AMTN

protein-coding

amelotin

Gene summary

The mineralized portions of teeth, the dentin and enamel, are formed by mesenchyme-derived odontoblasts and epithelium-derived ameloblasts, respectively. As ameloblasts differentiate, they deposit specific proteins necessary for enamel formation, including amelogenin (AMELX; MIM 300391), enamelin (ENAM; MIM 606585), and ameloblastin (AMBN; MIM 601259), in the organic enamel matrix. Amelotin is specifically expressed in maturation-stage ameloblasts (Iwasaki et al., 2005 [PubMed 16304441]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_212557.4

Inheritance

ClinVar variants

P:1U:23B:5

Top phenotype

Amelogenesis imperfecta, type IIIB

gnomAD constraint

pLI —, LoF o/e 1.22

Max pathogenic AF

—

Genomic locus

chr4:70,518,569-70,532,743

External References & Databases

Ensembl (ENSG00000187689)

Transcript & Mutation Effects

hg38 • Region Span ~14.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amelogenesis imperfecta type 3BLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0021547

Submitter: PanelApp Australia

amelogenesis imperfecta, type 3ASUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007538

Submitter: Orphanet

amelogenesis imperfecta type 3BLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0021547

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Amelogenesis imperfecta, type IIIBAD

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

Refs: 27412008

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AMTN variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 25

AMTN-related disorderTotal: 4

not providedTotal: 1

Amelogenesis imperfecta, type 3ATotal: 1

Amelogenesis imperfecta type 3BTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_212557.4. 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						0
missense			23 clinvar	3 clinvar	2 clinvar	28
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	1	0	23	3	2	29

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_212557.4	RefSeq	NP_997722.1	8	MANE Select
ENST00000339336.9	Ensembl	ENSP00000341013.4	8	MANE Select
NM_001286731.2	RefSeq	NP_001273660.1	8	Standard
ENST00000504451.1	Ensembl	ENSP00000422452.1	8	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

cell adhesion
biomineral tissue development
odontogenesis of dentin-containing tooth
post-translational protein modification
cellular protein metabolic process

Molecular Function

molecular_function
protein binding

Cellular Component

basement membrane
endoplasmic reticulum lumen
cell-cell junction
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000339336
Coding exons: 8
Length: 14203
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125730
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.380	99	110	0.898	0.00000539	1301
Missense (PolyPhen)		20	20.657	0.96818		260
Synonymous	-0.489	48	43.9	1.09	0.00000226	453
Loss of Function	-0.704	14	11.4	1.22	4.85e-7	138

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Is a promoter of calcium phosphate mineralization, playing a critical role in the formation of the compact, mineralized, aprismatic enamel surface layer during the maturation stage of amelogenesis. {ECO:0000269|PubMed:25407797}.;
Disease: DISEASE: Amelogenesis imperfecta 3B (AI3B) [MIM:617607]: An autosomal dominant form of amelogenesis imperfecta, a defect of enamel formation. AI3B is characterized by hypomineralized enamel that has reduced tickness and exhibits structural defects. {ECO:0000269|PubMed:27412008}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0547

Intolerance Scores

LoFtool: 0.763
RVIS EVS: 1.3
RVIS percentile EVS: 93.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0517

Gene Damage Prediction

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