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GeneBe

RNF2

ring finger protein 2, the group of Ring finger proteins

Basic information

Region (hg38): 1:185045525-185102603

Links

ENSG00000121481NCBI:6045OMIM:608985HGNC:10061Uniprot:Q99496AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Lou-Schoch-Yamamoto syndromeADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Neurologic33864376

ClinVar

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

  • Inborn genetic diseases (7 variants)
  • not provided (3 variants)
  • Luo-Schoch-Yamamoto syndrome (3 variants)
  • not specified (1 variants)
  • RNF2-associated neurodevelopmental condition (1 variants)
  • RNF2-related condition (1 variants)

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
clinvar
1
clinvar
1
clinvar
3
missense
9
clinvar
9
nonsense
0
start loss
0
frameshift
1
clinvar
1
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
0
non coding
1
clinvar
1
Total 0 0 13 1 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 Inborn genetic diseases Uncertain significance (Aug 02, 2021)2240040
1-185087566-G-T Inborn genetic diseases Uncertain significance (Mar 29, 2023)2515136
1-185087577-C-T Likely benign (Aug 01, 2022)2639639
1-185091700-G-A RNF2-associated neurodevelopmental condition • Luo-Schoch-Yamamoto syndrome Uncertain significance (May 17, 2018)988094
1-185091709-C-T Inborn genetic diseases Uncertain significance (Mar 22, 2022)2279359
1-185091737-T-G Luo-Schoch-Yamamoto syndrome Pathogenic (Aug 19, 2021)1189036
1-185091750-A-T not specified Uncertain significance (Oct 16, 2023)2637754
1-185093207-A-G Inborn genetic diseases Uncertain significance (Jun 13, 2023)2513133
1-185098071-G-A Luo-Schoch-Yamamoto syndrome Uncertain significance (Sep 01, 2023)2572444
1-185098250-G-T Inborn genetic diseases Uncertain significance (Oct 12, 2021)2255164
1-185098265-A-G Inborn genetic diseases Uncertain significance (Oct 26, 2022)2319271
1-185098265-A-AC Luo-Schoch-Yamamoto syndrome Uncertain significance (Feb 20, 2023)2500330
1-185098341-C-T Uncertain significance (Nov 01, 2021)1335004
1-185099874-G-A Inborn genetic diseases Uncertain significance (May 05, 2023)2508190
1-185099955-A-G Luo-Schoch-Yamamoto syndrome Uncertain significance (Mar 20, 2023)3066073
1-185100256-C-T Benign (Jul 01, 2022)2639640
1-185100285-C-A RNF2-related condition Uncertain significance (Oct 30, 2023)3038190
1-185100298-A-G RNF2-related condition Uncertain significance (Apr 04, 2023)2633881

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RNF2protein_codingprotein_codingENST00000367510 657245
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9970.00257125741041257450.0000159
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.52871830.4750.000009072238
Missense in Polyphen1557.5340.26072751
Synonymous0.4015761.00.9350.00000293603
Loss of Function3.88017.50.000.00000105199

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00003520.0000352
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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