GeneBe

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Meier-Gorlin syndrome 1ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal819054; 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 (276 variants)
  • Inborn_genetic_diseases (107 variants)
  • Meier-Gorlin_syndrome_1 (75 variants)
  • not_specified (27 variants)
  • ORC1-related_disorder (16 variants)
  • Meier-Gorlin_syndrome (1 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. These statistics are base on transcript: NM_000004153.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
4
clinvar
83
clinvar
3
clinvar
 91
missense
4
clinvar
4
clinvar
168
clinvar
23
clinvar
5
clinvar
 204
nonsense
5
clinvar
1
clinvar
 6
start loss
0
frameshift
8
clinvar
4
clinvar
2
clinvar
 14
splice donor/acceptor (+/-2bp)
2
clinvar
6
clinvar
1
clinvar
 9
Total 19 16 175 106 8

Highest pathogenic variant AF is 0.000297391

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ORC1protein_codingprotein_codingENST00000371568 1631631
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.73e-140.9311256960521257480.000207
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.2354554690.9690.00002915568
Missense in Polyphen125134.250.931081564
Synonymous0.5741741840.9460.00001131754
Loss of Function2.202944.90.6460.00000302503

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004490.000449
Ashkenazi Jewish0.000.00
East Asian0.0002170.000217
Finnish0.0001390.000139
European (Non-Finnish)0.0001940.000193
Middle Eastern0.0002170.000217
South Asian0.0003590.000359
Other0.0001630.000163

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

loftool
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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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