MARK3
protein-codingmicrotubule affinity regulating kinase 3, the group of Microtubule affinity regulating kinases
Gene summary
The protein encoded by this gene is activated by phosphorylation and in turn is involved in the phosphorylation of tau proteins MAP2 and MAP4. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~118.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0032655
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0032655
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0032655
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MARK3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001128918.3. 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 | 1 | 6 | 3 | 10 | ||
| missense | 1 | 83 | 2 | 1 | 87 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 1 | 0 | 87 | 8 | 4 | 100 |
Highest pathogenic variant AF is 0.000031597534
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001122390.2 | 18 | MANE Select | |
| Ensembl | ENSP00000411397.2 | 18 | MANE Select | |
| RefSeq | NP_001122391.2 | 17 | Standard | |
| RefSeq | NP_001122392.2 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- MAP2K and MAPK activation
- RAF activation
- Disease
- Signal Transduction
- Negative regulation of MAPK pathway
Biological Process
- MAPK cascade
- microtubule cytoskeleton organization
- protein phosphorylation
- peptidyl-serine phosphorylation
- establishment of cell polarity
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- tau protein binding
- tau-protein kinase activity
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
- dendrite
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000429436
- Coding exons
- 18
- Length
- 118440
- Individuals with no LoFs
- 124765
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 124797
- p
- 0.000128
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.51 | 344 | 432 | 0.796 | 0.0000249 | 4941 |
| Missense (PolyPhen) | 133 | 216.55 | 0.61419 | 2411 | ||
| Synonymous | -0.386 | 164 | 158 | 1.04 | 0.00000938 | 1441 |
| Loss of Function | 3.42 | 17 | 40.5 | 0.420 | 0.00000236 | 481 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00026 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase (PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule- associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216'. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). {ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}.;
- Disease
- DISEASE: Note=Defects in MARK3 may be involved in an autosomal recessive ocular disease characterized by visual impairment manifested at birth, and progressive eye degeneration. {ECO:0000269|PubMed:29771303}.;
Recessive Scores
- pRec
- 0.163
Intolerance Scores
- LoFtool
- 0.894
- RVIS EVS
- -0.69
- RVIS percentile EVS
- 15.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.974
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |