ORC6

Chr 16AR

origin recognition complex subunit 6

Also known as: ORC6L

NCBI Gene: 23594 ENSG00000091651 UniProt: Q9Y5N6 OMIM: 607213

ORC6 encodes a subunit of the origin recognition complex that binds to DNA replication origins in an ATP-dependent manner and is essential for assembling the pre-replication complex needed to initiate DNA replication. Biallelic mutations cause Meier-Gorlin syndrome 3, characterized by microcephaly, short stature, and small or absent patellae with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern observed clinically.

OMIM 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. The protein encoded by this gene is a subunit of the ORC complex. Gene silencing studies with small interfering RNA demonstrated that this protein plays an essential role in coordinating chromosome replication and segregation with cytokinesis. [provided by RefSeq, Oct 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Meier-Gorlin syndrome 3MIM #613803

Clinical highlights

Gene-disease validity (ClinGen)

Meier-Gorlin syndrome 3 · ARDefinitivesufficient evidence for diagnostic panels

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)

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P/LP submissions

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P/LP missense

1.39

LOEUF

LOF

Mechanism· G2P