GeneBe

MARK2

protein-coding

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

Gene summary

This gene encodes a member of the Par-1 family of serine/threonine protein kinases. The protein is an important regulator of cell polarity in epithelial and neuronal cells, and also controls the stability of microtubules through phosphorylation and inactivation of several microtubule-associating proteins. The protein localizes to cell membranes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

Previous symbols:
  • EMK1

MANE transcript

NM_001039469.3

Inheritance

AD

ClinVar variants

P:44U:112B:9

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr11:63,838,928-63,911,020

External References & Databases

Ensembl (ENSG00000072518)NCBI Gene (2011)OMIM (600526)HGNC:3332GenCCUniProt (Q7KZI7)AlphaFoldClinVar (MARK2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~72.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MARK2 variants in ClinVar

17 Conditions Cataloged
not providedTotal: 65
not specifiedTotal: 55
Autism spectrum disorderTotal: 28
Intellectual developmental disorder, autosomal dominant 76Total: 22
Intellectual disabilityTotal: 2
MARK2-associated neurodevelopmental disorderTotal: 2
Neurodevelopmental disorderTotal: 1
Compulsive behaviorsTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039469.3. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
2
clinvar
4
clinvar
 9
missense
5
clinvar
77
clinvar
2
clinvar
 84
nonsense
10
clinvar
5
clinvar
5
clinvar
 20
start loss
0
frameshift
9
clinvar
5
clinvar
17
clinvar
 31
splice donor/acceptor (+/-2bp)
3
clinvar
7
clinvar
10
clinvar
1
clinvar
 21
Total222211254165

Highest pathogenic variant AF is 0.000014872321

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001039469.3RefSeqNP_001034558.219MANE Select
ENST00000402010.8EnsemblENSP00000385751.219MANE Select
NM_001163296.2RefSeqNP_001156768.117Standard
NM_001163297.2RefSeqNP_001156769.116Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Regulation of Microtubule Cytoskeleton
  • Notch signaling pathway
  • TNFalpha
  • LKB1 signaling events

Biological Process

  • microtubule cytoskeleton organization
  • autophagy of mitochondrion
  • neuron migration
  • protein phosphorylation
  • positive regulation of neuron projection development

Molecular Function

  • magnesium ion binding
  • RNA binding
  • protein serine/threonine kinase activity
  • protein binding
  • ATP binding

Cellular Component

  • nucleoplasm
  • cytoplasm
  • mitochondrion
  • actin filament
  • plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000402010
Coding exons
19
Length
72092
Individuals with no LoFs
125741
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
125744
p
0.0000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense4.452124890.4340.00003155159
Missense (PolyPhen)48211.270.227192231
Synonymous0.7981761900.9260.00001211569
Loss of Function5.59240.30.04960.00000245436

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.0000990.000099rare
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.346

Intolerance Scores

LoFtool
0.436
RVIS EVS
-0.71
RVIS percentile EVS
14.5

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.999

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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