ENAM

enamelin

Basic information

Region (hg38): 4:70628743-70646824

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

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.

• Amelogenesis imperfecta (97 variants)
• Inborn genetic diseases (44 variants)
• not provided (34 variants)
• Amelogenesis imperfecta - hypoplastic autosomal dominant - local (6 variants)
• Amelogenesis Imperfecta, Dominant (4 variants)
• ENAM-related condition (4 variants)
• not specified (2 variants)
• Amelogenesis imperfecta type 1C (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.

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			8	4	3	15
missense			72	6	5	83
nonsense	1		1			2
start loss						0
frameshift	1	4				5
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region			2			2
non coding			31	5	17	53
Total	3	5	112	15	25

Highest pathogenic variant AF is 0.000171

Variants in ENAM

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

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

Position	Type	Phenotype	Significance	ClinVar
4-70628807-A-G		Amelogenesis imperfecta	Uncertain significance (Jan 13, 2018)
4-70628902-G-A		Amelogenesis imperfecta	Benign (Jan 13, 2018)
4-70628913-A-G		Amelogenesis imperfecta	Uncertain significance (Jan 13, 2018)
4-70628914-A-T		Amelogenesis imperfecta	Uncertain significance (Jan 12, 2018)
4-70628965-G-A		Amelogenesis imperfecta	Pathogenic (-)
4-70629437-T-A		Amelogenesis imperfecta	Uncertain significance (Jan 12, 2018)
4-70629456-A-G		Amelogenesis imperfecta	Uncertain significance (Jan 13, 2018)
4-70629476-G-A		Amelogenesis imperfecta	Uncertain significance (Jan 13, 2018)
4-70629518-C-G		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
4-70631370-A-C			Benign (Jun 20, 2021)
4-70631691-A-T		Amelogenesis imperfecta	Uncertain significance (Jan 12, 2018)
4-70631707-T-G		Amelogenesis imperfecta - hypoplastic autosomal dominant - local	Pathogenic/Likely pathogenic (Aug 03, 2017)
4-70631716-T-C		Amelogenesis imperfecta - hypoplastic autosomal dominant - local	Uncertain significance (Mar 01, 2023)
4-70631720-TA-T		ENAM-related disorder	Likely pathogenic (Jan 27, 2023)
4-70631727-G-T		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
4-70631740-T-G		Amelogenesis imperfecta - hypoplastic autosomal dominant - local	Pathogenic (Dec 23, 2017)
4-70631867-C-T		Inborn genetic diseases	Uncertain significance (Dec 20, 2021)
4-70631868-C-G		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
4-70631882-A-T		Amelogenesis imperfecta - hypoplastic autosomal dominant - local	Pathogenic (May 01, 2002)
4-70632586-G-A			Benign (Nov 11, 2018)
4-70632659-G-T		Amelogenesis imperfecta	Benign/Likely benign (Jul 16, 2018)
4-70632684-G-A		Inborn genetic diseases	Likely benign (Nov 30, 2022)
4-70634311-G-A		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
4-70634315-A-G		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
4-70634330-T-C		Amelogenesis imperfecta	Uncertain significance (Jan 12, 2018)

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

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