DSPP

Chr 4AD

dentin sialophosphoprotein

Also known as: DFNA39, DGI1, DMP3, DPP, DSP

NCBI Gene: 1834ENSG00000152591UniProt: Q9NZW4

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. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 39, with dentinogenesisMIM #605594
AD
Dentin dysplasia, type IIMIM #125420
AD
Dentinogenesis imperfecta, Shields type IIMIM #125490
AD
Dentinogenesis imperfecta, Shields type IIIMIM #125500
AD
UniProtDentin dysplasia 2
687
ClinVar variants
66
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DSPP
🧬
Gene-Disease Validity (ClinGen)
dentinogenesis imperfecta · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
66 Pathogenic / Likely Pathogenic· 346 VUS of 687 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.17LOEUF
pLI 0.000
Z-score 1.02
OE 0.74 (0.48–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.10Z-score
OE missense 0.88 (0.82–0.94)
596 obs / 676.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.74 (0.48–1.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.82–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.32
0≤1.21.6
LoF obs/exp: 13 / 17.6Missense obs/exp: 596 / 676.8Syn Z: -3.74

ClinVar Variant Classifications

687 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic19
VUS346
Likely Benign165
Benign79
Conflicting31
47
Pathogenic
19
Likely Pathogenic
346
VUS
165
Likely Benign
79
Benign
31
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
5
19
0
47
Likely Pathogenic
16
0
3
0
19
VUS
3
309
21
13
346
Likely Benign
0
30
35
100
165
Benign
0
21
38
20
79
Conflicting
—31
Total42365116133687

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DSPP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

DSPP-related deafness with dentinogenesis imperfecta

definitive
ADUndeterminedAltered Gene Product Structure
Dev. DisordersEar
G2P ↗
missense variantinframe deletioninframe insertion

DSPP-related dentinogenesis imperfecta, Shields type

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Deafness, autosomal dominant 39, with dentinogenesis

MIM #605594

Molecular basis of disorder known

Autosomal dominant

Dentin dysplasia, type II

MIM #125420

Molecular basis of disorder known

Autosomal dominant

Dentinogenesis imperfecta, Shields type II

MIM #125490

Molecular basis of disorder known

Autosomal dominant

Dentinogenesis imperfecta, Shields type III

MIM #125500

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — DSPP
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia.
Barron MJ et al.·Orphanet J Rare Dis
2008Review
Analysis of comorbidities and multimorbidity in adult patients in the International Severe Asthma Registry.
Scelo G et al.·Ann Allergy Asthma Immunol
2024Cohort
Hereditary dentin defects.
Kim JW et al.·J Dent Res
2007Review
A novel DSPP frameshift mutation causing dentin dysplasia type 2 and disease management strategies.
Yuan M et al.·Oral Dis
2023Review
Hereditary dentine diseases resulting from mutations in DSPP gene.
Maciejewska I et al.·J Dent
2012Review
FAM20A mutations and transcriptome analyses of dental pulp tissues of enamel renal syndrome.
Wang SK et al.·Int Endod J
2023
Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients.
Du Q et al.·Clin Oral Investig
2023Cohort
LL-37 regulates odontogenic differentiation of dental pulp stem cells in an inflammatory microenvironment.
Ma Y et al.·Stem Cell Res Ther
2024
Functions of secretory calcium-binding phosphoproteins in dental mineralization.
Chun YP et al.·J Bone Miner Res
2025Review
Mutant Dentin Sialophosphoprotein Causes Dentinogenesis Imperfecta.
Liang T et al.·J Dent Res
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Beyond the diagnosis: Unraveling DSPP genotype-phenotype correlations in dentin dysplasia and dentinogenesis imperfecta.
Boonyakanog A et al.·Jpn Dent Sci Rev
2026🔓 Open Access
Restoring Cell-Cell Junctions in DSPP-Deficient Odontoblasts Through Nanofibrous Topography and Wnt5a-Cdc42 Activation: A Laboratory Investigation.
Bae J et al.·Int Endod J
2025
[Clinical and genetic analysis of a Chinese pedigree affected with Hereditary dentin dysplasia type II due to a variant of DSPP gene].
Li F et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025
Unveiling Novel DSPP Variants and Dental Phenotypes in Dentinogenesis Imperfecta.
Boonyakanog A et al.·J Oral Pathol Med
2025
A Novel DSPP Mutation in Dentinogenesis Imperfecta Shields Type II: Clinical, Genetic and Stem Cell Perspectives.
Gao Q et al.·Int Dent J
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools