AMBN

ameloblastin

Basic information

Region (hg38): 4:70592256-70607288

Links

ENSG00000178522

∙ NCBI:258 ∙ OMIM:601259 ∙ HGNC:452 ∙ Uniprot:Q9NP70 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amelogenesis imperfecta, type IF	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	24858907

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AMBN 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				4 clinvar	3 clinvar	7
missense			22 clinvar	4 clinvar	5 clinvar	31
nonsense			3 clinvar			3
start loss						0
frameshift						0
inframe indel					1 clinvar	1
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
splice region				1		1
non coding				1 clinvar	1 clinvar	2
Total	0	1	26	9	10

Variants in AMBN

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

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

Position	Phenotype	Significance	ClinVar
4-70592374-G-A	Amelogenesis imperfecta type 1F	Uncertain significance (Mar 01, 2023)	2445235
4-70593387-G-A	Amelogenesis imperfecta type 1F	Likely pathogenic (May 04, 2023)	2501302
4-70597004-T-A	not specified	Uncertain significance (May 06, 2024)	3292302
4-70597028-T-C		Likely benign (Mar 29, 2018)	737428
4-70598364-A-C	not specified	Uncertain significance (Jun 07, 2024)	3292291
4-70598367-G-C	not specified	Uncertain significance (Dec 14, 2021)	2267120
4-70599554-G-A	not specified	Uncertain significance (Feb 22, 2023)	2465234
4-70599561-C-G	Amelogenesis imperfecta type 1F	Uncertain significance (Mar 01, 2023)	1702585
4-70599580-G-T		Benign (Dec 31, 2019)	715973
4-70599585-G-T	AMBN-related disorder	Benign (Aug 28, 2019)	3053002
4-70599633-A-G		Uncertain significance (Aug 24, 2017)	1025625
4-70599784-AGCCTATAACTGCTTTTAGCGCTTAAGAAATATTTTTAAATTTAAAACTATTTGCATATTTATTTAAAATAGGAAGATACAGCCTCCAAAATATGAGACCTATATTAAAGATATCAGTAAACAATCCTCGAAAATCAAAGCAGGCTACATCCTGGACAATTTTCATTTGAATCAAGATTTCCTAAATAATTCCTCAAAGGCTGATTTCAAATGATGACAATAATCCTGGTTAAAATACCATAGCCAGGTGCGATGGCTGACGCCTGTAATCCCAGCATTTTGGGAGGCCAAGGTGGGTGGATCACTTGAGGTCAGGAGTTCAAGACCAGCCTGGCCAACATGGTGAAACCCCGTCTCTACTAAAAATACAAAAATTAGCCAGGCATGGTGGCAGGCACCTGTAATCTCAGCTACTCTCAGGAGGCTGAGGCAGGACAATAGCTTGAACCTGGGAGGCAGAGGCTGCAGTGAGCCGAGATTGTGCCACTGCACTCCAGCCTGGGCAATAGAGTGAGACTCTGTCTCAAAAAAAATTAAGAAATTTAAAAAAAAAAAACATCATGAACCCTACAGAAGTCAATAAATATATCAATCTGTTAACCATTATTGATTAGGTGCCTAATAAATACATAAACCAAATTGTGGTTTGGTAGTAAAAGCGAAGACATTTAAGAATGGCTCCAAGGATTGTGAAATTTCATCTTATCTGATTCAGATAGGACAAGACAACATATTTCAAAGTGCTGAATTGTGACATGTGAGTAATGAATACTGCGTGAGCTCAGAGAGGGGTGATGGCTGGAGAGGCAAAGCAGAGCCCCAAATTGTTGCGAGACTTCCTTGCTGGTCTGAGGAGTTTACAATCAATCTACAAACAATAGGGAGCCATTCACCAAAAGTAATTTCTACAAGAAGTAACAAAACATGGTGATTTTAACGGGGAATTTTTTCGTTTAATATATGGACTCAGAACCAAGATTTAACAGGGAATTTTAGTTCCAGGCGGTCTTCCACAGCAGGAGCATTACCACGAGGTCACATTCAGTAGAACAATAAATTATGTTAATGGTGACTGTTTCTTAACTTAATTGTTTCCAAAGTGGACTCCATGATGCAAGAATTTGATTGGCATTTTAATTAATTACCCTTTATCCTTTCATTAACTCGAAAAATATATTAGGCACCCACCATGGGCCAGGCACTTGTTAGGAGCTATGTTATGTACACGGGCTATAAAGAAAAACAAAACATATCATTCTCTCTCCGTTGACTGGGGGACAAAGATTTATAACAAATAATTATCATCCAGTGAGAAAGTGGTAAAATAAAGATACAGATACATACAGACAGCTATGGGAACTTAGAGAAGGACATGACTCATCCTACCAGGAGGTTCATGTAGCTTCACCTTTACGAGCAATGGTGGTCCCAAAGGAGGTAGGGGAGGCACACACAAGACCTCCCCAAACAACATTAACACTAACTGGTGCTTGCTATGTAAACTCAACTTCAAGACAAGTCTCCTAGCCTCCCTTCCAGATAGAAAGCGCCCCAAGCCCCTTTGTTTAGAAATTCTAGGCACCGTTGTTTAATGAGCCATCCCTTCCTAACACTCTTTTCAAATTTCTCTGCAGTATGAATATTCTTTGCCTGTGCATCCCCCACCTCTCCCATCACAGCCATCCTTGAAGCCTCAACAGCCAGGACTGAAACCTTTTCTCCAGTCTGCTGCTGCAACCACCAACCAGGCCACAGCACTGAAAGAAGCACTTCAGCCTCCAATTCACCTGGGACATCTGCCCTTGCAGGAAGGAGAACTGCCTCTGGTTCAGCAGCAGGTGGCACCATCAGATAAGCCACCAAAGCCTGAGGTACTTCCTTTCTCTTGAAGTCAGATCAGAATCACCAGCTAACCTAATAGAAGAAAACGAATTTGCAGGGCACTTTTAAATAATCGTAGCCTTCAGGCATAATACGTGATATAAATATATTCTTAATCAGTCTTCCACATCTGAGATTTATTTTTTGAGTAAAACGTAAATATCCATTCCTATCTTTTGCCATCAGAGACAGGGCATGGATTCTAAAAGATACTGTGCCTATAAAACTGGGTTTCTTAGTTGCGAAAGATGAAAACTCCCATAGGAAATAGAATAAAACCCCAGAGAAGTCCAGGTTTCCTATCACTGGTCTTTTTTGGTATTGGAAAAACTGAAAAAAGTGATTGATCCCTCAGCATAACAAGTAGGATTTTGCATTATTATCTCTCTGACAAAGAGGTGACCACTATGCAAAAAGTATCTTGTAATAATGTAGAGAAAAGTGTAATGGATTAAAAAAAAAATGAAG-A	Amelogenesis imperfecta type 1F	Pathogenic (Oct 15, 2014)	183689
4-70601416-A-C		Likely pathogenic (Aug 15, 2023)	2575130
4-70601418-T-C	Amelogenesis imperfecta type 1F • not specified	Uncertain significance (Dec 15, 2023)	2233469
4-70601483-G-A		Uncertain significance (May 30, 2024)	3383837
4-70601611-T-A	not specified	Uncertain significance (Feb 27, 2023)	2489456
4-70601652-G-A	not specified	Uncertain significance (Apr 08, 2022)	2282540
4-70602615-G-C	AMBN-related disorder	Likely benign (Jul 11, 2019)	3050454
4-70602623-G-C	Amelogenesis imperfecta type 1F	Pathogenic (Nov 22, 2016)	372171
4-70602628-CAGG-C	AMBN-related disorder	Benign (Mar 21, 2019)	3056626
4-70602629-A-AG	Amelogenesis imperfecta type 1F	Pathogenic (May 04, 2023)	2501301
4-70602634-T-C	AMBN-related disorder	Likely benign (Dec 31, 2019)	770153
4-70602638-T-A	not specified	Uncertain significance (Dec 20, 2023)	3114612
4-70602640-T-C	not specified	Uncertain significance (Nov 03, 2023)	3114615
4-70602642-G-C	not specified	Uncertain significance (Aug 15, 2023)	2601335

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AMBN	protein_coding	protein_coding	ENST00000322937	13	15033

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.05e-9	0.519	125652	0	92	125744	0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.348	260	245	1.06	0.0000119	2899
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000339	0.000333
Ashkenazi Jewish	0.00	0.00
East Asian	0.000226	0.000218
Finnish	0.00106	0.00106
European (Non-Finnish)	0.000467	0.000457
Middle Eastern	0.000226	0.000218
South Asian	0.000163	0.000163
Other	0.000175	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in the mineralization and structural organization of enamel.;
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: 0.0665

Intolerance Scores

loftool: 0.780
rvis_EVS: 1.55
rvis_percentile_EVS: 95.64

Haploinsufficiency Scores

pHI: 0.119
hipred: N
hipred_score: 0.123
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.127

Gene Damage Prediction

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

Mouse Genome Informatics

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

Gene ontology

Biological process: cell adhesion;cell population proliferation;regulation of signaling receptor activity;biomineral tissue development;odontogenesis of dentin-containing tooth;post-translational protein modification;cellular protein metabolic process
Cellular component: extracellular region;endoplasmic reticulum lumen
Molecular function: protein binding;growth factor activity;structural constituent of tooth enamel