DSPP

dentin sialophosphoprotein, the group of SIBLING family

Basic information

Region (hg38): 4:87608529-87616873

Previous symbols: [ "DFNA39", "DGI1" ]

Links

ENSG00000152591 ∙ NCBI:1834 ∙ OMIM:125485 ∙ HGNC:3054 ∙ Uniprot:Q9NZW4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• deafness, autosomal dominant 39, with dentinogenesis imperfecta 1 (Moderate), mode of inheritance: AD
• deafness, autosomal dominant 39, with dentinogenesis imperfecta 1 (Definitive), mode of inheritance: AD
• dentinogenesis imperfecta type 2 (Definitive), mode of inheritance: AD
• dentin dysplasia type I (Supportive), mode of inheritance: AD
• dentin dysplasia type II (Supportive), mode of inheritance: AD
• dentinogenesis imperfecta type 2 (Supportive), mode of inheritance: AD
• dentinogenesis imperfecta type 3 (Supportive), mode of inheritance: AD
• deafness, autosomal dominant 39, with dentinogenesis imperfecta 1 (Limited), mode of inheritance: Unknown
• dentinogenesis imperfecta type 3 (Strong), mode of inheritance: AD
• dentinogenesis imperfecta (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant, 39, with dentinogenesis imperfecta 1; Dentinogenesis imperfecta 1; Dentinogenesis imperfecta, Shields type III; Dentin dysplasia, type II	AD	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	Audiologic/Otolaryngologic; Dental	11175790; 11175779; 12354781; 15592686; 17686168; 18456718; 19026876; 19029076; 19103209; 19131317; 20121932; 20146806; 20618350; 20949630; 21029264; 21736673; 22125647; 22310900; 22521702

ClinVar

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

• Dentinogenesis imperfecta type 2 (7 variants)
• not provided (5 variants)
• DSPP-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DSPP 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			13	60	34	107
missense	4	1	172	22	24	223
nonsense			1			1
start loss						0
frameshift	5	7	4			16
inframe indel			6	24	28	58
splice donor/acceptor (+/-2bp)	1	1				2
splice region			1	1		2
non coding			1	8	17	26
Total	10	9	197	114	103

Variants in DSPP

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

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

Position	Type	Phenotype	Significance	ClinVar
4-87610645-T-C			Likely benign (Jan 28, 2019)
4-87610648-C-T			Benign (Nov 11, 2018)
4-87610654-C-T			Likely benign (Jan 28, 2019)
4-87610715-C-T			Benign (Nov 11, 2018)
4-87610749-C-T			Likely benign (Feb 11, 2019)
4-87610888-T-C		Hearing impairment	Uncertain significance (Jan 01, 2017)
4-87610912-A-G			Uncertain significance (Jan 15, 2021)
4-87610918-A-C			Uncertain significance (Feb 19, 2022)
4-87610924-T-G		Denticles	Pathogenic (Oct 01, 2002)
4-87610927-T-G			Uncertain significance (Apr 27, 2021)
4-87610945-G-C			Uncertain significance (Feb 16, 2021)
4-87610952-C-T		Dentinogenesis imperfecta type 2	Pathogenic (Oct 23, 2020)
4-87610957-C-A		Deafness, autosomal dominant nonsyndromic sensorineural 39, with dentinogenesis imperfecta 1	Pathogenic (Jun 01, 2012)
4-87610957-C-T			Pathogenic (Jul 19, 2022)
4-87610958-C-T			Pathogenic (Nov 01, 2022)
4-87611029-TAGTGTGTG-T			Likely benign (Aug 24, 2019)
4-87611030-AGT-A			Benign (Aug 18, 2019)
4-87611030-AGTGT-A			Benign (Aug 06, 2019)
4-87611030-A-AGT			Benign (Aug 13, 2019)
4-87611030-A-AGTGT			Benign (Aug 08, 2019)
4-87611030-A-AGTGTGT			Benign (Aug 21, 2019)
4-87611030-A-AGTGTGTGTGT			Benign (Aug 21, 2019)
4-87611100-T-C			Likely benign (Dec 31, 2018)
4-87611900-C-T			Likely benign (Apr 03, 2019)
4-87612011-TTG-T			Benign (Jul 19, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DSPP	protein_coding	protein_coding	ENST00000399271	4	8382

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.12e-7	0.566	124774	0	12	124786	0.0000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	596	677	0.881	0.0000338	9522
Missense in Polyphen		94	103.67	0.90676		1598
Synonymous	-3.74	297	226	1.32	0.0000138	1636
Loss of Function	1.02	13	17.6	0.739	8.52e-7	258

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000994	0.0000993
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000442	0.0000441
Middle Eastern	0.00	0.00
South Asian	0.000163	0.000163
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:11175790, ECO:0000269|PubMed:22392858}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:11175779, ECO:0000269|PubMed:14758537, ECO:0000269|PubMed:17627120, ECO:0000269|PubMed:21029264, ECO:0000269|PubMed:22392858}. Note=The disease is caused by mutations 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 (PubMed:18521831 and PubMed:22392858).; DISEASE: 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. {ECO:0000269|PubMed:15592686, ECO:0000269|PubMed:18521831, ECO:0000269|PubMed:23509818}. Note=The disease is caused by mutations 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 (PubMed:18521831 and PubMed:22392858).; DISEASE: 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. {ECO:0000269|PubMed:12354781, ECO:0000269|PubMed:18521831}. Note=The disease is caused by mutations 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 (PubMed:18521831, PubMed:22392858). {ECO:0000269|PubMed:18521831, ECO:0000269|PubMed:22392858}.
• Pathway: Role of Osx and miRNAs in tooth development;Extracellular matrix organization;ECM proteoglycans (Consensus)

Intolerance Scores

• loftool: 0.0573
• rvis_EVS: 4.04
• rvis_percentile_EVS: 99.66

Haploinsufficiency Scores

• pHI: 0.799
• hipred: N
• hipred_score: 0.146

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.129

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dspp
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype; growth/size/body region phenotype; digestive/alimentary phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype

Gene ontology

• Biological process: skeletal system development;ossification;response to hypoxia;multicellular organism development;response to mechanical stimulus;response to carbohydrate;extracellular matrix organization;biomineral tissue development;cellular response to hormone stimulus;hair follicle maturation;cartilage development;positive regulation of enamel mineralization;cellular response to cell-matrix adhesion;cellular response to dexamethasone stimulus;response to transforming growth factor beta;odontoblast differentiation;dentinogenesis;regulation of odontoblast differentiation
• Cellular component: extracellular region;cytoplasm;extracellular matrix
• Molecular function: extracellular matrix structural constituent;calcium ion binding;protein binding;collagen binding