Deafness, autosomal dominant 39, with dentinogenesis imperfecta 1

Summary

Deafness, autosomal dominant 39, with dentinogenesis imperfecta 1 (MONDO:0011571) is a disease caused by DSPP (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: DSPP (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	deafness, autosomal dominant 39, with dentinogenesis imperfecta 1
Mondo ID	MONDO:0011571
MeSH	C565316
OMIM	605594
UMLS	C1854146
MedGen	340145
GARD	0015383
Is cancer (heuristic)	no

Also known as: deafness, autosomal dominant 39, with dentinogenesis · deafness, autosomal dominant 39, with dentinogenesis imperfecta 1 · deafness, autosomal dominant 39, with dentinogenesis imperfecta type 1

Data availability: 15 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › dentinogenesis imperfecta type 2 › deafness, autosomal dominant 39, with dentinogenesis imperfecta 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

15 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 benign, 4 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
817628	NM_014208.3(DSPP):c.2525del (p.Ser842fs)	DMP1-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627439	NM_014208.3(DSPP):c.3248_3249insC (p.Glu1083fs)	DMP1-AS1	Likely pathogenic	no assertion criteria provided
260354	NM_014208.3(DSPP):c.1060C>T (p.Arg354Cys)	DMP1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3242356	NM_014208.3(DSPP):c.3429C>A (p.Asp1143Glu)	DMP1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
689607	NM_014208.3(DSPP):c.1031C>A (p.Thr344Asn)	DMP1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
834048	NM_014208.3(DSPP):c.368_371delinsAACATATGTTCATCATGGGAAAGAAGAAA (p.Gly123fs)	DMP1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031808	NM_014208.3(DSPP):c.1847G>A (p.Ser616Asn)	DMP1-AS1	Uncertain significance	criteria provided, single submitter
1696681	NM_014208.3(DSPP):c.1661G>A (p.Ser554Asn)	DMP1-AS1	Uncertain significance	criteria provided, single submitter
3591281	NM_014208.3(DSPP):c.3444_3447delinsCGAT (p.Glu1149Asp)	DMP1-AS1	Uncertain significance	criteria provided, single submitter
982865	NM_014208.3(DSPP):c.3535_3537delinsGAC (p.Asn1179Asp)	DMP1-AS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1691573	NM_014208.3(DSPP):c.981G>T (p.Glu327Asp)	DSPP	Uncertain significance	criteria provided, multiple submitters, no conflicts
260353	NM_014208.3(DSPP):c.*17G>A	DMP1-AS1	Benign	criteria provided, multiple submitters, no conflicts
260356	NM_014208.3(DSPP):c.136-33T>C	DMP1-AS1	Benign	criteria provided, multiple submitters, no conflicts
260359	NM_014208.3(DSPP):c.897A>G (p.Ser299=)	DMP1-AS1	Benign	criteria provided, multiple submitters, no conflicts
523082	NM_014208.3(DSPP):c.3681C>A (p.Asp1227Glu)	DMP1-AS1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DSPP	Definitive	Autosomal dominant	dentinogenesis imperfecta	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DSPP	Orphanet:166260	Dentinogenesis imperfecta type 2
DSPP	Orphanet:166265	Dentinogenesis imperfecta type 3
DSPP	Orphanet:99789	Dentin dysplasia type I
DSPP	Orphanet:99791	Dentin dysplasia type II

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DSPP	HGNC:3054	ENSG00000152591	Q9NZW4	Dentin sialophosphoprotein	gencc,clinvar
DMP1-AS1	HGNC:58144	ENSG00000249001		DMP1 and DSPP antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DSPP	Dentin sialophosphoprotein	DSP may be an important factor in dentinogenesis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DSPP	Other/Unknown	no
DMP1-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
myocardium	1
tendon of biceps brachii	1
ganglionic eminence	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DSPP	76		marker	buccal mucosa cell, tendon of biceps brachii, myocardium
DMP1-AS1	108		yes	male germ line stem cell (sensu Vertebrata) in testis, sperm, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DSPP	1,199
DMP1-AS1	0

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DSPP	Q9NZW4	39.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
ECM proteoglycans	1	150.3×	0.007	DSPP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of odontoblast differentiation	1	8426.0×	5e-04	DSPP
odontoblast differentiation	1	2106.5×	6e-04	DSPP
dentinogenesis	1	2106.5×	6e-04	DSPP
biomineral tissue development	1	648.1×	0.002	DSPP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DSPP	0	0
DMP1-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	DSPP, DMP1-AS1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DSPP	0	—
DMP1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.