ORC1

Chr 1AR

origin recognition complex subunit 1

Also known as: HSORC1, ORC1L, PARC1

The origin recognition complex (ORC) is a highly conserved six subunits 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 the largest subunit of the ORC complex. While other ORC subunits are stable throughout the cell cycle, the levels of this protein vary during the cell cycle, which has been shown to be controlled by ubiquitin-mediated proteolysis after initiation of DNA replication. This protein is found to be selectively phosphorylated during mitosis. It is also reported to interact with MYST histone acetyltransferase 2 (MyST2/HBO1), a protein involved in control of transcription silencing. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.881 OMIM phenotype
Clinical SummaryORC1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.88LOEUF
pLI 0.000
Z-score 2.20
OE 0.65 (0.480.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.24Z-score
OE missense 0.97 (0.901.05)
455 obs / 469.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.65 (0.480.88)
00.351.4
Missense OE?0.97 (0.901.05)
00.61.4
Synonymous OE?0.95
01.21.6
LoF obs/exp: 29 / 44.9Missense obs/exp: 455 / 469.4Syn Z: 0.57

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ORC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.