ORC2

origin recognition complex subunit 2, the group of Origin recognition complex

Basic information

Region (hg38): 2:200908976-200963680

Previous symbols: [ "ORC2L" ]

Links

ENSG00000115942 ∙ NCBI:4999 ∙ OMIM:601182 ∙ HGNC:8488 ∙ Uniprot:Q13416 ∙ 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 ORC2 gene.

• Inborn genetic diseases (14 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ORC2 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			14			14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	14	0	0

Variants in ORC2

This is a list of pathogenic ClinVar variants found in the ORC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-200913299-T-G		not specified	Uncertain significance (Aug 02, 2023)
2-200913309-T-C		not specified	Uncertain significance (Feb 28, 2024)
2-200913384-A-C		not specified	Uncertain significance (Feb 06, 2023)
2-200913955-T-G		not specified	Uncertain significance (Aug 10, 2021)
2-200920235-T-G		not specified	Uncertain significance (May 04, 2022)
2-200920267-A-C		not specified	Uncertain significance (Aug 16, 2021)
2-200920392-C-T		not specified	Uncertain significance (Apr 28, 2022)
2-200925883-C-T		not specified	Uncertain significance (Feb 16, 2023)
2-200925902-C-T		not specified	Uncertain significance (Mar 31, 2022)
2-200926799-T-C		not specified	Uncertain significance (Jul 13, 2021)
2-200926900-G-C		not specified	Uncertain significance (Dec 02, 2021)
2-200931435-T-C		not specified	Uncertain significance (Feb 07, 2023)
2-200931444-G-A		not specified	Uncertain significance (May 17, 2023)
2-200933886-T-A		not specified	Uncertain significance (Sep 14, 2022)
2-200935749-C-G		not specified	Uncertain significance (Jan 23, 2024)
2-200949567-C-A		not specified	Uncertain significance (Jan 23, 2023)
2-200949574-G-T		not specified	Uncertain significance (Sep 25, 2023)
2-200957485-T-G		not specified	Uncertain significance (Oct 10, 2023)
2-200957500-T-G		not specified	Uncertain significance (May 11, 2022)
2-200958114-G-T		not specified	Uncertain significance (Dec 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ORC2	protein_coding	protein_coding	ENST00000234296	16	54708

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.844	0.156	125710	0	16	125726	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.06	235	285	0.823	0.0000140	3819
Missense in Polyphen		63	84.57	0.74494		1174
Synonymous	1.47	83	102	0.815	0.00000504	1025
Loss of Function	4.31	6	32.5	0.184	0.00000163	422

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000241
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.0000559	0.0000544
Finnish	0.0000468	0.0000462
European (Non-Finnish)	0.0000362	0.0000352
Middle Eastern	0.0000559	0.0000544
South Asian	0.0000687	0.0000653
Other	0.00	0.00

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, H3K20me3 and H4K27me3. Stabilizes LRWD1, by protecting it from ubiquitin- mediated proteasomal degradation. Also stabilizes ORC3. {ECO:0000269|PubMed:22427655, ECO:0000269|PubMed:22935713}.
• 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: 0.122

Intolerance Scores

• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.16

Haploinsufficiency Scores

• pHI: 0.953
• hipred: Y
• hipred_score: 0.825
• ghis: 0.626

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: Orc2

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;negative regulation of transcription by RNA polymerase II;DNA replication;DNA replication initiation
• Cellular component: nuclear chromosome, telomeric region;heterochromatin;origin recognition complex;condensed chromosome inner kinetochore;nucleus;nucleoplasm;nuclear origin of replication recognition complex;centrosome;membrane
• Molecular function: DNA replication origin binding;protein binding