AMELX

Summary

AMELX (amelogenin X-linked, HGNC:461) is a protein-coding gene on chromosome Xp22.2, encoding Amelogenin, X isoform (Q99217). Plays a role in biomineralization.

This gene encodes a member of the amelogenin family of extracellular matrix proteins. Amelogenins are involved in biomineralization during tooth enamel development. Mutations in this gene cause X-linked amelogenesis imperfecta. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 265 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amelogenesis imperfecta type 1E (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 80 total — 19 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_001142

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:461
Approved symbol	AMELX
Name	amelogenin X-linked
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000125363
Ensembl biotype	protein_coding
OMIM	300391
Entrez	265

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000348912, ENST00000380712, ENST00000380714

RefSeq mRNA: 3 — MANE Select: NM_001142 NM_001142, NM_182680, NM_182681

CCDS: CCDS14144, CCDS14145, CCDS14146

Canonical transcript exons

ENST00000380714 — 6 exons

Exon	Start	End
ENSE00000854583	11298236	11298277
ENSE00001027499	11293413	11293468
ENSE00001666420	11296779	11296826
ENSE00001695103	11298548	11298973
ENSE00001752221	11294777	11294842
ENSE00001956938	11300607	11300761

Expression profiles

Bgee: expression breadth broad, 35 present calls, max score 84.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0239 / max 8.3006, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195490	0.0239	9

Top tissues by expression

230 total, 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	84.58	gold quality
paraflocculus	UBERON:0005351	66.16	gold quality
frontal pole	UBERON:0002795	64.96	gold quality
middle frontal gyrus	UBERON:0002702	64.68	gold quality
Brodmann (1909) area 10	UBERON:0013541	63.59	gold quality
endometrium epithelium	UBERON:0004811	58.30	gold quality
decidua	UBERON:0002450	56.55	gold quality
colonic epithelium	UBERON:0000397	55.73	silver quality
calcaneal tendon	UBERON:0003701	54.66	gold quality
hair follicle	UBERON:0002073	52.88	gold quality
cerebellar vermis	UBERON:0004720	52.22	gold quality
thymus	UBERON:0002370	51.86	gold quality
quadriceps femoris	UBERON:0001377	51.46	gold quality
cranial nerve II	UBERON:0000941	51.45	silver quality
vastus lateralis	UBERON:0001379	50.97	gold quality
oviduct epithelium	UBERON:0004804	49.48	gold quality
ileal mucosa	UBERON:0000331	49.45	gold quality
metanephric glomerulus	UBERON:0004736	49.39	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
epithelial cell of pancreas	CL:0000083	49.24	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
tendon	UBERON:0000043	49.13	gold quality
deltoid	UBERON:0001476	49.01	silver quality
renal glomerulus	UBERON:0000074	48.92	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
pancreatic ductal cell	CL:0002079	48.72	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPD, DLX2, FOXJ1, MSX2, NFYA, PITX2, TBX1, TCF23, YY1

miRNA regulators (miRDB)

19 targeting AMELX, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4289	98.26	66.90	810
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-346	97.01	66.97	662
HSA-MIR-597-5P	96.82	67.57	732
HSA-MIR-5579-5P	96.32	68.54	730
HSA-MIR-668-3P	96.18	65.80	673
HSA-MIR-632	96.08	67.17	798
HSA-MIR-1231	95.10	65.63	663

Literature-anchored findings (GeneRIF, showing 40)

• frameshift mutation encoding a truncated amelogenin leads to X-linked amelogenesis imperfecta (PMID:11839357)
• self-assembly and apatite binding properties of amelogenin proteins lacking the hydrophilic C-terminal. (PMID:11852235)
• Altered amelogenin self-assembly based on mutations observed in human X-linked amelogenesis imperfecta (AIH1). (PMID:11877393)
• C-terminus of the normal amelogenin protein is important for controlling enamel thickness. (PMID:11922869)
• 2 mutations within coding region for amelogenin signal peptide predicted to interfere with secretion of amelogenin; could help clinicians in making diagnosis of X-linked AI. (PMID:15111628)
• Two synonymous single-nucleotide polymorphisms were found in databases. Alignment of the primate exon 6 sequences revealed that AMELX is highly constrained. (PMID:17645864)
• Amelogenin locus in chimerism monitoring of stem cell patients transplanted. (PMID:17688372)
• Having at least one copy of the rare amelogenin marker allele was associated with increased age-adjusted caries experience. (PMID:18042988)
• Binding of the P41T mutant amelogenin for matrix metalloproteinase 20 was significantly lower than that of wild-type amelogenin. (PMID:18434575)
• Prolines at the amelogenin C terminus are essential for the initial processing of amelogenin and amelogenin-mineral interactions. (PMID:18701806)
• A total of 463 individuals from 54 families were evaluated and mutations in the AMEL, ENAM and KLK4 genes were identified. (PMID:18714142)
• Overrepresentation of C allele of amelogenin marker was seen in dmft scores higher than 8 when compared to controls. Overrepresentation of T allele of ameloblastin marker was seen in dmfs scores higher than 10 when compared to controls. (PMID:18781068)
• Amelogenin can adsorb onto surfaces as small structures that “shed” or disassemble from the nanospheres that are present in solution. (PMID:19025992)
• Forensic genetic genotyping system using amelogenin using single nucleotide polymorphism. (PMID:19083859)
• In a family with a hypomaturation-type enamel defect, mutational and haplotype analyses revealed no mutations in the AMELX gene. (PMID:19966041)
• amelogenin may stimulate wound healing by providing connective tissue cells with a temporary extracellular matrix (PMID:20012165)
• Perturbed amelogenin secondary structure leads to uncontrolled aggregation in amelogenesis imperfecta mutant proteins. (PMID:20929860)
• A single Pro-70 to Thr (p.P70T) mutation of amelogenin affected the self-assembly and adsorption behaviour of amelogenin, resulting in increased binding to apatite and inhibited crystal growth. (PMID:21081224)
• These results suggest that SNPs of AMELX might be associated with dental caries susceptibility in Korean population. (PMID:21114591)
• These results suggest that hAm may be a key element in regulating hBMSCs osteogenic differentiation. (PMID:21514271)
• Deletion of AMELX results in males with a characteristic snow-capped enamel phenotype. (PMID:23251683)
• Evolutionary and statistical analyses showed that none of the SNPs identified in this study were associated with caries susceptibility, suggesting that AMELX is not a gene candidate in our studied population. (PMID:23525533)
• The 21 non-CODIS STR loci of the Russian ethnic minority group were characterized by high genetic diversity and therefore may be useful for elucidating the population’s genetic background, for individual identification. (PMID:23733431)
• Associations between TFIP11 (p=0.02), ENAM (p=0.00001), and AMELX (p=0.01) could be seen with caries independent of having MIH or genomic DNA copies of Streptococcus mutans detected by real time PCR in the Brazilian sample. (PMID:23790503)
• demonstrate the presence of copy number variations in regions containing 9 of the 13 CODIS(Combined DNA Index System) short tandem repeat(STR) and AMELX/Y loci (PMID:23948316)
• the interaction of amelogenin with Grp78/Bip contributed to cell proliferation, rather than correlate with the osteogenic differentiation (PMID:24167599)
• silent mutation in exon 4 of AMELX gene. generating and characterizing transgenic animal model, alteration of the ratio and quantity of the developmentally conserved alternative splicing repertoire of AMELX caused defects in enamel matrix mineralization. (PMID:25117480)
• Conversion to amelogenin expressing dental epithelial cells involved an up-regulation of the stem cell marker Sox2 and proliferation genes and decreased expression of mesenchymal markers (PMID:25122764)
• suggestive overrepresentation of TT genotype of amelogenin marker in cases w/severe erosion when compared to no dentine erosion. Amelogenin also associated with severe erosion in recessive model; TT genotype significantly more frequent in affected group (PMID:25791822)
• TRAP was found to augment chondrogenic differentiation of HACs via induction of SOX9 gene expression when cells were cultured in pro-chondrogenic media. (PMID:26404401)
• Studies indicate that a single point mutation (41Pro–>Thr) in the amelogenin gene causes severe dental enamel malformation known as amelogenesis imperfect. (PMID:26545753)
• sequencing data showed presence of mutation. Samples showing mutation (43.3%) showed high correlation with caries (80.7%) experience which was statistically significant. (PMID:26551370)
• Full-length amelogenin may have a negative mitogenic impact on human dental pulp stem cells. (PMID:26762641)
• a single-nucleotide polymorphism in the amelogenin gene using amplified product-length polymorphisms in combination with sex-determining region Y analysis, is reported. (PMID:28052096)
• 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)
• To the best of our knowledge, this is the first report of expression of human amelogenin in plants, offering the possibility to use this plant-made protein for nanotechnological applications. (PMID:28801830)
• High AMEL expression is associated with Aggressiveness in Odontogenic Tumors. (PMID:29802703)
• family study of a novel AMELX mutation with skewed X chromosome inactivation causing hypoplastic and hypomineralized amelogenesis imperfecta (PMID:31185186)
• AMELX and ODAM variations was not different between two populations of schoolchildren with respect to dental fluorosis (DF) severity; however, the presence of rs1784418 differed between phenotypes with regard to susceptibility to DF. Therefore, MMP20 might be related to the various phenotypes of DF (PMID:31838295)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Amelx	ENSMUSG00000031354
rattus_norvegicus	Amelx	ENSRNOG00000003965

Paralogs (1): AMELY (ENSG00000099721)

Protein

Protein identifiers

Amelogenin, X isoform — Q99217 (reviewed: Q99217)

All UniProt accessions (1): Q99217

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in biomineralization. Seems to regulate the formation of crystallites during the secretory stage of tooth enamel development. Thought to play a major role in the structural organization and mineralization of developing enamel.

Subunit / interactions. Interacts with KRT5.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Post-translational modifications. Phosphorylated by FAM20C in vitro.

Disease relevance. Amelogenesis imperfecta 1E (AI1E) [MIM:301200] An X-linked defect of dental enamel formation. Teeth have only a thin layer of enamel with normal hardness. The thinness of the enamel makes the teeth appear small. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the amelogenin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q99217-1	1	yes
Q99217-2	2
Q99217-3	3, Rare

RefSeq proteins (3): NP_001133, NP_872621, NP_872622 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004116	Amelogenin	Family

Pfam: PF02948

UniProt features (15 total): sequence variant 4, sequence conflict 3, compositionally biased region 2, splice variant 2, signal peptide 1, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99217-F1	59.51	0.00

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 (1): 32

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

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

MSigDB gene sets: 152 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, MODULE_52, BENPORATH_ES_WITH_H3K27ME3, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, MODULE_45, GOCC_CELL_SURFACE, GOBP_OSTEOBLAST_DIFFERENTIATION, GOMF_GROWTH_FACTOR_ACTIVITY, MODULE_16, GOBP_TOOTH_MINERALIZATION, GOBP_RESPONSE_TO_METAL_ION, MODULE_118, GOBP_ANIMAL_ORGAN_MORPHOGENESIS

GO Biological Process (17): osteoblast differentiation (GO:0001649), epithelial to mesenchymal transition (GO:0001837), chondrocyte differentiation (GO:0002062), cell adhesion (GO:0007155), signal transduction (GO:0007165), response to nutrient (GO:0007584), response to xenobiotic stimulus (GO:0009410), biomineral tissue development (GO:0031214), positive regulation of collagen biosynthetic process (GO:0032967), tooth mineralization (GO:0034505), regulation of cell population proliferation (GO:0042127), odontogenesis of dentin-containing tooth (GO:0042475), response to calcium ion (GO:0051592), enamel mineralization (GO:0070166), positive regulation of tooth mineralization (GO:0070172), amelogenesis (GO:0097186), multicellular organism development (GO:0007275)

GO Molecular Function (8): calcium ion binding (GO:0005509), growth factor activity (GO:0008083), structural constituent of tooth enamel (GO:0030345), sodium ion binding (GO:0031402), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), hydroxyapatite binding (GO:0046848), protein binding (GO:0005515)

GO Cellular Component (8): basement membrane (GO:0005604), endoplasmic reticulum lumen (GO:0005788), cell surface (GO:0009986), endocytic vesicle (GO:0030139), extracellular matrix (GO:0031012), protein-containing complex (GO:0032991), extracellular region (GO:0005576), obsolete collagen-containing extracellular matrix (GO:0062023)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	2
cellular process	2
regulation of cellular process	2
response to chemical	2
odontogenesis	2
tooth mineralization	2
cellular anatomical structure	2
ossification	1
mesenchymal cell differentiation	1
cartilage development	1
cell communication	1
signaling	1
cellular response to stimulus	1
response to nutrient levels	1
tissue development	1
animal organ development	1
positive regulation of biosynthetic process	1
positive regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
biomineral tissue development	1
cell population proliferation	1
response to metal ion	1
amelogenesis	1
positive regulation of biomineral tissue development	1
regulation of tooth mineralization	1
odontogenesis of dentin-containing tooth	1
anatomical structure formation involved in morphogenesis	1
multicellular organismal process	1
anatomical structure development	1
metal ion binding	1
receptor ligand activity	1
extracellular matrix structural constituent conferring compression resistance	1
alkali metal ion binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
small molecule binding	1
binding	1
extracellular matrix	1

Protein interactions and networks

STRING

756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMELX	ENAM	Q9NRM1	985
AMELX	AMBN	Q9NP70	984
AMELX	PRKY	O43930	952
AMELX	TSPY1	P09002	946
AMELX	AMTN	Q6UX39	934
AMELX	A0A087WUC5	A0A087WUC5	909
AMELX	TUFT1	Q9NNX1	908
AMELX	TBL1Y	Q9BQ87	896
AMELX	PRKX	P51817	847
AMELX	MMP20	O60882	832
AMELX	SACK1H	Q6ZRV2	815
AMELX	PCDH11X	Q9BZA7	800
AMELX	KLK4	Q9Y5K2	757
AMELX	WDR72	Q3MJ13	753
AMELX	ZFY	P08048	736

IntAct

1 interactions, top by confidence:

ESM2 similar proteins: C0P381, D2KFH1, D6QZM4, D6QZM5, P01089, P01090, P01091, P02863, P04706, P04721, P04722, P04723, P04724, P04725, P04726, P04727, P04728, P04729, P06470, P06471, P08031, P09893, P0CZ05, P0CZ07, P0CZ08, P0CZ09, P0CZ10, P0CZ11, P10385, P15322, P15460, P15461, P16315, P17333, P17990, P18573, P21292, P27740, P38057, P80198

Diamond homologs: O97646, O97647, P02817, P45561, P63277, P63278, Q28462, Q861X8, Q99004, Q99217, Q99218, Q9Z0K9, P12761

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	4
Uncertain significance	26
Likely benign	7
Benign	10

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
11136	NC_000023.11:g.(11295935_11295938)_(11300658_11300661)del	Pathogenic
11138	NM_001142.2(AMELX):c.14_22del (p.Ile5_Ala8delinsThr)	Pathogenic
11140	NM_001142.2(AMELX):c.110C>T (p.Thr37Ile)	Pathogenic
11141	NM_001142.2(AMELX):c.529G>T (p.Glu177Ter)	Pathogenic
11142	NM_001142.2(AMELX):c.166C>A (p.Pro56Thr)	Pathogenic
11144	NM_001142.2(AMELX):c.378del (p.Tyr127fs)	Pathogenic
11146	NM_001142.2(AMELX):c.11G>C (p.Trp4Ser)	Pathogenic
1808678	GRCh37/hg19 Xp22.33-22.2(chrX:2703633-14515021)x2	Pathogenic
253612	GRCh37/hg19 Xp22.33-22.2(chrX:71267-12032064)x1	Pathogenic
3901265	NM_001142.2(AMELX):c.88A>C (p.Asn30His)	Pathogenic
393940	GRCh37/hg19 Xp22.2(chrX:11258243-14177713)x1	Pathogenic
40896	NC_000023.10:g.11285049_11381288del	Pathogenic
40897	NG_012494.1:g.363924_416577delinsA	Pathogenic
4537506	NM_001142.2(AMELX):c.103-116T>C	Pathogenic
564694	GRCh37/hg19 Xp22.33-22.11(chrX:168546-23785738)x1	Pathogenic
58587	GRCh38/hg38 Xp22.31-22.2(chrX:6837101-13719231)x3	Pathogenic
59236	GRCh38/hg38 Xp22.31-22.2(chrX:9540020-13128124)x1	Pathogenic
617639	NM_001142.2(AMELX):c.143del (p.Pro48fs)	Pathogenic
686941	GRCh37/hg19 Xp22.33-22.2(chrX:2703632-14129100)x2	Pathogenic
146331	GRCh38/hg38 Xp22.33-22.2(chrX:4082541-12772302)x2	Likely pathogenic
3340173	NM_001142.2(AMELX):c.11G>A (p.Trp4Ter)	Likely pathogenic
3376363	NM_001142.2(AMELX):c.144+1G>A	Likely pathogenic
443332	GRCh37/hg19 Xp22.2(chrX:10810471-11339263)x3	Likely pathogenic

SpliceAI

753 predictions. Top by Δscore:

Variant	Effect	Δscore
X:11293467:AGG:A	donor_loss	1.0000
X:11298970:AGTGG:A	donor_loss	1.0000
X:11298971:GTG:G	donor_gain	1.0000
X:11298974:G:C	donor_loss	1.0000
X:11298975:T:A	donor_loss	1.0000
X:11293469:G:GG	donor_gain	0.9900
X:11296752:A:AG	acceptor_gain	0.9900
X:11296774:A:AG	acceptor_gain	0.9900
X:11296775:A:G	acceptor_gain	0.9900
X:11298546:A:AG	acceptor_gain	0.9900
X:11298547:G:GG	acceptor_gain	0.9900
X:11298968:G:GT	donor_gain	0.9900
X:11298974:G:GG	donor_gain	0.9900
X:11298976:GAGTA:G	donor_loss	0.9900
X:11300595:A:AG	acceptor_gain	0.9900
X:11300605:A:AG	acceptor_gain	0.9900
X:11300605:AG:A	acceptor_gain	0.9900
X:11300606:G:GG	acceptor_gain	0.9900
X:11300606:GG:G	acceptor_gain	0.9900
X:11294712:T:TA	acceptor_gain	0.9800
X:11296771:T:A	acceptor_gain	0.9800
X:11296777:A:AG	acceptor_gain	0.9800
X:11296778:G:GG	acceptor_gain	0.9800
X:11298234:A:G	acceptor_gain	0.9800
X:11298969:AAGTG:A	donor_gain	0.9800
X:11298970:AGTG:A	donor_gain	0.9800
X:11298971:GTGG:G	donor_gain	0.9800
X:11298972:TGGT:T	donor_gain	0.9800
X:11298973:GGTG:G	donor_gain	0.9800
X:11298977:AGTA:A	donor_loss	0.9800

AlphaMissense

1250 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:11296818:A:C	S32R	0.992
X:11296820:C:A	S32R	0.992
X:11296820:C:G	S32R	0.992
X:11298254:T:A	W41R	0.991
X:11298254:T:C	W41R	0.991
X:11296814:C:A	N30K	0.988
X:11296814:C:G	N30K	0.988
X:11294813:T:C	C9R	0.985
X:11294822:G:A	G12R	0.983
X:11294822:G:C	G12R	0.983
X:11296816:T:C	F31S	0.979
X:11296819:G:T	S32I	0.978
X:11298256:G:C	W41C	0.977
X:11298256:G:T	W41C	0.977
X:11298257:T:G	Y42D	0.977
X:11294811:C:A	A8D	0.963
X:11296825:A:T	E34V	0.963
X:11294823:G:A	G12E	0.960
X:11296819:G:A	S32N	0.957
X:11298581:T:A	W60R	0.956
X:11298581:T:C	W60R	0.956
X:11294829:C:A	A14D	0.955
X:11296810:T:A	I29N	0.955
X:11298246:C:G	P38R	0.955
X:11298938:T:A	W179R	0.952
X:11298938:T:C	W179R	0.952
X:11298940:G:C	W179C	0.948
X:11298940:G:T	W179C	0.948
X:11298243:C:T	T37I	0.945
X:11294798:T:A	W4R	0.944

dbSNP variants (sampled 300 via entrez): RS1000023079 (X:11306044 T>A,C), RS1000126506 (X:11293821 T>C), RS1000530069 (X:11301250 G>A), RS1000653575 (X:11291866 C>T), RS1000826817 (X:11294391 G>A), RS1001151760 (X:11301590 G>T), RS1001209376 (X:11294731 A>G), RS1001358097 (X:11295554 C>T), RS1001753535 (X:11303720 G>A), RS1001930983 (X:11303406 G>C), RS1002215194 (X:11296979 T>C), RS1002642327 (X:11296529 C>A,G), RS1002802584 (X:11305772 T>C), RS1003180752 (X:11306164 T>C), RS1003494897 (X:11309204 C>A,G,T)

Disease associations

OMIM: gene MIM:300391 | disease phenotypes: MIM:301200, MIM:104500, MIM:301201

GenCC curated gene-disease

Disease	Classification	Inheritance
amelogenesis imperfecta type 1E	Strong	X-linked
amelogenesis imperfecta type 2	Supportive	Autosomal recessive

Mondo (5): amelogenesis imperfecta type 1E (MONDO:0010521), amelogenesis imperfecta (MONDO:0019507), primary amenorrhea (MONDO:1060208), X-linked amelogenesis imperfecta hypoplastic/hypomaturation 2 (MONDO:0010522), amelogenesis imperfecta type 2 (MONDO:0015048)

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

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000705	Amelogenesis imperfecta
HP:0001423	X-linked dominant inheritance
HP:0006297	Enamel hypoplasia
HP:0009102	Anterior open-bite malocclusion
HP:0010299	Abnormal dentin morphology

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000567	Amelogenesis Imperfecta	C07.650.800.295.250; C07.793.700.295.250; C16.131.850.800.295.250
C536606	Amelogenesis Imperfecta hypomaturation type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Cadmium	decreases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

9 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01746121	Not specified	TERMINATED	Amelogenesis Imperfecta
NCT02994862	Not specified	UNKNOWN	E. Max Laminate Veneers With and Without Using Galla Chinnesis as Natural Cross Linking and Remineralizing Agent
NCT03810859	Not specified	UNKNOWN	Non-syndromic Inherited Anomalies of Mineralized Tooth Tissues: a Whole Exome Study to Identify New Pathogenic Variants
NCT04704089	Not specified	RECRUITING	Colorimetric, Ultra-structural and Elemental Comparison of Dental Enamel Defects
NCT04897724	Not specified	UNKNOWN	Clinical Performance of Composites in Patients With Amelogenesis Imperfecta
NCT04927962	Not specified	COMPLETED	Psycho-social Impact of Amelogenesis and Dentinogenesis Imperfecta
NCT05343247	Not specified	COMPLETED	Dental Age Estimation by Different Methods in Patients With Amelogenesis Imperfecta
NCT07250906	Not specified	RECRUITING	Oral Health Related Quality of Life of Children With Amelogenesis Imperfecta
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice