SIAH1
siah E3 ubiquitin protein ligase 1, the group of Ring finger proteins
Basic information
Region (hg38): 16:48356364-48448402
Links
Phenotypes
GenCC
Source:
- complex neurodevelopmental disorder (Moderate), mode of inheritance: AD
- Buratti-Harel syndrome (Strong), mode of inheritance: AD
- Buratti-Harel syndrome (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Buratti-Harel syndrome | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic | 28600779; 32430360 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (23 variants)
- Buratti-Harel_syndrome (14 variants)
- Inborn_genetic_diseases (11 variants)
- See_cases (8 variants)
- not_specified (3 variants)
- SIAH1-related_condition (2 variants)
- Neurodevelopmental_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIAH1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003031.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | |||||
| missense | 20 | 31 | ||||
| nonsense | 2 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 9 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 4 | 15 | 24 | 6 | 2 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SIAH1 | protein_coding | protein_coding | ENST00000356721 | 2 | 92039 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.699 | 0.301 | 125735 | 0 | 13 | 125748 | 0.0000517 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.23 | 61 | 184 | 0.331 | 0.00000997 | 2052 |
| Missense in Polyphen | 7 | 65.577 | 0.10674 | 777 | ||
| Synonymous | -1.00 | 78 | 67.5 | 1.15 | 0.00000380 | 634 |
| Loss of Function | 2.77 | 2 | 12.6 | 0.158 | 8.70e-7 | 123 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000528 | 0.0000527 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.0000981 | 0.0000980 |
| Other | 0.000163 | 0.000163 |
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 (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S- nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins. {ECO:0000269|PubMed:10747903, ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11483517, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:11752454, ECO:0000269|PubMed:12072443, ECO:0000269|PubMed:14506261, ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16085652, ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:20508617, ECO:0000269|PubMed:22483617, ECO:0000269|PubMed:9334332, ECO:0000269|PubMed:9858595}.;
- Pathway
- p53 signaling pathway - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Parkin-Ubiquitin Proteasomal System pathway;miRNA regulation of p53 pathway in prostate cancer;Developmental Biology;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Amyloid fiber formation;Class I MHC mediated antigen processing & presentation;Netrin-1 signaling;Axon guidance
(Consensus)
Intolerance Scores
- loftool
- 0.574
- rvis_EVS
- 0.13
- rvis_percentile_EVS
- 62.74
Haploinsufficiency Scores
- pHI
- 0.927
- hipred
- Y
- hipred_score
- 0.756
- ghis
- 0.404
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.633
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Siah1a
- Phenotype
- growth/size/body region phenotype; endocrine/exocrine gland phenotype; liver/biliary system phenotype; reproductive system 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;spermatogenesis;nervous system development;axon guidance;anatomical structure morphogenesis;protein catabolic process;protein destabilization;positive regulation of apoptotic process;proteasome-mediated ubiquitin-dependent protein catabolic process;cellular protein metabolic process;neuron apoptotic process;negative regulation of netrin-activated signaling pathway;positive regulation of intrinsic apoptotic signaling pathway
- Cellular component
- nucleus;cytoplasm;early endosome;cytosol;plasma membrane;beta-catenin destruction complex
- Molecular function
- ubiquitin-protein transferase activity;protein binding;protein C-terminus binding;zinc ion binding;ubiquitin conjugating enzyme binding;identical protein binding;ubiquitin protein ligase activity