RB1CC1
protein-codingRB1 inducible coiled-coil 1, the group of Protein phosphatase 1 regulatory subunits|Autophagy related
Gene summary
The protein encoded by this gene interacts with signaling pathways to coordinately regulate cell growth, cell proliferation, apoptosis, autophagy, and cell migration. This tumor suppressor also enhances retinoblastoma 1 gene expression in cancer cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~123.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Evidence or clinical applicability is unclear
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RB1CC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014781.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 19 | 6 | 27 | ||
| missense | 180 | 10 | 190 | |||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 10 | 10 | ||||
| Total | 0 | 1 | 195 | 29 | 6 | 231 |
Highest pathogenic variant AF is 7.176371e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055596.3 | 22 | MANE Select | |
| Ensembl | ENSP00000025008.5 | 22 | MANE Select | |
| RefSeq | NP_001077086.1 | 22 | Standard | |
| Ensembl | ENSP00000396067.2 | 22 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rb1cc1 | Danio rerio | Structure: optic cup Quality: decreased frequency abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
Biological Process
- autophagosome assembly
- autophagy of mitochondrion
- liver development
- positive regulation of protein phosphorylation
- autophagy
Molecular Function
- protein binding
- protein kinase binding
- protein-containing complex scaffold activity
Cellular Component
- phagophore assembly site
- lysosome
- endoplasmic reticulum membrane
- cytosol
- extrinsic component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000025008
- Coding exons
- 22
- Length
- 123388
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125745
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.812 | 709 | 772 | 0.918 | 0.0000376 | 10522 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000094 | 0.000092 | rare |
| European (Non-Finnish) | 0.000089 | 0.000088 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0.00036 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.215
Intolerance Scores
- LoFtool
- 0.345
- RVIS EVS
- -1.59
- RVIS percentile EVS
- 3.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.251
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |