MCPH1

Protein identityUniProt · HPA

UniProt accession

Q8NEM0

Gene

MCPH1

Ensembl

ENSG00000147316

Chromosome

8

Canonical length

835 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

OverviewNCBI Gene

This gene encodes a DNA damage response protein. The encoded protein may play a role in G2/M checkpoint arrest via maintenance of inhibitory phosphorylation of cyclin-dependent kinase 1. Mutations in this gene have been associated with primary autosomal recessive microcephaly 1 and premature chromosome condensation syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

Canonical amino-acid sequenceUniProt

835 residues, UniProt reviewed canonical sequence.

>Q8NEM0|MCPH1
     1  MAAPILKDVV AYVEVWSSNG TENYSKTFTT QLVDMGAKVS KTFNKQVTHV IFKDGYQSTW
    61  DKAQKRGVKL VSVLWVEKCR TAGAHIDESL FPAANMNEHL SSLIKKKRKC MQPKDFNFKT
   121  PENDKRFQKK FEKMAKELQR QKTNLDDDVP ILLFESNGSL IYTPTIEINS RHHSAMEKRL
   181  QEMKEKRENL SPTSSQMIQQ SHDNPSNSLC EAPLNISRDT LCSDEYFAGG LHSSFDDLCG
   241  NSGCGNQERK LEGSINDIKS DVCISSLVLK ANNIHSSPSF THLDKSSPQK FLSNLSKEEI
   301  NLQRNIAGKV VTPDQKQAAG MSQETFEEKY RLSPTLSSTK GHLLIHSRPR SSSVKRKRVS
   361  HGSHSPPKEK CKRKRSTRRS IMPRLQLCRS EDRLQHVAGP ALEALSCGES SYDDYFSPDN
   421  LKERYSENLP PESQLPSSPA QLSCRSLSKK ERTSIFEMSD FSCVGKKTRT VDITNFTAKT
   481  ISSPRKTGNG EGRATSSCVT SAPEEALRCC RQAGKEDACP EGNGFSYTIE DPALPKGHDD
   541  DLTPLEGSLE EMKEAVGLKS TQNKGTTSKI SNSSEGEAQS EHEPCFIVDC NMETSTEEKE
   601  NLPGGYSGSV KNRPTRHDVL DDSCDGFKDL IKPHEELKKS GRGKKPTRTL VMTSMPSEKQ
   661  NVVIQVVDKL KGFSIAPDVC ETTTHVLSGK PLRTLNVLLG IARGCWVLSY DWVLWSLELG
   721  HWISEEPFEL SHHFPAAPLC RSECHLSAGP YRGTLFADQP AMFVSPASSP PVAKLCELVH
   781  LCGGRVSQVP RQASIVIGPY SGKKKATVKY LSEKWVLDSI TQHKVCAPEN YLLSQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MCPH1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.55

Highest tissue expression

16 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MCPH1.

Disease | AllUniProt

Conditions MCPH1 is implicated in, by any mechanism.

• Microcephaly 1, primary, autosomal recessive (MCPH1) MIM:251200

Disease | GeneticClinVar

109 pathogenic / likely-pathogenic of 1,228 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Microcephaly 1, primary, autosomal recessive
• Autosomal recessive primary microcephaly
• See cases
• Abnormal brain morphology
• Acute myeloid leukemia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.44

gnomAD pLI

0

gnomAD missense Z

-4.76

DepMap mean gene effect

-0.19

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• bone development
• cerebral cortex development
• establishment of mitotic spindle orientation
• mitotic cell cycle
• negative regulation of transcription by RNA polymerase II
• neuronal stem cell population maintenance
• protein localization to centrosome
• regulation of centrosome cycle
• regulation of chromosome condensation
• regulation of inflammatory response

Molecular functions

• identical protein binding

Cellular components

• centrosome
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• BRCT domain
• BRCT domain superfamily
• twin BRCT domain
• Microcephalin-like
• Microcephalin, mammal
• Microcephalin protein

KeywordsUniProt

• Cytoplasm
• Cytoskeleton
• Intellectual disability
• Phosphoprotein
• Primary microcephaly
• Repeat

InteractionsUniProt · HPA

Protein binding partners of MCPH1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CDC27
• E2F1