MARK2
microtubule affinity regulating kinase 2, the group of Microtubule affinity regulating kinases
Basic information
Region (hg38): 11:63838928-63911020
Previous symbols: [ "EMK1" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (39 variants)
- not_specified (39 variants)
- Autism_spectrum_disorder (28 variants)
- INTELLECTUAL_DEVELOPMENTAL_DISORDER,_AUTOSOMAL_DOMINANT_76 (7 variants)
- Compulsive_behaviors (1 variants)
- Attention_deficit_hyperactivity_disorder (1 variants)
- Intellectual_disability (1 variants)
- MARK2-associated_neurodevelopmental_disorder (1 variants)
- Delayed_speech_and_language_development (1 variants)
- Autism (1 variants)
- Dyslexia (1 variants)
- Seizure (1 variants)
- Anxiety (1 variants)
- Developmental_disorder (1 variants)
- MARK2-associated_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MARK2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001039469.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | |||||
| missense | 45 | 51 | ||||
| nonsense | 12 | |||||
| start loss | 0 | |||||
| frameshift | 15 | 23 | ||||
| splice donor/acceptor (+/-2bp) | 11 | |||||
| Total | 14 | 11 | 69 | 5 | 4 |
Highest pathogenic variant AF is 0.000014872321
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MARK2 | protein_coding | protein_coding | ENST00000402010 | 19 | 72092 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000135 | 125741 | 0 | 3 | 125744 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.45 | 212 | 489 | 0.434 | 0.0000315 | 5159 |
| Missense in Polyphen | 48 | 211.27 | 0.22719 | 2231 | ||
| Synonymous | 0.798 | 176 | 190 | 0.926 | 0.0000121 | 1569 |
| Loss of Function | 5.59 | 2 | 40.3 | 0.0496 | 0.00000245 | 436 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. 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. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}.;
- Pathway
- Regulation of Microtubule Cytoskeleton;Notch signaling pathway;TNFalpha;LKB1 signaling events
(Consensus)
Recessive Scores
- pRec
- 0.346
Intolerance Scores
- loftool
- 0.436
- rvis_EVS
- -0.71
- rvis_percentile_EVS
- 14.5
Haploinsufficiency Scores
- pHI
- 0.395
- hipred
- Y
- hipred_score
- 0.662
- ghis
- 0.582
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mark2
- Phenotype
- homeostasis/metabolism phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; embryo phenotype;
Gene ontology
- Biological process
- microtubule cytoskeleton organization;autophagy of mitochondrion;neuron migration;protein phosphorylation;positive regulation of neuron projection development;Wnt signaling pathway;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;establishment of cell polarity;activation of protein kinase activity;intracellular signal transduction;establishment or maintenance of epithelial cell apical/basal polarity;protein autophosphorylation;regulation of axonogenesis;regulation of cytoskeleton organization;mitochondrion localization;axon development;regulation of microtubule cytoskeleton organization;establishment or maintenance of cell polarity regulating cell shape;regulation of microtubule binding
- Cellular component
- nucleoplasm;cytoplasm;mitochondrion;actin filament;plasma membrane;membrane;lateral plasma membrane;dendrite;microtubule bundle
- Molecular function
- magnesium ion binding;RNA binding;protein serine/threonine kinase activity;protein binding;ATP binding;lipid binding;protein kinase activator activity;cadherin binding;tau protein binding;tau-protein kinase activity