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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MAK
male germ cell associated kinase
Chromosome 6 Β· 6p24.2
NCBI Gene: 4117Ensembl: ENSG00000111837.12HGNC: HGNC:6816UniProt: A0A140VK28
42PubMed Papers
21Diseases
0Drugs
95Pathogenic Variants
FUNCTIONAL ROLE
KinaseTranscription Factor
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
transcription coactivator activityprotein bindingprotein phosphorylationprotein autophosphorylationretinitis pigmentosaretinitis pigmentosa 62Retinal dystrophyMAK-related retinopathy
✦AI Summary

MAK (male germ cell-associated kinase) is a serine/threonine protein kinase with critical roles in ciliary regulation and photoreceptor maintenance. Primary function: MAK regulates ciliary length and is essential for long-term photoreceptor survival through mechanisms involving cell cycle-dependent phosphorylation of FZR1 and transcriptional coactivation of androgen receptor (AR) 1. The protein localizes to multiple cellular compartments including centrosomes, the midbody, and photoreceptor inner segments, where it participates in intraciliary transport and cilium assembly. Mechanism: MAK exerts its effects through protein phosphorylation and intracellular signaling cascades, with evidence suggesting roles in chr6 stability and spermatogenesis, though detailed mechanistic pathways remain incompletely characterized. Disease relevance: MAK mutations cause autosomal recessive retinitis pigmentosa 62 (RP62), a progressive retinal degeneration. An Alu repeat insertion in MAK exon 9 causes loss of normal transcript and is enriched in Jewish populations, where it accounts for approximately one-third of recessive RP cases (1 in 55 carriers) 1. Clinical significance: Gene augmentation therapy shows promise; viral vector-mediated MAK restoration in patient-derived photoreceptor precursor cells and zebrafish models successfully restored ciliary length regulation and ameliorated visual defects without toxicity 1, supporting advancement toward clinical trials for MAK-associated RP treatment.

Sources cited
1
MAK regulates ciliary length, its mutations cause autosomal recessive retinitis pigmentosa via Alu repeat insertion in exon 9, enriched in Jewish populations, and gene augmentation therapy restores function in patient cells and animal models
PMID: 34518651
⚠Limited data available β€” This gene has 1 indexed publication. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
retinitis pigmentosaOpen Targets
0.77Strong
retinitis pigmentosa 62Open Targets
0.69Moderate
Retinal dystrophyOpen Targets
0.53Moderate
MAK-related retinopathyOpen Targets
0.44Moderate
Posterior column ataxia - retinitis pigmentosaOpen Targets
0.42Moderate
Alzheimer diseaseOpen Targets
0.40Moderate
eye diseaseOpen Targets
0.37Weak
lysosomal storage diseaseOpen Targets
0.35Weak
multiple sclerosisOpen Targets
0.35Weak
neurodegenerative diseaseOpen Targets
0.35Weak
Parkinson diseaseOpen Targets
0.35Weak
isolated macular dystrophyOpen Targets
0.34Weak
placenta praeviaOpen Targets
0.28Weak
genetic disorderOpen Targets
0.19Weak
alopecia areataOpen Targets
0.17Weak
parathyroid diseaseOpen Targets
0.08Suggestive
azoospermiaOpen Targets
0.08Suggestive
HypercalcemiaOpen Targets
0.08Suggestive
hyperparathyroidismOpen Targets
0.07Suggestive
spermatogenic failure 3Open Targets
0.06Suggestive
Retinitis pigmentosa 62UniProt
Pathogenic Variants95
NM_001242957.3(MAK):c.1294dup (p.Arg432fs)Pathogenic
not provided|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2026β†’ Residue 432
NM_001242957.3(MAK):c.1356_1357del (p.Glu454fs)Pathogenic
Retinal dystrophy|Retinitis pigmentosa 62|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 454
NM_001242957.3(MAK):c.79G>C (p.Gly27Arg)Pathogenic
not provided|Retinal dystrophy|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2026β†’ Residue 27
NM_001242957.3(MAK):c.1222del (p.Glu408fs)Pathogenic
not provided|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2025β†’ Residue 408
NM_001242957.3(MAK):c.814C>T (p.Arg272Ter)Pathogenic
Retinitis pigmentosa|not provided|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2025β†’ Residue 272
NM_001242957.3(MAK):c.1195_1196del (p.Thr399fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 399
NM_001242957.3(MAK):c.1698C>A (p.Tyr566Ter)Pathogenic
Retinitis pigmentosa|not provided|MAK-related disorder|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2025β†’ Residue 566
NM_001242957.3(MAK):c.79G>A (p.Gly27Arg)Pathogenic
not provided|Retinitis pigmentosa 62|Retinitis pigmentosa
β˜…β˜…β˜†β˜†2025β†’ Residue 27
NM_001242957.3(MAK):c.1600G>T (p.Glu534Ter)Pathogenic
not provided|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2025β†’ Residue 534
NM_001242957.3(MAK):c.7C>T (p.Arg3Ter)Pathogenic
not provided|MAK-related disorder|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2025β†’ Residue 3
NM_001242957.3(MAK):c.1700_1703del (p.Asn567fs)Pathogenic
not provided|Retinal dystrophy|Isolated macular dystrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 567
NM_001242957.3(MAK):c.1741C>T (p.Gln581Ter)Pathogenic
not provided|Retinal dystrophy|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2025β†’ Residue 581
NM_001242957.3(MAK):c.1051C>T (p.Gln351Ter)Pathogenic
not provided|Retinal dystrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 351
NM_001242957.3(MAK):c.1087_1088del (p.Gln364fs)Pathogenic
not provided|Retinitis pigmentosa|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2025β†’ Residue 364
NM_001242957.3(MAK):c.497G>A (p.Arg166His)Pathogenic
Retinitis pigmentosa 62|Retinitis pigmentosa|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 166
NM_001242957.3(MAK):c.340dup (p.Ala114fs)Pathogenic
Retinitis pigmentosa|not provided|Retinal dystrophy|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2024β†’ Residue 114
NM_001242957.3(MAK):c.394_395insCTTC (p.Leu132fs)Pathogenic
not provided|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2024β†’ Residue 132
NM_001242957.3(MAK):c.170_171del (p.Leu57fs)Pathogenic
not provided|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2024β†’ Residue 57
NM_001242957.3(MAK):c.947dup (p.Leu316fs)Pathogenic
not provided|Retinitis pigmentosa 62
β˜…β˜…β˜†β˜†2024β†’ Residue 316
NM_001242957.3(MAK):c.1366_1367del (p.Lys456fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 456
View on ClinVar β†—
Related Genes
MCM5Protein interaction100%MCM4Protein interaction100%ORC3Protein interaction100%ORC5Protein interaction100%ORC4Protein interaction100%MCM7Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
65%
Brain
51%
Ovary
46%
Liver
23%
Heart
13%
Gene Interaction Network
Click a node to explore
MAKMCM5MCM4ORC3ORC5ORC4MCM7
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P20794
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.89LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.70 [0.55–0.89]
RankingsWhere MAK stands among ~20K protein-coding genes
  • #9,901of 20,598
    Most Researched42
  • #815of 5,498
    Most Pathogenic Variants95 Β· top quartile
  • #8,040of 17,882
    Most Constrained (LOEUF)0.89
Genes detectedMAK
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Biophysical and mechanobiological considerations for T-cell-based immunotherapy.
PMID: 37172572
Trends Pharmacol Sci Β· 2023
1.00
2
Development and biological characterization of a clinical gene transfer vector for the treatment of MAK-associated retinitis pigmentosa.
PMID: 34518651
Gene Ther Β· 2022
0.90
3
Allenburys Feeder.
PMID: 32554822
Hong Kong Med J Β· 2020
0.80
4
RET oncogene.
PMID: 8791480
Curr Opin Genet Dev Β· 1996
0.70
5
Steatotic liver disease: Know your enemies.
PMID: 38302189
Clin Mol Hepatol Β· 2024
0.60