DPM3

dolichyl-phosphate mannosyltransferase subunit 3, regulatory, the group of Dolichyl-phosphate mannosyltransferase subunits

Basic information

Region (hg38): 1:155139891-155140595

Links

ENSG00000179085 ∙ NCBI:54344 ∙ OMIM:605951 ∙ HGNC:3007 ∙ Uniprot:Q9P2X0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• DPM3-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• DPM3-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• DPM3-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• DPM3-congenital disorder of glycosylation (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy-dystroglycanopathy, type C, 15 (Congenital disorder of glycosylation, type Io)	AR	Cardiovascular; Hematologic	Dilated cardiomyopathy has been described, and awareness may allow early management; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	19576565; 28803818; 31266720; 31469168
In a reported patient, dilated cardiomyopathy was the presenting complaint; Heart transplant has been described; Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPM3 gene.

• DPM3-congenital disorder of glycosylation (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPM3 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				8	1	9
missense	1	1	31			33
nonsense	4					4
start loss						0
frameshift	4					4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				5		5
Total	9	1	31	13	1

Highest pathogenic variant AF is 0.0000131

Variants in DPM3

This is a list of pathogenic ClinVar variants found in the DPM3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-155139960-T-C		not specified	Likely benign (Feb 25, 2016)
1-155139975-C-T		DPM3-congenital disorder of glycosylation	Uncertain significance (Jul 26, 2022)
1-155139982-G-A		not specified	Uncertain significance (Sep 23, 2023)
1-155139984-G-A		not specified	Uncertain significance (Jul 16, 2021)
1-155139984-G-T		DPM3-congenital disorder of glycosylation	Uncertain significance (Jul 05, 2022)
1-155139987-A-G		DPM3-congenital disorder of glycosylation	Pathogenic (Jul 01, 2009)
1-155139987-A-T		DPM3-congenital disorder of glycosylation • Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15	Pathogenic (Aug 25, 2020)
1-155139992-G-T		DPM3-congenital disorder of glycosylation • DPM3-related disorder	Conflicting classifications of pathogenicity (Jan 19, 2024)
1-155139993-G-A		DPM3-congenital disorder of glycosylation	Uncertain significance (Oct 25, 2022)
1-155139997-G-A		DPM3-congenital disorder of glycosylation	Pathogenic (Jun 12, 2021)
1-155140012-G-A		DPM3-congenital disorder of glycosylation	Pathogenic (Oct 19, 2020)
1-155140021-G-A			Likely benign (Jul 31, 2018)
1-155140023-T-G		DPM3-congenital disorder of glycosylation • not specified	Uncertain significance (Apr 25, 2023)
1-155140026-C-T		DPM3-congenital disorder of glycosylation	Uncertain significance (Feb 28, 2022)
1-155140033-C-T		DPM3-congenital disorder of glycosylation	Uncertain significance (Jan 19, 2020)
1-155140035-TC-T		DPM3-congenital disorder of glycosylation	Pathogenic (Jan 12, 2024)
1-155140045-C-A		DPM3-congenital disorder of glycosylation	Uncertain significance (Jun 19, 2020)
1-155140048-G-A		DPM3-congenital disorder of glycosylation	Uncertain significance (Aug 21, 2022)
1-155140054-T-A		not specified	Uncertain significance (Dec 21, 2023)
1-155140056-G-A		DPM3-congenital disorder of glycosylation	Uncertain significance (Jan 08, 2024)
1-155140057-C-G		DPM3-congenital disorder of glycosylation	Uncertain significance (Aug 04, 2021)
1-155140061-AC-A		DPM3-congenital disorder of glycosylation	Pathogenic (Oct 13, 2022)
1-155140062-C-A		DPM3-congenital disorder of glycosylation • not specified	Uncertain significance (Dec 06, 2023)
1-155140063-G-A		DPM3-congenital disorder of glycosylation	Uncertain significance (Mar 08, 2023)
1-155140065-T-G		DPM3-congenital disorder of glycosylation	Uncertain significance (Jul 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPM3	protein_coding	protein_coding	ENST00000368399	1	705

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.233	0.655	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.416	59	68.7	0.859	0.00000304	747
Missense in Polyphen		20	24.875	0.80403		284
Synonymous	0.0516	34	34.4	0.989	0.00000153	295
Loss of Function	1.14	1	3.20	0.313	1.37e-7	35

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stabilizer subunit of the dolichol-phosphate mannose (DPM) synthase complex; tethers catalytic subunit DPM1 to the ER. {ECO:0000269|PubMed:10835346}.
• Disease: DISEASE: Congenital disorder of glycosylation 1O (CDG1O) [MIM:612937]: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1O patients have increased serum creatine kinase, dystrophic changes on muscle biopsy, and reduced O- mannosylation of alpha-dystroglycan. {ECO:0000269|PubMed:19576565}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: N-Glycan biosynthesis - Homo sapiens (human);Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins;dolichyl-diphosphooligosaccharide biosynthesis;Synthesis of dolichyl-phosphate mannose;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.0627

Intolerance Scores

• loftool: 0.324
• rvis_EVS: -0.01
• rvis_percentile_EVS: 52.85

Haploinsufficiency Scores

• pHI: 0.0477
• hipred: N
• hipred_score: 0.171
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.925

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dpm3
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: dpm3
• Affected structure: muscle
• Phenotype tag: abnormal
• Phenotype quality: dystrophic

Gene ontology

• Biological process: carbohydrate metabolic process;GPI anchor biosynthetic process;protein C-linked glycosylation via 2'-alpha-mannosyl-L-tryptophan;regulation of protein stability;protein mannosylation;protein O-linked mannosylation
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of endoplasmic reticulum membrane;mannosyltransferase complex;dolichol-phosphate-mannose synthase complex
• Molecular function: dolichyl-phosphate beta-D-mannosyltransferase activity;protein binding