MARK1

Chr 1

microtubule affinity regulating kinase 1

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

The protein functions as a serine/threonine kinase that regulates microtubule dynamics and cell polarity by phosphorylating microtubule-associated proteins including tau, MAP2, and DCX, and plays a role in neuronal migration and Wnt signaling. Mutations cause autosomal recessive intellectual disability with seizures and macrocephaly. The gene shows high constraint against loss-of-function variants (LOEUF 0.363), indicating intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.36
Clinical SummaryMARK1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.60) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 79 VUS of 134 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.36LOEUF
pLI 0.600
Z-score 4.98
OE 0.21 (0.130.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.73Z-score
OE missense 0.64 (0.580.70)
289 obs / 452.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.21 (0.130.36)
00.351.4
Missense OE0.64 (0.580.70)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 10 / 46.7Missense obs/exp: 289 / 452.3Syn Z: 1.87

ClinVar Variant Classifications

134 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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