DPM2

dolichyl-phosphate mannosyltransferase subunit 2, regulatory, the group of Dolichyl-phosphate mannosyltransferase subunits|Glycosylphosphatidylinositol-N-acetylglucosaminyltransferase complex

Basic information

Region (hg38): 9:127935098-127937854

Links

ENSG00000136908 ∙ NCBI:8818 ∙ OMIM:603564 ∙ HGNC:3006 ∙ Uniprot:O94777 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital muscular dystrophy with intellectual disability and severe epilepsy (Strong), mode of inheritance: AR
• congenital muscular dystrophy with intellectual disability and severe epilepsy (Limited), mode of inheritance: AR
• congenital muscular dystrophy with intellectual disability and severe epilepsy (Strong), mode of inheritance: AR
• congenital muscular dystrophy with intellectual disability and severe epilepsy (Supportive), mode of inheritance: AR
• congenital muscular dystrophy with intellectual disability and severe epilepsy (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Iu	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Musculoskeletal; Neurologic	19901254; 23109149
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPM2 gene.

• Congenital muscular dystrophy with intellectual disability and severe epilepsy (80 variants)
• not specified (10 variants)
• not provided (9 variants)
• Inborn genetic diseases (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPM2 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				16	1	17
missense		1	25	1	1	28
nonsense	1	1				2
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			5	2		7
non coding			11	23	1	35
Total	1	2	39	40	3

Variants in DPM2

This is a list of pathogenic ClinVar variants found in the DPM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-127935169-C-T		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jan 12, 2018)
9-127935193-C-T		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jan 13, 2018)
9-127935212-T-C		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Mar 30, 2018)
9-127935318-G-A		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jan 13, 2018)
9-127935491-G-A		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jan 12, 2018)
9-127935598-C-G		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jan 13, 2018)
9-127935673-C-A		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jan 13, 2018)
9-127935708-T-A		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jan 12, 2018)
9-127935740-C-T		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Likely benign (Jun 29, 2023)
9-127935748-T-C		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Oct 26, 2019)
9-127935750-G-C		not specified • Congenital muscular dystrophy with intellectual disability and severe epilepsy	Benign (Feb 01, 2024)
9-127935763-CA-TG		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jun 23, 2022)
9-127935764-A-G		not specified • Congenital muscular dystrophy with intellectual disability and severe epilepsy	Benign (Feb 01, 2024)
9-127935764-AT-GC		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Oct 10, 2018)
9-127935765-T-C		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jun 04, 2022)
9-127935769-A-C		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jul 27, 2022)
9-127935769-A-G		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Jul 26, 2022)
9-127935780-C-T		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Likely pathogenic (-)
9-127935785-G-A		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Conflicting classifications of pathogenicity (Jan 18, 2024)
9-127935788-A-AT		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Uncertain significance (Feb 19, 2020)
9-127936362-G-C			Likely benign (Jun 28, 2018)
9-127936533-G-A		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Likely benign (Dec 13, 2023)
9-127936534-G-A		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Likely benign (Oct 09, 2021)
9-127936535-G-C		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Likely benign (Sep 08, 2023)
9-127936540-G-A		Congenital muscular dystrophy with intellectual disability and severe epilepsy	Likely benign (Aug 30, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPM2	protein_coding	protein_coding	ENST00000314392	4	3386

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.318	0.620	125677	0	4	125681	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.604	31	42.0	0.738	0.00000200	517
Missense in Polyphen		15	16.882	0.88853		233
Synonymous	0.612	16	19.4	0.823	9.68e-7	175
Loss of Function	1.44	1	4.17	0.240	1.77e-7	51

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000269	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates the biosynthesis of dolichol phosphate- mannose. Regulatory subunit of the dolichol-phosphate mannose (DPM) synthase complex; essential for the ER localization and stable expression of DPM1. When associated with the GPI-GlcNAc transferase (GPI-GnT) complex enhances but is not essential for its activity. {ECO:0000269|PubMed:10944123}.
• Disease: DISEASE: Congenital disorder of glycosylation 1U (CDG1U) [MIM:615042]: 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. Some CDG1U patients have dystrophic changes seen on muscle biopsy and reduced O-mannosyl glycans on alpha- dystroglycan. {ECO:0000269|PubMed:23109149}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycosylphosphatidylinositol (GPI)-anchor biosynthesis - Homo sapiens (human);N-Glycan biosynthesis - Homo sapiens (human);Synthesis of glycosylphosphatidylinositol (GPI);Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins;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: 0.0778

Intolerance Scores

• loftool: 0.656
• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.16

Haploinsufficiency Scores

• pHI: 0.0270
• hipred: N
• hipred_score: 0.241

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.741

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dpm2
• Phenotype: homeostasis/metabolism 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); 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)

Zebrafish Information Network

• Gene name: dpm2
• Affected structure: skeletal muscle
• Phenotype tag: abnormal
• Phenotype quality: damaged

Gene ontology

• Biological process: GPI anchor biosynthetic process;preassembly of GPI anchor in ER membrane;dolichol metabolic process;regulation of protein stability;protein O-linked mannosylation;regulation of catalytic activity
• Cellular component: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex;endoplasmic reticulum membrane;integral component of endoplasmic reticulum membrane;dolichol-phosphate-mannose synthase complex
• Molecular function: dolichyl-phosphate beta-D-mannosyltransferase activity;protein binding;enzyme regulator activity