SIAH3

siah E3 ubiquitin protein ligase family member 3

Basic information

Region (hg38): 13:45777241-45851753

Links

ENSG00000215475 ∙ NCBI:283514 ∙ OMIM:615609 ∙ HGNC:30553 ∙ Uniprot:Q8IW03 ∙ 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 SIAH3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIAH3 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						0
missense			18	2		20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	2	0

Variants in SIAH3

This is a list of pathogenic ClinVar variants found in the SIAH3 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-45783462-A-T		not specified	Uncertain significance (Sep 20, 2023)
13-45783678-C-G		not specified	Uncertain significance (Mar 20, 2023)
13-45783716-C-A		not specified	Uncertain significance (Apr 06, 2022)
13-45783718-T-C		not specified	Uncertain significance (Aug 04, 2023)
13-45783747-T-G		not specified	Uncertain significance (Dec 20, 2023)
13-45783786-A-T		not specified	Uncertain significance (Jan 10, 2023)
13-45783810-C-T		not specified	Uncertain significance (Dec 14, 2023)
13-45783871-T-A		not specified	Uncertain significance (May 09, 2023)
13-45783897-G-A		not specified	Uncertain significance (Feb 08, 2023)
13-45783898-C-T		not specified	Likely benign (May 02, 2024)
13-45783939-G-A		not specified	Uncertain significance (Aug 02, 2023)
13-45783942-T-C		not specified	Uncertain significance (Apr 20, 2024)
13-45783957-T-C		not specified	Uncertain significance (Jan 17, 2024)
13-45783960-T-A		not specified	Uncertain significance (Jan 17, 2024)
13-45783966-C-T		not specified	Likely benign (May 02, 2023)
13-45783970-G-A		not specified	Uncertain significance (Jan 16, 2024)
13-45783976-A-G		not specified	Likely benign (Jan 17, 2024)
13-45784012-C-T		not specified	Uncertain significance (Mar 27, 2023)
13-45784023-G-A		not specified	Uncertain significance (Dec 18, 2023)
13-45784032-G-C		not specified	Uncertain significance (Feb 14, 2024)
13-45784035-A-G		not specified	Uncertain significance (May 30, 2024)
13-45851505-T-C		not specified	Uncertain significance (Apr 25, 2023)
13-45851553-C-T		not specified	Uncertain significance (Mar 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIAH3	protein_coding	protein_coding	ENST00000400405	2	71467

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000963	0.600	124797	0	18	124815	0.0000721

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.349	188	175	1.07	0.0000113	1782
Missense in Polyphen		60	57.449	1.0444		660
Synonymous	0.355	74	78.0	0.949	0.00000565	549
Loss of Function	0.511	5	6.39	0.782	2.74e-7	69

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000323	0.000322
Ashkenazi Jewish	0.00	0.00
East Asian	0.000223	0.000167
Finnish	0.00	0.00
European (Non-Finnish)	0.0000626	0.0000618
Middle Eastern	0.000223	0.000167
South Asian	0.0000995	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negative regulator of PRKN translocation to damaged mitochondria. Acts probably by destabilizing PINK1 protein, hence inhibiting PRKN targeting to dysfunctional depolarized mitochondria. {ECO:0000269|PubMed:24270810}.

Intolerance Scores

• loftool: 0.362
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.303
• ghis: 0.465

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.180

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Siah3

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;multicellular organism development;protein ubiquitination;regulation of protein stability;proteasome-mediated ubiquitin-dependent protein catabolic process;negative regulation of protein targeting to mitochondrion
• Cellular component: nucleus;mitochondrion
• Molecular function: ubiquitin conjugating enzyme binding;metal ion binding;ubiquitin protein ligase activity