AMELY

Chr Y

amelogenin Y-linked

Also known as: AMGL, AMGY

AMELY encodes an extracellular matrix protein that regulates crystallite formation and mineralization during tooth enamel development. Mutations cause amelogenesis imperfecta affecting tooth enamel structure and quality. The gene shows low constraint against loss-of-function variants and inheritance pattern varies depending on the specific variant and family history.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.95
Clinical SummaryAMELY
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 10 VUS of 81 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.95LOEUF
pLI 0.000
Z-score -1.12
OE 1.70 (0.761.95)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.13Z-score
OE missense 1.06 (0.811.42)
33 obs / 31.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.70 (0.761.95)
00.351.4
Missense OE1.06 (0.811.42)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 5 / 2.9Missense obs/exp: 33 / 31.0Syn Z: -0.36
DN
0.83top 10%
GOF
0.77top 25%
LOF
0.10100th %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

81 submitted variants in ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic2
VUS10
Likely Benign12
54
Pathogenic
2
Likely Pathogenic
10
VUS
12
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
54
Likely Pathogenic
2
VUS
10
Likely Benign
12
Benign
0
Total78

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AMELY · 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 →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Se Amable.
Jones-Schenk J·J Contin Educ Nurs
2023
Amor Rodriguez.
·Angew Chem Int Ed Engl
2023
Amor fati: Memento mori.
Zarzaur BL·J Trauma Acute Care Surg
2025
Regeneration: AT-AMIC Technique: Limits and Indication.
Maccario C et al.·Foot Ankle Clin
2024
Top 5 full-text resultsSearch PubTator3 ↗