ENAM

enamelin

Basic information

Region (hg38): 4:70628744-70646824

Previous symbols: [ "AIH2" ]

Links

ENSG00000132464

∙ NCBI:10117 ∙ OMIM:606585 ∙ HGNC:3344 ∙ Uniprot:Q9NRM1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

amelogenesis imperfecta type 1B (Strong), mode of inheritance: Semidominant
amelogenesis imperfecta type 1 (Supportive), mode of inheritance: AD
amelogenesis imperfecta type 1B (Strong), mode of inheritance: AD
amelogenesis imperfecta type 1C (Strong), mode of inheritance: AR
amelogenesis imperfecta type 1B (Definitive), mode of inheritance: AD
amelogenesis imperfecta type 1C (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amelogenesis imperfecta, type IB; Amelogenesis imperfecta, type IC	AD/AR	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	11487571; 11978766; 14684688; 22243262

ClinVar

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

Inborn_genetic_diseases (140 variants)
Amelogenesis_imperfecta (56 variants)
not_provided (36 variants)
Amelogenesis_imperfecta_-_hypoplastic_autosomal_dominant_-_local (15 variants)
ENAM-related_disorder (9 variants)
Amelogenesis_imperfecta_type_1C (5 variants)
not_specified (2 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ENAM gene is commonly pathogenic or not. These statistics are base on transcript: NM_000031889.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			10 clinvar	9 clinvar	3 clinvar	22
missense		1 clinvar	172 clinvar	14 clinvar	3 clinvar	190
nonsense	3 clinvar		2 clinvar			5
start loss						0
frameshift		5 clinvar	1 clinvar			6
splice donor/acceptor (+/-2bp)	4 clinvar	1 clinvar				5
Total	7	7	185	23	6

Highest pathogenic variant AF is 0.0002973952

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ENAM	protein_coding	protein_coding	ENST00000396073	8	58073

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.30e-12	0.981	125559	0	188	125747	0.000748

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.456	618	587	1.05	0.0000295	7554
Missense in Polyphen		144	141.89	1.0149		2036
Synonymous	-1.58	235	206	1.14	0.0000103	2179
Loss of Function	2.41	26	43.1	0.604	0.00000198	558

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000745	0.000745
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.000272	0.000272
Finnish	0.000418	0.000416
European (Non-Finnish)	0.00119	0.00118
Middle Eastern	0.000272	0.000272
South Asian	0.000600	0.000588
Other	0.000332	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in the mineralization and structural organization of enamel. Involved in the extension of enamel during the secretory stage of dental enamel formation. {ECO:0000250|UniProtKB:O97939}.;
Disease: DISEASE: Amelogenesis imperfecta 1B (AI1B) [MIM:104500]: An autosomal dominant defect of enamel formation. Clinical manifestations may be variable. Some cases present with generalized enamel hypoplasia resulting in small, smooth, yellow and widely spaced teeth (smooth hypoplastic AI). Others show horizontal rows of pits, grooves or a hypoplastic area in the enamel (local hypoplastic AI). {ECO:0000269|PubMed:11487571, ECO:0000269|PubMed:11978766, ECO:0000269|PubMed:20439930, ECO:0000269|PubMed:25789606}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Amelogenesis imperfecta 1C (AI1C) [MIM:204650]: An autosomal recessive defect of dental enamel formation. Teeth show local hypoplastic and unmineralized enamel, and a yellow-brown discoloration. Enamel defects can be associated with facial and oral features including vertical dysgnathia and anterior openbite malocclusion. {ECO:0000269|PubMed:14684688, ECO:0000269|PubMed:20439930, ECO:0000269|PubMed:25789606}. 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: 0.118

Intolerance Scores

loftool: 0.789
rvis_EVS: -0.08
rvis_percentile_EVS: 47.26

Haploinsufficiency Scores

pHI: 0.0936
hipred: N
hipred_score: 0.173
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.0891

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Enam
Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); craniofacial phenotype; homeostasis/metabolism phenotype; skeleton phenotype; hematopoietic system phenotype; digestive/alimentary phenotype;

Gene ontology

Biological process: regulation of cell morphogenesis;biomineral tissue development;ameloblast differentiation;post-translational protein modification;cellular protein metabolic process;positive regulation of enamel mineralization;amelogenesis
Cellular component: endoplasmic reticulum lumen;extracellular matrix
Molecular function: protein binding;structural constituent of tooth enamel