RB1CC1

RB1 inducible coiled-coil 1, the group of Protein phosphatase 1 regulatory subunits|Autophagy related

Basic information

Region (hg38): 8:52622458-52745843

Links

ENSG00000023287 ∙ NCBI:9821 ∙ OMIM:606837 ∙ HGNC:15574 ∙ Uniprot:Q8TDY2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schizophrenia	AD	General	Evidence or clinical applicability is unclear	Neurologic	21822266

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RB1CC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RB1CC1 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				5	8	13
missense			49	8		57
nonsense		1				1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding						0
Total	0	1	50	13	8

Variants in RB1CC1

This is a list of pathogenic ClinVar variants found in the RB1CC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-52623805-C-T		not specified	Uncertain significance (Jan 10, 2022)
8-52628135-T-C			Benign (Dec 31, 2019)
8-52630500-G-A		not specified	Uncertain significance (May 25, 2022)
8-52634960-T-C			Benign (Jun 29, 2018)
8-52636051-C-A		not specified	Uncertain significance (Apr 17, 2023)
8-52636056-T-C			Likely benign (Dec 31, 2019)
8-52636059-G-T		not specified	Uncertain significance (Feb 21, 2024)
8-52642404-T-G			Benign (Jun 19, 2018)
8-52642415-C-T		not specified	Uncertain significance (Jun 07, 2024)
8-52642416-G-A			Benign (Apr 30, 2018)
8-52642475-T-C		not specified	Likely benign (Mar 19, 2024)
8-52642541-T-C		not specified	Uncertain significance (Jun 13, 2024)
8-52642559-G-A		not specified	Uncertain significance (Apr 23, 2024)
8-52642713-G-A		not specified	Uncertain significance (Dec 15, 2023)
8-52642728-T-C		not specified	Uncertain significance (Mar 16, 2024)
8-52642766-T-C		not specified	Uncertain significance (Dec 20, 2021)
8-52642778-A-G		not specified	Uncertain significance (Nov 19, 2022)
8-52645747-A-T			Benign/Likely benign (Dec 01, 2022)
8-52645838-G-A		not specified	Uncertain significance (Aug 30, 2021)
8-52645858-A-G			Likely benign (Mar 29, 2018)
8-52656080-T-G		not specified	Uncertain significance (Aug 14, 2023)
8-52656122-CAATT-C			Uncertain significance (Jul 01, 2023)
8-52656182-C-T		not specified	Likely benign (Dec 12, 2022)
8-52656183-T-C		not specified	Uncertain significance (Sep 28, 2023)
8-52656213-C-T		not specified	Uncertain significance (Nov 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RB1CC1	protein_coding	protein_coding	ENST00000025008	22	123388

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.61e-9	125725	0	20	125745	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.812	709	772	0.918	0.0000376	10522
Missense in Polyphen		210	320.61	0.655		4464
Synonymous	-1.65	307	272	1.13	0.0000136	2841
Loss of Function	7.57	5	76.4	0.0654	0.00000404	1030

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000188	0.000181
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.00	0.00
Finnish	0.0000937	0.0000924
European (Non-Finnish)	0.0000892	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.0000337	0.0000327
Other	0.000356	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in autophagy (PubMed:21775823). Regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1 (PubMed:23392225). Required for the formation of the autophagosome-like double-membrane structure that surrounds the Salmonella-containing vacuole (SCV) during S.typhimurium infection and subsequent xenophagy (By similarity). Involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis (By similarity). Inhibits PTK2/FAK1 and PTK2B/PYK2 kinase activity, affecting their downstream signaling pathways (PubMed:10769033, PubMed:12221124). Plays a role as a modulator of TGF-beta-signaling by restricting substrate specificity of RNF111 (By similarity). Functions as a DNA-binding transcription factor (PubMed:12095676). Is a potent regulator of the RB1 pathway through induction of RB1 expression (PubMed:14533007). Plays a crucial role in muscular differentiation (PubMed:12163359). Plays an indispensable role in fetal hematopoiesis and in the regulation of neuronal homeostasis (By similarity). {ECO:0000250|UniProtKB:Q9ESK9, ECO:0000269|PubMed:10769033, ECO:0000269|PubMed:12095676, ECO:0000269|PubMed:12163359, ECO:0000269|PubMed:12221124, ECO:0000269|PubMed:14533007, ECO:0000269|PubMed:21775823, ECO:0000269|PubMed:23392225}.
• Pathway: Autophagy - animal - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Senescence and Autophagy in Cancer;Macroautophagy;Cellular responses to external stimuli;mTOR signaling pathway (Consensus)

Recessive Scores

• pRec: 0.215

Intolerance Scores

• loftool: 0.345
• rvis_EVS: -1.59
• rvis_percentile_EVS: 3.11

Haploinsufficiency Scores

• pHI: 0.820
• hipred: Y
• hipred_score: 0.853
• ghis: 0.607

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.251

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rb1cc1
• Phenotype: immune system phenotype; digestive/alimentary 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); normal phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: rb1cc1
• Affected structure: optic cup
• Phenotype tag: abnormal
• Phenotype quality: decreased frequency

Gene ontology

• Biological process: autophagosome assembly;autophagy of mitochondrion;liver development;positive regulation of protein phosphorylation;autophagy;cell cycle;heart development;macroautophagy;regulation of macroautophagy;autophagy of peroxisome;piecemeal microautophagy of the nucleus;positive regulation of cell size;positive regulation of JNK cascade;reticulophagy;glycophagy;negative regulation of extrinsic apoptotic signaling pathway
• Cellular component: phagophore assembly site;lysosome;endoplasmic reticulum membrane;cytosol;extrinsic component of membrane;nuclear membrane;phagophore assembly site membrane;Atg1/ULK1 kinase complex
• Molecular function: protein binding;protein kinase binding;protein-containing complex scaffold activity