DSPP

Chr 4AD

dentin sialophosphoprotein

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

NCBI Gene: 1834 ENSG00000152591 UniProt: Q9NZW4 OMIM: 125485

The encoded protein is secreted by odontoblasts and proteolytically processed to generate dentin sialoprotein and dentin phosphoprotein, which facilitate dentin mineralization by binding calcium and regulating crystal formation in tooth dentin. Autosomal dominant mutations cause dentinogenesis imperfecta (Shields types II and III), dentin dysplasia type II, and autosomal dominant deafness with dentinogenesis defects. The gene shows very low constraint against loss-of-function variants (pLI near zero), suggesting the associated dental and hearing phenotypes may involve other mutational mechanisms.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 39, with dentinogenesisMIM #605594

Dentin dysplasia, type IIMIM #125420

Dentinogenesis imperfecta, Shields type IIMIM #125490

Dentinogenesis imperfecta, Shields type IIIMIM #125500

UniProtDentin dysplasia 2

Clinical highlights

Gene-disease validity (ClinGen)

dentinogenesis imperfecta · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

174

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.17

LOEUF

LOF*

Mechanism· G2P

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