GeneBe

RNF2

protein-coding

ring finger protein 2, the group of Ring finger proteins

Gene summary

Polycomb group (PcG) of proteins form the multiprotein complexes that are important for the transcription repression of various genes involved in development and cell proliferation. The protein encoded by this gene is one of the PcG proteins. It has been shown to interact with, and suppress the activity of, transcription factor CP2 (TFCP2/CP2). Studies of the mouse counterpart suggested the involvement of this gene in the specification of anterior-posterior axis, as well as in cell proliferation in early development. This protein was also found to interact with huntingtin interacting protein 2 (HIP2), an ubiquitin-conjugating enzyme, and possess ubiquitin ligase activity. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007212.4

Inheritance

AD

ClinVar variants

P:1U:38B:5

Top phenotype

Lou-Schoch-Yamamoto syndrome

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr1:185,045,497-185,102,603

External References & Databases

Ensembl (ENSG00000121481)NCBI Gene (6045)OMIM (608985)HGNC:10061GenCCUniProt (Q99496)AlphaFoldClinVar (RNF2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~57.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Luo-Schoch-Yamamoto syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0859171

Submitter: PanelApp Australia

Luo-Schoch-Yamamoto syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859171

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Lou-Schoch-Yamamoto syndromeAD

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 33864376Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RNF2 variants in ClinVar

5 Conditions Cataloged
not specifiedTotal: 22
Luo-Schoch-Yamamoto syndromeTotal: 10
not providedTotal: 8
RNF2-related disorderTotal: 4
RNF2-associated neurodevelopmental conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007212.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
1
clinvar
 4
missense
1
clinvar
34
clinvar
1
clinvar
 36
nonsense
0
start loss
0
frameshift
2
clinvar
1
clinvar
 3
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total10384144
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_007212.4RefSeqNP_009143.16MANE Select
ENST00000367510.8EnsemblENSP00000356480.36MANE Select
ENST00000367509.8EnsemblENSP00000356479.45Standard
ENST00000367509.9EnsemblENSP00000356479.45Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
rnf2Danio rerio

Structure: xanthophore

Quality: decreased branchiness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

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

Molecular Function

  • chromatin binding
  • ubiquitin-protein transferase activity
  • protein binding
  • zinc ion binding
  • ubiquitin protein ligase activity

Cellular Component

  • ubiquitin ligase complex
  • euchromatin
  • sex chromatin
  • nucleus
  • nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000367510
Coding exons
6
Length
57245
Individuals with no LoFs
125741
Homozygous LoFs
0
Heterozygous LoFs
4
Defined
125745
p
0.0000159
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.52871830.4750.000009072238
Missense (PolyPhen)1557.5340.26072751
Synonymous0.4015761.00.9350.00000293603
Loss of Function3.88017.50.000.00000105199

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000350.000035rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.450

Intolerance Scores

LoFtool
0.223
RVIS EVS
-0.1
RVIS percentile EVS
46.2

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.973

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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