DMP1

dentin matrix acidic phosphoprotein 1, the group of SIBLING family

Basic information

Region (hg38): 4:87650279-87664361

Links

ENSG00000152592 ∙ NCBI:1758 ∙ OMIM:600980 ∙ HGNC:2932 ∙ Uniprot:Q13316 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypophosphatemic rickets, autosomal recessive, 1 (Definitive), mode of inheritance: AR
• hypophosphatemic rickets, autosomal recessive, 1 (Moderate), mode of inheritance: AR
• hypophosphatemic rickets, autosomal recessive, 1 (Strong), mode of inheritance: AR
• autosomal recessive hypophosphatemic rickets (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypophosphatemic rickets, autosomal recessive 1	AR	Endocrine	Supplementation (eg, with phosphate and vitamin D) can be beneficial	Endocrine	17033621; 17033625

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DMP1 gene.

• not provided (138 variants)
• Hypophosphatemic rickets, autosomal recessive, 1 (70 variants)
• Inborn genetic diseases (15 variants)
• not specified (7 variants)
• Hypophosphatemic Rickets, Recessive (4 variants)
• Hypophosphatemic rickets (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DMP1 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			3	19	2	24
missense			82	8	4	94
nonsense	3	1	1			5
start loss	1					1
frameshift	1					1
inframe indel					1	1
splice donor/acceptor (+/-2bp)		2				2
splice region			3	2		5
non coding			18	7	19	44
Total	5	3	104	34	26

Highest pathogenic variant AF is 0.00000657

Variants in DMP1

This is a list of pathogenic ClinVar variants found in the DMP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-87650292-CA-C		Hypophosphatemic Rickets, Recessive	Likely benign (Jun 14, 2016)
4-87656267-T-C			Benign (Mar 03, 2015)
4-87656421-A-G			Benign (Mar 03, 2015)
4-87656493-A-G		Hypophosphatemic rickets, autosomal recessive, 1 • not specified	Conflicting classifications of pathogenicity (Jan 12, 2024)
4-87656494-T-A		Hypophosphatemic rickets	Pathogenic (Feb 07, 2022)
4-87656496-A-T			Pathogenic (Aug 11, 2021)
4-87656503-G-C		Hypophosphatemic rickets, autosomal recessive, 1	Uncertain significance (Jan 13, 2018)
4-87656532-T-G			Uncertain significance (Mar 14, 2022)
4-87656564-G-A			Likely benign (Jun 27, 2022)
4-87656602-A-G			Benign (Mar 03, 2015)
4-87657018-AC-A			Benign (Oct 06, 2023)
4-87657019-C-T			Likely benign (Nov 18, 2023)
4-87657029-T-G		Hypophosphatemic rickets, autosomal recessive, 1	Uncertain significance (Aug 19, 2022)
4-87657031-G-C		Hypophosphatemic rickets, autosomal recessive, 1	Pathogenic/Likely pathogenic (Feb 08, 2023)
4-87657053-G-C		Inborn genetic diseases	Uncertain significance (Jun 17, 2022)
4-87657056-T-C		DMP1-related disorder	Likely benign (Nov 28, 2023)
4-87657068-G-A		Hypophosphatemic rickets, autosomal recessive, 1	Conflicting classifications of pathogenicity (Jan 24, 2024)
4-87657075-G-A			Pathogenic (Jan 31, 2018)
4-87657092-A-G			Likely benign (Jun 29, 2023)
4-87657158-A-G			Benign (Aug 16, 2018)
4-87657335-T-C			Benign (Aug 16, 2018)
4-87658902-A-G			Likely benign (Aug 30, 2018)
4-87659196-TTTCC-T			Likely benign (May 12, 2023)
4-87659209-C-T			Likely benign (Aug 09, 2022)
4-87659241-A-C			Uncertain significance (Jul 20, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DMP1	protein_coding	protein_coding	ENST00000339673	5	14055

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.49e-7	0.628	125655	0	93	125748	0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.273	255	268	0.953	0.0000134	3519
Missense in Polyphen		84	93.3	0.90032		1260
Synonymous	0.466	94	99.9	0.941	0.00000590	852
Loss of Function	1.11	13	18.1	0.719	7.84e-7	246

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000380	0.000380
Ashkenazi Jewish	0.00466	0.00467
East Asian	0.000218	0.000217
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000218	0.000217
South Asian	0.0000980	0.0000980
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a dual function during osteoblast differentiation. In the nucleus of undifferentiated osteoblasts, unphosphorylated form acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the osteoblast to osteocyte transition phase it is phosphorylated and exported into the extracellular matrix, where it regulates nucleation of hydroxyapatite. {ECO:0000269|PubMed:12615915}.
• Disease: DISEASE: Hypophosphatemic rickets, autosomal recessive, 1 (ARHR1) [MIM:241520]: A hereditary form of hypophosphatemic rickets, a disorder of proximal renal tubule function that causes phosphate loss, hypophosphatemia and skeletal deformities, including rickets and osteomalacia unresponsive to vitamin D. Symptoms are bone pain, fractures and growth abnormalities. {ECO:0000269|PubMed:17033621, ECO:0000269|PubMed:17033625}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Role of Osx and miRNAs in tooth development;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);ECM proteoglycans;AP-1 transcription factor network (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.794
• rvis_EVS: 0.51
• rvis_percentile_EVS: 80.3

Haploinsufficiency Scores

• pHI: 0.593
• hipred: N
• hipred_score: 0.123

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0337

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dmp1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype

Gene ontology

• Biological process: ossification;positive regulation of cell-substrate adhesion;extracellular matrix organization;biomineral tissue development;post-translational protein modification;cellular protein metabolic process;regulation of enamel mineralization
• Cellular component: extracellular region;nucleus;endoplasmic reticulum lumen;extracellular matrix
• Molecular function: integrin binding;calcium ion binding;extracellular matrix binding