AMBN

Summary

AMBN (ameloblastin, HGNC:452) is a protein-coding gene on chromosome 4q13.3, encoding Ameloblastin (Q9NP70). Involved in the mineralization and structural organization of enamel.

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.

Source: NCBI Gene 258 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amelogenesis imperfecta type 1F (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 104 total — 5 pathogenic, 2 likely-pathogenic
• GTEx eGene: eQTL in 3 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 6
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.34 (unconstrained)
• MANE Select transcript: NM_016519

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:452
Approved symbol	AMBN
Name	ameloblastin
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178522
Ensembl biotype	protein_coding
OMIM	601259
Entrez	258

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

MANE Select: ENST00000322937

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 5: 1

ENST00000322937, ENST00000449493

RefSeq mRNA: 1 — MANE Select: NM_016519 NM_016519

CCDS: CCDS3543

Canonical transcript exons

ENST00000322937 — 13 exons

Exon	Start	End
ENSE00001264291	70601418	70601654
ENSE00001264299	70599536	70599646
ENSE00001264306	70598356	70598403
ENSE00001264314	70596999	70597049
ENSE00001332138	70593327	70593395
ENSE00001365763	70603260	70603319
ENSE00001370813	70603877	70603921
ENSE00001371888	70603416	70603460
ENSE00001838737	70592256	70592373
ENSE00001935357	70606185	70607288
ENSE00002502393	70602972	70603010
ENSE00002513079	70602624	70602662
ENSE00002528837	70602798	70602836

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 91.03.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5103 / max 226.2252, expressed in 75 samples.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, periodontal ligament, diaphragm, type B pancreatic cell, olfactory bulb.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AMBN is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 3 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

3 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Nucleus accumbens basal ganglia	eqtl	6.1e-03	-0.55	4:70592237:T:TTTCTAATC
Cells EBV-transformed lymphocytes	eqtl	4.2e-02	+0.89	4:71586640:G:A
Brain Putamen basal ganglia	eqtl	4.7e-02	-0.13	4:70593015:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
47985	0.2779	52
47987	0.2094	30
47986	0.0230	9

Top tissues by expression

showing 100 of 276 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.03	gold quality
periodontal ligament	UBERON:0008266	71.12	silver quality
diaphragm	UBERON:0001103	68.67	gold quality
type B pancreatic cell	CL:0000169	67.66	gold quality
olfactory bulb	UBERON:0002264	64.98	gold quality
putamen	UBERON:0001874	64.84	gold quality
buccal mucosa cell	CL:0002336	64.59	gold quality
mucosa of paranasal sinus	UBERON:0005030	64.05	gold quality
gingival epithelium	UBERON:0001949	61.71	gold quality
caudate nucleus	UBERON:0001873	60.64	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	60.57	gold quality
male germ cell	CL:0000015	59.93	gold quality
endothelial cell	CL:0000115	59.65	gold quality
sperm	CL:0000019	59.11	gold quality
epithelium of nasopharynx	UBERON:0001951	58.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	58.51	gold quality
superficial temporal artery	UBERON:0001614	58.25	gold quality
lateral globus pallidus	UBERON:0002476	57.35	gold quality
gluteal muscle	UBERON:0002000	57.17	gold quality
thymus	UBERON:0002370	56.91	gold quality
subthalamic nucleus	UBERON:0001906	56.88	gold quality
decidua	UBERON:0002450	56.55	gold quality
dorsal plus ventral thalamus	UBERON:0001897	56.48	gold quality
ventral tegmental area	UBERON:0002691	56.30	gold quality
inferior vagus X ganglion	UBERON:0005363	56.28	gold quality
amniotic fluid	UBERON:0000173	55.83	gold quality
saphenous vein	UBERON:0007318	55.75	gold quality
gingiva	UBERON:0001828	55.74	gold quality
trigeminal ganglion	UBERON:0001675	55.69	gold quality
synovial joint	UBERON:0002217	55.49	gold quality
pharyngeal mucosa	UBERON:0000355	55.48	gold quality
biceps brachii	UBERON:0001507	55.30	gold quality
body of tongue	UBERON:0011876	55.11	gold quality
superior vestibular nucleus	UBERON:0007227	54.87	gold quality
germinal epithelium of ovary	UBERON:0001304	54.82	gold quality
superior surface of tongue	UBERON:0007371	54.68	gold quality
pericardium	UBERON:0002407	54.66	gold quality
squamous epithelium	UBERON:0006914	54.64	gold quality
tongue	UBERON:0001723	54.53	gold quality
dorsal root ganglion	UBERON:0000044	54.49	gold quality
nipple	UBERON:0002030	54.30	gold quality
penis	UBERON:0000989	54.13	gold quality
pylorus	UBERON:0001166	54.13	gold quality
medulla oblongata	UBERON:0001896	53.91	gold quality
substantia nigra pars compacta	UBERON:0001965	53.91	gold quality
pons	UBERON:0000988	53.85	gold quality
layer of synovial tissue	UBERON:0007616	53.78	gold quality
cerebellar vermis	UBERON:0004720	53.72	gold quality
trachea	UBERON:0003126	53.68	gold quality
cardia of stomach	UBERON:0001162	53.67	gold quality
nucleus accumbens	UBERON:0001882	53.58	gold quality
substantia nigra pars reticulata	UBERON:0001966	53.55	gold quality
nasal cavity epithelium	UBERON:0005384	53.45	gold quality
lateral nuclear group of thalamus	UBERON:0002736	53.26	gold quality
islet of Langerhans	UBERON:0000006	53.19	gold quality
Brodmann (1909) area 46	UBERON:0006483	53.01	gold quality
choroid plexus epithelium	UBERON:0003911	52.87	silver quality
vena cava	UBERON:0004087	52.72	gold quality
epithelium of esophagus	UBERON:0001976	52.65	gold quality
quadriceps femoris	UBERON:0001377	52.56	gold quality
vastus lateralis	UBERON:0001379	52.33	gold quality
bronchus	UBERON:0002185	52.33	gold quality
epithelium of bronchus	UBERON:0002031	52.28	gold quality
esophagus squamous epithelium	UBERON:0006920	52.28	gold quality
bronchial epithelial cell	CL:0002328	51.80	gold quality
tibia	UBERON:0000979	51.55	gold quality
left ventricle myocardium	UBERON:0006566	51.49	gold quality
epithelial cell of pancreas	CL:0000083	50.98	gold quality
deltoid	UBERON:0001476	50.94	gold quality
trabecular bone tissue	UBERON:0002483	50.72	gold quality
myocardium	UBERON:0002349	50.48	gold quality
renal medulla	UBERON:0000362	50.46	gold quality
oral cavity	UBERON:0000167	50.43	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cardiac muscle of right atrium	UBERON:0003379	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
oocyte	CL:0000023	48.96	gold quality
kidney epithelium	UBERON:0004819	48.91	gold quality
cervix epithelium	UBERON:0004801	48.75	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
urethra	UBERON:0000057	48.48	gold quality
oviduct epithelium	UBERON:0004804	48.38	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
lower lobe of lung	UBERON:0008949	48.09	silver quality
upper arm skin	UBERON:0004263	48.06	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
muscle tissue	UBERON:0002385	47.89	gold quality
skeletal muscle tissue	UBERON:0001134	47.80	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
renal glomerulus	UBERON:0000074	46.99	gold quality
metanephric glomerulus	UBERON:0004736	46.96	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
jejunum	UBERON:0002115	46.54	gold quality
mammalian vulva	UBERON:0000997	45.86	gold quality
globus pallidus	UBERON:0001875	45.64	gold quality
tibialis anterior	UBERON:0001385	45.52	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
adult organism	UBERON:0007023	45.08	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.42
E-GEOD-75140	no	114.95

HPA expression

RNA tissue specificity: Tissue enhanced

34 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Spinal cord	tissue	4.9
Periaqueductal gray	tissue	3.2
Medulla oblongata	tissue	3.1
Midbrain	tissue	3.0
Substantia nigra	tissue	2.5
Corpus callosum	tissue	2.3
Hypothalamus	tissue	2.1
Thalamus	tissue	2.0
Olfactory bulb	tissue	2.0
Pons	tissue	1.9
Superior colliculi	tissue	1.9
Hippocampal formation	tissue	1.9
Basal ganglia	tissue	1.8
Putamen	tissue	1.7
Ventral forebrain	tissue	1.7
Amygdala	tissue	1.6
Cerebral cortex	tissue	1.5
Cerebellum	tissue	1.5
Septum	tissue	1.5
Insular cortex	tissue	1.5
Entorhinal cortex	tissue	1.4
Retrosplenial cortex	tissue	1.4
Retrosplenial and cingulate cortex	tissue	1.3
Temporal cortex	tissue	1.3
Prefrontal cortex	tissue	1.2
Somatosensory cortex	tissue	1.2
Motor cortex	tissue	1.1
Occipital cortex	tissue	0.9
Nucleus accumbens	tissue	0.8
Testis	tissue	0.1
Retina	tissue	0.1
Choroid plexus	tissue	0.1
Spleen	tissue	0.1
Thymus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 33; highest nTPM — Ventral spinal cord (4.9), Dorsal spinal cord (4.2), White matter (2.3), Dorsal hippocampus (1.9), Ventral hippocampus (1.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX2

miRNA regulators (miRDB)

Targeting AMBN by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 44 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-633	98.35	69.45	1167

Functional genomics

gnomAD constraint: pLI 2.66e-12, LOEUF 1.34, missense Z -0.0744 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000322937 — one region, missense o/e 1.04.

Literature-anchored findings (GeneRIF, showing 20)

• The frequently detected AMBN alterations in ameloblastomas are polymorphisms, which appear to be unrelated to the occurrence of ameloblastomas. (PMID:17331365)
• a bipolar calcium-binding molecule [with] a possible role in protein-protein interactions (PMID:18353005)
• Mutation of ameloblastin gene is associated with calcifying epithelial odontogenic tumor. (PMID:19661317)
• The identification of a fibronectin-binding domain in ameloblastin might permit interesting applications for dental implantology. (PMID:20043904)
• found to induce, directly and indirectly, signal transducer and activator of transcription (STAT) 1 and 2 and downstream factors in the interferon pathway (PMID:20831578)
• Findings suggest a role for this protein in early bone formation and repair. (PMID:20854943)
• ameloblastin is expressed in osteoblasts and functions as a promoting factor for osteogenic differentiation via a novel pathway through the interaction between CD63 and integrin beta1 (PMID:21149578)
• AMBN does not influence osteogenic activity in vitro under the conditions used (PMID:21761392)
• AMBN ribbons exhibited lengths ranging from tens to hundreds of nm. Deletion analysis and NMR spectroscopy revealed that N-terminal segment encoded by exon 5 comprises two short independently structured regions and plays a role in self-assembly of AMBN (PMID:23782691)
• We found a trend for association between variation in AMBN and MIH in both cohorts, which may suggest that variation in the regulation of AMBN is a mechanism that leads to MIH. (PMID:23790503)
• Association between caries experience (caries-free versus caries affected) depending on asthma status and SNPs was tested. Logistic regression showed an association between AMBN rs4694075 and caries experience. Ameloblastin is associated w/caries in asthmatic children. (PMID:24203249)
• Report shows for the first time that AMBN mutations cause non-syndromic human amelogenesis imperfecta and confirms that mouse models with disrupted Ambn function are valid. (PMID:24858907)
• two genetic variants (rs2337359 upstream of TUFT1 and missense rs7439186 in AMBN) involved in gene-by-fluoride interactions. (PMID:25373699)
• Protein interaction between Ambn and Psma3 can facilitate redistribution of ameloblastin domains within forming enamel. (PMID:26070558)
• Authors perform an evolutionary analysis of mammalian AMBN sequences in order to predict functionally important sites of the protein and to identify candidate disease-associated mutations responsible for the protein function and identify AMBN as a candidate for amelogenesis imperfect in humans. (PMID:26223266)
• these results indicate that AMBN enhances IL-1beta production in LPS-treated U937 cells through ERK1/2 phosphorylation and caspase-1 activation, suggesting that AMBN upregulates the inflammatory response in human macrophages and plays an important role in innate immunity. (PMID:28295583)
• Single nucleotide polymorphisms in the AMELX and AMBN genes may be genetic variants that contribute to developmental defects of enamel in primary dentition of Polish children. (PMID:28382465)
• the calcium level was associated with genetic variations in AMELX, AMNB and ESRRB. AMELX and AMNB are involved in enamel mineralization. Mutations in both these genes are responsible for the amelogenesis imperfecta phenotype (OMIN), which supports their link with enamel alterations as well as enamel mineralization. (PMID:28395292)
• Ameloblastin is critical for the initiation of enamel ribbon formation, and its absence results in pathological mineralization within the enamel organ epithelia. (PMID:31402633)
• Novel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes. (PMID:38058155)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ambn	ENSMUSG00000029288
rattus_norvegicus	Ambn	ENSRNOG00000003718

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104655) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 15 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal jaw morphology	1
microphthalmia	1
increased tumor incidence	1
abnormal skin morphology	1
abnormal eye morphology	1
abnormal tooth morphology	1
abnormal kidney morphology	1
abnormal ameloblast morphology	1
small kidney	1
enlarged kidney	1
absent enamel	1
abnormal molar crown morphology	1
abnormal incisor morphology	1
abnormal incisor color	1
abnormal tooth attrition	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Sus scrofa	Q28989	74.9%	Diamond
Bos taurus	Q9XSX7	74.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ENAM-AS1	ncRNA	101927297
JCHAIN	protein-coding	3512
AMTN	protein-coding	401138
ENAM	protein-coding	10117
MUC7	protein-coding	4589
UTP3	protein-coding	57050
OPRPN	protein-coding	58503
SMR3B	protein-coding	10879

Protein

Protein identifiers

Ameloblastin — Q9NP70 (reviewed: Q9NP70)

All UniProt accessions (2): Q546D7, Q9NP70

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the mineralization and structural organization of enamel.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Ameloblast-specific. Located at the Tomes processes of secretory ameloblasts and in the sheath space between rod-interrod enamel.

Disease relevance. Amelogenesis imperfecta 1F (AI1F) [MIM:616270] A form of amelogenesis imperfecta, a disorder characterized by defective enamel formation. The enamel may be hypoplastic, hypomineralized or both, and affected teeth may be discoloured, sensitive or prone to disintegration. AI1F is characterized by hypoplastic enamel of the primary and secondary dentition. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ameloblastin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NP70-1	1	yes
Q9NP70-2	2

RefSeq proteins (1): NP_057603* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007798	Amelin	Family

Pfam: PF05111

UniProt features (22 total): sequence conflict 6, sequence variant 5, region of interest 3, repeat 2, modified residue 2, signal peptide 1, chain 1, splice variant 1, glycosylation site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP70-F1	44.05	0.00

Human Protein Atlas

Protein class: Predicted secreted proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; nucleoplasm

Antibody reliability (HPA): IF uncertain

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2)

Type	Positions
Hydroxyproline	37
Phosphoserine	43

Glycosylation sites (1)

Type	Positions
O-linked (galnac…) serine	112

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-8957275	Post-translational protein phosphorylation	curated
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	curated
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 103 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOMF_GROWTH_FACTOR_ACTIVITY, chr4q13, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, WTGAAAT_UNKNOWN, TGANTCA_AP1_C, GATA1_04, GOBP_ODONTOGENESIS_OF_DENTIN_CONTAINING_TOOTH, FOXJ2_02, IK3_01, GOMF_SIGNALING_RECEPTOR_BINDING, NFE2_01

GO Biological Process (5): cell adhesion (GO:0007155), biomineral tissue development (GO:0031214), regulation of cell population proliferation (GO:0042127), odontogenesis of dentin-containing tooth (GO:0042475), signal transduction (GO:0007165)

GO Molecular Function (3): growth factor activity (GO:0008083), structural constituent of tooth enamel (GO:0030345), protein binding (GO:0005515)

GO Cellular Component (1): endoplasmic reticulum lumen (GO:0005788)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Metabolism of proteins	2
Post-translational protein modification	1

GO top-level categories

14 GO namespaces:

Category	Terms
cellular process	2
regulation of cellular process	2
tissue development	1
animal organ development	1
cell population proliferation	1
odontogenesis	1
cell communication	1
signaling	1
cellular response to stimulus	1
receptor ligand activity	1
extracellular matrix structural constituent conferring compression resistance	1
binding	1
endoplasmic reticulum	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

showing 15 of 646 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMBN	ENAM	Q9NRM1	993
AMBN	AMTN	Q6UX39	982
AMBN	AMELX	Q99217	964
AMBN	TUFT1	Q9NNX1	958
AMBN	KLK4	Q9Y5K2	898
AMBN	MMP20	O60882	881
AMBN	DSPP	Q9NZW4	853
AMBN	IBSP	P21815	809
AMBN	ODAM	A1E959	780
AMBN	BMP3	P12645	758
AMBN	WDR72	Q3MJ13	734
AMBN	ODAPH	Q17RF5	718
AMBN	SACK1H	Q6ZRV2	708
AMBN	SPP1	P10451	678
AMBN	ACP4	Q9BZG2	671

IntAct

Human interaction partners of AMBN in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
BAG6	physical association	0.560	3
COL26A1	physical association	0.560	3
DNAJB6	physical association	0.560	3
F11R	physical association	0.560	3
ICAM5	physical association	0.560	3
KLF11	physical association	0.560	3
NUP58	physical association	0.560	3
UBQLN2	physical association	0.560	3
FAM20C	phosphorylation reaction	0.440	2
LRP2	physical association	0.400	1

BioGRID (5 interactions; top human partners by supporting records): LRP2 (Affinity Capture-MS; 2 records), TRIM28 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), UBQLN2 (Two-hybrid)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
FAM20C	“up-regulates activity”	AMBN	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for AMBN: 104 ClinVar records (7 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

104 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	66
Likely benign	13
Benign	13

Top pathogenic / likely-pathogenic (7)

Showing all 7 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2575130	NM_016519.6(AMBN):c.295-2A>C	Likely pathogenic	criteria provided, single submitter	1
2685970	GRCh37/hg19 4q13.1-13.3(chr4:63684557-71480358)x3	Pathogenic	criteria provided, single submitter	1
183689	NM_016519.6(AMBN):c.294+140_531+479del	Pathogenic	no assertion criteria provided	1
372171	NM_016519.6(AMBN):c.532-1G>C	Pathogenic	no assertion criteria provided	1
2501301	NM_016519.6(AMBN):c.539dup (p.Val181fs)	Pathogenic	no assertion criteria provided	1
2501302	NM_016519.6(AMBN):c.76G>A (p.Ala26Thr)	Likely pathogenic	no assertion criteria provided	1
147584	GRCh38/hg38 4q13.2-13.3(chr4:68902161-70620273)x3	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore AMBN’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 746):

Position(s)	Effect	Δscore	Sites
4:70592374–70592375	donor_loss	1.0000	4
4:70599527	acceptor_gain	1.0000
4:70599534–70599535	acceptor_loss	1.0000	6
4:70599647	donor_loss	1.0000	2
4:70601416–70601417	acceptor_loss	1.0000	6
4:70601635	donor_gain	1.0000
4:70606184	acceptor_gain	1.0000
4:70593325–70593326	acceptor_loss	0.9900	6
4:70593396–70593397	donor_loss	0.9900	5
4:70598404–70598405	donor_loss	0.9900	6

AlphaMissense

234 missense substitutions predicted likely pathogenic (of 2,924 scored), across 69 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
S43	7	0.829	0.955
E45	7	0.788	0.939
D301	7	0.788	0.842
D307	7	0.771	0.847
E264	7	0.672	0.773
S261	6	0.894	0.974
S41	6	0.838	0.954
E100	6	0.835	0.897
E305	6	0.770	0.827
M47	6	0.749	0.876
V105	6	0.671	0.777
Y101	5	0.890	0.952
F302	5	0.879	0.923
Y99	5	0.864	0.918
W75	5	0.858	0.920
E263	5	0.801	0.902
H106	5	0.780	0.864
R48	5	0.765	0.856
P104	5	0.708	0.788
W88	4	0.824	0.850

HPA cancer prognostics

RNA cancer specificity: Group enriched (Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma, Uterine Corpus Endometrial Carcinoma)

Disease associations

OMIM: gene MIM:601259 | disease phenotypes: MIM:616270

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
amelogenesis imperfecta type 1F	Strong	Autosomal recessive	3
amelogenesis imperfecta type 1	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Amelogenesis imperfecta	green

Mondo (2): amelogenesis imperfecta type 1F (MONDO:0014560), amelogenesis imperfecta type 1 (MONDO:0015047)

Orphanet (1): Amelogenesis imperfecta (Orphanet:88661)

HPO phenotypes

6 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000705	Amelogenesis imperfecta
HP:0003593	Infantile onset
HP:0006297	Enamel hypoplasia
HP:0009722	Dental enamel pits
HP:0011073	Abnormality of dental color

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ethyl-p-hydroxybenzoate	increases expression	1
ferrous chloride	increases expression	1
Benzo(a)pyrene	increases methylation	1
Valproic Acid	affects expression	1
Zinc	decreases expression	1
Acrylamide	decreases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.