SUOX
protein-codingsulfite oxidase
Gene summary
Sulfite oxidase is a homodimeric protein localized to the intermembrane space of mitochondria. Each subunit contains a heme domain and a molybdopterin-binding domain. The enzyme catalyzes the oxidation of sulfite to sulfate, the final reaction in the oxidative degradation of the sulfur amino acids cysteine and methionine. Sulfite oxidase deficiency results in neurological abnormalities which are often fatal at an early age. Alternative splicing results in multiple transcript variants encoding identical proteins. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0010089
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0010089
Submitter: ClinGen
The relationship between SUOX and isolated sulfite oxidase deficiency (autosomal recessive) was evaluated using the ClinGen Clinical Validity Framework as of February, 2019. Variants in SUOX were first reported in humans with this disease as early as 1996 (Rupar et al., PMID 9050047). At least 31 variants (missense, nonsense, frameshift, splicing) in 47 patients have been reported in the literature (Claerhout et al., 2018; PMID 28980090). Evidence supporting this gene-disease relationship includes case-level and experimental data. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease association is supported by biochemical assays. In summary, SUOX is definitively associated with autosomal recessive isolated sulfite oxidase deficiency. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. The classification was approved by the ClinGen Aminoacidopathy Gene Curation Expert Panel on March 22nd, 2019.
Inheritance Pattern: AR
Disease ID:MONDO:0010089
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0010089
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0010089
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Neurologic; Ophthalmologic
Intervention: Biochemical
Rationale: Dietary measures (eg, low protein diet and synthetic amino acid mixture without cystine or methionine) have been described as beneficial in early reports
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SUOX variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001032386.2. 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 | 167 | 1 | 168 | |||
| missense | 21 | 186 | 15 | 1 | 223 | |
| nonsense | 17 | 6 | 23 | |||
| start loss | 0 | |||||
| frameshift | 33 | 9 | 42 | |||
| splice donor/acceptor (+/-2bp) | 4 | 1 | 5 | |||
| Total | 50 | 40 | 187 | 182 | 2 | 461 |
Highest pathogenic variant AF is 0.000086739085
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001027558.1 | 3 | MANE Select | |
| Ensembl | ENSP00000266971.3 | 3 | MANE Select | |
| RefSeq | NP_000447.2 | 3 | Standard | |
| RefSeq | NP_001027559.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sulfur metabolism - Homo sapiens (human)
- Sulfate/Sulfite Metabolism
- Sulfite oxidase deficiency
- Sulfide oxidation to sulfate
- Degradation of cysteine and homocysteine
Biological Process
- sulfur compound metabolic process
- nitrate assimilation
- sulfide oxidation, using sulfide:quinone oxidoreductase
Molecular Function
- protein binding
- sulfite oxidase activity
- heme binding
- molybdenum ion binding
- molybdopterin cofactor binding
Cellular Component
- mitochondrion
- mitochondrial intermembrane space
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394109
- Coding exons
- 3
- Length
- 9462
- Individuals with no LoFs
- 125689
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 59
- Defined
- 125748
- p
- 0.000235
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.448 | 289 | 311 | 0.928 | 0.0000185 | 3490 |
| Missense (PolyPhen) | 75 | 103.51 | 0.7246 | 1150 | ||
| Synonymous | 0.851 | 108 | 120 | 0.901 | 0.00000609 | 1185 |
| Loss of Function | 1.31 | 12 | 18.0 | 0.666 | 8.71e-7 | 207 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00092 | 0.00092 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Disease
- DISEASE: Sulfite oxidase deficiency, isolated (ISOD) [MIM:272300]: A life-threatening, autosomal recessive neurometabolic disorder characterized by severe neurological impairment. Classic ISOD manifests in the first few hours to days of life and is characterized by intractable seizures, feeding difficulties, rapidly progressive encephalopathy, microcephaly, and profound intellectual disability. Children usually die during the first few months of life. Mild ISOD manifests in infancy or early childhood and is characterized by ectopia lentis that is variably present, developmental delay and regression, movement disorder characterized by dystonia and choreoathetosis, ataxia, and rarely acute hemiplegia due to metabolic stroke. {ECO:0000269|PubMed:10519592, ECO:0000269|PubMed:12112661, ECO:0000269|PubMed:12368985, ECO:0000269|PubMed:9428520, ECO:0000269|PubMed:9600976}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.233
Intolerance Scores
- LoFtool
- 0.0692
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.61
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.989
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |