RNF2

ring finger protein 2, the group of Ring finger proteins

Basic information

Region (hg38): 1:185045525-185102603

Links

ENSG00000121481 ∙ NCBI:6045 ∙ OMIM:608985 ∙ HGNC:10061 ∙ Uniprot:Q99496 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Luo-Schoch-Yamamoto syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lou-Schoch-Yamamoto syndrome	AD	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; Musculoskeletal; Neurologic	33864376

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNF2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF2 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			1	1	1	3
missense			12			12
nonsense						0
start loss						0
frameshift				1		1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding			1			1
Total	0	0	15	2	1

Variants in RNF2

This is a list of pathogenic ClinVar variants found in the RNF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-185087566-G-A		not specified	Uncertain significance (Aug 02, 2021)
1-185087566-G-T		not specified	Uncertain significance (Mar 29, 2023)
1-185087577-C-T			Likely benign (Aug 01, 2022)
1-185091700-G-A		RNF2-associated neurodevelopmental condition • Luo-Schoch-Yamamoto syndrome	Uncertain significance (May 17, 2018)
1-185091709-C-T		not specified	Uncertain significance (Mar 22, 2022)
1-185091737-T-G		Luo-Schoch-Yamamoto syndrome	Pathogenic (Aug 19, 2021)
1-185091750-A-T		not specified	Uncertain significance (Oct 16, 2023)
1-185093207-A-G		not specified	Uncertain significance (Jun 13, 2023)
1-185098071-G-A		Luo-Schoch-Yamamoto syndrome	Uncertain significance (Sep 01, 2023)
1-185098250-G-T		not specified	Uncertain significance (Oct 12, 2021)
1-185098265-A-G		not specified	Uncertain significance (Oct 26, 2022)
1-185098265-A-AC		Luo-Schoch-Yamamoto syndrome	Likely benign (Jun 20, 2022)
1-185098341-C-T			Uncertain significance (Nov 01, 2021)
1-185099819-G-C		Luo-Schoch-Yamamoto syndrome	Uncertain significance (-)
1-185099874-G-A		not specified	Uncertain significance (May 05, 2023)
1-185099955-A-G		Luo-Schoch-Yamamoto syndrome	Uncertain significance (Mar 20, 2023)
1-185100256-C-T			Benign (Jul 01, 2022)
1-185100265-G-C		not specified	Uncertain significance (Mar 01, 2024)
1-185100285-C-A		RNF2-related disorder	Uncertain significance (Oct 30, 2023)
1-185100298-A-G		RNF2-related disorder	Uncertain significance (Apr 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF2	protein_coding	protein_coding	ENST00000367510	6	57245

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00257	125741	0	4	125745	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.52	87	183	0.475	0.00000907	2238
Missense in Polyphen		15	57.534	0.26072		751
Synonymous	0.401	57	61.0	0.935	0.00000293	603
Loss of Function	3.88	0	17.5	0.00	0.00000105	199

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase that mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), thereby playing a central role in histone code and gene regulation (PubMed:15386022, PubMed:16359901, PubMed:25519132, PubMed:21772249, PubMed:25355358, PubMed:26151332). H2AK119Ub gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. May be involved in the initiation of both imprinted and random X inactivation (By similarity). Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:16359901, PubMed:26151332). PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility (PubMed:26151332). E3 ubiquitin-protein ligase activity is enhanced by BMI1/PCGF4 (PubMed:21772249). Acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity (Probable). Association with the chromosomal DNA is cell-cycle dependent. In resting B- and T-lymphocytes, interaction with AURKB leads to block its activity, thereby maintaining transcription in resting lymphocytes (By similarity). {ECO:0000250|UniProtKB:Q9CQJ4, ECO:0000269|PubMed:11513855, ECO:0000269|PubMed:15386022, ECO:0000269|PubMed:16359901, ECO:0000269|PubMed:16714294, ECO:0000269|PubMed:20696397, ECO:0000269|PubMed:21772249, ECO:0000269|PubMed:25355358, ECO:0000269|PubMed:25519132, ECO:0000269|PubMed:26151332, ECO:0000305}.
• Pathway: Signal Transduction;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Transcriptional Regulation by E2F6;Generic Transcription Pathway;Oxidative Stress Induced Senescence;SUMOylation of DNA damage response and repair proteins;Cellular Senescence;SUMOylation of chromatin organization proteins;Cellular responses to stress;SUMOylation of RNA binding proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;RNA Polymerase II Transcription;SUMOylation;Cellular responses to external stimuli;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Intracellular signaling by second messengers;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.450

Intolerance Scores

• loftool: 0.223
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.634
• hipred: Y
• hipred_score: 0.831
• ghis: 0.596

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnf2
• Phenotype: immune system phenotype; skeleton 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); 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); hematopoietic system phenotype; neoplasm; embryo phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: rnf2
• Affected structure: xanthophore
• Phenotype tag: abnormal
• Phenotype quality: decreased branchiness

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;mitotic cell cycle;gastrulation with mouth forming second;germ cell development;anterior/posterior axis specification;histone H2A monoubiquitination;histone H2A-K119 monoubiquitination;negative regulation of DNA-binding transcription factor activity;negative regulation of G0 to G1 transition
• Cellular component: ubiquitin ligase complex;euchromatin;sex chromatin;nucleus;nucleoplasm;nuclear body;PcG protein complex;PRC1 complex;MLL1 complex
• Molecular function: chromatin binding;ubiquitin-protein transferase activity;protein binding;zinc ion binding;ubiquitin protein ligase activity;RING-like zinc finger domain binding