SIAH2
siah E3 ubiquitin protein ligase 2, the group of Ring finger proteins
Basic information
Region (hg38): 3:150741125-150763477
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIAH2 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 | 2 | |||||
| missense | 13 | 13 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 13 | 0 | 2 |
Variants in SIAH2
This is a list of pathogenic ClinVar variants found in the SIAH2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-150742148-C-T | not specified | Uncertain significance (Aug 22, 2023) | ||
| 3-150742261-G-A | Benign (Dec 31, 2019) | |||
| 3-150742270-C-G | Benign (Dec 31, 2019) | |||
| 3-150742331-G-C | not specified | Uncertain significance (Apr 29, 2022) | ||
| 3-150742394-C-G | not specified | Uncertain significance (May 12, 2024) | ||
| 3-150742661-G-A | not specified | Uncertain significance (May 25, 2022) | ||
| 3-150762621-G-A | not specified | Uncertain significance (Nov 07, 2022) | ||
| 3-150762626-G-A | not specified | Uncertain significance (Nov 17, 2022) | ||
| 3-150762662-C-A | not specified | Uncertain significance (Apr 12, 2024) | ||
| 3-150762720-C-T | not specified | Uncertain significance (Jun 24, 2022) | ||
| 3-150762756-G-A | not specified | Uncertain significance (Mar 16, 2022) | ||
| 3-150762770-G-C | not specified | Uncertain significance (Dec 20, 2021) | ||
| 3-150762803-C-T | not specified | Uncertain significance (Apr 07, 2023) | ||
| 3-150762809-G-T | not specified | Uncertain significance (Feb 16, 2023) | ||
| 3-150762815-T-C | not specified | Uncertain significance (Jul 06, 2021) | ||
| 3-150762819-C-A | not specified | Uncertain significance (Sep 17, 2021) | ||
| 3-150762831-T-G | not specified | Uncertain significance (Sep 26, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SIAH2 | protein_coding | protein_coding | ENST00000312960 | 2 | 22351 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.687 | 0.309 | 125746 | 0 | 2 | 125748 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.43 | 81 | 170 | 0.476 | 0.00000940 | 2094 |
| Missense in Polyphen | 17 | 66.78 | 0.25457 | 791 | ||
| Synonymous | 0.229 | 72 | 74.5 | 0.966 | 0.00000444 | 681 |
| Loss of Function | 2.31 | 1 | 8.09 | 0.124 | 3.44e-7 | 103 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000177 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes. Has some overlapping function with SIAH1. Triggers the ubiquitin- mediated degradation of TRAF2, whereas SIAH1 does not. Promotes monoubiquitination of SNCA. {ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:12411493, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:9334332}.;
- Pathway
- Parkin-Ubiquitin Proteasomal System pathway;Endoderm Differentiation;Developmental Biology;Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Amyloid fiber formation;Class I MHC mediated antigen processing & presentation;Ub-specific processing proteases;Deubiquitination;Netrin-1 signaling;Axon guidance
(Consensus)
Recessive Scores
- pRec
- 0.203
Intolerance Scores
- loftool
- 0.0751
- rvis_EVS
- -0.16
- rvis_percentile_EVS
- 41.25
Haploinsufficiency Scores
- pHI
- 0.386
- hipred
- Y
- hipred_score
- 0.621
- ghis
- 0.530
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.942
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Siah2
- Phenotype
- skeleton phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- protein polyubiquitination;ubiquitin-dependent protein catabolic process;apoptotic process;cell cycle;small GTPase mediated signal transduction;multicellular organism development;protein deubiquitination;regulation of protein ubiquitination;regulation of circadian rhythm;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;proteasome-mediated ubiquitin-dependent protein catabolic process;cellular protein catabolic process;cellular protein metabolic process;negative regulation of canonical Wnt signaling pathway;negative regulation of netrin-activated signaling pathway;negative regulation of nucleic acid-templated transcription;negative regulation of extrinsic apoptotic signaling pathway
- Cellular component
- nucleoplasm;cytoplasm;early endosome;cytosol;neuron projection;neuronal cell body;intracellular membrane-bounded organelle
- Molecular function
- transcription corepressor activity;ubiquitin-protein transferase activity;protein binding;zinc ion binding;ubiquitin conjugating enzyme binding;ubiquitin protein ligase activity