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Relevance to Autism

Studies have found rare variants in the MCPH1 gene that are associated with autism (e.g. Ozgen et al., 2009; Neale et al., 2012).

Molecular Function

This protein is implicated in chromosome condensation and DNA damage induced cellular responses. May play a role in neurogenesis and regulation of the size of the cerebral cortex.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Copy number changes of the microcephalin 1 gene (MCPH1) in patients with autism spectrum disorders.
ASD
Support
Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.
ASD
Support
Transmitted duplication of 8p23.1-8p23.2 associated with speech delay, autism and learning difficulties.
ASD
Support
Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.
ASD
Support
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.
DD, microcephaly
Support
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.
ASD
Support
Integrating de novo and inherited variants in 42
ASD
Support
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
ASD
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Support
Patterns and rates of exonic de novo mutations in autism spectrum disorders.
ASD
Support
Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
ASD
Support
Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism.
ASD
Highly Cited
Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans.
Highly Cited
Identification of microcephalin, a protein implicated in determining the size of the human brain.
Recent Recommendation
De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.
Recent Recommendation
Molecular basis for the association of microcephalin (MCPH1) protein with the cell division cycle protein 27 (Cdc27) subunit of the anaphase-promot...
Recent Recommendation
A pocket on the surface of the N-terminal BRCT domain of Mcph1 is required to prevent abnormal chromosome condensation.
Recent Recommendation
Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN155R001 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN155R002 
 complex_structural_alteration 
  
  
  
  
  
 GEN155R003 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN155R004 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Multiplex 
 GEN155R005 
 synonymous_variant 
 c.2484T>A 
 p.Pro828= 
 De novo 
  
 Simplex 
 GEN155R006 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN155R007 
 copy_number_loss 
  
  
 Unknown 
  
 Unknown 
 GEN155R008 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN155R009 
 copy_number_gain 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN155R010 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN155R011 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN155R012a 
 copy_number_loss 
  
  
 Familial 
 Both parents 
 Multiplex 
 GEN155R013 
 missense_variant 
 c.974C>T 
 p.Thr325Met 
 De novo 
  
 Simplex 
 GEN155R014 
 missense_variant 
 c.2078G>A 
 p.Arg693His 
 Familial 
  
 Simplex 
 GEN155R015 
 splice_site_variant 
 c.1826-1G>C 
  
 Familial 
 Maternal 
 Multiplex 
 GEN155R016 
 stop_gained 
 c.2445G>A 
 p.Trp815Ter 
 Familial 
 Paternal 
 Multiplex 
 GEN155R017 
 missense_variant 
 c.322C>T 
 p.Arg108Cys 
 Unknown 
  
  
 GEN155R018 
 stop_gained 
 c.1651G>T 
 p.Glu551Ter 
 De novo 
  
 Simplex 
 GEN155R019 
 missense_variant 
 c.2445G>C 
 p.Trp815Cys 
 De novo 
  
 Simplex 
 GEN155R020 
 splice_site_variant 
 c.322-1G>C 
  
 Familial 
 Maternal 
 Multiplex 
 GEN155R021 
 stop_gained 
 c.1561G>T 
 p.Glu521Ter 
 Familial 
 Maternal 
 Multiplex 
 GEN155R022 
 stop_gained 
 c.2145G>A 
 p.Trp715Ter 
 Familial 
 Paternal 
 Multiplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
8
Deletion-Duplication
 47
 
8
Deletion-Duplication
 11
 
8
Duplication
 1
 
8
Duplication
 1
 
8
Deletion
 3
 
8
Duplication
 6
 
8
Deletion
 27
 
8
Duplication
 1
 
8
Deletion
 1
 

Model Summary

Better define the physiological role and demonstrate MCPH1's essential role in regulation of both programmed and IR-induced DNA damage response.

References

Type
Title
Author, Year
Primary
BRIT1/MCPH1 is essential for mitotic and meiotic recombination DNA repair and maintaining genomic stability in mice.

M_MCPH1_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Gene targeted deletion of exon 2 of MCPH1 gene resulting in out of reading frame mutation of MCPH1.
Allele Type: Targeted (Knock Out)
Strain of Origin: 129/SvEv
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_MCPH1_2_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Gene targeted deletion of exon 2 of MCPH1 gene resulting in out of reading frame mutation of MCPH1.
Allele Type: Targeted (Knock Out)
Strain of Origin: 129/SvEv
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_MCPH1_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Radiation sensitivity1
Increased
Description: Increased sensitivity to radiation resulting in death after 9 days of exposure to radiation
Exp Paradigm: General observations after exposure of one dose of 7 gy.
 General observations
 Unreported
Apoptosis1
Increased
Description: Increased apoptosis in seminiferous tubules
Exp Paradigm: Tunel assay
 Tunel assay
 Unreported
Size/growth1
Decreased
Description: Decreased size/growth
Exp Paradigm: General observations
 General observations
 8 weeks
Developmental trajectory1
Abnormal
Description: Abnormal developmental trajectory with meiotic arrest prior to the pachytene stage during the assembly of the synaptonemal complex
Exp Paradigm: Immunohistochemical staining using antibodies against synaptonemal complex protein 3 (scp3) of synaptonemal complex in spermatocyte nuclei
 Immunohistochemistry
 Unreported
Reproductive system development1
Decreased
Description: Decreased reproductive ability demonstrated by infertility, smaller and thinner testicular tubes, and fewer spermatocytes produced.
Exp Paradigm: General observations
 General observations
 Unreported
Developmental trajectory1
Decreased
Description: Decreased synapsis in spermatocytes
Exp Paradigm: Double staining assay using anti-scp1/scp3 antibodies of spermatocytes
 Immunohistochemistry
 Unreported
Developmental trajectory1
Decreased
Description: Decreased number of spermatocytes in seminiferous tubules
Exp Paradigm: Histological analysis with double-immunostained with anti-tra98 and anti-sox9 antibodies in testes
 Histology
 P14, p21, p28
Developmental trajectory1
 No change
 Histology
 P7
Dna repair1
 No change
 Immunohistochemistry
 P17.5-p22.5
Protein expression level evidence1
 No change
 Western blot
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_MCPH1_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Radiation sensitivity1
Increased
Description: Increased sensitivity to radiation resulting in death after 9 days of exposure to radiation
Exp Paradigm: General observations after exposure of one dose of 7-gy.
 General observations
 Unreported
Size/growth1
 No change
 General observations
 8 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior





Download MCPH1's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ANGPT2 angiopoietin 2 285 O15123 ChIP; WB; EMSA
Kopparapu PK , et al. 2015
BRCA2 breast cancer 2, early onset 675 P51587 IP/WB; GST
Wu X , et al. 2009
DNMT1 DNA (cytosine-5-)-methyltransferase 1 1786 P26358 IP/WB
Kopparapu PK , et al. 2015
DNMT3B DNA (cytosine-5-)-methyltransferase 3 beta 1789 Q9UBC3 IP/WB
Kopparapu PK , et al. 2015
E2F1 E2F transcription factor 1 1869 Q01094 IP/WB; Bimolecular fluorescence complementation assay
Yang SZ , et al. 2008
E2F1 E2F transcription factor 1 1869 Q01094 IP/WB
Kopparapu PK , et al. 2015
EFCAB4B EF-hand calcium binding domain 4B 84766 Q9BSW2 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
NCAPG2 non-SMC condensin II complex, subunit G2 54892 Q86XI2 Affinity chromatography; MS; IP/WB
Wood JL , et al. 2008
RAD51 RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae) 5888 Q06609 IP/WB
Wu X , et al. 2009
TERF2 telomeric repeat binding factor 2 7014 Q9NYB0 IP/WB; GST
Kim H , et al. 2009
FOXP2 forkhead box P2 114142 P58463 ChIP
Vernes SC , et al. 2011

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