GeneBe

RNF213

ring finger protein 213, the group of Ring finger proteins

Basic information

Region (hg38): 17:80260852-80398794

Previous symbols: [ "C17orf27", "KIAA1618", "MYMY2" ]

Links

ENSG00000173821 ∙ NCBI:57674 ∙ OMIM:613768 ∙ HGNC:14539 ∙ Uniprot:Q63HN8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Moyamoya disease 2 (Strong), mode of inheritance: AD
  • Moyamoya disease 2 (Strong), mode of inheritance: AR
  • Moyamoya disease 2 (Strong), mode of inheritance: AD
  • Moyamoya disease 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Moyamoya disease 2AD/ARCardiovascularThe condition can manifest with transient ischemic attacks, cerebral infarction, and intracranial hemorrhage, and surveillance, preventive measures and early medical treatment may ameliorate/prevent severe sequelaeCardiovascular21048783; 22377813; 22931863
Individuals with biallelic variants typically have earlier onset of manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNF213 gene.

  • not_provided (718 variants)
  • Moyamoya_disease_2 (91 variants)
  • RNF213-related_disorder (87 variants)
  • not_specified (28 variants)
  • See_cases (9 variants)
  • Inborn_genetic_diseases (4 variants)
  • Moyamoya_angiopathy (3 variants)
  • Moyamoya_disease (2 variants)
  • Stroke_disorder (2 variants)
  • Nephrocalcinosis (1 variants)
  • Atrial_septal_dilatation (1 variants)
  • Middle_cerebral_artery_stenosis (1 variants)
  • Moyamoya_disease_1 (1 variants)
  • Anaplastic_ependymoma (1 variants)
  • Hemangioma (1 variants)
  • Inguinal_hernia (1 variants)
  • Atypical_coarctation_of_aorta (1 variants)
  • Carotid_artery_stenosis (1 variants)
  • Seizure (1 variants)
  • Coronary_artery_disorder (1 variants)
  • Patent_foramen_ovale (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF213 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001256071.3. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
179
clinvar
74
clinvar
 254
missense
6
clinvar
18
clinvar
287
clinvar
105
clinvar
48
clinvar
 464
nonsense
11
clinvar
 11
start loss
0
frameshift
8
clinvar
 8
splice donor/acceptor (+/-2bp)
1
clinvar
2
clinvar
1
clinvar
1
clinvar
 5
Total 6 19 309 285 123

Highest pathogenic variant AF is 0.000242845

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RNF213protein_codingprotein_codingENST00000582970 67137922
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
4.91e-551.0012526614811257480.00192
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.3025392.89e+30.8790.00018634248
Missense in Polyphen667919.690.7252411235
Synonymous-2.0413241.23e+31.070.000089010147
Loss of Function6.011262230.5660.00001172688

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.007980.00792
Ashkenazi Jewish0.001390.00139
East Asian0.003260.00239
Finnish0.0008830.000878
European (Non-Finnish)0.001250.00125
Middle Eastern0.003260.00239
South Asian0.003280.00317
Other0.001150.000978

dbNSFP

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}.;
Pathway
Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Intolerance Scores

loftool
0.208
rvis_EVS
1.99
rvis_percentile_EVS
97.65

Haploinsufficiency Scores

pHI
0.277
hipred
N
hipred_score
0.449
ghis
0.482

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.866

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyHighMediumHigh
CancerHighMediumHigh

Mouse Genome Informatics

Gene name
Rnf213
Phenotype
homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; normal phenotype; 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); growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Zebrafish Information Network

Gene name
rnf213a
Affected structure
nucleate erythrocyte
Phenotype tag
abnormal
Phenotype quality
decreased fluid flow

Gene ontology

Biological process
protein polyubiquitination;angiogenesis;sprouting angiogenesis;ubiquitin-dependent protein catabolic process;protein ubiquitination;protein homooligomerization;protein autoubiquitination;negative regulation of non-canonical Wnt signaling pathway
Cellular component
nucleolus;cytoplasm;cytosol;membrane
Molecular function
ubiquitin-protein transferase activity;ATPase activity;metal ion binding