ORC3

origin recognition complex subunit 3, the group of Origin recognition complex

Basic information

Region (hg38): 6:87590066-87667453

Previous symbols: [ "ORC3L" ]

Links

ENSG00000135336 ∙ NCBI:23595 ∙ OMIM:604972 ∙ HGNC:8489 ∙ Uniprot:Q9UBD5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ORC3 gene.

• Inborn genetic diseases (30 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ORC3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			28	1		29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1	1	2
Total	0	0	28	2	1

Variants in ORC3

This is a list of pathogenic ClinVar variants found in the ORC3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-87590087-T-C			Benign (Jun 16, 2018)
6-87590167-C-G			Likely benign (Jul 15, 2018)
6-87590186-G-A		not specified	Uncertain significance (Dec 21, 2021)
6-87590295-A-G			Benign (Jun 19, 2018)
6-87594362-G-T		not specified	Uncertain significance (Jan 04, 2024)
6-87594371-C-T		not specified	Uncertain significance (Jun 30, 2023)
6-87594377-T-A		not specified	Uncertain significance (Feb 27, 2024)
6-87601790-A-G		not specified	Uncertain significance (Feb 16, 2023)
6-87601837-G-A		not specified	Uncertain significance (Oct 20, 2021)
6-87601855-T-C		not specified	Uncertain significance (Dec 15, 2023)
6-87601869-A-C		not specified	Uncertain significance (Feb 23, 2023)
6-87603408-A-G		not specified	Uncertain significance (Feb 28, 2024)
6-87603451-C-G		not specified	Uncertain significance (Nov 09, 2021)
6-87603511-C-T		not specified	Uncertain significance (May 09, 2022)
6-87605949-G-A		not specified	Likely benign (Aug 09, 2021)
6-87607748-A-G		not specified	Uncertain significance (Feb 22, 2023)
6-87607759-G-A		not specified	Uncertain significance (Aug 12, 2021)
6-87609100-C-T		not specified	Uncertain significance (Sep 15, 2021)
6-87609163-T-A		ORC3-related disorder	Likely pathogenic (Aug 30, 2023)
6-87612130-T-A		not specified	Uncertain significance (Dec 16, 2022)
6-87612222-G-A		not specified	Uncertain significance (Jan 16, 2024)
6-87612252-A-G		ORC3-related disorder	Likely pathogenic (Aug 30, 2023)
6-87616365-G-A		not specified	Likely benign (Dec 17, 2023)
6-87616408-A-C		not specified	Uncertain significance (Nov 30, 2022)
6-87621466-G-A		not specified	Uncertain significance (Apr 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ORC3	protein_coding	protein_coding	ENST00000257789	20	77331

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.62e-9	1.00	125663	0	84	125747	0.000334

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.515	330	357	0.923	0.0000173	4685
Missense in Polyphen		87	105.54	0.82437		1453
Synonymous	0.298	128	132	0.967	0.00000699	1288
Loss of Function	3.12	22	44.4	0.495	0.00000233	553

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000519	0.000518
Ashkenazi Jewish	0.000993	0.000993
East Asian	0.000275	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000413	0.000404
Middle Eastern	0.000275	0.000272
South Asian	0.000238	0.000229
Other	0.00100	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3. {ECO:0000269|PubMed:22427655}.
• Pathway: Cell cycle - Homo sapiens (human);Cell Cycle;G1 to S cell cycle control;DNA Replication;cdk regulation of dna replication;Activation of ATR in response to replication stress;G2/M Checkpoints;Cell Cycle Checkpoints;Activation of the pre-replicative complex;E2F mediated regulation of DNA replication;Mitotic G1-G1/S phases;Orc1 removal from chromatin;DNA Replication;Switching of origins to a post-replicative state;Synthesis of DNA;S Phase;G1/S Transition;E2F-enabled inhibition of pre-replication complex formation;Assembly of the ORC complex at the origin of replication;CDC6 association with the ORC:origin complex;CDT1 association with the CDC6:ORC:origin complex;Assembly of the pre-replicative complex;DNA Replication Pre-Initiation;M/G1 Transition;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.117

Intolerance Scores

• rvis_EVS: 0.67
• rvis_percentile_EVS: 84.64

Haploinsufficiency Scores

• pHI: 0.885
• hipred: Y
• hipred_score: 0.706
• ghis: 0.544

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Orc3
• Phenotype: limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;DNA replication;pre-replicative complex assembly involved in nuclear cell cycle DNA replication;DNA replication initiation;neural precursor cell proliferation
• Cellular component: nuclear chromosome, telomeric region;origin recognition complex;nucleoplasm;nuclear pre-replicative complex;nuclear origin of replication recognition complex;nuclear body;DNA replication preinitiation complex
• Molecular function: DNA replication origin binding;protein binding