GeneBe

RNF213

protein-coding

ring finger protein 213, the group of Ring finger proteins

Gene summary

This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. The protein also contains an AAA domain, which is associated with ATPase activity. This gene is a susceptibility gene for Moyamoya disease, a vascular disorder of intracranial arteries. This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

Previous symbols:
  • C17orf27
  • KIAA1618
  • MYMY2

MANE transcript

NM_001256071.3

Inheritance

AR, AD

ClinVar variants

P:28U:441B:539

Top phenotype

Moyamoya disease 2

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr17:80,260,852-80,398,794

External References & Databases

Ensembl (ENSG00000173821)NCBI Gene (57674)OMIM (613768)HGNC:14539GenCCUniProt (Q63HN8)AlphaFoldClinVar (RNF213)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~137.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Moyamoya disease 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011784

Submitter: Genomics England PanelApp

Moyamoya disease 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011784

Submitter: Genomics England PanelApp

Moyamoya disease 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011784

Submitter: Labcorp Genetics (formerly Invitae)

Moyamoya disease 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011784

Submitter: Labcorp Genetics (formerly Invitae)

Moyamoya disease 2MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0011784

Submitter: G2P

Moyamoya disease 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011784

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Moyamoya disease 2AD/AR

Manifestation: Cardiovascular

Intervention: Cardiovascular

Rationale: The condition can manifest with transient ischemic attacks, cerebral infarction, and intracranial hemorrhage, and surveillance, preventive measures and early medical treatment may ameliorate/prevent severe sequelae

Comments: Individuals with biallelic variants typically have earlier onset of manifestations

Refs: 21048783; 22377813; 22931863Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RNF213 variants in ClinVar

21 Conditions Cataloged
not providedTotal: 902
not specifiedTotal: 257
RNF213-related disorderTotal: 145
Moyamoya disease 2Total: 104
See casesTotal: 9
Inborn genetic diseasesTotal: 5
Moyamoya angiopathyTotal: 3
Moyamoya diseaseTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001256071.3. 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
9
clinvar
299
clinvar
47
clinvar
 355
missense
7
clinvar
19
clinvar
385
clinvar
149
clinvar
42
clinvar
 602
nonsense
16
clinvar
 16
start loss
0
frameshift
1
clinvar
13
clinvar
 14
splice donor/acceptor (+/-2bp)
1
clinvar
18
clinvar
1
clinvar
1
clinvar
 21
Total721441449901008

Highest pathogenic variant AF is 0.00024284475

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001256071.3RefSeqNP_001243000.267MANE Select
ENST00000582970.6EnsemblENSP00000464087.167MANE Select
NM_001410195.1RefSeqNP_001397124.168Standard
NM_020914.5RefSeqNP_065965.568Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
rnf213aDanio rerio

Structure: nucleate erythrocyte

Quality: decreased fluid flow

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Immune System
  • Adaptive Immune System
  • Antigen processing: Ubiquitination & Proteasome degradation
  • Class I MHC mediated antigen processing & presentation

Biological Process

  • protein polyubiquitination
  • angiogenesis
  • sprouting angiogenesis
  • ubiquitin-dependent protein catabolic process
  • protein ubiquitination

Molecular Function

  • ubiquitin-protein transferase activity
  • ATPase activity
  • metal ion binding

Cellular Component

  • nucleolus
  • cytoplasm
  • cytosol
  • membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000582970
Coding exons
67
Length
137922
Individuals with no LoFs
125266
Homozygous LoFs
1
Heterozygous LoFs
481
Defined
125748
p
0.00192
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.3025392.89e+30.8790.00018634248
Missense (PolyPhen)667919.690.7252411235
Synonymous-2.0413241.23e+31.070.000089010147
Loss of Function6.011262230.5660.00001172688

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00620.0062notable
Latino/Admixed American0.00180.0017notable
Ashkenazi Jewish0.00140.0014notable
East Asian0.00330.0024notable
Finnish0.000880.00088rare
European (Non-Finnish)0.00130.0012notable
South Asian0.00330.0032notable
Other0.00120.00098notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: E3 ubiquitin-protein ligase involved in angiogenesis (PubMed:21799892, PubMed:26278786, PubMed:26766444, PubMed:26126547). Involved in the non-canonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway and promoting vessel regression (PubMed:26766444). Also has ATPase activity (PubMed:24658080, PubMed:26126547). {ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:24658080, ECO:0000269|PubMed:26126547, ECO:0000269|PubMed:26278786, ECO:0000269|PubMed:26766444}.;
Disease
DISEASE: Moyamoya disease 2 (MYMY2) [MIM:607151]: A progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults. {ECO:0000269|PubMed:21048783, ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:23110205, ECO:0000269|PubMed:23994138, ECO:0000269|PubMed:25278557, ECO:0000269|PubMed:25956231, ECO:0000269|PubMed:26126547, ECO:0000269|PubMed:26198278, ECO:0000269|PubMed:27736983}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving RNF213 is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALK. {ECO:0000269|PubMed:12112524}.;

Intolerance Scores

LoFtool
0.208
RVIS EVS
1.99
RVIS percentile EVS
97.65

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.866

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyHighMediumHigh
CancerHighMediumHigh
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