On this page
DOLK
dolichol kinase
The DOLK gene encodes the dolichol kinase enzyme, which is essential for the production of dolichol phosphate, a molecule critical for protein glycosylation and cell surface protein anchoring. The DOLK gene provides the blueprint for dolichol kinase, an enzyme involved in forming dolichol phosphate.
DOLK is located on the long (q) arm of chromosome 9, at band 9q34.11. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 9 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The DOLK gene, or dolichol kinase, instructs the body to produce an enzyme of the same name. This enzyme plays a fundamental role in the creation of dolichol phosphate, a key molecule required for a process known as glycosylation. Glycosylation is crucial for normal protein function and cellular processes, with implications for overall health.
Inherited changes in the DOLK gene are associated with certain conditions, primarily affecting metabolic pathways.
What the gene does
The dolichol kinase enzyme, synthesised from the DOLK gene, performs the final step in creating dolichol phosphate. This process involves adding a phosphate group to dolichol. Dolichol phosphate then serves as a lipid carrier, transporting sugar chains (oligosaccharides) within the endoplasmic reticulum, a cellular compartment involved in protein processing.
These sugar chains are essential for glycosylation, which modifies proteins by attaching sugars. Glycosylation is vital for proper protein folding, stability, and function. Additionally, dolichol phosphate is necessary for forming GPI anchors. These anchors secure specific proteins to the outer surface of the cell membrane, ensuring their availability for cellular interactions.
Video: Genetics 101
Chromosome location
The DOLK gene is situated on chromosome 9, specifically at position 9q34.11. This precise location helps geneticists identify and study the gene's role in human health.
Protein structure
The dolichol kinase protein consists of 538 amino acids. A crucial element within this protein is the CTP-binding domain, found between amino acids 459 and 474. This specific domain is integral to the enzyme's capacity to bind CTP (cytidine triphosphate), a molecule required for its enzymatic activity.
Key variants
Variants within the DOLK gene can alter the structure or function of the dolichol kinase enzyme. These genetic changes may disrupt the normal production of dolichol phosphate, subsequently affecting glycosylation and GPI anchor formation, which can lead to various health implications.
Sample of pathogenic variants
8 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.2T>C | p.Met1Thr | Pathogenic/Likely pathogenic | ★★☆☆ | Cardiovascular phenotype |
g.128945857G>T | - | Pathogenic | ★☆☆☆ | not provided |
c.1342G>C | p.Gly448Arg | Pathogenic | ★☆☆☆ | DK1-congenital disorder of glycosylation |
c.3G>A | p.Met1Ile | Pathogenic | ★☆☆☆ | DK1-congenital disorder of glycosylation |
c.734_737del | p.Phe245fs | Pathogenic | ★☆☆☆ | Cardiovascular phenotype |
c.1322A>C | p.Tyr441Ser | Pathogenic | - | DK1-congenital disorder of glycosylation |
c.295T>A | p.Cys99Ser | Pathogenic | - | DK1-congenital disorder of glycosylation |
c.912G>T | p.Trp304Cys | Pathogenic | - | DK1-congenital disorder of glycosylation |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the DOLK gene are primarily associated with DOLK-congenital disorder of glycosylation (DOLK-CDG), previously known as congenital disorder of glycosylation type Im. This condition can manifest with a range of symptoms, including dilated cardiomyopathy (a weakened and enlarged heart). At least six specific mutations in the DOLK gene have been identified as causing DOLK-CDG.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic DOLK variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The DOLK gene is included in several NHS England Genomic Medicine Service national test directories. It is covered by panels for Congenital disorders of glycosylation, Congenital muscular dystrophy (R79), DDG2P, Dilated and arrhythmogenic cardiomyopathy (R132), Early onset or syndromic epilepsy (R59), Foetal anomalies (R21), Intellectual disability (R29), Likely inborn error of metabolism (R98), Paediatric or syndromic cardiomyopathy (R135), and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the DOLK gene?
The DOLK gene provides instructions for making the dolichol kinase enzyme, which is critical for producing dolichol phosphate. This compound is essential for glycosylation, a process that modifies proteins by attaching sugar molecules, and for forming GPI anchors that attach proteins to cell membranes.
What is DOLK-congenital disorder of glycosylation?
DOLK-congenital disorder of glycosylation (DOLK-CDG) is an inherited condition caused by genetic changes in the DOLK gene. It can lead to a variety of symptoms, including heart problems like dilated cardiomyopathy, due to impaired protein glycosylation.
Is DOLK-CDG an inherited condition?
Yes, DOLK-CDG is an inherited condition. It follows an autosomal recessive inheritance pattern, meaning an individual must inherit two copies of a pathogenic variant (one from each parent) to develop the condition.
References
- Buczkowska A, Swiezewska E, Lefeber DJ. Genetic defects in dolichol metabolism. Journal of inherited metabolic disease. 2015. PMID: 25270028
- Denecke J, Kranz C. Hypoglycosylation due to dolichol metabolism defects. Biochimica et biophysica acta. 2009. PMID: 19419701
- Shridas P, Waechter CJ. Human dolichol kinase, a polytopic endoplasmic reticulum membrane protein with a cytoplasmically oriented CTP-binding site. The Journal of biological chemistry. 2006. PMID: 16923818