RNF213

ring finger protein 213, the group of Ring finger proteins

Basic information

Region (hg38): 17:80260851-80398794

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Moyamoya disease 2	AD/AR	Cardiovascular	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	Cardiovascular	21048783; 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.

• Moyamoya disease 2 (3 variants)
• Moyamoya disease (1 variants)
• not provided (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.

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				156	72	228
missense	3	8	171	72	60	314
nonsense			5			5
start loss						0
frameshift			7			7
inframe indel	1		4	2	1	8
splice donor/acceptor (+/-2bp)		1	1	1	1	4
splice region			8	16	3	27
non coding			1	23	23	47
Total	4	9	189	254	157

Highest pathogenic variant AF is 0.0000197

Variants in RNF213

This is a list of pathogenic ClinVar variants found in the RNF213 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-80263695-C-T			Benign (May 04, 2023)
17-80263696-G-A			Likely benign (May 30, 2022)
17-80263744-C-T			Likely benign (Nov 27, 2023)
17-80263746-G-A		Moyamoya disease 2	Uncertain significance (-)
17-80263756-G-T			Likely benign (Feb 14, 2022)
17-80273221-T-G			Benign (Feb 03, 2023)
17-80273246-G-A			Benign (Jan 11, 2024)
17-80273257-C-G		Hemangioma;Seizure;Inguinal hernia;Nephrocalcinosis;Stroke disorder	Likely pathogenic (Dec 04, 2020)
17-80273268-C-T			Uncertain significance (Nov 22, 2022)
17-80273269-G-A			Benign (Dec 11, 2023)
17-80273288-A-G			Benign (Dec 07, 2023)
17-80273325-C-T			Benign (Nov 27, 2023)
17-80273326-G-A		RNF213-related disorder	Likely benign (Feb 28, 2024)
17-80273337-C-T			Uncertain significance (Aug 15, 2022)
17-80273365-C-T			Benign (Jan 14, 2024)
17-80278887-G-T			Likely benign (Jun 01, 2023)
17-80287795-G-A			Benign (Jan 13, 2024)
17-80287831-G-A			Likely benign (Oct 27, 2023)
17-80287858-C-G		Moyamoya disease 2 • RNF213-related disorder	Likely benign (May 10, 2023)
17-80287859-C-T			Likely benign (Jun 14, 2017)
17-80287899-A-G		not specified	Uncertain significance (May 08, 2024)
17-80287905-T-C		Moyamoya disease 2	Benign (Nov 19, 2023)
17-80287931-G-A		RNF213-related disorder	Benign (Jan 25, 2024)
17-80287950-C-A		Moyamoya disease 2	Likely benign (Mar 01, 2024)
17-80287993-C-T			Uncertain significance (Jun 25, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF213	protein_coding	protein_coding	ENST00000582970	67	137922

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.91e-55	1.00	125266	1	481	125748	0.00192

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.30	2539	2.89e+3	0.879	0.000186	34248
Missense in Polyphen		667	919.69	0.72524		11235
Synonymous	-2.04	1324	1.23e+3	1.07	0.0000890	10147
Loss of Function	6.01	126	223	0.566	0.0000117	2688

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00798	0.00792
Ashkenazi Jewish	0.00139	0.00139
East Asian	0.00326	0.00239
Finnish	0.000883	0.000878
European (Non-Finnish)	0.00125	0.00125
Middle Eastern	0.00326	0.00239
South Asian	0.00328	0.00317
Other	0.00115	0.000978

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

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

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