RBL2

RB transcriptional corepressor like 2

Basic information

Region (hg38): 16:53433977-53491648

Links

ENSG00000103479 ∙ NCBI:5934 ∙ OMIM:180203 ∙ HGNC:9894 ∙ Uniprot:Q08999 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AR
• Brunet-Wagner neurodevelopmental syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brunet-Wagner neurodevelopmental syndrome	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; Neurologic; Ophthalmologic	32105419; 33980986

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RBL2 gene.

• Brunet-Wagner neurodevelopmental syndrome (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RBL2 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				2	2	4
missense			62	1	2	65
nonsense	1	1				2
start loss						0
frameshift	1	2				3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	2	3	62	3	4

Variants in RBL2

This is a list of pathogenic ClinVar variants found in the RBL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-53434567-G-A		not specified	Uncertain significance (Jul 17, 2024)
16-53434570-G-A		not specified	Uncertain significance (Jul 05, 2024)
16-53434579-C-T		not specified	Uncertain significance (Apr 04, 2023)
16-53434609-C-T		not specified	Uncertain significance (Apr 23, 2024)
16-53434628-G-T		not specified	Uncertain significance (Aug 26, 2024)
16-53434647-G-A		not specified	Uncertain significance (Oct 12, 2022)
16-53434656-G-T		not specified	Uncertain significance (Oct 05, 2023)
16-53434698-C-T		not specified	Uncertain significance (Jan 24, 2024)
16-53434704-G-T		not specified	Uncertain significance (Nov 13, 2024)
16-53434718-C-T			Benign (Dec 31, 2019)
16-53434719-C-T		not specified	Uncertain significance (Nov 26, 2024)
16-53434741-C-T		not specified	Uncertain significance (Nov 15, 2024)
16-53439022-G-A		not specified	Uncertain significance (Sep 01, 2021)
16-53439025-C-T		not specified	Uncertain significance (Feb 28, 2023)
16-53439026-T-A		not specified	Uncertain significance (Sep 27, 2021)
16-53439043-G-A		not specified	Uncertain significance (Feb 22, 2023)
16-53439052-G-A		not specified	Uncertain significance (Jun 30, 2023)
16-53439076-A-G		not specified	Uncertain significance (May 17, 2023)
16-53439107-A-G		not specified	Uncertain significance (Mar 29, 2024)
16-53439121-A-G		not specified	Uncertain significance (Jun 23, 2023)
16-53442709-A-G			Benign (Dec 31, 2019)
16-53442728-C-T		not specified	Uncertain significance (Feb 17, 2023)
16-53442771-T-A		not specified	Uncertain significance (Dec 18, 2023)
16-53442803-A-G		not specified	Uncertain significance (Jun 02, 2024)
16-53442842-C-T		Brunet-Wagner neurodevelopmental syndrome	Likely pathogenic (Jun 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RBL2	protein_coding	protein_coding	ENST00000262133	22	57673

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00165	125712	0	35	125747	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.23	519	604	0.860	0.0000307	7489
Missense in Polyphen		106	171.98	0.61635		2138
Synonymous	1.61	178	208	0.857	0.0000102	2152
Loss of Function	5.80	8	54.0	0.148	0.00000260	698

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000410	0.000408
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000152	0.000149
Middle Eastern	0.0000544	0.0000544
South Asian	0.000119	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Cell cycle - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Human Thyroid Stimulating Hormone (TSH) signaling pathway;Adipogenesis;TGF-beta Signaling Pathway;PI3K-Akt Signaling Pathway;ID signaling pathway;DNA Damage Response (only ATM dependent);Monoamine Transport;Gene expression (Transcription);mets affect on macrophage differentiation;Generic Transcription Pathway;RNA Polymerase II Transcription;Transcription of E2F targets under negative control by DREAM complex;Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1;G0 and Early G1;Cyclin D associated events in G1;G1 Phase;Mitotic G1-G1/S phases;TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest;TGF_beta_Receptor;TP53 Regulates Transcription of Cell Cycle Genes;Transcriptional Regulation by TP53;Cell Cycle;ID;Cell Cycle, Mitotic;FoxO family signaling;E2F transcription factor network (Consensus)

Intolerance Scores

• loftool: 0.0964
• rvis_EVS: -0.73
• rvis_percentile_EVS: 14.15

Haploinsufficiency Scores

• pHI: 0.844
• hipred: Y
• hipred_score: 0.756
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.648

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rbl2
• Phenotype: neoplasm; 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); reproductive system phenotype; normal 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); respiratory system phenotype; embryo phenotype; renal/urinary system phenotype; skeleton phenotype; vision/eye phenotype; muscle phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; endocrine/exocrine gland phenotype; growth/size/body region 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); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin organization;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;regulation of mitotic cell cycle;negative regulation of gene expression;cell differentiation;regulation of lipid kinase activity;regulation of cell division;negative regulation of G1/S transition of mitotic cell cycle
• Cellular component: chromatin;nucleus;nucleoplasm;transcription factor complex;nucleolus;cytosol;extracellular exosome
• Molecular function: RNA polymerase II regulatory region DNA binding;RNA polymerase II activating transcription factor binding;protein binding;promoter-specific chromatin binding