MAK

Chr 6AR

male germ cell associated kinase

Also known as: RP62

NCBI Gene: 4117ENSG00000111837UniProt: P20794

The product of this gene is a serine/threonine protein kinase related to kinases involved in cell cycle regulation. Studies of the mouse and rat homologs have localized the kinase to the chromosomes during meiosis in spermatogenesis, specifically to the synaptonemal complex that exists while homologous chromosomes are paired. Mutations in this gene have been associated with ciliary defects resulting in retinitis pigmentosa 62. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Retinitis pigmentosa 62MIM #614181
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— MAK
🧬
Gene-Disease Validity (ClinGen)
MAK-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.21LOEUF
pLI 0.000
Z-score 0.60
OE 0.89 (0.66–1.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.40Z-score
OE missense 0.94 (0.85–1.03)
309 obs / 329.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.89 (0.66–1.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.85–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 30 / 33.8Missense obs/exp: 309 / 329.4Syn Z: 1.04

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MAK · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MAK-related retinitis pigmentosa

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Retinitis pigmentosa 62

MIM #614181

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MAK
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Setting evidence-based occupational exposure limits for manganese.
Bevan R et al.·Neurotoxicology
2017Review
Development and biological characterization of a clinical gene transfer vector for the treatment of MAK-associated retinitis pigmentosa.
Tucker BA et al.·Gene Ther
2022
Amelanotic Melanoma-Biochemical and Molecular Induction Pathways.
Misiąg P et al.·Int J Mol Sci
2024Review
Safety and usability of the MAK exoskeleton in patients with stroke.
Cumplido-Trasmonte C et al.·Physiother Res Int
2024Clinical trial
Ellipsoid Zone Loss as an Outcome Measure in MAK-Associated Retinitis Pigmentosa.
Kong MD et al.·Am J Ophthalmol
2025
Ebola Virus Encodes Two microRNAs in Huh7-Infected Cells.
Diallo I et al.·Int J Mol Sci
2022
Theories of truth and teaching clinical reasoning and problem solving.
Custers EJFM·Adv Health Sci Educ Theory Pract
2019
Overview of the anti-inflammatory function of the innate immune sensor NLRC3.
Zhao Y et al.·Mol Immunol
2023Review
Generation of phagocytic MAK and MAC-DC for therapeutic use: characterization and in vitro functional properties.
Boyer A et al.·Exp Hematol
1999Functional
Fundoscopy-directed genetic testing to re-evaluate negative whole exome sequencing results.
Cho A et al.·Orphanet J Rare Dis
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Formononetin ameliorates SP-induced urticaria in mice via suppressing TAK1/MAK signaling pathway.
Wu Y et al.·PLoS One
2026🔓 Open Access
Single-cell RNA-seq reveals a key role for Vibrio cholerae Mak toxins in Tetrahymena pyriformis killing and bacterial survival.
Moon JM et al.·Front Microbiol
2025🔓 Open Access
Chlamydomonas protein kinase MAK phosphorylates FAP256/CEP104 and regulates axonemal microtubule assembly.
Zhang Y et al.·Proc Natl Acad Sci U S A
2025
N,N',N''-Tris(β-hydroxyethyl)hexahydro-1,3,5-triazine: MAK Value Documentation, addendum - Translation of the German version from 2023.
Hartwig A et al.·MAK Collect Occup Health Saf
2025🔓 Open Access
Tetramethylol acetylenediurea: MAK Value Documentation - Translation of the German version from 2023.
Hartwig A et al.·MAK Collect Occup Health Saf
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
COVID-19Antibody COVID-19

The Role of Obesity in Severe COVID-19 Pathophysiology

RECRUITING
NCT06968442Phase NAFranciscus GasthuisStarted 2025-04-22
Venipuncture
Carcinoma, Non-Small-Cell LungNeoplasm Metastasis

A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer

RECRUITING
NCT06119581Phase PHASE3Eli Lilly and CompanyStarted 2023-12-21
LY3537982PembrolizumabPlacebo

External Resources

Links to major genomics databases and tools