Amelogenesis imperfecta: genes and variants
Amelogenesis imperfecta is linked to 3 analyzed proteins (COL17A1, LAMB3 and PRKAR1A). 5 DNA variants are known to cause it; 17 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Amelogenesis imperfecta type 1; amelogenesis imperfecta type 1A; amelogenesis imperfecta type 1G
Genes linked to Amelogenesis imperfecta
COL17A1: Collagen alpha-1(XVII) chain
It anchors basal keratinocytes to the basement membrane through hemidesmosomes and is essential for stable epidermal adhesion. Biallelic loss-of-function variants cause junctional epidermolysis bullosa, while autoantibodies against the protein cause bullous pemphigoid.
4 disease-causing and 2 uncertain variants in COL17A1 are linked to Amelogenesis imperfecta.
LAMB3: Laminin subunit beta-3
It contributes the beta3 chain of laminin-332, an essential ligand for hemidesmosomal adhesion at the epidermal basement membrane. Biallelic loss-of-function variants cause junctional epidermolysis bullosa, and selected variants can also cause amelogenesis imperfecta.
1 disease-causing and 12 uncertain variants in LAMB3 are linked to Amelogenesis imperfecta.
PRKAR1A: cAMP-dependent protein kinase type I-alpha regulatory subunit
It restrains protein kinase A activity in the absence of cyclic AMP and thereby controls a wide range of endocrine and growth signals. Germline loss-of-function variants cause Carney complex, with endocrine overactivity, spotty pigmentation, myxomas, and multiple tumor predispositions.
0 disease-causing and 1 uncertain variants in PRKAR1A are linked to Amelogenesis imperfecta.
Weakly linked (only a few uncertain records): COL7A1 and LAMC2.
Known disease-causing variants in Amelogenesis imperfecta
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| LAMB3 E210K | 210 | Laminin N-terminal | Disease-causing (★★) |
| COL17A1 G677D | 677 | Triple-helical region | Disease-causing |
| COL17A1 G567E | 567 | Triple-helical region | Disease-causing |
| COL17A1 E1199Q | 1199 | Triple-helical region | Disease-causing |
| COL17A1 D1200Y | 1200 | Triple-helical region | Disease-causing |
Same protein, different disease
- Junctional epidermolysis bullosa is also caused by LAMB3 variants; they fall mostly in different places as the Amelogenesis imperfecta variants (4 disease-causing).
Diseases related to Amelogenesis imperfecta
- Junctional epidermolysis bullosa, also linked to COL17A1 and LAMB3
- Junctional epidermolysis bullosa, non-Herlitz type, also linked to COL17A1 and LAMB3
- Carney complex, also linked to PRKAR1A
- Junctional epidermolysis bullosa gravis of Herlitz, also linked to LAMB3
- Acrodysostosis 1 with or without hormone resistance, also linked to PRKAR1A
- Epidermolysis bullosa, junctional 4, intermediate, also linked to COL17A1
- Epithelial recurrent erosion dystrophy, also linked to COL17A1
Frequently asked questions
Which genes are linked to Amelogenesis imperfecta?
In CATVariant, Amelogenesis imperfecta is linked to 3 analyzed proteins: COL17A1 (Collagen alpha-1(XVII) chain), LAMB3 (Laminin subunit beta-3) and PRKAR1A (cAMP-dependent protein kinase type I-alpha regulatory subunit).
How many genetic variants are linked to Amelogenesis imperfecta?
46 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 17 are of uncertain significance or have conflicting reports.
Which uncertain variants in Amelogenesis imperfecta look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
Download every variant as CSV · Browse all diseases · Methods · About the Center