MARK1

Chr 1

microtubule affinity regulating kinase 1

Also known as: MARK, Par-1c, Par1c

NCBI Gene: 4139ENSG00000116141UniProt: Q9P0L2

Enables several functions, including ATP binding activity; magnesium ion binding activity; and phospholipid binding activity. Involved in intracellular signal transduction; negative regulation of epithelial to mesenchymal transition; and protein phosphorylation. Located in cytoplasm; dendrite; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

115
ClinVar variants
28
Pathogenic / LP
0.60
pLI score
0
Active trials
Clinical Summary— MARK1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.60) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 79 VUS of 115 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.36LOEUF
pLI 0.600
Z-score 4.98
OE 0.21 (0.13–0.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.73Z-score
OE missense 0.64 (0.58–0.70)
289 obs / 452.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.21 (0.13–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.58–0.70)
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.0.81
0≤1.21.6
LoF obs/exp: 10 / 46.7Missense obs/exp: 289 / 452.3Syn Z: 1.87

ClinVar Variant Classifications

115 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic1
VUS79
Likely Benign6
Benign2
27
Pathogenic
1
Likely Pathogenic
79
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
1
0
1
VUS
0
72
7
0
79
Likely Benign
0
1
0
5
6
Benign
0
1
1
0
2
Total074365115

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MARK1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Escape from TGF-β-induced senescence promotes aggressive hallmarks in epithelial hepatocellular carcinoma cells.
Kalyoncu M et al.·Mol Oncol
2025
The KLDpT activation loop motif is critical for MARK kinase activity.
Sonntag T et al.·PLoS One
2019
Multi-frequency time-difference complex conductivity imaging of canine and human lungs using the KHU Mark1 EIT system.
Kuen J et al.·Physiol Meas
2009
A Distinguishable Peripheral Blood and Conjunctival Transcriptome and Gut Microbiome in Sjögren's Disease: A Pilot Study.
Nguyen RD et al.·Eye Contact Lens
2025
Tumor-derived exosomes promote tumor progression and T-cell dysfunction through the regulation of enriched exosomal microRNAs in human nasopharyngeal carcinoma.
Ye SB et al.·Oncotarget
2014
Genome-wide association study in bipolar patients stratified by co-morbidity.
Kerner B et al.·PLoS One
2011Cohort
Hepatoid adenocarcinoma of the stomach: a unique subgroup with distinct clinicopathological and molecular features.
Wang Y et al.·Gastric Cancer
2019
Genetic variation in the tau kinases pathway may modify the risk and age at onset of Alzheimer's disease.
Vázquez-Higuera JL et al.·J Alzheimers Dis
2011
Analysis of resting noise characteristics of three EIT systems in order to compare suitability for time difference imaging with scalp electrodes during epileptic seizures.
Fabrizi L et al.·Physiol Meas
2007
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools