FAM83H
Chr 8ADscaffolding CK1 anchoring protein H
Also known as: AI3, AI3A, FAM83H
The protein encoded by this gene plays a major role in the structural organization and calcification of developing tooth enamel and may regulate epithelial cell migration through keratin cytoskeleton disassembly. Mutations cause amelogenesis imperfecta type IIIA, a dental disorder affecting enamel formation, with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.89, LOEUF 0.36), indicating intolerance to protein disruption.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
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
405 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 | 0 | 0 | 41 | 0 | 41 |
Likely Pathogenic | 3 | 0 | 5 | 0 | 8 |
VUS | 2 | 273 | 4 | 0 | 279 |
Likely Benign | 0 | 14 | 5 | 14 | 33 |
Benign | 0 | 14 | 6 | 9 | 29 |
Conflicting | — | 1 | |||
| Total | 5 | 301 | 61 | 23 | 391 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FAM83H · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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