ORC1

origin recognition complex subunit 1, the group of Origin recognition complex |AAA ATPases

Basic information

Region (hg38): 1:52372829-52404423

Previous symbols: [ "ORC1L" ]

Links

ENSG00000085840 ∙ NCBI:4998 ∙ OMIM:601902 ∙ HGNC:8487 ∙ Uniprot:Q13415 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Meier-Gorlin syndrome 1 (Definitive), mode of inheritance: AR
• Meier-Gorlin syndrome 1 (Strong), mode of inheritance: AR
• Meier-Gorlin syndrome (Supportive), mode of inheritance: AD
• Meier-Gorlin syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Meier-Gorlin syndrome 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal	819054; 11477602; 14564153; 21358632; 21358633; 21358631; 22333897

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ORC1 gene.

• not provided (8 variants)
• Meier-Gorlin syndrome 1 (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ORC1 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			3	63	3	69
missense	2	3	134	9	6	154
nonsense	3					3
start loss						0
frameshift	6	1				7
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	5	1			7
splice region			5	7	1	13
non coding			4	27	14	45
Total	12	9	144	99	23

Highest pathogenic variant AF is 0.0000131

Variants in ORC1

This is a list of pathogenic ClinVar variants found in the ORC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-52372950-G-A		Meier-Gorlin syndrome 1	Benign (Jun 20, 2021)
1-52372955-C-G		Meier-Gorlin syndrome 1	Uncertain significance (Jan 13, 2018)
1-52373087-G-A		Meier-Gorlin syndrome 1	Uncertain significance (Jan 13, 2018)
1-52373187-G-A		Meier-Gorlin syndrome 1 • ORC1-related disorder	Conflicting classifications of pathogenicity (Dec 13, 2023)
1-52373196-C-T		not specified	Conflicting classifications of pathogenicity (Dec 06, 2023)
1-52373197-G-A		Meier-Gorlin syndrome 1	Uncertain significance (Aug 19, 2022)
1-52373199-A-G			Likely benign (Sep 21, 2021)
1-52373213-C-A		Inborn genetic diseases	Uncertain significance (Feb 06, 2024)
1-52373223-G-A			Likely benign (Jun 29, 2022)
1-52373230-C-T			Uncertain significance (Jul 01, 2022)
1-52373231-G-A		Meier-Gorlin syndrome 1	Uncertain significance (Jan 12, 2018)
1-52373236-C-T			Uncertain significance (Jul 15, 2022)
1-52373237-G-A		Inborn genetic diseases	Uncertain significance (Apr 12, 2023)
1-52373249-C-T			Uncertain significance (Jun 21, 2013)
1-52373250-G-A			Likely benign (Mar 23, 2023)
1-52373254-C-G		Inborn genetic diseases	Uncertain significance (Apr 22, 2024)
1-52373256-G-A			Likely benign (Aug 19, 2022)
1-52373262-C-A			Uncertain significance (Jun 26, 2022)
1-52373279-G-A			Uncertain significance (Feb 14, 2020)
1-52373282-AG-A		-	no classification for the single variant (-)
1-52373284-G-A		-	no classification for the single variant (-)
1-52373296-G-C		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
1-52373303-C-G			Uncertain significance (Jun 13, 2022)
1-52373304-G-A		ORC1-related disorder	Likely benign (Nov 28, 2022)
1-52373320-A-G		not specified • Meier-Gorlin syndrome 1	Benign (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ORC1	protein_coding	protein_coding	ENST00000371568	16	31631

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.73e-14	0.931	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.235	455	469	0.969	0.0000291	5568
Missense in Polyphen		125	134.25	0.93108		1564
Synonymous	0.574	174	184	0.946	0.0000113	1754
Loss of Function	2.20	29	44.9	0.646	0.00000302	503

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000449	0.000449
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000217	0.000217
South Asian	0.000359	0.000359
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The 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.
• Disease: DISEASE: Meier-Gorlin syndrome 1 (MGORS1) [MIM:224690]: A syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. {ECO:0000269|PubMed:21358631, ECO:0000269|PubMed:21358632, ECO:0000269|PubMed:21358633}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell cycle - Homo sapiens (human);Cell Cycle;Mitotic G1-G1-S phases;Retinoblastoma (RB) in Cancer;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 E2F1 target genes at G1/S;G1/S-Specific Transcription;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;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• rvis_EVS: 0.61
• rvis_percentile_EVS: 82.93

Haploinsufficiency Scores

• pHI: 0.899
• hipred: Y
• hipred_score: 0.640
• ghis: 0.602

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: Orc1
• 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); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: orc1
• Affected structure: otolith
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;regulation of transcription involved in G1/S transition of mitotic cell cycle;mitotic cell cycle;DNA replication;DNA replication initiation;mitotic DNA replication checkpoint
• Cellular component: nuclear chromosome, telomeric region;origin recognition complex;nucleus;nucleoplasm;nuclear origin of replication recognition complex;nucleolus;cytosol;plasma membrane
• Molecular function: DNA binding;chromatin binding;DNA replication origin binding;protein binding;ATP binding;metal ion binding