ORC4 gene

origin recognition complex subunit 4

The ORC4 gene provides instructions for making a protein that is important in the copying of a cell's DNA before the cell divides (a process known as DNA replication). The protein produced from this gene, ORC4, is one of a group of proteins known as the origin recognition complex (ORC). (The complex is made up of the proteins ORC1 to ORC6, which are produced from different genes.) ORC attaches (binds) to certain regions of DNA known as origins of replication (or origins), where the process of DNA copying begins. This complex attracts additional proteins to bind to it, forming a larger group of proteins called the pre-replication complex. When the pre-replication complex is attached to the origin, replication is able to begin at that location. This tightly controlled process, called replication licensing, helps ensure that DNA replication occurs only once per cell division and is required for cells to divide.

ORC also attaches to a form of DNA called heterochromatin. Heterochromatin is densely packed DNA that contains few functional genes, but it is important for controlling gene activity and maintaining the structure of chromosomes. It is unclear what effect ORC binding has on heterochromatin.

Mutations in the ORC4 gene cause Meier-Gorlin syndrome, a condition characterized by short stature, underdeveloped kneecaps, and small ears. These mutations alter the ORC4 protein, typically by changing single protein building blocks (amino acids) or by leading to production of an abnormally short version of the ORC4 protein. The most common ORC4 gene mutation in people with this condition replaces the amino acid tyrosine at position 174 with the amino acid cysteine (written as Tyr174Cys). As a result of these changes, assembly of the pre-replication complex is impaired, which disrupts replication licensing; however, it is not clear how a reduction in replication licensing leads to Meier-Gorlin syndrome. Researchers speculate that such a reduction delays the cell division process, which slows growth of the bones and other tissues during development. It is not known why development of the kneecaps and ears is particularly affected.

Cytogenetic Location: 2q23.1, which is the long (q) arm of chromosome 2 at position 23.1

Molecular Location: base pairs 147,930,397 to 148,021,604 on chromosome 2 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 2q23.1, which is the long (q) arm of chromosome 2 at position 23.1
  • HsORC4
  • ORC4_HUMAN
  • ORC4L
  • ORC4P
  • origin recognition complex, subunit 4
  • origin recognition complex, subunit 4 homolog