Property Summary

NCBI Gene PubMed Count 108
PubMed Score 106.08
PubTator Score 96.43

Knowledge Summary


No data available


  Differential Expression (9)

Disease log2 FC p
astrocytic glioma -1.100 3.9e-02
osteosarcoma -1.802 3.9e-06
glioblastoma 1.100 3.1e-05
sonic hedgehog group medulloblastoma 1.700 2.8e-05
medulloblastoma, large-cell 1.200 2.7e-04
primitive neuroectodermal tumor 1.100 1.2e-02
lung cancer 1.500 1.1e-03
atypical teratoid/rhabdoid tumor 1.100 3.9e-05
ovarian cancer -1.300 4.4e-04

Protein-protein Interaction (2)

Gene RIF (70)

26820313 These findings collectively provide strong evidence for MCHP1 being a novel breast cancer susceptibility gene, which warrants further investigations in other populations.
26683461 Results show that in addition to the scaffolding function in complex formation, BRUCE has an E3 ligase function to promote BRIT1 deubiquitination by USP8 leading to accumulation of BRIT1 at DNA double-strand break.
26192461 Data indicate splice-acceptor site homozygous mutation in intron 4 of microcephalin (MCPH1) gene in 2 children.
25845520 Characterization of the effects of MCPH1 loss-of-function on chromosome morphology.
25733871 BRUCE acts as a scaffold, bridging the ubiquitin-specific peptidase 8 (USP8) and BRIT1 in a complex to coordinate USP8-catalyzed deubiquitination of BRIT1.
25301947 Phosphorylation of BRIT1 protein coordinates TopBP1 protein recruitment and amplifies ATR signaling in cell DNA damage.
25197360 in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is directly regulated by miR-27a.
24975899 SNTB1 and MCPH1 are located on chromosome 8, which may be involved in neuroticism, avoidant personality and depression.
24830737 microcephalin and ASPM expression are deregulated in epithelial ovarian cancer progression
24633962 MCPH1 has an important role in regulating cell growth through regulating the cell cycle and apoptosis
24507884 This study identified MCPH1 significantly associated loci with a biologically plausible role in schizophrenia.
24460291 Low MCPH1 protein expression is associated with lung tumorigenesis.
23908141 Polymorphism in MCPH1 gene is associated with pancreatic cancer.
23729656 BRIT1 regulates p53 stability and functions as a tumor suppressor in breast cancer.
23697381 The divergence of MCPH1 protein sequences under Darwinian positive selection led to functional modifications, providing a possible molecular mechanism of how MCPH1 contributed to brain enlargement during primate evolution and human origin.
23472065 in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a
23472065 MCPH1 also functions as a tumor suppressor in oral squamous cell carcinoma
23296058 The MCPH1 polymorphisms and protein expression were associated with tumorigenesis in breast cancer
23117476 Reduced protein expression of MCPH1 is associated with breast carcinoma.
22952573 MCPH1 encodes different isoforms that are differentially regulated at the transcript level and have different functions at the protein level
22908299 MCPH1 recruitment to sites of DNA damage is linked to both states of histone H2A.X.
22240313 It was shown that MCPH1 directly binds to the promoter of human telomerase reverse transcriptase and represses telomerase activity. An intact N terminal BRCT domain was essential for the proper inhibiting function of MCPH1.
22154951 the crystal structures of MCPH1 natural variant (A761) C-terminal tandem BRCT domains alone as well as in complex with gammaH2AX tail
22139841 the biochemical, structural, and cellular determinants of the novel interaction between MCPH1 and Cdc27 and suggest that this interaction may occur within the larger context of MCPH1-APC/C.
22136275 The MCPH1 promoter region was sequenced in human, chimpanzee and rhesus macaque; sequence comparison of vertebrate species suggested that the identified E2F1 binding motif is primate specific.
21934293 MCPH1 expression is downregulated in blood cells of CML patients compared to control subjects; this downregulation is independent of BCR/ABL. CML cells exhibit defective G2/M arrest; data confirm role of MCPH1 as regulator of G2/M checkpoint.
21911480 MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II
21799462 these findings show that genetic variants in the microcephalin 1 locus are suggestively associated with the risk of epirubicin-induced adverse drug reactions.
21515671 SET is an important regulator of chromosome condensation/decondensation and disruption of the MCPH1-SET interaction might be important for the pathogenesis of primary microcephaly
21297427 We conclude that the common variations we measured in the 4 microcephaly genes, ASPM, MCPH1, CDK5RAP2, and CENPJ, do not affect the risk of Alzheimer disease
21150325 Results indicate that the DNA damage response in human cells with truncating MCPH1 mutations differs significantly from the damage responses in cells of certain model organisms and in cells depleted of MCPH1 by RNAi.
20949544 The first study of MCPH1 in a large cohort of non-consanguineous patients with microcephaly, is reported.
20632086 Microcephalin is an independent predictor of breast cancer-specific survival in invasive ductal breast cancer patients and may prove to be a useful biomarker for the identification of aggressive breast cancers
20602615 Observational study of gene-disease association. (HuGE Navigator)
20508983 Observational study of gene-disease association. (HuGE Navigator)
20485444 Observational study of gene-disease association. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20101680 Craniosynostosis-microcephaly with chromosomal breakage and other abnormalities is caused by a truncating MCPH1 mutation
20080800 Observational study of gene-disease association. (HuGE Navigator)
20056645 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19925808 Compared with other BRCT domain structures, the most striking differences are an elongated, ordered beta1-alpha1 loop and an adjacent hydrophobic pocket.
19829069 discuss our current findings and future perspectives about how BRIT1/MCPH1, a human disease gene, specifies the function of chromatin remodelers and links chromatin remodeling to genome maintenance.[review]
19793310 Copy number changes of the microcephalin 1 gene (MCPH1) in patients with autism spectrum disorders.
19690177 Observational study of gene-disease association. (HuGE Navigator)
19549900 Role of MCPH1 in the DNA damage response is in part associated with the ability to localize BRCA2 to sites of DNA double-stand breaks.
19546241 Results show that a lack of microcephalin or pericentrin results in a loss of Chk1 from centrosomes with subsequently deregulated activation of centrosomal cyclin B-Cdk1.
19525936 The findings therefore identify BRIT1 as a key molecule that links chromatin remodelling with response to DNA damage in the control of DNA repair, and its dysfunction contributes to human disease.
19475667 Observational study of gene-disease association. (HuGE Navigator)
19267414 There is little or no association between the MCPH1 c.940G allele and either microcephaly or mental retardation. However, there are significant racial differences in the c.940G > C SNP allele frequencies between African-American and Caucasian populations.
19267414 Observational study of gene-disease association. (HuGE Navigator)
18718915 Microcephalin/MCPH1 associates with the Condensin II complex to function in homologous recombination repair
18660752 Data show that MCPH1 cooperates with E2F1 to regulate genes involved in DNA repair, checkpoint and apoptosis, and might participate in the maintenance of genomic integrity.
18635967 MDC1 and BRIT1 may function as tumor-suppressor genes, at least in part by orchestrating proper centrosome duplication and mitotic spindle assembly.
18204051 A non-synonymous SNP (rs1057090, V761A in BRCA1 C-terminus (BRCT) domain) of MCPH1 other than the two known tag SNPs is significantly associated with cranial volume in Chinese males.
18204051 Observational study of gene-disease association. (HuGE Navigator)
17925396 MCPH1 functions in an H2AX-dependent but MDC1-independent pathway in response to DNA damage
17566767 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
17566767 phenotypes other than brain size may have been selected for in ASPM and MCPH1 variants during evolution of modern humans.
17251122 no relationship was found between polymorphisms of brain regulator gene Microcephalin Microcephalin and any general mental ability, head circumference and social intelligence
17251122 Observational study of gene-disease association. (HuGE Navigator)
17220170 Studies using 2393 subjects do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ.
17102619 review: MCPH1 functions in the ATR-dependent DNA damage response pathway. Additionally, MCPH1 has a function in the regulation of mitotic entry that is ATR-independent
16872911 BRIT1 is a crucial DNA damage regulator in the ATM/ATR pathways and suggest that it functions as a tumor suppressor gene
16783362 We conclude that MCPH1 has a function downstream of Chk1 in the ATR-signalling pathway.
16687438 The study found no evidence that the selected alleles of MCPH1 and ASPM were associated with increases or decreases in brain volume.
16217032 Data suggest that the microcephaly observed in patients with MCPH1 deficiencies is due to disruption of the ATR-BRCA1-Chk1 signaling pathway that is also disrupted in Seckel syndrome patients.
16151009 findings show that one genetic variant of Microcephalin in modern humans, which arose approximately 37,000 years ago, increased in frequency too rapidly to be compatible with neutral drift; this indicates that it has spread under strong positive selection
15220350 Mcph1 is involved in DNA damage-induced cellular responses and may have a role in regulation of Brca1 and/or Chk1
12571366 microcephalin and ASPM determine the size of the human brain
12046007 Identification of microcephalin, a protein implicated in determining the size of the human brain, which is mapped to the MCPH1 locus and is mutated in primary microcephaly.

AA Sequence


Text Mined References (111)

PMID Year Title
26912502 2016 The Impact of rs3762271 and rs930557 Polymorphisms of ASPM and MCPH1 Genes on the Anatomy and Function of the Brain.
26870219 2016 Overexpression of MCPH1 inhibits uncontrolled cell growth by promoting cell apoptosis and arresting the cell cycle in S and G2/M phase in lung cancer cells.
26820313 2016 Targeted Next-Generation Sequencing Identifies a Recurrent Mutation in MCPH1 Associating with Hereditary Breast Cancer Susceptibility.
26683461 2015 The UBC Domain Is Required for BRUCE to Promote BRIT1/MCPH1 Function in DSB Signaling and Repair Post Formation of BRUCE-USP8-BRIT1 Complex.
26651848 2016 High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences.
26626498 2016 Refining the phenotype associated with CASC5 mutation.
26205471 2016 Expression of proteins involved in DNA damage response in familial and sporadic breast cancer patients.
26192461 2015 A case report: Autosomal recessive microcephaly caused by a novel mutation in MCPH1 gene.
26165835 2016 Opposing effects of pericentrin and microcephalin on the pericentriolar material regulate CHK1 activation in the DNA damage response.
25951892 2015 Molecular genetics of human primary microcephaly: an overview.
25950475 2015 Platelet-activating factor induces cell cycle arrest and disrupts the DNA damage response in mast cells.
25870538 2015 MCPH1: a window into brain development and evolution.
25845520 2015 Chromosome structure deficiencies in MCPH1 syndrome.
25733871 2015 BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1.
25703238 2015 MCPH1 maintains long-term epigenetic silencing of ANGPT2 in chronic lymphocytic leukemia.
25548773 2014 Molecular and cellular basis of autosomal recessive primary microcephaly.
25504234 2014 Rare variant testing of imputed data: an analysis pipeline typified.
25465325 2014 Microcephaly.
25301947 2014 Phosphorylation of the BRCA1 C terminus (BRCT) repeat inhibitor of hTERT (BRIT1) protein coordinates TopBP1 protein recruitment and amplifies ataxia telangiectasia-mutated and Rad3-related (ATR) Signaling.
25197360 2014 Primary microcephaly gene MCPH1 shows a novel molecular biomarker of human renal carcinoma and is regulated by miR-27a.
25008867 2016 Pharmacogenetic association between GSTP1 genetic polymorphism and febrile neutropenia in Japanese patients with early breast cancer.
24995331 2014 A critical role for ZDHHC2 in metastasis and recurrence in human hepatocellular carcinoma.
24975899 2014 Association of microcephalin 1, syntrophin-beta 1, and other genes with automatic thoughts in the Japanese population.
24830737 2014 Deregulation of microcephalin and ASPM expression are correlated with epithelial ovarian cancer progression.
24780602 2014 Autosomal recessive primary microcephalies (MCPH).
24633962 2014 The overexpression of MCPH1 inhibits cell growth through regulating cell cycle-related proteins and activating cytochrome c-caspase 3 signaling in cervical cancer.
24560403 2014 Emerging roles of MCPH1: expedition from primary microcephaly to cancer.
24507884 2014 Combined analysis of exon splicing and genome wide polymorphism data predict schizophrenia risk loci.
24483146 2014 Discovery of genetic biomarkers contributing to variation in drug response of cytidine analogues using human lymphoblastoid cell lines.
24460291 2013 MCPH1 Protein Expression in Normal and Neoplastic Lung Tissues.
24288161 2014 Human-specific hypomethylation of CENPJ, a key brain size regulator.
24148351 2013 Exploring evolution of brain genes involved in microcephaly through phylogeny and synteny analysis.
24080358 2013 MCPH1 deletion in a newborn with severe microcephaly and premature chromosome condensation.
24013099 2013 Combined deletion of two Condensin II system genes (NCAPG2 and MCPH1) in a case of severe microcephaly and mental deficiency.
23983231 2014 A high-throughput assay to identify modifiers of premature chromosome condensation.
23958183 2014 The genome in three dimensions: a new frontier in human brain research.
23908141 2013 Interaction of polymorphisms in mitotic regulator genes with cigarette smoking and pancreatic cancer risk.
23866422 2012 A novel mutation in MCPH1 gene in an Iranian family with primary microcephaly.
23815819 2013 Chromosomal imbalance letter: Phenotypic consequences of combined deletion 8pter and duplication 15qter.
23729656 2013 BRIT1 regulates p53 stability and functions as a tumor suppressor in breast cancer.
23697381 2013 Functional divergence of the brain-size regulating gene MCPH1 during primate evolution and the origin of humans.
23695280 2014 Rare copy number variation in cerebral palsy.
23587236 2013 Clinical and cellular features in patients with primary autosomal recessive microcephaly and a novel CDK5RAP2 mutation.
23575222 2013 An eQTL mapping approach reveals that rare variants in the SEMA5A regulatory network impact autism risk.
23472065 2013 Primary microcephaly gene MCPH1 shows signatures of tumor suppressors and is regulated by miR-27a in oral squamous cell carcinoma.
23296058 2013 MCPH1 protein expression and polymorphisms are associated with risk of breast cancer.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23117476 2013 Frequent alterations of MCPH1 and ATM are associated with primary breast carcinoma: clinical and prognostic implications.
22952573 2012 A novel MCPH1 isoform complements the defective chromosome condensation of human MCPH1-deficient cells.
22908299 2012 Dual recognition of phosphoserine and phosphotyrosine in histone variant H2A.X by DNA damage response protein MCPH1.
22240313 2012 MCPH1/BRIT1 represses transcription of the human telomerase reverse transcriptase gene.
22154951 2012 Specific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structure.
22139841 2012 Molecular basis for the association of microcephalin (MCPH1) protein with the cell division cycle protein 27 (Cdc27) subunit of the anaphase-promoting complex.
22136275 2012 Identification and functional characterization of a primate-specific E2F1 binding motif regulating MCPH1 expression.
21993531 2012 Genome-wide association study does not reveal major genetic determinants for anti-cytomegalovirus antibody response.
21934293 2011 BRIT1/MCPH1 expression in chronic myeloid leukemia and its regulation of the G2/M checkpoint.
21911480 2011 MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II.
21799462 2011 Genome-wide association study of epirubicin-induced leukopenia in Japanese patients.
21515671 2011 SET nuclear oncogene associates with microcephalin/MCPH1 and regulates chromosome condensation.
21297427 Microcephaly genes and risk of late-onset Alzheimer disease.
21150325 2010 MCPH1 patient cells exhibit delayed release from DNA damage-induced G2/M checkpoint arrest.
20949544 2010 Absence of microcephalin gene mutations in a large cohort of non-consanguineous patients with autosomal recessive primary microcephaly.
20638839 2010 Double strand break repair components are frequent targets of microsatellite instability in endometrial cancer.
20632086 2011 Microcephalin is a new novel prognostic indicator in breast cancer associated with BRCA1 inactivation.
20602615 2010 Physiogenomic analysis of statin-treated patients: domain-specific counter effects within the ACACB gene on low-density lipoprotein cholesterol?
20508983 2011 Centrosome-related genes, genetic variation, and risk of breast cancer.
20485444 2010 Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20101680 2010 Craniosynostosis-microcephaly with chromosomal breakage and other abnormalities is caused by a truncating MCPH1 mutation and is allelic to premature chromosomal condensation syndrome and primary autosomal recessive microcephaly type 1.
20080800 2010 Sex-dependent association of common variants of microcephaly genes with brain structure.
20056645 2010 Association of mitotic regulation pathway polymorphisms with pancreatic cancer risk and outcome.
19925808 2010 A pocket on the surface of the N-terminal BRCT domain of Mcph1 is required to prevent abnormal chromosome condensation.
19829069 2009 The linkage of chromatin remodeling to genome maintenance: contribution from a human disease gene BRIT1/MCPH1.
19793310 2009 Copy number changes of the microcephalin 1 gene (MCPH1) in patients with autism spectrum disorders.
19690177 2009 Polymorphic variants in hereditary pancreatic cancer genes are not associated with pancreatic cancer risk.
19549900 2009 Microcephalin regulates BRCA2 and Rad51-associated DNA double-strand break repair.
19546241 2009 Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1.
19525936 2009 BRIT1/MCPH1 links chromatin remodelling to DNA damage response.
19475667 2009 SNCA variants are associated with increased risk for multiple system atrophy.
19287395 2009 TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs.
19267414 2009 The c.940G variant of the Microcephalin (MCPH1) gene is not associated with microcephaly or mental retardation.
18718915 2008 Microcephalin/MCPH1 associates with the Condensin II complex to function in homologous recombination repair.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18660752 2008 MCPH1/BRIT1 cooperates with E2F1 in the activation of checkpoint, DNA repair and apoptosis.
18635967 2008 Differential regulation of centrosome integrity by DNA damage response proteins.
18204051 2008 A common SNP of MCPH1 is associated with cranial volume variation in Chinese population.
17925396 2007 MCPH1 functions in an H2AX-dependent but MDC1-independent pathway in response to DNA damage.
17566767 2007 Investigation of MCPH1 G37995C and ASPM A44871G polymorphisms and brain size in a healthy cohort.
17251122 2007 No evidence that polymorphisms of brain regulator genes Microcephalin and ASPM are associated with general mental ability, head circumference or altruism.
17220170 2007 The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence.
17102619 2006 Microcephalin: a causal link between impaired damage response signalling and microcephaly.
16872911 2006 BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer.
16783362 2006 Regulation of mitotic entry by microcephalin and its overlap with ATR signalling.
16687438 2006 Normal variants of Microcephalin and ASPM do not account for brain size variability.
16479174 2006 Microcephalin encodes a centrosomal protein.
16421571 2006 DNA sequence and analysis of human chromosome 8.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16217032 2005 BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly.
16211557 2005 The first missense alteration in the MCPH1 gene causes autosomal recessive microcephaly with an extremely mild cellular and clinical phenotype.
16151009 2005 Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15220350 2004 Microcephalin is a DNA damage response protein involved in regulation of CHK1 and BRCA1.
15199523 2004 Mutations in microcephalin cause aberrant regulation of chromosome condensation.
15056608 2004 Molecular evolution of microcephalin, a gene determining human brain size.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12837246 2003 Multiple tumor suppressor pathways negatively regulate telomerase.
12571366 2002 Primary microcephaly: microcephalin and ASPM determine the size of the human brain.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12046007 2002 Identification of microcephalin, a protein implicated in determining the size of the human brain.
11857108 2002 Premature chromosome condensation in humans associated with microcephaly and mental retardation: a novel autosomal recessive condition.
9683597 1998 Primary autosomal recessive microcephaly (MCPH1) maps to chromosome 8p22-pter.