Hypophosphatemic rickets, autosomal recessive, 1

Summary

Hypophosphatemic rickets, autosomal recessive, 1 (MONDO:0009430) is a disease caused by DMP1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: DMP1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 121

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypophosphatemic rickets, autosomal recessive, 1
Mondo ID	MONDO:0009430
MeSH	C562792
OMIM	241520
UMLS	C4551495
MedGen	1632314
GARD	0018416
Is cancer (heuristic)	no

Also known as: ARHR1 · autosomal recessive hypophosphatemic rickets caused by mutation in DMP1 · DMP1 autosomal recessive hypophosphatemic rickets · hypophosphatemic rickets, AR · hypophosphatemic rickets, autosomal recessive, 1 · hypophosphatemic rickets, autosomal recessive, type 1

Data availability: 121 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary hypophosphatemic rickets › autosomal recessive hypophosphatemic rickets › hypophosphatemic rickets, autosomal recessive, 1

Related subtypes (1): hypophosphatemic rickets, autosomal recessive, 2

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

121 retrieved; paginated sample, class counts are floors:

84 uncertain significance, 13 conflicting classifications of pathogenicity, 13 benign, 4 benign/likely benign, 3 pathogenic, 2 pathogenic/likely pathogenic, 1 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3591292	NM_004407.4(DMP1):c.403G>T (p.Gly135Ter)	DMP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8575	NM_004407.4(DMP1):c.1A>G (p.Met1Val)	DMP1	Pathogenic	criteria provided, multiple submitters, no conflicts
8573	NM_004407.4(DMP1):c.362del (p.Pro121fs)	DMP1-AS1	Pathogenic	criteria provided, single submitter
8574	NM_004407.4(DMP1):c.55-1G>C	DMP1-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8576	NM_004407.4(DMP1):c.1485_1491del (p.Tyr496fs)	DMP1-AS1	Pathogenic	no assertion criteria provided
3591285	NM_004407.4(DMP1):c.103-1G>A	DMP1-AS1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179102	NM_004407.4(DMP1):c.135+1G>T	DMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198171	NM_004407.4(DMP1):c.879T>C (p.Ser293=)	DMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2048257	NM_004407.4(DMP1):c.124A>C (p.Thr42Pro)	DMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2081480	NM_004407.4(DMP1):c.424G>T (p.Asp142Tyr)	DMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
349969	NM_004407.4(DMP1):c.91G>A (p.Glu31Lys)	DMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
349978	NM_004407.4(DMP1):c.815G>A (p.Arg272His)	DMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
349980	NM_004407.4(DMP1):c.943G>C (p.Gly315Arg)	DMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
349981	NM_004407.4(DMP1):c.1023C>T (p.Ser341=)	DMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
903752	NM_004407.4(DMP1):c.159C>T (p.Gly53=)	DMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290776	NM_004407.4(DMP1):c.1107C>T (p.Asp369=)	DMP1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3591297	NM_004407.4(DMP1):c.522G>A (p.Val174=)	DMP1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
903753	NM_004407.4(DMP1):c.312C>T (p.Asp104=)	DMP1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
907171	NM_004407.4(DMP1):c.1356C>T (p.Asp452=)	DMP1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1935888	NM_004407.4(DMP1):c.787C>G (p.Pro263Ala)	DMP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2079270	NM_004407.4(DMP1):c.1493A>G (p.Asn498Ser)	DMP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2150686	NM_004407.4(DMP1):c.1040C>T (p.Ser347Leu)	DMP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
288212	NM_004407.4(DMP1):c.55-3T>G	DMP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3272400	NM_004407.4(DMP1):c.699C>G (p.Asn233Lys)	DMP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
349971	NM_004407.4(DMP1):c.289A>G (p.Lys97Glu)	DMP1	Uncertain significance	criteria provided, single submitter
349972	NM_004407.4(DMP1):c.370A>C (p.Lys124Gln)	DMP1	Uncertain significance	criteria provided, single submitter
349973	NM_004407.4(DMP1):c.428C>T (p.Thr143Ile)	DMP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
349976	NM_004407.4(DMP1):c.674G>A (p.Ser225Asn)	DMP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
349986	NM_004407.4(DMP1):c.1408G>A (p.Glu470Lys)	DMP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
349988	NM_004407.4(DMP1):c.1456A>G (p.Ile486Val)	DMP1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
DMP1	Definitive	Autosomal recessive	hypophosphatemic rickets, autosomal recessive, 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DMP1	Orphanet:289176	Autosomal recessive hypophosphatemic rickets

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
DMP1	HGNC:2932	ENSG00000152592	Q13316	Dentin matrix acidic phosphoprotein 1	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)
DMP1	Dentin matrix acidic phosphoprotein 1	May have a dual function during osteoblast differentiation.

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)
DMP1	Other/Unknown	no		DMP1
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
male germ line stem cell (sensu Vertebrata) in testis	2
periodontal ligament	1
tibia	1
ganglionic eminence	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DMP1	40	tissue_specific	marker	periodontal ligament, tibia, male germ line stem cell (sensu Vertebrata) in testis
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
DMP1	850
DMP1-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DMP1	Q13316	47.80

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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×	0.012	DMP1
Post-translational protein phosphorylation	1	100.2×	0.012	DMP1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	DMP1

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 enamel mineralization	1	5617.3×	9e-04	DMP1
biomineral tissue development	1	648.1×	0.003	DMP1
positive regulation of cell-substrate adhesion	1	495.6×	0.003	DMP1
ossification	1	227.7×	0.005	DMP1
extracellular matrix organization	1	122.1×	0.008	DMP1

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
DMP1	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	DMP1, 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)
DMP1	0	—
DMP1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.