SIAH3
protein-codingsiah E3 ubiquitin protein ligase family member 3
Gene summary
Predicted to enable ubiquitin conjugating enzyme binding activity and ubiquitin protein ligase activity. Involved in obsolete negative regulation of protein targeting to mitochondrion and regulation of protein stability. Located in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~74.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SIAH3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198849.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 54 | 3 | 57 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 54 | 3 | 0 | 57 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_942146.2 | 2 | MANE Select | |
| Ensembl | ENSP00000383256.2 | 2 | MANE Select | |
| Ensembl | ENSP00000812170.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- ubiquitin-dependent protein catabolic process
- multicellular organism development
- protein ubiquitination
- regulation of protein stability
- proteasome-mediated ubiquitin-dependent protein catabolic process
Molecular Function
- ubiquitin conjugating enzyme binding
- metal ion binding
- ubiquitin protein ligase activity
Cellular Component
- nucleus
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000400405
- Coding exons
- 2
- Length
- 71467
- Individuals with no LoFs
- 124797
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 124815
- p
- 0.0000721
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.349 | 188 | 175 | 1.07 | 0.0000113 | 1782 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00032 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00017 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.180
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |