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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MCPH1
microcephalin 1
Chromosome 8 Β· 8p23.1
NCBI Gene: 79648Ensembl: ENSG00000147316.15HGNC: HGNC:6954UniProt: A0A8I5KPV6
153PubMed Papers
21Diseases
0Drugs
106Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
identical protein bindingnegative regulation of transcription by RNA polymerase IIprotein bindingmitotic cell cyclemicrocephaly 1, primary, autosomal recessiveautosomal recessive primary microcephalylymphatic malformation 10neurodegenerative disease
✦AI Summary

MCPH1 (microcephalin 1) is a multifunctional centrosomal protein with three BRCT domains that plays critical roles in neurogenesis and genome stability 1. In the developing brain, MCPH1 regulates neuroprogenitor cell proliferation and self-renewal by coordinating the cell cycle and centrosome cycle, preventing progenitor pool exhaustion and thereby determining cerebral cortex size 2. MCPH1 functions as a chromosome 8 antagonist during interphase; it binds condensin II's CAP-G2 subunit and is displaced by M18BP1 at mitotic onset, allowing condensin II activation for proper chromosome 8 3. The protein coordinates two of seven known DNA repair mechanisms and is essential for telomere maintenance and DNA damage response 45. Biallelic loss-of-function mutations in MCPH1 cause primary microcephaly type 1, characterized by reduced brain size, intellectual disability, and neuronal migration defects 6. Beyond neurodevelopment, MCPH1 functions as a tumor suppressor; its downregulation occurs across multiple cancers including breast, lung, cervical, and ovarian cancers, and correlates with reduced survival 7. MCPH1 loss promotes genome instability and deregulates transcriptional programs related to invasion and metastasis 8, establishing it as a multivalent therapeutic target.

Sources cited
1
MCPH1 dysfunction impairs neuroprogenitor proliferation and self-renewal, causing primary microcephaly; multifunctional roles in DNA damage signaling, chromosome condensation, cell-cycle progression, and centrosome activity
PMID: 35053391
2
MCPH1 acts as condensin II antagonist binding CAP-G2 subunit; M18BP1-MCPH1 switch at mitotic onset activates condensin II for chromosome condensation
PMID: 40614722
3
MCPH1 coordinates two of seven DNA repair mechanisms; pathogenic variants associated with microcephaly and congenital hearing impairment
PMID: 38463519
4
Biallelic MCPH1 mutations cause nonsyndromic microcephaly with intellectual disability, language delay, and neuronal migration defects
PMID: 35456440
5
MCPH1/BRIT1 downregulation occurs in breast, lung, cervical, prostate, and ovarian cancers; loss promotes genome instability; associated with reduced overall and relapsed-free survival
PMID: 36845691
6
MCPH1 mutations de-regulate transcriptional programs related to invasion and metastasis; MCPH1 p.Arg304ValfsTer3 identified as breast cancer susceptibility allele
PMID: 30809794
7
MCPH1 coordinates cell cycle and centrosome cycle to regulate neuroprogenitor division; functions in telomere integrity, DNA damage response, chromosome condensation, and tumor suppression
PMID: 27197793
8
MCPH1 encodes centrosomal protein with three BRCT domains; key regulator of DNA repair and cell cycle checkpoints; tumor suppressor functions in cancer
PMID: 24560403
Disease Associationsβ“˜21
microcephaly 1, primary, autosomal recessiveOpen Targets
0.78Strong
autosomal recessive primary microcephalyOpen Targets
0.62Moderate
lymphatic malformation 10Open Targets
0.44Moderate
neurodegenerative diseaseOpen Targets
0.41Moderate
Primary microcephalyOpen Targets
0.37Weak
isolated congenital microcephalyOpen Targets
0.37Weak
microcephaly with intellectual disabilityOpen Targets
0.37Weak
Decreased total leukocyte countOpen Targets
0.29Weak
papillary renal cell carcinomaOpen Targets
0.29Weak
liver diseaseOpen Targets
0.28Weak
self-injurious ideationOpen Targets
0.28Weak
ovarian dysfunctionOpen Targets
0.28Weak
malignant renal pelvis neoplasmOpen Targets
0.28Weak
trauma complicationOpen Targets
0.27Weak
Abnormal brain morphologyOpen Targets
0.27Weak
Abnormality of the nervous systemOpen Targets
0.27Weak
cataractOpen Targets
0.26Weak
hemorrhoidOpen Targets
0.23Weak
myopathyOpen Targets
0.23Weak
scoliosisOpen Targets
0.22Weak
Microcephaly 1, primary, autosomal recessiveUniProt
Pathogenic Variants106
NM_024596.5(MCPH1):c.698C>A (p.Ser233Ter)Pathogenic
Autosomal recessive primary microcephaly|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 233
NM_024596.5(MCPH1):c.321dup (p.Arg108fs)Pathogenic
not provided|Microcephaly 1, primary, autosomal recessive
β˜…β˜…β˜†β˜†2025β†’ Residue 108
NM_024596.5(MCPH1):c.321+2T>CLikely pathogenic
not provided|Microcephaly 1, primary, autosomal recessive
β˜…β˜…β˜†β˜†2024
NM_024596.5(MCPH1):c.571del (p.Ser191fs)Pathogenic
not provided|Microcephaly 1, primary, autosomal recessive
β˜…β˜…β˜†β˜†2024β†’ Residue 191
NM_024596.5(MCPH1):c.733G>T (p.Gly245Ter)Pathogenic
not provided|Microcephaly 1, primary, autosomal recessive
β˜…β˜…β˜†β˜†2024β†’ Residue 245
NM_024596.5(MCPH1):c.826_829del (p.Ser276fs)Pathogenic
not provided|Microcephaly 1, primary, autosomal recessive
β˜…β˜…β˜†β˜†2024β†’ Residue 276
NM_024596.5(MCPH1):c.215C>T (p.Ser72Leu)Pathogenic
Microcephaly 1, primary, autosomal recessive|See cases|Autosomal recessive primary microcephaly
β˜…β˜…β˜†β˜†2024β†’ Residue 72
NM_024596.5(MCPH1):c.321del (p.Lys107fs)Pathogenic
Abnormality of the nervous system|not provided|Microcephaly 1, primary, autosomal recessive
β˜…β˜…β˜†β˜†2024β†’ Residue 107
NM_024596.5(MCPH1):c.76_77del (p.Lys26fs)Pathogenic
not provided|Microcephaly 1, primary, autosomal recessive
β˜…β˜…β˜†β˜†2024β†’ Residue 26
NM_024596.5(MCPH1):c.595C>T (p.Gln199Ter)Pathogenic
not provided|Autosomal recessive primary microcephaly
β˜…β˜…β˜†β˜†2024β†’ Residue 199
NM_024596.5(MCPH1):c.566dup (p.Asn189fs)Pathogenic
Microcephaly 1, primary, autosomal recessive|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 189
NM_024596.5(MCPH1):c.1869_1870del (p.Ser623_Cys624insTer)Pathogenic
Microcephaly 1, primary, autosomal recessive|Autosomal recessive primary microcephaly|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 623
NM_024596.5(MCPH1):c.313A>T (p.Lys105Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 105
NM_024596.5(MCPH1):c.1924_1925insCA (p.Arg642fs)Likely pathogenic
Microcephaly 1, primary, autosomal recessive|Autosomal recessive primary microcephaly
β˜…β˜…β˜†β˜†2019β†’ Residue 642
NM_024596.5(MCPH1):c.1625T>G (p.Leu542Ter)Pathogenic
not provided|Microcephaly 1, primary, autosomal recessive
β˜…β˜…β˜†β˜†2018β†’ Residue 542
NM_024596.5(MCPH1):c.427dup (p.Thr143fs)Pathogenic
Microcephaly 1, primary, autosomal recessive|Abnormal brain morphology
β˜…β˜…β˜†β˜†2016β†’ Residue 143
NM_024596.5(MCPH1):c.322-1G>CLikely pathogenic
Microcephaly 1, primary, autosomal recessive|not provided|Acute myeloid leukemia
β˜…β˜†β˜†β˜†2026
NM_024596.5(MCPH1):c.786_789del (p.Cys263fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 263
NM_024596.5(MCPH1):c.857C>G (p.Ser286Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 286
NM_024596.5(MCPH1):c.2453-1G>ALikely pathogenic
Microcephaly 1, primary, autosomal recessive
β˜…β˜†β˜†β˜†2025
View on ClinVar β†—
Related Genes
ATRProtein interaction100%E2F1Protein interaction99%CHEK1Protein interaction99%ASPMProtein interaction99%CDK5RAP2Protein interaction94%STILProtein interaction93%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
59%
Heart
38%
Ovary
28%
Lung
28%
Liver
23%
Gene Interaction Network
Click a node to explore
MCPH1ATRE2F1CHEK1ASPMCDK5RAP2STIL
PROTEIN STRUCTURE
Preparing viewer…
PDB3PA6 Β· 1.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.34LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.12 [0.94–1.34]
RankingsWhere MCPH1 stands among ~20K protein-coding genes
  • #2,956of 20,598
    Most Researched153 Β· top quartile
  • #730of 5,498
    Most Pathogenic Variants106 Β· top quartile
  • #14,042of 17,882
    Most Constrained (LOEUF)1.34
Genes detectedMCPH1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Multifaceted Microcephaly-Related Gene MCPH1.
PMID: 35053391
Cells Β· 2022
1.00
2
The emerging role of MCPH1/BRIT1 in carcinogenesis.
PMID: 36845691
Front Oncol Β· 2023
0.90
3
Condensin II activation by M18BP1.
PMID: 40614722
Mol Cell Β· 2025
0.80
4
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.
PMID: 30306255
J Cancer Res Clin Oncol Β· 2018
0.76
5
The analyses of human MCPH1 DNA repair machinery and genetic variations.
PMID: 38463519
Open Med (Wars) Β· 2024
0.70