DOLK

dolichol kinase

Basic information

Region (hg38): 9:128945529-128947603

Previous symbols: [ "TMEM15" ]

Links

ENSG00000175283 ∙ NCBI:22845 ∙ OMIM:610746 ∙ HGNC:23406 ∙ Uniprot:Q9UPQ8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• SRD5A3-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• DK1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• DK1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• DK1-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• DK1-congenital disorder of glycosylation (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Im	AR	Cardiovascular; Hematologic	In overall mildly affected individuals, cardiovascular manifestations such as dilated cardiomyopathy can result in severe sequelae, and early diagnosis may allow beneficial management; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Cardiovascular; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic	17273964; 22242004; 23890587
Hepatic-metabolized agents should be avoided

ClinVar

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

• DK1-congenital disorder of glycosylation (392 variants)
• Cardiovascular phenotype (185 variants)
• not provided (48 variants)
• not specified (31 variants)
• Inborn genetic diseases (6 variants)
• DOLK-related condition (1 variants)
• Primary dilated cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOLK 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			5	125		130
missense	1	1	262	4		268
nonsense		1	2			3
start loss	1	1		1		3
frameshift			12			12
inframe indel			6			6
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			10	1		11
Total	2	3	297	131	0

Highest pathogenic variant AF is 0.00000657

Variants in DOLK

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

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

Position	Type	Phenotype	Significance	ClinVar
9-128945563-T-C		DK1-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
9-128945667-C-T		DK1-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
9-128945688-T-C		DK1-congenital disorder of glycosylation	Uncertain significance (Feb 17, 2022)
9-128945698-G-C		DK1-congenital disorder of glycosylation	Uncertain significance (Jul 03, 2022)
9-128945701-A-G		DK1-congenital disorder of glycosylation	Likely benign (May 12, 2022)
9-128945704-T-C		DK1-congenital disorder of glycosylation	Uncertain significance (May 25, 2022)
9-128945706-A-C		Cardiovascular phenotype	Uncertain significance (Nov 09, 2023)
9-128945707-G-A		DK1-congenital disorder of glycosylation • Cardiovascular phenotype	Likely benign (Sep 28, 2023)
9-128945708-G-C		DK1-congenital disorder of glycosylation	Likely benign (Jan 08, 2024)
9-128945710-G-A		DK1-congenital disorder of glycosylation • Cardiovascular phenotype	Uncertain significance (Oct 03, 2023)
9-128945718-G-A		Cardiovascular phenotype	Uncertain significance (Mar 06, 2020)
9-128945723-AAGG-A		DK1-congenital disorder of glycosylation	Uncertain significance (Mar 22, 2022)
9-128945725-G-A		DK1-congenital disorder of glycosylation	Uncertain significance (Aug 27, 2021)
9-128945728-G-A		DK1-congenital disorder of glycosylation	Uncertain significance (May 07, 2022)
9-128945730-T-C		DK1-congenital disorder of glycosylation	Uncertain significance (Aug 16, 2022)
9-128945733-T-A		DK1-congenital disorder of glycosylation	Uncertain significance (May 25, 2022)
9-128945735-T-C		Cardiovascular phenotype	Uncertain significance (Nov 06, 2020)
9-128945734-C-CAGATT		DK1-congenital disorder of glycosylation	Uncertain significance (Oct 15, 2021)
9-128945736-A-G		DK1-congenital disorder of glycosylation • Cardiovascular phenotype	Uncertain significance (Dec 29, 2023)
9-128945737-T-A		Cardiovascular phenotype	Uncertain significance (Oct 12, 2023)
9-128945741-T-C		DK1-congenital disorder of glycosylation	Likely benign (Apr 06, 2022)
9-128945746-T-C		DK1-congenital disorder of glycosylation • Cardiovascular phenotype • DOLK-related disorder	Conflicting classifications of pathogenicity (Oct 05, 2023)
9-128945747-G-A		DK1-congenital disorder of glycosylation • Cardiovascular phenotype	Likely benign (Jan 19, 2024)
9-128945763-G-C		DK1-congenital disorder of glycosylation	Uncertain significance (Aug 26, 2021)
9-128945768-A-C		DK1-congenital disorder of glycosylation	Likely benign (Jul 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DOLK	protein_coding	protein_coding	ENST00000372586	1	2090

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00124	0.963	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.977	251	298	0.841	0.0000170	3421
Missense in Polyphen		85	108.08	0.78649		1272
Synonymous	-0.842	141	129	1.09	0.00000720	1238
Loss of Function	1.85	7	14.6	0.479	8.52e-7	147

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: Involved in the synthesis of the sugar donor Dol-P-Man which is required in the synthesis of N-linked and O-linked oligosaccharides and for that of GPI anchors. {ECO:0000250}.
• Pathway: N-Glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;dolichol and dolichyl phosphate biosynthesis;Synthesis of Dolichyl-phosphate;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: 0.140

Intolerance Scores

• loftool: 0.198
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.18

Haploinsufficiency Scores

• pHI: 0.215
• hipred: N
• hipred_score: 0.441
• ghis: 0.577

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.640

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dolk
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: dolichyl diphosphate biosynthetic process;phosphorylation;dolichyl monophosphate biosynthetic process
• Cellular component: endoplasmic reticulum membrane;integral component of endoplasmic reticulum membrane
• Molecular function: dolichol kinase activity;protein binding