MARK1

Chr 1

microtubule affinity regulating kinase 1

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

NCBI Gene: 4139 ENSG00000116141 UniProt: Q9P0L2 OMIM: 606511

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.36

Clinical Summary— MARK1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.60) — some intolerance to loss-of-function variants.

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ClinVar Variants

72 VUS of 99 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.21 (0.13–0.36)

0≤0.351.4

Missense OE?0.64 (0.58–0.70)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 10 / 46.7Missense obs/exp: 289 / 452.3Syn Z: 1.87

ClinVar Variant Classifications

99 submitted variants in ClinVar

ClinVar

Classification Summary

VUS72

Likely Benign6

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	72	0	0	72
Likely Benign	1	0	5	6
Benign	1	1	0	2
Total	74	1	5	80

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap MARK1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →