li M et al.·Mov Disord
2026Cohort
Integrated analysis of mRNA and extrachromosomal circular DNA profiles to identify the potential mRNA biomarkers in breast cancer.
Ouyang Y et al.·Gene
2023
Prognostic and Immunological Role of FAT Family Genes in Non-Small Cell Lung Cancer.
Feng Z et al.·Cancer Control
2022
Comprehensive characterization of viral integrations and genomic aberrations in HBV-infected intrahepatic cholangiocarcinomas.
An J et al.·Hepatology
2022
Exome sequencing in a family with restless legs syndrome.
Weissbach A et al.·Mov Disord
2012
Bromodomain protein BRDT directs ΔNp63 function and super-enhancer activity in a subset of esophageal squamous cell carcinomas.
Wang X et al.·Cell Death Differ
2021
Familial paroxysmal kinesigenic dyskinesia with a novel missense variant (Arg2866Trp) in NBEA.
Miura S et al.·J Hum Genet
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools