MCPH1

Chr 8AR

microcephalin 1

Also known as: BRIT1, MCT

The protein functions as a DNA damage response protein that maintains inhibitory phosphorylation of cyclin-dependent kinase 1 during G2/M checkpoint arrest. Mutations cause primary autosomal recessive microcephaly 1 and premature chromosome condensation syndrome, inherited in an autosomal recessive pattern. Loss of function leads to defective cell cycle checkpoint control, resulting in abnormal chromosome condensation and impaired brain development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.442 OMIM phenotypes
Clinical SummaryMCPH1
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Gene-Disease Validity (ClinGen)
microcephaly with intellectual disability · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

3 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
68 unique Pathogenic / Likely Pathogenic· 90 VUS of 400 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.44LOEUF
pLI 0.000
Z-score -0.65
OE 1.11 (0.871.44)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-4.76Z-score
OE missense 1.63 (1.531.73)
736 obs / 451.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.11 (0.871.44)
00.351.4
Missense OE1.63 (1.531.73)
00.61.4
Synonymous OE1.56
01.21.6
LoF obs/exp: 42 / 37.7Missense obs/exp: 736 / 451.4Syn Z: -5.87

ClinVar Variant Classifications

400 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic37
VUS90
Likely Benign203
Benign5
Conflicting3
31
Pathogenic
37
Likely Pathogenic
90
VUS
203
Likely Benign
5
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
19
0
31
Likely Pathogenic
36
1
0
0
37
VUS
3
79
8
0
90
Likely Benign
2
6
71
124
203
Benign
1
2
2
0
5
Conflicting
3
Total5488100124369

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MCPH1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗