ARIH1

ariadne RBR E3 ubiquitin protein ligase 1, the group of RBR E3 ubiquitin ligases

Basic information

Region (hg38): 15:72474329-72602987

Links

ENSG00000166233 ∙ NCBI:25820 ∙ OMIM:605624 ∙ HGNC:689 ∙ Uniprot:Q9Y4X5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARIH1 gene.

• not provided (127 variants)
• Inborn genetic diseases (6 variants)
• Familial thoracic aortic aneurysm and aortic dissection (3 variants)
• not specified (1 variants)
• Aortic aneurysm (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARIH1 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				36	3	39
missense			35			35
nonsense						0
start loss						0
frameshift						0
inframe indel			19	2	2	23
splice donor/acceptor (+/-2bp)						0
splice region			2	5		7
non coding				21	8	29
Total	0	0	54	59	13

Variants in ARIH1

This is a list of pathogenic ClinVar variants found in the ARIH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-72474660-C-T			Likely benign (Oct 22, 2021)
15-72474682-G-C		Aortic aneurysm	association (-)
15-72474683-A-C			Uncertain significance (Dec 28, 2023)
15-72474693-TGAG-T			Benign (Oct 28, 2023)
15-72474693-TGAGGAGGACAGCGGCGCCGAGGAG-T			Uncertain significance (Dec 15, 2022)
15-72474699-G-C			Uncertain significance (Sep 17, 2023)
15-72474708-C-T			Likely benign (Sep 01, 2023)
15-72474711-CGAG-C		Familial thoracic aortic aneurysm and aortic dissection • ARIH1-related disorder	Benign/Likely benign (Jan 29, 2024)
15-72474711-C-CGAG			Uncertain significance (Mar 18, 2022)
15-72474716-A-C			Uncertain significance (May 08, 2023)
15-72474716-A-G			Uncertain significance (Aug 07, 2021)
15-72474716-A-T		not specified	Uncertain significance (May 11, 2022)
15-72474722-A-G			Uncertain significance (Aug 09, 2022)
15-72474723-G-C			Uncertain significance (Aug 09, 2023)
15-72474745-G-T			Uncertain significance (Jan 05, 2023)
15-72474747-C-A			Uncertain significance (Nov 14, 2023)
15-72474747-C-T			Likely benign (Aug 01, 2022)
15-72474755-C-T			Uncertain significance (Dec 14, 2022)
15-72474756-C-T			Likely benign (Nov 17, 2023)
15-72474768-C-A			Likely benign (Oct 26, 2022)
15-72474770-A-G		Aortic aneurysm	Uncertain significance (Apr 12, 2022)
15-72474797-G-A			Uncertain significance (Dec 18, 2023)
15-72474804-C-T			Benign (Jan 29, 2024)
15-72474808-G-C			Uncertain significance (Aug 09, 2022)
15-72474829-G-A			Uncertain significance (Mar 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARIH1	protein_coding	protein_coding	ENST00000379887	14	113026

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000339	125731	0	6	125737	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.59	74	297	0.250	0.0000150	3718
Missense in Polyphen		6	98.022	0.061211		1266
Synonymous	0.307	97	101	0.961	0.00000483	932
Loss of Function	5.40	2	37.9	0.0528	0.00000209	412

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000163	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin- conjugating enzyme E2 UBE2L3 (PubMed:15236971, PubMed:21532592, PubMed:24076655, PubMed:27565346, PubMed:23707686). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets (PubMed:27565346). The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2 (PubMed:27565346). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin- RING ubiquitin ligase complexes (PubMed:24076655, PubMed:27565346). Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear (PubMed:25624349). According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest (PubMed:25624349). According to another report EIF4E2 ubiquitination leads to its subsequent degradation (PubMed:14623119). Acts as the ligase involved in ISGylation of EIF4E2 (PubMed:17289916). {ECO:0000269|PubMed:14623119, ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:17289916, ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:25624349, ECO:0000269|PubMed:27565346}.
• Pathway: Cytokine Signaling in Immune system;Immune System;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling (Consensus)

Intolerance Scores

• loftool: 0.0347
• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.420
• hipred: Y
• hipred_score: 0.819
• ghis: 0.650

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.966

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arih1

Gene ontology

• Biological process: protein polyubiquitination;ubiquitin-dependent protein catabolic process;protein ubiquitination;positive regulation of proteasomal ubiquitin-dependent protein catabolic process
• Cellular component: ubiquitin ligase complex;cytoplasm;cytosol;Cajal body;nuclear body;SCF ubiquitin ligase complex;Cul2-RING ubiquitin ligase complex;Cul3-RING ubiquitin ligase complex;Cul4A-RING E3 ubiquitin ligase complex;Lewy body
• Molecular function: ubiquitin-protein transferase activity;protein binding;zinc ion binding;ubiquitin-like protein transferase activity;ubiquitin conjugating enzyme binding;ubiquitin protein ligase binding;ubiquitin protein ligase activity