ORC6

Chr 16AR

origin recognition complex subunit 6

Also known as: ORC6L

NCBI Gene: 23594ENSG00000091651UniProt: Q9Y5N6

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]

Primary Disease Associations & Inheritance

Meier-Gorlin syndrome 3MIM #613803
AR
0
Active trials
30
Pathogenic / LP
207
ClinVar variants
8
Pubs (1 yr)
-0.5
Missense Z
1.39
LOEUF
Clinical Summary— ORC6
🧬
Gene-Disease Validity (ClinGen)
Meier-Gorlin syndrome 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 103 VUS of 207 total submissions

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.
1.39LOEUF
pLI 0.000
Z-score 0.52
OE 0.84 (0.53–1.39)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.49Z-score
OE missense 1.12 (0.98–1.28)
151 obs / 135.1 exp
Tolerant

Tolerant to missense variation

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.0.84 (0.53–1.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (0.98–1.28)
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.1.17
0≤1.21.6
LoF obs/exp: 11 / 13.0Missense obs/exp: 151 / 135.1Syn Z: -0.95

ClinVar Variant Classifications

207 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic5
VUS103
Likely Benign58
Benign9
Conflicting7
25
Pathogenic
5
Likely Pathogenic
103
VUS
58
Likely Benign
9
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
4
18
0
25
Likely Pathogenic
5
0
0
0
5
VUS
0
60
43
0
103
Likely Benign
0
6
19
33
58
Benign
0
0
8
1
9
Conflicting
—7
Total8708834207

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ORC6 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ORC6-related Meier-Gorlin syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Meier-Gorlin Syndrome: Clinical Misdiagnosis, Genetic Testing and Functional Analysis of ORC6 Mutations and the Development of a Prenatal Test
Nazarenko MS et al.·Int J Mol Sci
2022Functional
ORC6 acts as a biomarker and reflects poor outcome in clear cell renal cell carcinoma
Pan Q et al.·J Cancer
2022
Multi-omics analysis reveals the involvement of origin recognition complex subunit 6 in tumor immune regulation and malignant progression
Zhu J et al.·Front Immunol
2023
scRNA-seq reveals that origin recognition complex subunit 6 regulates mouse spermatogonial cell proliferation and apoptosis via activation of Wnt/beta-catenin signaling
Liu SW et al.·Asian J Androl
2023Functional
Phosphorylation of Orc6 During Mitosis Regulates DNA Replication and Ribosome Biogenesis.
Kurniawan F et al.·Mol Cell Biol
2024
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients