Summary Statistics:
Gene Score: 4
Relevance to Autism
Several SNPs within the MARK1 gene were significantly associated with ASDs by transmission disequilibrium tests in a family-based association study of multiplex ASD families. The ASD-associated SNP rs12410279 was found to modulate the level of MARK1 transcription. Furthermore, MARK1 was overexpressed in the prefrontal cortex of patients with autism and causes changes in the function of cortical dendrites (Maussion et al., 2008).
Molecular Function
Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2, MAP4 and MAPT/TAU. 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).
References
Primary
Convergent evidence identifying MAP/microtubule affinity-regulating kinase 1 (MARK1) as a susceptibility gene for autism.
ASD
Support
De novo mutations in schizophrenia implicate synaptic networks.
ASD
Support
Integrating de novo and inherited variants in 42
ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Unknown diagnosis
Highly Cited
MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption.
Highly Cited
Microtubule-associated protein/microtubule affinity-regulating kinase (p110mark). A novel protein kinase that regulates tau-microtubule interaction...
Recent Recommendation
Structural variations in the catalytic and ubiquitin-associated domains of microtubule-associated protein/microtubule affinity regulating kinase (M...
Recent Recommendation
De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.
Recent Recommendation
Interactions of MAP/microtubule affinity regulating kinases with the adaptor complex AP-2 of clathrin-coated vesicles.
Recent Recommendation
Genetic defects underlying Peutz-Jeghers syndrome (PJS) and exclusion of the polarity-associated MARK/Par1 gene family as potential PJS candidates.
Recent Recommendation
Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity.
GEN151R001
missense_variant
c.692A>G
p.Lys231Arg
De novo
Unknown
GEN151R002
synonymous_variant
c.2094G>A
p.Pro698=
De novo
GEN151R003
synonymous_variant
c.2091G>A
p.Lys697%3D
De novo
GEN151R004
frameshift_variant
c.2168_2169del
p.Arg723GlnfsTer7
De novo
GEN151R005
missense_variant
c.1511C>T
p.Thr504Ile
De novo
Simplex
GEN151C001
5KB_upstream_variant
rs3753873
A/T
Discovery population: 116 multiplex families from AGRE.
Discovery
GEN151C002
intergenic_variant
rs12410279
A/G
Discovery population: 116 multiplex families from AGRE.
Discovery
GEN151C003
intergenic_variant
rs12410279
A/G
Replication population: 276 families from AGRE (116 sib-pair families from discovery stage and an additional 160 multiplex families).
Replication
GEN151C004
intron_variant
rs4846655
c.309+7473T>C;c.-94-5313T>C
C/T
Discovery population: 116 multiplex families from AGRE.
Discovery
GEN151C005
intron_variant
rs3737296
c.1736+31A>G;c.1670+31A>G;c.1472+31A>G;c.1244+31A>G
Discovery population: 116 multiplex families from AGRE
Discovery
GEN151C006
intron_variant
rs3737296
c.1736+31A>G;c.1670+31A>G;c.1472+31A>G;c.1244+31A>G
Replication population: 276 families from AGRE (116 sib-pair families from discovery stage and an additional 160 multiplex families).
Replication
GEN151C007
intron_variant
rs6695583
c.2037-1164C>T;c.1989-1164C>T;c.1923-1164C>T;c.2034-1164C>T;c.1992-1164C>T;c.1773-1164C>T;c.1545-116
C/T
Discovery population: 116 multiplex families from AGRE.
Discovery
GEN151C008
intron_variant
rs17584152
c.51+18345T>C
C/T
Replication population: 276 families from AGRE (116 sib-pair families from discovery stage and an additional 160 multiplex families).
Discovery
GEN151C009
intron_variant
rs11590946
c.52-23499A>G
Replication population: 276 families from AGRE (116 sib-pair families from discovery stage and an additional 160 multiplex families).
Discovery
GEN151C010
intron_variant
rs12740310
c.309+8064C>T;c.-94-4722C>T
Replication population: 276 families from AGRE (116 sib-pair families from discovery stage and an additional 160 multiplex families).
Discovery
1
Deletion-Duplication
16
Summary Statistics:
Show all nodes
Hide non-ASD
Interactor Symbol
Interactor Name
Interactor Organism
Entrez ID
Uniprot ID
Interaction Type
Evidence
Reference
CCDC102B
coiled-coil domain containing 102B
NM_001093729
A1A4H1
Y2H
Corominas R , et al. 2014
CDH19
CDH19 protein
Q96KY9
IP; LC-MS/MS
Huttlin EL , et al. 2015
COL4A3BP
collagen, type IV, alpha 3 (Goodpasture antigen) binding protein
10087
Q9Y5P4
IP; LC-MS/MS
Huttlin EL , et al. 2015
FMR1
fragile X mental retardation 1
2332
G8JLE9
PAR-CLIP
Ascano M Jr , et al. 2012
GJA5
gap junction protein, alpha 5, 40kDa
2702
P36382
Y2H
Wang J , et al. 2011
MARK2
MAP/microtubule affinity-regulating kinase 2
2011
Q7KZI7
IP; LC-MS/MS
Sowa ME , et al. 2009
TOP3B
topoisomerase (DNA) III beta
8940
O95985
HITS-CLIP
Xu D , et al. 2013
UBC
ubiquitin C
7316
P63279
MS
Wagner SA , et al. 2011
USP21
ubiquitin specific peptidase 21
27005
Q9UK80
IP; LC-MS/MS
Sowa ME , et al. 2009
MIB1
mindbomb E3 ubiquitin protein ligase 1
307594
D3ZUV2
Affinity chromatography; LC-MS/MS
Mertz J , et al. 2015
