Alt. symbols: CDC21 | CDC54 | hCdc21 | P1-Cdc21 | MGC33310

Approved name: minichromosome maintenance complex component 4
Alt. names: MCM4 minichromosome maintenance deficient 4 (S. cerevisiae) | DNA replication licensing factor MCM4

Location: 8q11.21: 47960185 - 47978160 (+)
Gene type: protein_coding, 28 transcripts.

Scores: LoFtool: 0.813000 | pLI: 0.00030184 | LOEUF: 0.552

HGNC: 6947

NCBI: 4173, RefSeq: NG_032967.1

Ensembl: ENSG00000104738.19

LRG_1239 | Status: public

OMIM: 602638

Expression | ProteinAtlas

The protein encoded by MCM4 is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 6 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase involved in the repair of DNA double-strand breaks.

Mutations in MCM4 have been shown to cause an autosomal recessive form of primary immunodeficiency (Immunodeficiency 54 [MIM:609981]), which is characterized by severe intra- and extrauterine growth retardation, microcephaly, decreased numbers of natural killer (NK) cells, and recurrent viral infections, most often affecting the respiratory tract and leading to respiratory failure. Affected individuals also have adrenal insufficiency requiring corticosteroid replacement therapy and may have an i ncreased susceptibility to cancer. In vitro studies in patient-derived cells showed a DNA repair defect. There are at least 8 unrelated kindreds reported from 3 different studies (Hughes et al. 2012; Gineau et al. 2012; Casey et al. 2020). However, only 2 pathogenic mutations are described, both of them alter mRNA splicing: c.71-2A>G and c.70_71insG. [Load More]