On this page
MAK
male germ cell associated kinase
MAK is located on the short (p) arm of chromosome 6, at band 6p24.2. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 6 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The MAK gene is located on chromosome 6 and encodes a protein kinase of 623 amino acids. This enzyme belongs to a family of regulatory proteins that control cellular processes by adding phosphate groups to target molecules. Although originally identified in male germ cells, research has revealed that MAK performs essential functions in photoreceptor cells within the retina, where it supports the development and maintenance of specialised cellular structures called cilia. These thread-like extensions enable photoreceptors to sense light and initiate the cascade of signals that ultimately produce vision. Pathogenic variants in MAK disrupt these critical processes, leading to progressive retinal degeneration.
What the gene does
MAK functions as a serine/threonine kinase, meaning it transfers phosphate groups to specific amino acids on target proteins, thereby regulating their activity and localisation. Within photoreceptor cells, the protein concentrates in the ciliary compartment, where it orchestrates the proper assembly and function of the connecting cilium - a narrow bridge that links the cell body to the light-sensing outer segment. This ciliary structure serves as a critical transport corridor, shuttling proteins and other molecules essential for phototransduction. By phosphorylating key ciliary proteins, MAK helps coordinate the intricate machinery required for photoreceptors to renew their outer segments and maintain responsiveness to light. Disruption of MAK activity compromises ciliary integrity, impairing the delivery of vital components and ultimately triggering photoreceptor degeneration.
Video: Genetics 101
Chromosome location
MAK is located on the short arm of chromosome 6 at position 24.2 (6p24.2). The gene spans multiple exons that together encode the 623-amino-acid protein. This chromosomal region contains several other genes, but MAK itself is a discrete locus with well-defined boundaries. The genomic architecture allows for regulated expression, with transcription patterns varying across different cell types and developmental stages.
Protein structure
The MAK protein exhibits a modular organisation centred on its catalytic activity. The Protein kinase domain extends from amino acids 4 to 284, forming the functional core responsible for phosphate transfer. This domain contains the conserved structural features characteristic of serine/threonine kinases, including ATP-binding and substrate-recognition motifs. Beyond the kinase domain, the protein includes two Disordered regions spanning amino acids 328-396 and 416-469. These intrinsically unstructured segments likely provide regulatory flexibility, enabling the protein to interact with diverse binding partners and respond dynamically to cellular signals.
Key variants
Pathogenic variants in MAK typically result in loss of kinase function, either through disruption of the catalytic domain or introduction of premature termination signals. Missense changes that alter critical residues within the kinase active site can abolish enzymatic activity, whilst frameshift and nonsense variants lead to truncated proteins lacking essential functional regions. The distribution of pathogenic variants reflects the importance of the kinase domain, with most disease-causing changes clustering in this region.
Sample of pathogenic variants
10 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.1051C>T | p.Gln351Ter | Pathogenic | ★★☆☆ | Retinal dystrophy |
c.1222del | p.Glu408fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 62 |
c.1294dup | p.Arg432fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 62 |
c.1741C>T | p.Gln581Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 62 |
c.393dup | p.Leu132fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa |
c.394_395insCTTC | p.Leu132fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 62 |
c.639C>A | p.Cys213Ter | Pathogenic | ★★☆☆ | not provided |
c.79G>A | p.Gly27Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa |
c.7C>T | p.Arg3Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 62 |
c.947dup | p.Leu316fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 62 |
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 MAK are associated with inherited retinal dystrophies characterised by progressive loss of photoreceptor function. Affected individuals typically experience night blindness and gradual constriction of the visual field as rod photoreceptors degenerate, followed by declining central vision as cone cells are affected. The age of onset and rate of progression can vary, reflecting the specific molecular consequence of individual variants and potential modifying factors. Because ciliary function is fundamental to photoreceptor survival, disruption of MAK activity leads to cumulative cellular damage over time.
No disease links recorded for this gene in our reference set.
UK clinical status
MAK is included on the NHS Genomic Medicine Service Retinal disorders panel with green classification (R32), indicating strong evidence supporting its role in inherited retinal disease. This classification reflects the gene's established clinical validity and supports its use in diagnostic testing for individuals presenting with relevant retinal phenotypes within the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the MAK gene do?
MAK encodes a protein kinase that regulates ciliary function in photoreceptor cells of the retina. The enzyme modifies target proteins through phosphorylation, supporting the structural integrity and transport processes essential for light detection.
How do MAK variants cause vision loss?
Pathogenic variants impair the kinase's ability to maintain ciliary structures in photoreceptors. Without functional MAK, these cells cannot properly renew their light-sensing components, leading to progressive degeneration and gradual loss of vision.
Is MAK testing available through the NHS?
Yes, MAK is included on the NHS Genomic Medicine Service Retinal disorders panel. Testing may be offered to individuals with clinical features consistent with inherited retinal dystrophy, following assessment by an ophthalmology or clinical genetics service.