AMELX

amelogenin X-linked

Basic information

Region (hg38): X:11293412-11300761

Previous symbols: [ "AMG", "AIH1" ]

Links

ENSG00000125363 ∙ NCBI:265 ∙ OMIM:300391 ∙ HGNC:461 ∙ Uniprot:Q99217 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amelogenesis imperfecta type 1E (Strong), mode of inheritance: XL
• amelogenesis imperfecta type 1E (Strong), mode of inheritance: XL
• amelogenesis imperfecta type 2 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amelogenesis imperfecta, type 1E	XL	General	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	Dental	1916828; 7782077; 15111628

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AMELX gene.

• not provided (14 variants)
• Inborn genetic diseases (6 variants)
• X-linked amelogenesis imperfecta hypoplastic/hypomaturation 2 (3 variants)
• Amelogenesis imperfecta type 1E (3 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AMELX gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	3	5
missense	1	1	6	1	1	10
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding					4	4
Total	1	2	6	3	8

Variants in AMELX

This is a list of pathogenic ClinVar variants found in the AMELX region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-11294477-A-T			Benign (Jun 18, 2021)
X-11294790-T-C		Amelogenesis imperfecta type 1E	Pathogenic (May 01, 2004)
X-11294799-G-C		Amelogenesis imperfecta type 1E	Pathogenic (May 01, 2004)
X-11294801-ATTTTATTTG-A		Amelogenesis imperfecta type 1E	Pathogenic (Mar 01, 1995)
X-11294835-C-A		Amelogenesis imperfecta type 1E	Likely pathogenic (Mar 01, 2023)
X-11294907-T-C			Benign (Nov 10, 2018)
X-11296514-G-A			Benign (Jun 20, 2021)
X-11298125-A-G		Inborn genetic diseases	Uncertain significance (Apr 07, 2022)
X-11298242-AC-A		Amelogenesis imperfecta type 1E	Pathogenic (Apr 01, 2002)
X-11298243-C-T		Amelogenesis imperfecta type 1E	Pathogenic (Apr 01, 2002)
X-11298259-C-T			Likely benign (Dec 01, 2022)
X-11298262-G-C		X-linked amelogenesis imperfecta hypoplastic/hypomaturation 2	not provided (-)
X-11298264-G-A		X-linked amelogenesis imperfecta hypoplastic/hypomaturation 2	not provided (-)
X-11298265-C-A		X-linked amelogenesis imperfecta hypoplastic/hypomaturation 2	not provided (-)
X-11298274-AC-A		Amelogenesis imperfecta	Pathogenic (Jul 24, 2018)
X-11298285-G-C			Likely benign (May 04, 2018)
X-11298569-C-A		Amelogenesis imperfecta type 1E	Pathogenic (May 21, 2020)
X-11298573-T-C		Inborn genetic diseases	Uncertain significance (Feb 02, 2022)
X-11298574-G-A		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
X-11298622-C-T		not specified	Benign (Jun 09, 2021)
X-11298628-G-A		AMELX-related disorder	Likely benign (Dec 06, 2022)
X-11298682-C-T			Likely benign (Mar 01, 2022)
X-11298683-G-A		Inborn genetic diseases	Uncertain significance (Jun 12, 2015)
X-11298692-C-T		Amelogenesis imperfecta type 1E	Likely pathogenic (Nov 08, 2021)
X-11298710-G-A		Inborn genetic diseases	Uncertain significance (Jun 30, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AMELX	protein_coding	protein_coding	ENST00000380712	6	7349

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0745	0.878	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.957	59	83.6	0.706	0.00000626	1340
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000376	0.0000376
Ashkenazi Jewish	0.00	0.00
East Asian	0.000219	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000122	0.00000879
Middle Eastern	0.000219	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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) (Consensus)

Recessive Scores

• pRec: 0.248

Intolerance Scores

• loftool: 0.142
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.26

Haploinsufficiency Scores

• pHI: 0.146
• hipred: N
• hipred_score: 0.323

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Amelx
• Phenotype: skeleton phenotype; neoplasm; growth/size/body region phenotype; craniofacial phenotype

Gene ontology

• Biological process: osteoblast differentiation;epithelial to mesenchymal transition;chondrocyte differentiation;cell adhesion;signal transduction;response to nutrient;regulation of signaling receptor activity;biomineral tissue development;positive regulation of collagen biosynthetic process;tooth mineralization;regulation of cell population proliferation;odontogenesis of dentin-containing tooth;response to drug;post-translational protein modification;cellular protein metabolic process;response to calcium ion;enamel mineralization;positive regulation of tooth mineralization
• Cellular component: endoplasmic reticulum lumen;Golgi apparatus;cell surface;endocytic vesicle;collagen-containing extracellular matrix
• Molecular function: protein binding;growth factor activity;structural constituent of tooth enamel;identical protein binding;hydroxyapatite binding