MARK2

microtubule affinity regulating kinase 2, the group of Microtubule affinity regulating kinases

Basic information

Region (hg38): 11:63838928-63911020

Previous symbols: [ "EMK1" ]

Links

ENSG00000072518 ∙ NCBI:2011 ∙ OMIM:600526 ∙ HGNC:3332 ∙ Uniprot:Q7KZI7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MARK2 gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	4	6
missense			20	2		22
nonsense			2			2
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1	1		2
splice region				2		2
non coding						0
Total	0	0	24	5	4

Variants in MARK2

This is a list of pathogenic ClinVar variants found in the MARK2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-63895154-C-T			Likely benign (Jul 30, 2018)
11-63895252-A-G		not specified	Uncertain significance (Dec 21, 2022)
11-63895260-C-G		not specified	Uncertain significance (Nov 22, 2023)
11-63895315-C-T		Autism spectrum disorder	Likely pathogenic (Jul 03, 2024)
11-63895578-A-G		Autism spectrum disorder	Likely pathogenic (Jul 03, 2024)
11-63895584-C-T		Autism spectrum disorder	Likely pathogenic (Jul 03, 2024)
11-63895601-A-AAG		Autism spectrum disorder	Likely pathogenic (Jul 03, 2024)
11-63895609-A-G			Likely benign (Jul 23, 2018)
11-63895630-G-GA		Autism spectrum disorder	Pathogenic (Jul 03, 2024)
11-63898281-G-T		Autism spectrum disorder	Pathogenic (Jul 03, 2024)
11-63898288-C-G			Likely benign (Aug 24, 2018)
11-63898668-G-A		not specified	Uncertain significance (Feb 15, 2023)
11-63898673-G-A		Autism spectrum disorder	Likely pathogenic (Jul 03, 2024)
11-63898761-A-C			Uncertain significance (Dec 08, 2022)
11-63898762-G-A		Developmental disorder	Likely benign (Nov 23, 2020)
11-63898816-C-T			Uncertain significance (Aug 24, 2023)
11-63899923-T-C		Autism spectrum disorder	Uncertain significance (Apr 09, 2020)
11-63900099-C-T		Autism spectrum disorder	Pathogenic (Jul 03, 2024)
11-63900573-G-C			Likely benign (Jul 06, 2018)
11-63900600-AT-A		Autism spectrum disorder	Pathogenic (Jul 03, 2024)
11-63900795-C-T		Autism spectrum disorder	Uncertain significance (May 12, 2020)
11-63900796-G-A		Autism spectrum disorder	Uncertain significance (Jul 03, 2024)
11-63900815-C-T			Benign (Mar 30, 2018)
11-63900956-G-A		Autism spectrum disorder	Pathogenic (Jul 03, 2024)
11-63900965-G-A		not specified	Uncertain significance (Jul 26, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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