ORC5

Chr 7

origin recognition complex subunit 5

ENSG00000164815UniProt: O43913

Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication

0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ORC5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.86LOEUF
pLI 0.000
Z-score 2.08
OE 0.54 (0.35–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.63Z-score
OE missense 0.88 (0.78–0.99)
194 obs / 220.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.54 (0.35–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.78–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.32
0≤1.21.6
LoF obs/exp: 13 / 24.0Missense obs/exp: 194 / 220.2Syn Z: -2.28

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ORC5 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A human cancer cell line initiates DNA replication normally in the absence of ORC5 and ORC2 proteins.
Shibata E et al.·J Biol Chem
2020
Specific origin selection and excess functional MCM2-7 loading in ORC-deficient cells.
Shibata Y et al.·Nucleic Acids Res
2025Functional
Protein phosphatase 1 dephosphorylates Orc2.
Lee KY et al.·Biochem Biophys Res Commun
2014
Orc5 induces large-scale chromatin decondensation in a GCN5-dependent manner.
Giri S et al.·J Cell Sci
2016
The Absence of Intra-Tumoral Tertiary Lymphoid Structures is Associated with a Worse Prognosis and mTOR Signaling Activation in Hepatocellular Carcinoma with Liver Transplantation: A Multicenter Retrospective Study.
Li J et al.·Adv Sci (Weinh)
2024
Interactive effects of genotype with prenatal stress on DNA methylation at birth.
Mulder RH et al.·Mol Psychiatry
2025
Isolation of human and fission yeast homologues of the budding yeast origin recognition complex subunit ORC5: human homologue (ORC5L) maps to 7q22.
Ishiai M et al.·Genomics
1997
A novel disulfidptosis-related mRNA signature predicts prognosis and therapeutic response in lung squamous cell carcinoma.
Bai W et al.·BMC Pulm Med
2025
Sequence analysis of the 33 kb long region between ORC5 and SUI1 from the left arm of chromosome XIV from Saccharomyces cerevisiae.
Sen-Gupta M et al.·Yeast
1997
The ORC ubiquitin ligase OBI1 promotes DNA replication origin firing.
Coulombe P et al.·Nat Commun
2019
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools