AMELX

Chr XXLD

amelogenin X-linked

Also known as: AI1E, AIH1, ALGN, AMG, AMGL, AMGX

This gene encodes amelogenin, an extracellular matrix protein that regulates crystallite formation and mineralization during tooth enamel development. Mutations cause X-linked amelogenesis imperfecta type 1E, a condition affecting enamel formation and tooth structure. The inheritance pattern is X-linked dominant.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismXLDLOEUF 0.951 OMIM phenotype
Clinical SummaryAMELX
Population Constraint (gnomAD)
Low constraint (pLI 0.07) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.075
Z-score 1.68
OE 0.37 (0.170.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.96Z-score
OE missense 0.71 (0.570.88)
59 obs / 83.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.170.95)
00.351.4
Missense OE0.71 (0.570.88)
00.61.4
Synonymous OE1.34
01.21.6
LoF obs/exp: 3 / 8.2Missense obs/exp: 59 / 83.6Syn Z: -1.54
DN
0.78top 25%
GOF
0.6540th %ile
LOF
0.11100th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

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

AMELX · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗