DSPP

Summary

DSPP (dentin sialophosphoprotein, HGNC:3054) is a protein-coding gene on chromosome 4q22.1, encoding Dentin sialophosphoprotein (Q9NZW4). DSP may be an important factor in dentinogenesis.

This gene encodes a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of proteins. The encoded preproprotein is secreted by odontoblasts and proteolytically processed to generate two principal proteins of the dentin extracellular matrix of the tooth, dentin sialoprotein and dentin phosphoprotein. These two protein products may play distinct but related roles in dentin mineralization. Mutations in this gene are associated with dentinogenesis imperfecta and dentin dysplasia. This gene is present in a gene cluster on chromosome 4. Allelic differences due to repeat polymorphisms have been found for this gene.

Source: NCBI Gene 1834 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dentinogenesis imperfecta (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 32 total — 4 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 14
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_014208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3054
Approved symbol	DSPP
Name	dentin sialophosphoprotein
Location	4q22.1
Locus type	gene with protein product
Status	Approved
Aliases	DMP3
Ensembl gene	ENSG00000152591
Ensembl biotype	protein_coding
OMIM	125485
Entrez	1834

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000651931

RefSeq mRNA: 1 — MANE Select: NM_014208 NM_014208

CCDS: CCDS43248

Canonical transcript exons

ENST00000651931 — 5 exons

Exon	Start	End
ENSE00001006069	87612322	87613308
ENSE00001006070	87612105	87612188
ENSE00001313251	87610881	87610959
ENSE00003843596	87613785	87616873
ENSE00003849973	87608529	87608620

Expression profiles

Bgee: expression breadth broad, 76 present calls, max score 87.89.

Top tissues by expression

182 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	87.89	gold quality
tendon of biceps brachii	UBERON:0008188	83.98	gold quality
myocardium	UBERON:0002349	74.42	silver quality
medial globus pallidus	UBERON:0002477	74.01	silver quality
epithelium of esophagus	UBERON:0001976	73.03	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	71.49	silver quality
esophagus squamous epithelium	UBERON:0006920	71.46	silver quality
globus pallidus	UBERON:0001875	71.39	silver quality
gingival epithelium	UBERON:0001949	71.23	silver quality
lower lobe of lung	UBERON:0008949	68.17	gold quality
cerebellar vermis	UBERON:0004720	67.91	silver quality
nipple	UBERON:0002030	67.70	silver quality
trabecular bone tissue	UBERON:0002483	67.02	silver quality
mucosa of sigmoid colon	UBERON:0004993	66.72	silver quality
vena cava	UBERON:0004087	66.43	gold quality
triceps brachii	UBERON:0001509	66.13	gold quality
mucosa of urinary bladder	UBERON:0001259	65.39	silver quality
cardia of stomach	UBERON:0001162	64.78	silver quality
cranial nerve II	UBERON:0000941	64.60	gold quality
synovial joint	UBERON:0002217	64.43	silver quality
colonic mucosa	UBERON:0000317	64.42	silver quality
cartilage tissue	UBERON:0002418	64.40	silver quality
pharyngeal mucosa	UBERON:0000355	64.39	silver quality
palpebral conjunctiva	UBERON:0001812	64.32	silver quality
gluteal muscle	UBERON:0002000	64.30	gold quality
body of tongue	UBERON:0011876	63.73	gold quality
pylorus	UBERON:0001166	63.71	silver quality
penis	UBERON:0000989	63.64	gold quality
postcentral gyrus	UBERON:0002581	63.62	silver quality
parietal lobe	UBERON:0001872	63.16	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF6, CEBPB, DLX3, DLX5, DMTF1, FOS, HNF4A, JUN, KLF4, MSX2, MXD1, NFIC, NR0B2, NRF1, RUNX2, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SP7, TCF3, TRPS1, TWIST1

miRNA regulators (miRDB)

21 targeting DSPP, 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-186-5P	99.99	70.83	3707
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-152-5P	96.42	66.59	960

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Transient DSPP expression was seen in the presecretory ameloblasts with continuous expression in the odontoblasts. (PMID:11856645)
• DSPP is expressed in salivary gland ducts, particularly the striated duct. (PMID:15329369)
• there is a novel signaling function for phosphophoryn in cell differentiation beyond the hypothesized role of PP in biomineralization (PMID:15371433)
• DSPP is expressed in the proximal and distal tubules of kidney nephron. (PMID:15954904)
• Dentin sialophosphoprotein expressed by transgenic presecretory ameloblasts contributes to the unique properties of the dentino-enamel junction. (PMID:16014627)
• study shows for the first time that DSPP is ectopically expressed in human prostate cancer; expression of this SIBLING protein strongly correlates with conventional histopathological prognostic indicators of prostate cancer progression (PMID:16108038)
• Mutational analyses identified no coding or intron junction sequence variations associated with affection status in DMP1, MEPE, or the DSP portion of DSPP. The defects in the permanent dentition were typically mild and consistent with DD-II. (PMID:16567553)
• DMP1 regulates the expression of the DSPP gene (PMID:16679514)
• 2 mutation hotspots may be causative for multiple unrelated dentinogenesis imperfecta families with different clinical phenotypes (PMID:16920545)
• mutation p.Pro17Ser causes type II dentinogenesis imperfecta in the Chinese family (PMID:17686168)
• The results show high expression levels of DSPP in human tooth germs indicating that it may play an essential role for physiological and pathological events in tooth development. (PMID:18211748)
• Data provide the first evidence that DPP mutations can cause hereditary dentin disorders and suggest that in-frame length variations and missense SNPs in DPP have no obvious pathogenetic effects on dentin formation. (PMID:18456718)
• Within 9 dentin dysplasia (type II) and dentinogenesis imperfecta (type II and III) patient/families, 7 have 1 of 4 net -1 deletions within the a 2-kb coding repeat domain of the DSPP gene while the remaining 2 patients have splice-site mutations. (PMID:18521831)
• The aim of this study was to perform phenotype analysis and dentin sialophosphoprotein (DSPP) mutational analysis on 3 Brazilian families diagnosed with dentinogenesis imperfecta type II. (PMID:18797159)
• Identification of DSPP splice junction mutation (IVS2-6T>G) in a family with dentin dysplasia type II. Mutation is in 6th nucleotide from the end of intron 2, perfectly segregates with the disease phenotype. (PMID:19026876)
• A novel -1 bp frameshift (c.3141delC) falls within the portion of the DSPP repeat domain previously associated solely with the DGI phenotype. This new frameshift mutation shows that overlapping DSPP mutations can give rise to either DGI or DD phenotypes. (PMID:19029076)
• The heterozygous deletion mutation in DSPP contributed to the pathogenesis of dentinogenesis imperfecta type II. (PMID:19103209)
• A severely affected primary dentition with wide-open pulp chambers and multiple pulp exposures resembling a DGI-III pattern was analyzed to reveal a novel mutation (c.53T>A, p.V18D) near the intron-exon boundary in the third exon of the DSPP gene. (PMID:19131317)
• A novel mutation in the first exon of the DSPP gene were found in all dentinogenesis imperfecta patients in a Chinese family. (PMID:19806576)
• Mutation analysis revealed mutation (c.53T>A, p.V18D, g.1192T>A) involving 2nd nucleotide of 1st codon within exon 3 of DSPP gene. This is 7th mutation in DSPP V18 residue. Only 1 other was shown as de novo mutation; it also affected V18 AA residue. (PMID:20121932)
• Direct DNA sequencing identified a novel A–>G transition mutation adjacent to the donor splicing site within intron 3 in all affected individuals. (PMID:20146806)
• This review of genetic studies demonstrates that mutations in, or knockout of the Dspp gene result in mineralization defects in dentin and/or bone. (PMID:20367116)
• Data identified novel single bp deletional DSPP mutations in three Korean families with DGI type II. (PMID:20618350)
• High dentin expression is associated with dental caries. (PMID:20802180)
• Frameshift mutations in the part of the DSPP gene coding for DPP explain a significant part of inherited and isolated dentin diseases, i.e., dentin dysplasia type II and dentinogenesis imperfecta variants. (PMID:20949630)
• DSPP gene mutation not only influences dentinogenesis but also affects early stage amelogenesis. (PMID:21029264)
• Data show there was a direct correlation between the degree of DSPP-silencing and suppression of MMP-2, MMP-3 and MMP-9. (PMID:21103065)
• Results suggest that DSPP is regulated post-transcriptionally by mir32, mir885-5p and mir586 during odontoblast differentiation. (PMID:21687927)
• predictions of exon 3 skipping in specific DSPP mutations have been validated; cryptic splicing donor site has been identified. possible insight into DSPP mutations in the pathogenesis and genotype-phenotype correlations of hereditary dentin defects. (PMID:21736673)
• Data show that the novel dentin sialophosphoprotein (DSPP) mutation was considered as the causation of dentinogenesis imperfecta type II (DGI-II). (PMID:22125647)
• study concludes that enamel defects can be part of the dental phenotype caused by DSPP mutations, although DSPP is not critical for dental enamel formation (PMID:22243242)
• The P17 residue of DSPP is a mutational hotspot in a Chinese family with Dentinogenesis Imperfecta type II. (PMID:22310900)
• Data shows all known DSPP mutations (except Y6D) cause nonsyndromic dentin dysplasia,DD-II, and dentinogenesis imperfecta, DGI II & III, by retention of mutant proteins in the endoplasmic reticulum with associated decreased secretion of normal DSPP. (PMID:22392858)
• This study presents evidence of a shared underlying mechanism of capturing of normal DSPP by two different classes of DSPP mutations. (PMID:22392858)
• DSPP, OPN, or MMP-9 expressions at histologically-negative surgical margins predict Oral squamous cell carcinoma recurrence with MMP-9 being the preferred predictor. (PMID:22410369)
• A review of hereditary dentine diseases resulting from mutations in DSPP gene suggests that the localization of mutation in the sequence of the DSPP gene might result in a different phenotype due to the diverse cellular fate of the mutated protein. (PMID:22521702)
• efficiency of dentin sialoprotein-phosphophoryn processing is affected by mutations both flanking and distant from the cleavage site (PMID:23297400)
• analysis of a mutation in DSPP causing dentinogenesis imperfecta and characterization of the mutational effect (PMID:23509818)
• DSS domain of DPP functions as a novel cell-penetrating peptide, and these findings demonstrate new opportunities for intracellular delivery of therapeutic proteins and cell tracking in vivo. (PMID:23589294)
• Domain of dentine sialoprotein mediates proliferation and differentiation of human periodontal ligament stem cells. (PMID:24400037)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dspp	ENSMUSG00000053268
rattus_norvegicus	Dspp	ENSRNOG00000002168

Protein

Protein identifiers

Dentin sialophosphoprotein — Q9NZW4 (reviewed: Q9NZW4)

All UniProt accessions (1): Q9NZW4

UniProt curated annotations — full annotation on UniProt →

Function. DSP may be an important factor in dentinogenesis. DPP may bind high amount of calcium and facilitate initial mineralization of dentin matrix collagen as well as regulate the size and shape of the crystals.

Subunit / interactions. Interacts with FBLN7.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in teeth. DPP is synthesized by odontoblast and transiently expressed by pre-ameloblasts.

Post-translational modifications. DSP is glycosylated.

Disease relevance. Deafness, autosomal dominant, 39, with dentinogenesis imperfecta 1 (DFNA39/DGI1) [MIM:605594] A disorder characterized by the association of progressive sensorineural high-frequency hearing loss with dentinogenesis imperfecta. The disease is caused by variants affecting the gene represented in this entry. Dentinogenesis imperfecta, Shields type 2 (DGI2) [MIM:125490] A form of dentinogenesis imperfecta, an autosomal dominant dentin disorder characterized by amber-brown, opalescent teeth that fracture and shed their enamel during mastication, thereby exposing the dentin to rapid wear. Radiographically, the crown appears bulbous and pulpal obliteration is common. The pulp chambers are initially larger than normal prior and immediately after tooth eruption, and then progressively close down to become almost obliterated by abnormal dentin formation. Roots are short and thin. Both primary and permanent teeth are affected. DGI2 is not associated with osteogenesis imperfecta. The disease is caused by variants affecting the gene represented in this entry. DSPP defects causing dentin abnormalities act in a dominant negative manner and include missense, splice-site, frameshift mutations. 5’ frameshift mutations cause dentin dysplasia while frameshift mutations at the 3’ end cause the more severe dentinogenesis imperfecta phenotype. Dentinogenesis imperfecta, Shields type 3 (DGI3) [MIM:125500] A form of dentinogenesis imperfecta, an autosomal dominant dentin disorder characterized by amber-brown, opalescent teeth that fracture and shed their enamel during mastication, thereby exposing the dentin to rapid wear. Radiographically, the crown appears bulbous and pulpal obliteration is common. The pulp chambers are initially larger than normal prior and immediately after tooth eruption, and then progressively close down to become almost obliterated by abnormal dentin formation. Roots are short and thin. Both primary and permanent teeth are affected. DGI3 teeth typically manifest multiple periapical radiolucencies. DGI3 is not associated with osteogenesis imperfecta. The disease is caused by variants affecting the gene represented in this entry. DSPP defects causing dentin abnormalities act in a dominant negative manner and include missense, splice-site, frameshift mutations. 5’ frameshift mutations cause dentin dysplasia while frameshift mutations at the 3’ end cause the more severe dentinogenesis imperfecta phenotype. Dentin dysplasia 2 (DTDP2) [MIM:125420] A dental defect in which the deciduous teeth are opalescent. The permanent teeth are of normal shape, form, and color in most cases. The root length is normal. On radiographs, the pulp chambers of permanent teeth are obliterated, have a thistle-tube deformity and contain pulp stones. The disease is caused by variants affecting the gene represented in this entry. DSPP defects causing dentin abnormalities act in a dominant negative manner and include missense, splice-site, frameshift mutations. 5’ frameshift mutations cause dentin dysplasia while frameshift mutations at the 3’ end cause the more severe dentinogenesis imperfecta phenotype.

RefSeq proteins (1): NP_055023* (*=MANE)

Domains & families (InterPro)

UniProt features (74 total): compositionally biased region 22, sequence conflict 21, glycosylation site 12, sequence variant 9, chain 3, region of interest 3, modified residue 2, signal peptide 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZW4-F1	39.36	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 (2): 259, 301

Glycosylation sites (12): 41, 49, 81, 130, 150, 190, 191, 209, 222, 275, 336, 387

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3000178	ECM proteoglycans

MSigDB gene sets: 103 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, NKX25_02, GOZGIT_ESR1_TARGETS_DN, LHX3_01, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, MCLACHLAN_DENTAL_CARIES_DN, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GATA6_01, IRF1_Q6, INGRAM_SHH_TARGETS_UP, GATA1_04, GOBP_COLUMNAR_CUBOIDAL_EPITHELIAL_CELL_DIFFERENTIATION, GATA1_03, AACTTT_UNKNOWN

GO Biological Process (4): biomineral tissue development (GO:0031214), odontoblast differentiation (GO:0071895), dentinogenesis (GO:0097187), regulation of odontoblast differentiation (GO:1901329)

GO Molecular Function (3): extracellular matrix structural constituent (GO:0005201), calcium ion binding (GO:0005509), collagen binding (GO:0005518)

GO Cellular Component (4): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
tissue development	1
animal organ development	1
neuroepithelial cell differentiation	1
odontogenesis of dentin-containing tooth	1
anatomical structure formation involved in morphogenesis	1
regulation of epithelial cell differentiation	1
odontoblast differentiation	1
structural molecule activity	1
extracellular matrix	1
metal ion binding	1
protein-containing complex binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

1196 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DSPP	DMP1	Q13316	979
DSPP	MEPE	Q9NQ76	954
DSPP	IBSP	P21815	929
DSPP	ENAM	Q9NRM1	899
DSPP	SPP1	P10451	897
DSPP	AMBN	Q9NP70	837
DSPP	BGLAP	P02818	834
DSPP	TUFT1	Q9NNX1	750
DSPP	BMP2	P12643	749
DSPP	FBLN7	Q53RD9	709
DSPP	RUNX2	Q13950	698
DSPP	BMP4	P12644	684
DSPP	AMELX	Q99217	667
DSPP	ACSL4	O60488	649
DSPP	MMP20	O60882	609

IntAct

0 interactions, top by confidence:

BioGRID (3): DSPP (Affinity Capture-MS), DSPP (Synthetic Lethality), DSPP (Affinity Capture-MS)

ESM2 similar proteins: A0A1M6T247, A1C3L3, A8AWU7, B4UN32, C4XZ24, O33479, O96614, O96615, P05790, P06620, P07856, P08640, P09593, P09815, P0CL27, P0CL28, P0CL29, P0CL30, P0CL31, P12027, P13822, P16239, P18127, P18165, P20469, P23490, P29229, P43537, P46804, P54681, P97399, Q49537, Q54GV8, Q54KD5, Q54M35, Q54PA8, Q54R01, Q54T37, Q59SG9, Q59XL0

Diamond homologs: P97399, Q62598, Q9NZW4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DMTF1	“up-regulates quantity by expression”	DSPP	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	4
Uncertain significance	21
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
16856	NM_014208.3(DSPP):c.52G>T (p.Val18Phe)	Pathogenic
16859	NM_014208.3(DSPP):c.44C>T (p.Ala15Val)	Pathogenic
2579753	NM_014208.3(DSPP):c.2317del (p.Ser773fs)	Pathogenic
2663798	NM_014208.3(DSPP):c.3538_3550del (p.Ser1180fs)	Pathogenic
1299353	NM_014208.3(DSPP):c.3611del (p.Ser1204fs)	Likely pathogenic
1679356	NM_014208.3(DSPP):c.3565_3566insCAGCAGCGATA (p.Ser1189fs)	Likely pathogenic
2499472	NM_014208.3(DSPP):c.2833del (p.Ser945fs)	Likely pathogenic
3775878	NM_014208.3(DSPP):c.1531G>T (p.Glu511Ter)	Likely pathogenic

SpliceAI

396 predictions. Top by Δscore:

Variant	Effect	Δscore
4:87610880:GCC:G	acceptor_gain	1.0000
4:87612316:TTTCA:T	acceptor_loss	1.0000
4:87612318:TCAG:T	acceptor_loss	1.0000
4:87612319:CA:C	acceptor_loss	1.0000
4:87612320:A:T	acceptor_loss	1.0000
4:87612320:AG:A	acceptor_gain	1.0000
4:87612320:AGGAT:A	acceptor_gain	1.0000
4:87612321:GG:G	acceptor_gain	1.0000
4:87612321:GGAT:G	acceptor_gain	1.0000
4:87612321:GGATG:G	acceptor_gain	1.0000
4:87613304:A:G	donor_gain	1.0000
4:87613304:ATAAG:A	donor_loss	1.0000
4:87613306:AAG:A	donor_loss	1.0000
4:87613307:AGG:A	donor_loss	1.0000
4:87613309:GTTA:G	donor_loss	1.0000
4:87608618:AAGG:A	donor_loss	0.9900
4:87608620:GGTAA:G	donor_loss	0.9900
4:87608621:GTAA:G	donor_loss	0.9900
4:87610876:TACA:T	acceptor_loss	0.9900
4:87610877:ACAG:A	acceptor_loss	0.9900
4:87610878:C:G	acceptor_gain	0.9900
4:87610878:CA:C	acceptor_loss	0.9900
4:87610879:A:AC	acceptor_loss	0.9900
4:87610879:A:AG	acceptor_gain	0.9900
4:87610880:G:GG	acceptor_gain	0.9900
4:87610880:GC:G	acceptor_gain	0.9900
4:87610880:GCCAT:G	acceptor_gain	0.9900
4:87610955:TTCCA:T	donor_gain	0.9900
4:87610960:G:GG	donor_gain	0.9900
4:87612179:GTC:G	donor_gain	0.9900

AlphaMissense

9719 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:87610930:T:C	C8R	0.989
4:87610936:T:A	W10R	0.984
4:87610936:T:C	W10R	0.984
4:87610948:T:A	W14R	0.981
4:87610948:T:C	W14R	0.981
4:87610951:G:C	A15P	0.968
4:87610952:C:A	A15D	0.955
4:87610946:C:A	A13E	0.950
4:87610934:T:A	I9N	0.933
4:87610939:G:C	A11P	0.930
4:87610940:C:A	A11E	0.919
4:87610924:T:G	Y6D	0.907
4:87610943:T:A	V12E	0.907
4:87610945:G:C	A13P	0.903
4:87615966:A:C	S1102R	0.885
4:87615968:C:A	S1102R	0.885
4:87615968:C:G	S1102R	0.885
4:87610932:C:G	C8W	0.869
4:87615948:A:C	S1096R	0.865
4:87615950:C:A	S1096R	0.865
4:87615950:C:G	S1096R	0.865
4:87616164:A:C	S1168R	0.865
4:87616166:C:A	S1168R	0.865
4:87616166:C:G	S1168R	0.865
4:87610955:T:C	I16T	0.860
4:87616155:A:C	S1165R	0.859
4:87616157:C:A	S1165R	0.859
4:87616157:C:G	S1165R	0.859
4:87616149:A:C	S1163R	0.856
4:87616151:C:A	S1163R	0.856

dbSNP variants (sampled 300 via entrez): RS1000260898 (4:87606616 A>G), RS1000349125 (4:87614021 T>C), RS1000402907 (4:87613724 T>C), RS1001735481 (4:87607724 G>C), RS1002068171 (4:87609147 T>C), RS1002186402 (4:87607430 C>T), RS1002470757 (4:87609394 C>T), RS1003110538 (4:87609237 A>T), RS1003276115 (4:87616618 G>A), RS1003592231 (4:87616980 T>A,C,G), RS1003698155 (4:87610887 A>G), RS1003752143 (4:87610311 T>C), RS1004142808 (4:87615205 G>A), RS1004883754 (4:87617273 T>A), RS1005192170 (4:87616316 C>A,T)

Disease associations

OMIM: gene MIM:125485 | disease phenotypes: MIM:125490, MIM:125500, MIM:605594

GenCC curated gene-disease

Disease	Classification	Inheritance
dentinogenesis imperfecta	Definitive	Autosomal dominant
deafness, autosomal dominant 39, with dentinogenesis imperfecta 1	Definitive	Autosomal dominant
dentinogenesis imperfecta type 2	Definitive	Autosomal dominant
dentinogenesis imperfecta type 3	Strong	Autosomal dominant
dentin dysplasia type I	Supportive	Autosomal dominant
dentin dysplasia type II	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dentinogenesis imperfecta	Definitive	AD

Mondo (7): dentinogenesis imperfecta type 2 (MONDO:0007441), dentinogenesis imperfecta type 3 (MONDO:0007442), deafness, autosomal dominant 39, with dentinogenesis imperfecta 1 (MONDO:0011571), breast ductal adenocarcinoma (MONDO:0005590), dentinogenesis imperfecta (MONDO:0018849), dentin dysplasia type I (MONDO:0007436), dentin dysplasia type II (MONDO:0007437)

Orphanet (3): Dentinogenesis imperfecta type 2 (Orphanet:166260), Dentinogenesis imperfecta type 3 (Orphanet:166265), Dentin dysplasia (Orphanet:1653)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000360	Tinnitus
HP:0000694	Odontodysplasia
HP:0000700	Periapical bone loss
HP:0000703	Dentinogenesis imperfecta
HP:0003593	Infantile onset
HP:0003771	Pulp calcification
HP:0005101	High-frequency hearing impairment
HP:0006286	Yellow-brown discoloration of the teeth
HP:0008619	Bilateral sensorineural hearing impairment
HP:0009102	Anterior open-bite malocclusion
HP:0009722	Dental enamel pits
HP:0011060	Dentinogenesis imperfecta limited to primary teeth
HP:0033790	Thistle tube shaped pulp

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001713_23	Dental caries	7.000000e-08
GCST005588_24	Idiopathic dilated cardiomyopathy	3.000000e-06
GCST010314_7	Serum omega-6 to omega-3 polyunsaturated fatty acid ratio in metabolic syndrome	4.000000e-06
GCST010316_11	Serum docosahexaenoic fatty acid concentration in metabolic syndrome	3.000000e-06
GCST010318_6	Serum omega-3 polyunsaturated fatty acid concentration in metabolic syndrome	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0010732	omega-6:omega-3 polyunsaturated fatty acid ratio
EFO:0007761	docosahexaenoic acid measurement
EFO:0010119	omega-3 polyunsaturated fatty acid measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D003811	Dentinogenesis Imperfecta	C07.650.800.270; C07.793.700.270; C16.131.850.800.270
C565316	Deafness, Autosomal Dominant 39, with Dentinogenesis Imperfecta 1 (supp.)
C538215	Dentin dysplasia, type 1 (supp.)
C538216	Dentinogenesis imperfecta, shields type 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
ascorbate-2-phosphate	affects cotreatment, increases expression, decreases reaction	1
kojic acid	decreases expression	1
lead nitrate	affects cotreatment, decreases reaction, increases expression	1
manganese chloride	increases expression	1
beta-glycerophosphoric acid	decreases reaction, affects cotreatment, increases expression	1
phenylamil	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
Decitabine	increases expression	1
Acetylcysteine	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Cadmium	increases abundance, decreases expression	1
Cannabidiol	increases expression	1
Cisplatin	decreases response to substance	1
Dexamethasone	affects cotreatment, increases expression, decreases reaction	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Glucosamine	decreases expression	1
Malathion	decreases expression	1
Manganese	increases expression	1
Quercetin	decreases reaction, increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Simvastatin	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT03810859	Not specified	UNKNOWN	Non-syndromic Inherited Anomalies of Mineralized Tooth Tissues: a Whole Exome Study to Identify New Pathogenic Variants
NCT04927962	Not specified	COMPLETED	Psycho-social Impact of Amelogenesis and Dentinogenesis Imperfecta
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery