MARK1
protein-codingmicrotubule affinity regulating kinase 1, the group of Microtubule affinity regulating kinases
Gene summary
Enables anion binding activity; magnesium ion binding activity; and tau-protein kinase 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, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~136.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MARK1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018650.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 5 | 7 | |||
| missense | 77 | 1 | 1 | 79 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 82 | 6 | 1 | 89 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061120.3 | 18 | MANE Select | |
| Ensembl | ENSP00000355884.5 | 18 | MANE Select | |
| RefSeq | NP_001273053.1 | 18 | Standard | |
| RefSeq | NP_001273055.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- WNT-Ncore
- Regulation of Microtubule Cytoskeleton
Biological Process
- microtubule cytoskeleton organization
- neuron migration
- protein phosphorylation
- cytoskeleton organization
- regulation of neuron projection development
Molecular Function
- magnesium ion binding
- phosphatidylserine binding
- protein serine/threonine kinase activity
- protein binding
- ATP binding
Cellular Component
- cytoplasm
- cytoskeleton
- plasma membrane
- microtubule cytoskeleton
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000366917
- Coding exons
- 18
- Length
- 136236
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125748
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.73 | 289 | 452 | 0.639 | 0.0000252 | 5192 |
| Missense (PolyPhen) | 73 | 187.57 | 0.38918 | 2168 | ||
| Synonymous | 1.87 | 127 | 157 | 0.810 | 0.00000850 | 1525 |
| Loss of Function | 4.98 | 10 | 46.7 | 0.214 | 0.00000313 | 509 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule- associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}.;
- Disease
- DISEASE: Note=Genetic variations in MARK1 may be associated with susceptibility to autism. MARK1 is overexpressed in the prefrontal cortex of patients with autism and causes changes in the function of cortical dendrites.;
Recessive Scores
- pRec
- 0.131
Intolerance Scores
- LoFtool
- 0.503
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 31.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.920
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |