RBL1

Summary

RBL1 (RB transcriptional corepressor like 1, HGNC:9893) is a protein-coding gene on chromosome 20q11.23, encoding Retinoblastoma-like protein 1 (P28749). Key regulator of entry into cell division.

The protein encoded by this gene is similar in sequence and possibly function to the product of the retinoblastoma 1 (RB1) gene. The RB1 gene product is a tumor suppressor protein that appears to be involved in cell cycle regulation, as it is phosphorylated in the S to M phase transition and is dephosphorylated in the G1 phase of the cell cycle. Both the RB1 protein and the product of this gene can form a complex with adenovirus E1A protein and SV40 large T-antigen, with the SV40 large T-antigen binding only to the unphosphorylated form of each protein. In addition, both proteins can inhibit the transcription of cell cycle genes containing E2F binding sites in their promoters. Due to the sequence and biochemical similarities with the RB1 protein, it is thought that the protein encoded by this gene may also be a tumor suppressor. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5933 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 294 total
• MANE Select transcript: NM_002895

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9893
Approved symbol	RBL1
Name	RB transcriptional corepressor like 1
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	p107, cp107, PRB1
Ensembl gene	ENSG00000080839
Ensembl biotype	protein_coding
OMIM	116957
Entrez	5933

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000344359, ENST00000373664, ENST00000525052, ENST00000527999, ENST00000927851, ENST00000927852

RefSeq mRNA: 4 — MANE Select: NM_002895 NM_001323281, NM_001323282, NM_002895, NM_183404

CCDS: CCDS13289, CCDS13290

Canonical transcript exons

ENST00000373664 — 22 exons

Exon	Start	End
ENSE00000520640	37018279	37018369
ENSE00000661832	37020659	37020730
ENSE00000661833	37022650	37022826
ENSE00000661834	37032665	37032876
ENSE00000661835	37035242	37035508
ENSE00000661836	37040153	37040285
ENSE00000661837	37044086	37044250
ENSE00000661838	37047053	37047190
ENSE00000661839	37055553	37055656
ENSE00000661840	37056146	37056258
ENSE00000661841	37061103	37061269
ENSE00000661842	37062084	37062270
ENSE00000661843	37065424	37065473
ENSE00000661844	37066724	37066884
ENSE00000661845	37066993	37067121
ENSE00000661846	37067233	37067297
ENSE00000661847	37067986	37068186
ENSE00000661848	37088989	37089122
ENSE00000800463	37007411	37007559
ENSE00001381636	37003702	37003866
ENSE00001461182	36996349	36998929
ENSE00003890397	37095773	37095997

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 92.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8926 / max 242.2669, expressed in 1470 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187170	5.1376	1387
187169	1.2985	724
184465	0.4564	202

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	92.25	gold quality
calcaneal tendon	UBERON:0003701	90.01	gold quality
ventricular zone	UBERON:0003053	87.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.90	gold quality
ganglionic eminence	UBERON:0004023	81.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.33	gold quality
bone marrow cell	CL:0002092	80.40	gold quality
tendon	UBERON:0000043	79.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.73	gold quality
bone marrow	UBERON:0002371	77.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.69	gold quality
epithelium of nasopharynx	UBERON:0001951	76.44	gold quality
corpus callosum	UBERON:0002336	75.86	gold quality
tonsil	UBERON:0002372	75.65	gold quality
colonic epithelium	UBERON:0000397	75.56	gold quality
adrenal tissue	UBERON:0018303	75.05	gold quality
muscle of leg	UBERON:0001383	74.67	gold quality
lymph node	UBERON:0000029	74.59	gold quality
stromal cell of endometrium	CL:0002255	74.58	gold quality
embryo	UBERON:0000922	73.69	gold quality
muscle organ	UBERON:0001630	73.57	gold quality
gastrocnemius	UBERON:0001388	73.46	gold quality
vermiform appendix	UBERON:0001154	72.85	gold quality
sural nerve	UBERON:0015488	72.78	gold quality
rectum	UBERON:0001052	72.21	gold quality
skeletal muscle tissue	UBERON:0001134	72.19	gold quality
vastus lateralis	UBERON:0001379	72.08	silver quality
leukocyte	CL:0000738	72.01	gold quality
gingival epithelium	UBERON:0001949	71.95	silver quality
monocyte	CL:0000576	71.90	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.60

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
BRCA1	Repression
CCNA2	Repression
H2AC8	Repression
MYC	Unknown
TFDP1	Repression

Upstream regulators (CollecTRI, top): ARID3A, E2F3, E2F4, RB1

miRNA regulators (miRDB)

107 targeting RBL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 29)

• may have a role in the mechanisms of proliferation and differentiation during human placental development (PMID:11642725)
• regulation of expression of p130, p107 and E2F-4 in human cells (PMID:12006580)
• suggests that the p107 N-terminus provides an interaction domain for transcription factors involved in cell cycle control (PMID:12439743)
• report shows hypophosphorylation of the retinoblastoma family proteins induced by H2O2 was because of the activity of protein phosphatase 2A (PMID:12621062)
• p107 plays a constitutive role in the progression of papillary carcinoma of the thyroid and that decreased p107 expression may contribute to the transformation from follicular adenoma to follicular carcinoma and anaplastic transformation. (PMID:14666683)
• Induction of p130 and p107 play an important role in the inhibition of growth of C33A cells by MIS. (PMID:14671316)
• the PP2A catalytic subunit (PP2A/C) specifically interacts with both p130 and p107 in quiescent cells as well as cells progressing throughout the cell cycle (PMID:15467457)
• Data suggest that p107, in addition to its interaction with E2F, inhibits cell proliferation through the control of Skp2 expression and the resulting stabilization of p27. (PMID:15631990)
• p130/p107/p105Rb has a role in transcriptional repression in DNA-damage-induced cell-cycle exit at G2 (PMID:15827088)
• developmental expression of RB, p130 and p107 in mouse and human retina (PMID:15939381)
• p107 is a trancriptional regulator of the cell cycle genes. (PMID:16135806)
• These results demonstrate a mechanistic role for p130 and compensatory roles for p107 and RB in the long-term senescence-like growth arrest response of breast cancer cells to DNA damage. (PMID:16537896)
• These studies have revealed a novel mechanism of Trichostatin A action through derecruitment of a repressor from the Luteinizing hormone receptor gene promoter in a PI3K/PKCzeta-induced Sp1 phosphorylation-dependent manner. (PMID:16943418)
• The repressor complex that Mip/LIN-9 forms with p107 takes functional precedence over the transcriptional activation linked to the Mip/LIN-9 and B-Myb interaction. (PMID:17563750)
• Differentiating human adipose-derived human stem cells (hASC), do not undergo clonal expansion and p130 expression gradually diminishes across differentiation. However, p107 expression is transiently increased during hASC differentiation. (PMID:18086563)
• P107 is needed for initiation of accelerated cellular senescence in the absence of Rb and introduces the concept that p130 may be required to prevent the onset of terminal growth arrest in unstimulated prostate cancer cells lacking a functional Rb allele. (PMID:18418057)
• These data suggest that the FTS/Hook/FHIP complex functions to promote vesicle trafficking and/or fusion via the homotypic vacuolar protein sorting complex. (PMID:18799622)
• Data show that RB is associated with promoters in a manner similar to p107/p130 and that association is modulated by phosphorylation during cell cycle progression. (PMID:19279001)
• identification of a PP2A trimeric holoenzyme containing B55alpha, which plays a major role in restricting the phosphorylation state of p107 and inducing its activation in human cells. (PMID:20663872)
• Concomitant germline large cytogenetic 13q deletion and somatic mutations in the RB1 gene in unilateral retinoblastoma. (PMID:22303805)
• Single nucleotide polymorphism in the ultraconserved elements of RBL1 gene is associated with recurrence in colorectal adenocarcinoma. (PMID:22673945)
• Sequence analysis of the RB1 gene detected a novel mutation in bilateral retinoblastoma. (PMID:22729126)
• MAGE-A11 is a proto-oncogene whose increased expression in prostate cancer reverses retinoblastoma-related protein p107 from a transcriptional repressor to a transcriptional activator of the androgen receptor and E2F1. (PMID:23853093)
• The authors found that phosphorylation of residues S650 and S975 in p107 weakens the E2F4 transactivation domain binding. (PMID:27567532)
• Study found that the methylation of global DNA decreased gradually after irradiation, and the methylation of the promoter of RBL1 gene may play an important role in the induction of radioresistance for three dimensional cultured carcinoma cells. (PMID:27779109)
• These findings in human skeletal muscle suggest that attenuated transcriptional repression through p107 may be a novel mechanism by which exercise stimulates mitochondrial biogenesis following exercise. (PMID:28270591)
• UL97 phosphorylates and inactivates the retinoblastoma protein-related p107 and p130 proteins (PMID:28289097)
• PP2A/B55alpha substrate recruitment as defined by the retinoblastoma-related protein p107. (PMID:34661528)
• Simultaneous depletion of RB, RBL1 and RBL2 affects endoderm differentiation of human embryonic stem cells. (PMID:36413521)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbl1	ENSDARG00000008141
mus_musculus	Rbl1	ENSMUSG00000027641
rattus_norvegicus	Rbl1	ENSRNOG00000006921
drosophila_melanogaster	Rbf	FBGN0015799
drosophila_melanogaster	Rbf2	FBGN0038390
caenorhabditis_elegans	lin-35	WBGENE00003020

Paralogs (2): RBL2 (ENSG00000103479), RB1 (ENSG00000139687)

Protein

Protein identifiers

Retinoblastoma-like protein 1 — P28749 (reviewed: P28749)

Alternative names: 107 kDa retinoblastoma-associated protein, pRb1

All UniProt accessions (3): P28749, E9PNB6, H0YE05

UniProt curated annotations — full annotation on UniProt →

Function. Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 ‘Lys-20’ trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation. May act as a tumor suppressor.

Subunit / interactions. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2. Interacts with AATF. Interacts with KDM5A. Interacts with KMT5B and KMT5C. Interacts with USP4. Interacts with RBBP9. (Microbial infection) Interacts with SV40 and JC virus large T antigens. Large T antigen, but not E1A, binds only to the unphosphorylated form. (Microbial infection) Interacts with JC virus small t antigen.

Subcellular location. Nucleus.

Post-translational modifications. Cell-cycle arrest properties are inactivated by phosphorylation on Thr-332, Ser-640, Ser-964 and Ser-975 by CDK4.

Similarity. Belongs to the retinoblastoma protein (RB) family.

Isoforms (2)

UniProt ID	Names	Canonical?
P28749-1	1	yes
P28749-2	2

RefSeq proteins (4): NP_001310210, NP_001310211, NP_002886, NP_899662 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002719	RB_B	Domain
IPR002720	RB_A	Domain
IPR013763	Cyclin-like_dom	Domain
IPR015030	RB_C	Domain
IPR024599	RB_N	Domain
IPR028309	RB_fam	Family
IPR036915	Cyclin-like_sf	Homologous_superfamily

Pfam: PF01857, PF01858, PF08934, PF11934

UniProt features (57 total): helix 24, modified residue 13, strand 5, region of interest 4, mutagenesis site 4, sequence conflict 2, turn 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
7SMD	X-RAY DIFFRACTION	2.15
4YOZ	X-RAY DIFFRACTION	2.25
4YOS	X-RAY DIFFRACTION	2.3
4YOO	X-RAY DIFFRACTION	2.4
9C6B	ELECTRON MICROSCOPY	2.6
7SME	X-RAY DIFFRACTION	2.64
7SMC	X-RAY DIFFRACTION	2.7
1H28	X-RAY DIFFRACTION	2.8
5TUV	X-RAY DIFFRACTION	2.9
7SMF	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28749-F1	72.56	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (13): 749, 762, 964, 975, 988, 997, 1009, 1041, 332, 369, 385, 640, 650

Mutagenesis-validated functional residues (4):

Position	Phenotype
640	strongly reduces phosphorylation by cdk2 and cdk4.
643	no effect on s-640 phosphorylation, but strongly increases s-640 phosphorylation; when associated with 657-a–a-660.
650	no effect on phosphorylation by cdk2.
657–660	reduces s-640 phosphorylation by cdk2 and cdk4.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex
R-HSA-1362300	Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-1538133	G0 and Early G1
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-6804114	TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-69205	G1/S-Specific Transcription
R-HSA-69231	Cyclin D associated events in G1

MSigDB gene sets: 400 (showing top): E2F_Q4, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, E2F4DP1_01, GOBP_REGULATION_OF_PHOSPHORYLATION, PAL_PRMT5_TARGETS_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, KYNG_DNA_DAMAGE_DN, GOBP_CELLULAR_SENESCENCE, KONG_E2F3_TARGETS

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin organization (GO:0006325), negative regulation of gene expression (GO:0010629), cell differentiation (GO:0030154), regulation of lipid kinase activity (GO:0043550), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), negative regulation of cellular senescence (GO:2000773), regulation of transcription by RNA polymerase II (GO:0006357), regulation of gene expression (GO:0010468), negative regulation of macromolecule biosynthetic process (GO:0010558), regulation of cell cycle (GO:0051726)

GO Molecular Function (3): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), promoter-specific chromatin binding (GO:1990841), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
G0 and Early G1	2
Mitotic G1 phase and G1/S transition	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
TP53 Regulates Transcription of Cell Cycle Genes	1
G1/S Transition	1
G1 Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
gene expression	2
regulation of macromolecule biosynthetic process	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cellular component organization	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
cellular developmental process	1
lipid kinase activity	1
regulation of kinase activity	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
negative regulation of cellular process	1
cellular senescence	1
regulation of cellular senescence	1
regulation of DNA-templated transcription	1
macromolecule biosynthetic process	1
negative regulation of biosynthetic process	1
negative regulation of macromolecule metabolic process	1
cell cycle	1
regulation of cellular process	1
transcription cis-regulatory region binding	1
chromatin binding	1
binding	1
chromosome	1
nuclear lumen	1
protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1239 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBL1	E2F4	Q16254	674
RBL1	E2F5	Q15329	615
RBL1	CDK2	P24941	598
RBL1	LIN52	Q52LA3	567
RBL1	KMT5C	Q86Y97	480
RBL1	CCNE1	P24864	446
RBL1	SAP30BP	Q9UHR5	439
RBL1	RBL2	Q08999	399
RBL1	ZDHHC14	Q8IZN3	390
RBL1	E2F2	Q14209	389
RBL1	E2F8	A0AVK6	360
RBL1	DGCR8	Q8WYQ5	354
RBL1	VARS1	P26640	350
RBL1	E2F1	Q01094	343
RBL1	PLK1	P53350	337

IntAct

130 interactions, top by confidence:

A	B	Type	Score
E2F1	RB1	psi-mi:“MI:0914”(association)	0.980
CDK2	CCNE2	psi-mi:“MI:0914”(association)	0.940
CDK2	CCNB1	psi-mi:“MI:0914”(association)	0.890
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
E7	RBL1	psi-mi:“MI:0914”(association)	0.820
RBL1	E7	psi-mi:“MI:0915”(physical association)	0.820
E7	RBL1	psi-mi:“MI:0915”(physical association)	0.820
E7	RBL1	psi-mi:“MI:0407”(direct interaction)	0.820
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
RBL1	E7	psi-mi:“MI:0915”(physical association)	0.740
E7	RBL1	psi-mi:“MI:0407”(direct interaction)	0.740
E7	RBL1	psi-mi:“MI:0915”(physical association)	0.740
CDC20	BUB1	psi-mi:“MI:0914”(association)	0.730
LIN37	MYBL2	psi-mi:“MI:0914”(association)	0.730
E7	RB1	psi-mi:“MI:0914”(association)	0.700
CTBP1	CBX4	psi-mi:“MI:0914”(association)	0.700
DYRK1A	RB1	psi-mi:“MI:0914”(association)	0.670
DYRK1A	RBL1	psi-mi:“MI:0915”(physical association)	0.670
DYRK1B	RBL1	psi-mi:“MI:0915”(physical association)	0.670
RBL1	DYRK1A	psi-mi:“MI:0915”(physical association)	0.670
CCNA2	GMNN	psi-mi:“MI:0914”(association)	0.640
LIN37	MYBL1	psi-mi:“MI:0914”(association)	0.640
CDK2	GMNN	psi-mi:“MI:0914”(association)	0.640

BioGRID (229): RBL1 (Affinity Capture-MS), RBL1 (Reconstituted Complex), RBL1 (Affinity Capture-MS), RBL1 (Affinity Capture-MS), RBL1 (Affinity Capture-MS), RBL1 (Affinity Capture-MS), BEGAIN (Two-hybrid), RBL1 (Affinity Capture-MS), RBL1 (Two-hybrid), RBL1 (Affinity Capture-MS), BEGAIN (Affinity Capture-Western), RBL1 (Affinity Capture-Western), RBL1 (Affinity Capture-Western), RBL1 (Affinity Capture-MS), RBL1 (Affinity Capture-MS)

ESM2 similar proteins: A4VCH4, A7P514, A9UL14, B1ABR6, B1ABS0, B5X165, B9GLX8, B9SVG9, D3ZS28, F1ND48, F1R7R1, F8VPU6, O42611, O55081, O75694, P28749, P32780, P59764, Q08999, Q1LXC9, Q3UVG3, Q4JF75, Q4R8N2, Q5JSJ4, Q5RHQ8, Q5U4W6, Q64700, Q64701, Q66WV0, Q68CZ1, Q6DC03, Q6PCM2, Q6WKZ8, Q7SYD9, Q80V94, Q8C735, Q8CG73, Q8H252, Q8N1I0, Q8QFR2

Diamond homologs: D3ZS28, O55081, P28749, Q08999, Q54FX2, Q64700, Q64701

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PPP2CA	up-regulates	RBL1	dephosphorylation
CDK4	“up-regulates activity”	RBL1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	9	66.8×	3e-13
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	8	62.7×	2e-11
G0 and Early G1	11	59.6×	5e-15
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	6	52.9×	5e-08
Transcription of E2F targets under negative control by DREAM complex	7	47.0×	5e-09
Polo-like kinase mediated events	6	47.0×	9e-08
Cyclin E associated events during G1/S transition	12	42.3×	1e-14
Cyclin A:Cdk2-associated events at S phase entry	12	39.4×	2e-14

GO biological processes:

GO term	Partners	Fold	FDR
G1/S transition of mitotic cell cycle	11	23.7×	9e-10
positive regulation of fibroblast proliferation	6	19.1×	2e-04
negative regulation of cell cycle	5	15.6×	2e-03
regulation of mitotic cell cycle	6	15.5×	4e-04
double-strand break repair	5	10.9×	5e-03
cell division	16	7.9×	6e-08
cellular response to hypoxia	6	7.8×	5e-03
regulation of cell cycle	9	7.2×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

294 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	253
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3299 predictions. Top by Δscore:

Variant	Effect	Δscore
20:36998928:CT:C	acceptor_gain	1.0000
20:37007406:CATA:C	donor_loss	1.0000
20:37007407:ATAC:A	donor_loss	1.0000
20:37007408:TACC:T	donor_loss	1.0000
20:37007409:A:AC	donor_gain	1.0000
20:37007409:A:AT	donor_loss	1.0000
20:37007410:C:CC	donor_gain	1.0000
20:37007410:C:CT	donor_loss	1.0000
20:37007414:ATGGT:A	donor_gain	1.0000
20:37007557:AGT:A	acceptor_gain	1.0000
20:37007559:TCTGT:T	acceptor_loss	1.0000
20:37007560:C:CC	acceptor_gain	1.0000
20:37007560:C:T	acceptor_loss	1.0000
20:37020657:A:AC	donor_gain	1.0000
20:37020658:C:CC	donor_gain	1.0000
20:37020658:CGTGA:C	donor_gain	1.0000
20:37020730:CCT:C	acceptor_loss	1.0000
20:37020731:C:CC	acceptor_gain	1.0000
20:37020731:CT:C	acceptor_loss	1.0000
20:37020732:T:A	acceptor_loss	1.0000
20:37035259:A:C	donor_gain	1.0000
20:37035264:ATGT:A	donor_gain	1.0000
20:37035267:T:TA	donor_gain	1.0000
20:37035276:T:TA	donor_gain	1.0000
20:37035378:T:TA	donor_gain	1.0000
20:37040148:CCTA:C	donor_loss	1.0000
20:37040149:CTAC:C	donor_loss	1.0000
20:37040150:TACCT:T	donor_loss	1.0000
20:37040151:ACC:A	donor_loss	1.0000
20:37040152:C:A	donor_loss	1.0000

AlphaMissense

7042 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:37007482:A:C	Y934D	1.000
20:37007493:A:G	L930P	1.000
20:37007493:A:T	L930H	1.000
20:37018362:C:G	R880T	1.000
20:37020707:A:C	F861L	1.000
20:37020707:A:T	F861L	1.000
20:37020709:A:G	F861L	1.000
20:37022748:A:G	W821R	1.000
20:37022748:A:T	W821R	1.000
20:37044154:A:G	W568R	1.000
20:37044154:A:T	W568R	1.000
20:37067257:A:G	W178R	1.000
20:37067257:A:T	W178R	1.000
20:37007470:A:C	Y938D	0.999
20:37007483:A:C	F933L	0.999
20:37007483:A:T	F933L	0.999
20:37007484:A:G	F933S	0.999
20:37007485:A:G	F933L	0.999
20:37018356:A:T	V882D	0.999
20:37018361:T:A	R880S	0.999
20:37018361:T:G	R880S	0.999
20:37018362:C:A	R880I	0.999
20:37020688:A:C	Y868D	0.999
20:37020708:A:C	F861C	0.999
20:37020708:A:G	F861S	0.999
20:37022664:A:C	Y849D	0.999
20:37022671:A:C	C846W	0.999
20:37022672:C:T	C846Y	0.999
20:37022673:A:G	C846R	0.999
20:37022675:A:G	L845P	0.999

dbSNP variants (sampled 300 via entrez): RS1000011456 (20:37044097 T>C), RS1000031273 (20:37096837 C>A,G,T), RS1000044352 (20:37003481 A>C), RS1000153257 (20:37096330 G>T), RS1000154159 (20:37051354 A>G), RS1000163461 (20:37086461 G>A), RS1000186742 (20:37023666 A>G), RS1000210577 (20:37073550 T>C), RS1000222679 (20:37023304 G>A), RS1000270204 (20:37076788 C>T), RS1000270909 (20:37031419 T>C), RS1000275559 (20:37077387 T>C), RS1000384085 (20:37044457 C>G), RS1000400997 (20:37024681 G>A), RS1000417121 (20:37037482 A>G)

Disease associations

OMIM: gene MIM:116957 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002702_19	Height	9.000000e-12
GCST006804_52	Red cell distribution width	4.000000e-13
GCST90002390_696	Mean corpuscular hemoglobin	2.000000e-15
GCST90002392_103	Mean corpuscular volume	3.000000e-18
GCST90002396_55	Mean reticulocyte volume	8.000000e-14
GCST90002397_276	Mean spheric corpuscular volume	3.000000e-15
GCST90002404_576	Red cell distribution width	1.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

74 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	3
bisphenol A	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
palbociclib	decreases expression, decreases reaction, affects binding, increases reaction, increases ubiquitination (+2 more)	2
Copper	increases expression, decreases expression, affects binding	2
Cycloheximide	decreases reaction, increases expression, decreases expression, increases reaction, affects reaction	2
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, increases expression	2
Valproic Acid	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
UF010 compound	increases activity	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
riddelliine	increases metabolic processing, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
calyculin A	decreases phosphorylation, decreases reaction	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression, increases ubiquitination, increases reaction, decreases expression, decreases reaction	1
alvocidib	decreases expression	1
CGP 52608	affects binding, increases reaction	1
6-(methylamino)pyrido(3,4-d)pyrimidine	decreases expression	1
GW 3965	decreases expression	1
abrine	decreases expression	1
incobotulinumtoxinA	decreases expression	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	decreases expression	1
NSC 689534	affects binding, decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2DI	Abcam HeLa RBL1 KO	Cancer cell line	Female
CVCL_D8UG	Ubigene HCT 116 RBL1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.