AMBN

protein-coding

ameloblastin

Gene summary

This gene encodes the nonamelogenin enamel matrix protein ameloblastin. The encoded protein may be important in enamel matrix formation and mineralization. This gene is located in the calcium-binding phosphoprotein gene cluster on chromosome 4. Mutations in this gene may be associated with dentinogenesis imperfect and autosomal dominant amylogenesis imperfect. [provided by RefSeq, Aug 2011]

MANE transcript

NM_016519.6

Inheritance

SD, AD, AR

ClinVar variants

P:6U:66B:19

Top phenotype

Amelogenesis imperfecta, type IF

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr4:70,592,256-70,607,288

External References & Databases

Ensembl (ENSG00000178522)

Transcript & Mutation Effects

hg38 • Region Span ~15.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amelogenesis imperfecta type 1FLIMITED

Inheritance Pattern: SD

Disease ID:MONDO:0014560

Submitter: Ambry Genetics

amelogenesis imperfecta type 1FSTRONG

Inheritance Pattern: SD

Disease ID:MONDO:0014560

Submitter: PanelApp Australia

amelogenesis imperfecta type 1SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015047

Submitter: Orphanet

amelogenesis imperfecta type 1FSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014560

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Amelogenesis imperfecta, type IFAR

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: 24858907

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AMBN variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 55

not providedTotal: 24

AMBN-related disorderTotal: 13

Amelogenesis imperfecta type 1FTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016519.6. 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 clinvar	6 clinvar	2 clinvar	9
missense		1 clinvar	57 clinvar	6 clinvar	5 clinvar	69
nonsense			3 clinvar			3
start loss						0
frameshift	1 clinvar		3 clinvar			4
splice donor/acceptor (+/-2bp)	2 clinvar	2 clinvar	2 clinvar			6
Total	3	3	66	12	7	91

Highest pathogenic variant AF is 0.0000934439

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016519.6	RefSeq	NP_057603.1	13	MANE Select
ENST00000322937.10	Ensembl	ENSP00000313809.6	13	MANE Select
ENST00000449493.2	Ensembl	ENSP00000391234.2	13	Standard
ENST00000449493.3	Ensembl	ENSP00000391234.2	13	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
cell population proliferation
regulation of signaling receptor activity
biomineral tissue development
odontogenesis of dentin-containing tooth

Molecular Function

protein binding
growth factor activity
structural constituent of tooth enamel

Cellular Component

extracellular region
endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000322937
Coding exons: 13
Length: 15033
Individuals with no LoFs: 125652
Homozygous LoFs: 0
Heterozygous LoFs: 92
Defined: 125744
p: 0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.348	260	245	1.06	0.0000119	2899
Missense (PolyPhen)		81	80.997	1		959
Synonymous	-0.562	97	90.2	1.08	0.00000535	875
Loss of Function	1.16	17	23.0	0.740	9.75e-7	284

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0.0011	0.0011	notable
European (Non-Finnish)	0.00047	0.00046	rare
South Asian	0.00016	0.00016	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the mineralization and structural organization of enamel.;

Recessive Scores

pRec: 0.0665

Intolerance Scores

LoFtool: 0.780
RVIS EVS: 1.55
RVIS percentile EVS: 95.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.127

Gene Damage Prediction

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