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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ORC6
origin recognition complex subunit 6
Chromosome 16 Β· 16q11.2
NCBI Gene: 23594Ensembl: ENSG00000091651.10HGNC: HGNC:17151UniProt: Q9Y5N6
68PubMed Papers
21Diseases
0Drugs
17Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
membraneorigin recognition complexDNA replication initiationfibrillar centerEar-patella-short stature syndromeneurodegenerative diseaseMeier-Gorlin syndromemicrocephalic primordial dwarfism
✦AI Summary

ORC6 (origin recognition complex subunit 6) is a component of the origin recognition complex (ORC) that facilitates DNA replication initiation. ORC6 functions in ATP-dependent binding to replication origins and assembly of the pre-replication complex required for loading the MCM2-7 replicative helicase double hexamer onto DNA 1. In human cells, unlike in budding yeast, ORC6 is not essential but enhances MCM loading through recruitment of ORC to the MCM dimerization interface, and human MCM loading can proceed through multiple alternative pathways independent of ORC6 12. ORC6 mutations cause Meier-Gorlin syndrome (MGS), a rare autosomal recessive primordial dwarfism disorder characterized by microtia, patellar anomalies, and growth retardation; ORC6 mutations account for approximately 67-78% of detected pre-replication complex gene mutations in MGS patients 3. Beyond its canonical replication function, elevated ORC6 expression promotes cancer cell proliferation in non-small cell lung cancer and pancreatic ductal adenocarcinoma by enhancing cell cycle progression through cyclin upregulation and p53 inhibition 45. ORC6 overexpression correlates with reduced overall survival in colorectal and lung adenocarcinoma 6, and ORC6 knockdown sensitizes colon cancer cells to chemotherapy 7.

Sources cited
1
ORC6 enhances but is not essential for human MCM loading; human MCM loading proceeds through multiple mechanisms with or without ORC6
PMID: 39604729
2
ORC6 is not essential for initial MCM recruitment or double hexamer loading in humans but contributes to alternative assembly pathway
PMID: 39604733
3
ORC6 mutations cause Meier-Gorlin syndrome; mutations in ORC6 and other pre-replication complex genes detected in 67-78% of MGS patients
PMID: 26381604
4
Elevated ORC6 expression in NSCLC correlates with reduced survival and advanced disease; ORC6 promotes cell proliferation, cycle progression, and migration through cyclin upregulation
PMID: 39349930
5
ORC6 overexpression in PDAC promotes progression via p53 inhibition; METTL3/IGF2BP3 regulates ORC6 mRNA stability
PMID: 40185346
6
ORC6 expression is significantly upregulated in colorectal cancer and associated with survival outcomes
PMID: 32021241
7
ORC6 reduction sensitizes colon cancer cells to 5-fluorouracil and cisplatin via p53-mediated p21 induction
PMID: 19112505
Disease Associationsβ“˜21
Ear-patella-short stature syndromeOpen Targets
0.78Strong
neurodegenerative diseaseOpen Targets
0.52Moderate
Meier-Gorlin syndromeOpen Targets
0.42Moderate
microcephalic primordial dwarfismOpen Targets
0.37Weak
genetic disorderOpen Targets
0.19Weak
neoplasmOpen Targets
0.10Weak
cancerOpen Targets
0.10Suggestive
gliomaOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.06Suggestive
lung adenocarcinomaOpen Targets
0.06Suggestive
Alzheimer diseaseOpen Targets
0.04Suggestive
attention deficit hyperactivity disorderOpen Targets
0.04Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.04Suggestive
histidinemiaOpen Targets
0.04Suggestive
placenta praeviaOpen Targets
0.03Suggestive
Mungan syndromeOpen Targets
0.03Suggestive
Meier-Gorlin syndrome 3UniProt
Pathogenic Variants17
NM_014321.4(ORC6):c.507dup (p.Ala170fs)Pathogenic
not provided|Meier-Gorlin syndrome 3
β˜…β˜…β˜†β˜†2025β†’ Residue 170
NM_014321.4(ORC6):c.257_258del (p.Ser85_Phe86insTer)Pathogenic
Meier-Gorlin syndrome 3
β˜…β˜…β˜†β˜†2018β†’ Residue 85
NM_014321.4(ORC6):c.196-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2026
NM_014321.4(ORC6):c.65+2T>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_014321.4(ORC6):c.49G>T (p.Glu17Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 17
NM_014321.4(ORC6):c.440C>G (p.Ser147Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 147
NM_014321.4(ORC6):c.214del (p.Ser72fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 72
NM_014321.4(ORC6):c.359+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_014321.4(ORC6):c.352del (p.Ile117_Leu118insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 117
NM_014321.4(ORC6):c.173G>A (p.Trp58Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 58
NM_014321.4(ORC6):c.509del (p.Ala170fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 170
NM_014321.4(ORC6):c.1A>G (p.Met1Val)Pathogenic
Meier-Gorlin syndrome 3
β˜…β˜†β˜†β˜†2017β†’ Residue 1
NM_014321.4(ORC6):c.71C>T (p.Ala24Val)Pathogenic
Meier-Gorlin syndrome 3
β˜…β˜†β˜†β˜†β†’ Residue 24
NM_014321.4(ORC6):c.695A>C (p.Tyr232Ser)Pathogenic
Meier-Gorlin syndrome 3
β˜…β˜†β˜†β˜†β†’ Residue 232
NM_014321.4(ORC6):c.65G>A (p.Arg22Lys)Pathogenic
Meier-Gorlin syndrome 3
β˜…β˜†β˜†β˜†β†’ Residue 22
NM_014321.4(ORC6):c.602_605del (p.Lys201fs)Pathogenic
Meier-Gorlin syndrome 3
β˜†β˜†β˜†β˜†2019β†’ Residue 201
NM_014321.4(ORC6):c.360-1G>TLikely pathogenic
Meier-Gorlin syndrome 3
β˜†β˜†β˜†β˜†
View on ClinVar β†—
Related Genes
MCM2Protein interaction100%MCM3Protein interaction100%MCM4Protein interaction100%MCM5Protein interaction100%MCM6Protein interaction100%MCM7Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
27%
Liver
15%
Heart
10%
Ovary
9%
Lung
9%
Gene Interaction Network
Click a node to explore
ORC6MCM2MCM3MCM4MCM5MCM6MCM7
PROTEIN STRUCTURE
Preparing viewer…
PDB3M03 Β· 2.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.78LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.30 [0.94–1.78]
RankingsWhere ORC6 stands among ~20K protein-coding genes
  • #6,927of 20,598
    Most Researched68
  • #2,346of 5,498
    Most Pathogenic Variants17
  • #16,493of 17,882
    Most Constrained (LOEUF)1.78
Genes detectedORC6
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Multiple mechanisms for licensing human replication origins.
PMID: 39604729
Nature Β· 2024
1.00
2
Meier-Gorlin syndrome.
PMID: 26381604
Orphanet J Rare Dis Β· 2015
0.90
3
MCM double hexamer loading visualized with human proteins.
PMID: 39604733
Nature Β· 2024
0.80
4
Elevated origin recognition complex subunit 6 expression promotes non-small cell lung cancer cell growth.
PMID: 39349930
Cell Death Dis Β· 2024
0.70
5
Identification and characterization of the human ORC6 homolog.
PMID: 10945994
J Biol Chem Β· 2000
0.60