ORC4 (Origin Recognition Complex Subunit 4)
A key component of the origin recognition complex essential for DNA replication initiation
Gene Information Card
| Symbol | ORC4 |
|---|---|
| Full Name | origin recognition complex subunit 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q23.1 |
| NCBI Gene ID | 5000 ncbi.nlm.nih.gov/gene/5000 |
| Ensembl ID | ENSG00000115947 |
| UniProt ID | O43929 |
| OMIM ID | 603056 |
| HGNC ID | 8490 |
| Aliases | ORC4L, ORC4P, HsORC4 |
Description
The ORC4 gene encodes subunit 4 of the origin recognition complex (ORC), a multi-protein complex that binds to origins of replication in eukaryotic DNA. ORC is essential for the initiation of DNA replication and plays a role in cell cycle regulation. ORC4 is one of six subunits (ORC1-6) that form the core complex. Mutations in ORC4 are associated with Meier-Gorlin syndrome, a rare autosomal recessive disorder characterized by microcephaly, short stature, and skeletal abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Meier-Gorlin syndrome 4 | Loss-of-function mutations in ORC4 impair ORC complex assembly or DNA binding, reducing replication initiation efficiency and leading to cell proliferation defects during development. | OMIM #613800; ClinVar; PMID: 21211730 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Lymph node | 8.2 | Low |
| Brain | 6.1 | Low |
| Liver | 5.4 | Low |
| Kidney | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.3 | Cervical carcinoma cell line |
| K562 | 7.8 | Leukemia cell line |
| HEK293 | 6.5 | Embryonic kidney cells |
| HepG2 | 5.2 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense/Start loss | Rare | Loss of function; associated with Meier-Gorlin syndrome |
| c.2T>C (p.Met1?) | Missense/Start loss | Rare | Loss of function; associated with Meier-Gorlin syndrome |
| c.5C>T (p.Ala2Val) | Missense | Rare | Likely loss of function; reported in Meier-Gorlin syndrome |
Mutation functional classification
Loss of Function (LOF)
Most ORC4 mutations are loss-of-function, leading to reduced ORC complex stability or DNA binding, causing Meier-Gorlin syndrome.
Gain of Function (GOF)
No gain-of-function mutations reported for ORC4.
Dominant Negative (DN)
No dominant-negative mutations reported for ORC4.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication origin binding | • origin recognition complex |
| • nucleus | • protein binding |
| • ATP binding |
Pathways
• DNA replication (KEGG: hsa03030)
• Cell cycle (KEGG: hsa04110)
Protein Summary
ORC4 is a 436-amino acid protein that forms part of the origin recognition complex. It contains an AAA+ ATPase domain and is involved in ATP-dependent binding to replication origins. The protein localizes to the nucleus and interacts with other ORC subunits. Structural studies indicate ORC4 contributes to the overall architecture of the ORC ring complex.
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