ORC6

origin recognition complex subunit 6, the group of Origin recognition complex

Basic information

Region (hg38): 16:46689643-46698394

Previous symbols: [ "ORC6L" ]

Links

ENSG00000091651 ∙ NCBI:23594 ∙ OMIM:607213 ∙ HGNC:17151 ∙ Uniprot:Q9Y5N6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Meier-Gorlin syndrome 3 (Definitive), mode of inheritance: AR
• Meier-Gorlin syndrome 3 (Strong), mode of inheritance: AR
• Meier-Gorlin syndrome (Supportive), mode of inheritance: AD
• Meier-Gorlin syndrome 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Meier-Gorlin syndrome 3	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; Genitourinary; Musculoskeletal	7710253; 21358632; 22333897

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ORC6 gene.

• Meier-Gorlin syndrome 3 (5 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ORC6 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				28	1	29
missense	3		40	1		44
nonsense	2					2
start loss	1					1
frameshift	3		1			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			5	1		6
non coding			24	12	7	43
Total	9	0	66	41	8

Highest pathogenic variant AF is 0.0000197

Variants in ORC6

This is a list of pathogenic ClinVar variants found in the ORC6 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-46689659-G-A		not specified • Meier-Gorlin syndrome • Parkinson Disease, Dominant • Meier-Gorlin syndrome 3	Conflicting classifications of pathogenicity (Jan 13, 2018)
16-46689686-T-C		not specified • Meier-Gorlin syndrome • Parkinson Disease, Dominant • Meier-Gorlin syndrome 3	Benign (Sep 05, 2021)
16-46689687-T-C		Meier-Gorlin syndrome 3	Uncertain significance (Jan 13, 2018)
16-46689706-A-G		Meier-Gorlin syndrome 3	Pathogenic (May 24, 2017)
16-46689707-T-C		Meier-Gorlin syndrome 3 • ORC6-related disorder	Conflicting classifications of pathogenicity (Jun 10, 2024)
16-46689709-G-A			Uncertain significance (Oct 07, 2022)
16-46689713-C-T			Uncertain significance (Dec 06, 2023)
16-46689714-G-T			Likely benign (Jun 14, 2023)
16-46689717-G-A			Likely benign (Feb 10, 2023)
16-46689720-G-A			Likely benign (Jan 01, 2022)
16-46689723-C-T			Likely benign (Dec 09, 2023)
16-46689728-G-A			Uncertain significance (Aug 28, 2021)
16-46689728-G-T		Meier-Gorlin syndrome 3 • Inborn genetic diseases	Uncertain significance (Apr 07, 2022)
16-46689731-T-C			Uncertain significance (Apr 01, 2022)
16-46689732-A-G		Meier-Gorlin syndrome 3	Conflicting classifications of pathogenicity (Aug 16, 2023)
16-46689733-G-T			Uncertain significance (Aug 09, 2022)
16-46689737-C-G		Meier-Gorlin syndrome 3	Uncertain significance (Feb 18, 2022)
16-46689754-G-T			Pathogenic (Oct 17, 2022)
16-46689759-C-G			Likely benign (Jan 09, 2024)
16-46689770-G-A		Meier-Gorlin syndrome 3	Pathogenic (-)
16-46690971-C-T			Likely benign (Dec 15, 2022)
16-46690972-A-C			Benign (Jun 20, 2023)
16-46690996-C-T		Meier-Gorlin syndrome 3	Pathogenic (-)
16-46691017-C-T		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
16-46691019-C-A			Likely benign (May 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ORC6	protein_coding	protein_coding	ENST00000219097	7	8752

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.36e-7	0.345	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.487	151	135	1.12	0.00000674	1631
Missense in Polyphen		37	37.017	0.99955		472
Synonymous	-0.953	59	50.4	1.17	0.00000253	489
Loss of Function	0.525	11	13.0	0.843	6.17e-7	167

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000170	0.000167
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
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 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. Does not bind histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3. {ECO:0000269|PubMed:22427655}.
• Disease: DISEASE: Meier-Gorlin syndrome 3 (MGORS3) [MIM:613803]: 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:21358632}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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: 0.103

Intolerance Scores

• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.290
• hipred: Y
• hipred_score: 0.626
• ghis: 0.687

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: Orc6
• 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)

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;DNA replication;DNA replication initiation;negative regulation of cell division
• Cellular component: origin recognition complex;fibrillar center;nucleus;nucleoplasm;nuclear origin of replication recognition complex;membrane
• Molecular function: DNA replication origin binding;protein binding