MCPH1

Chr 8AR

microcephalin 1

Also known as: BRIT1, MCT

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]

Primary Disease Associations & Inheritance

Microcephaly 1, primary, autosomal recessiveMIM #251200
AR
Microcephaly 1, primary, autosomal recessiveMIM #251200
AR
0
Active trials
62
Pathogenic / LP
365
ClinVar variants
12
Pubs (1 yr)
-4.8
Missense Z
1.44
LOEUF
Clinical SummaryMCPH1
🧬
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
62 Pathogenic / Likely Pathogenic· 157 VUS of 365 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

365 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic35
VUS157
Likely Benign141
Benign2
Conflicting3
27
Pathogenic
35
Likely Pathogenic
157
VUS
141
Likely Benign
2
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
23
0
27
Likely Pathogenic
20
1
14
0
35
VUS
2
145
10
0
157
Likely Benign
1
9
49
82
141
Benign
1
1
0
0
2
Conflicting
3
Total281569682365

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

View in ClinVar →

MCPH1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MCPH1-related microcephaly primary

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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 ↗