AMELX
protein-codingamelogenin X-linked
Gene summary
This gene encodes a member of the amelogenin family of extracellular matrix proteins. Amelogenins are involved in biomineralization during tooth enamel development. Mutations in this gene cause X-linked amelogenesis imperfecta. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
- AMG
- AIH1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0010521
Submitter: PanelApp Australia
Inheritance Pattern: XL
Disease ID:MONDO:0010521
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0015048
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0010521
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Dental
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AMELX variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001142.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 5 | 3 | 9 | ||
| missense | 4 | 2 | 28 | 2 | 1 | 37 |
| nonsense | 1 | 3 | 1 | 5 | ||
| start loss | 1 | 1 | 2 | |||
| frameshift | 4 | 1 | 5 | |||
| splice donor/acceptor (+/-2bp) | 2 | 3 | 5 | |||
| Total | 10 | 9 | 33 | 7 | 4 | 63 |
Highest pathogenic variant AF is 0.0000127526155
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001133.1 | 5 | MANE Select | |
| Ensembl | ENSP00000370090.3 | 5 | MANE Select | |
| RefSeq | NP_872621.1 | 6 | Standard | |
| RefSeq | NP_872622.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein phosphorylation
- Post-translational protein modification
- Metabolism of proteins
- Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Biological Process
- osteoblast differentiation
- epithelial to mesenchymal transition
- chondrocyte differentiation
- cell adhesion
- signal transduction
Molecular Function
- protein binding
- growth factor activity
- structural constituent of tooth enamel
- identical protein binding
- hydroxyapatite binding
Cellular Component
- endoplasmic reticulum lumen
- Golgi apparatus
- cell surface
- endocytic vesicle
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380712
- Coding exons
- 6
- Length
- 7349
- Individuals with no LoFs
- 125743
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125748
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.957 | 59 | 83.6 | 0.706 | 0.00000626 | 1340 |
| Missense (PolyPhen) | 15 | 20.361 | 0.7367 | 348 | ||
| Synonymous | -1.54 | 44 | 32.8 | 1.34 | 0.00000276 | 403 |
| Loss of Function | 1.68 | 3 | 8.18 | 0.367 | 5.22e-7 | 119 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000038 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000012 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in biomineralization. Seems to regulate the formation of crystallites during the secretory stage of tooth enamel development. Thought to play a major role in the structural organization and mineralization of developing enamel.;
- Disease
- DISEASE: Amelogenesis imperfecta 1E (AI1E) [MIM:301200]: A X- linked defect of dental enamel formation. Teeth have only a thin layer of enamel with normal hardness. The thinness of the enamel makes the teeth appear small. {ECO:0000269|PubMed:10669095, ECO:0000269|PubMed:15111628, ECO:0000269|PubMed:7599636, ECO:0000269|PubMed:7782077, ECO:0000269|PubMed:9188994}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.248
Intolerance Scores
- LoFtool
- 0.142
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58.26
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |