ORC4

Chr 2

origin recognition complex subunit 4

Also known as: ORC4L, ORC4P

NCBI Gene: 5000 ENSG00000115947 UniProt: O43929

ORC4 encodes a component of the origin recognition complex that binds to origins of DNA replication in an ATP-dependent manner and is required for assembly of the pre-replication complex necessary to initiate DNA replication. Biallelic mutations cause Meier-Gorlin syndrome 2, characterized by microcephaly, short stature, and small ears, with an autosomal recessive inheritance pattern. The gene shows minimal constraint against loss-of-function variants (pLI near zero), consistent with the recessive disease mechanism.

ResearchSummary from RefSeq, OMIM, UniProt

The origin recognition complex (ORC) is a highly conserved six subunit protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. This gene encodes a subunit of the ORC complex. Several alternatively spliced transcript variants, some of which encode the same protein, have been reported for this gene. [provided by RefSeq, Oct 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMeier-Gorlin syndrome 2

Clinical highlights

Gene-disease validity (ClinGen)

Meier-Gorlin syndrome 2 · ARModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

1.13

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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