SQOR
protein-codingsulfide quinone oxidoreductase
Gene summary
The protein encoded by this gene may function in mitochondria to catalyze the conversion of sulfide to persulfides, thereby decreasing toxic concencrations of sulfide. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2012]
- SQRDL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0030982
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009723
Submitter: ClinGen
The relationship between SQOR and Leigh syndrome spectrum was evaluated using the ClinGen Clinical Validity Framework as of November 23, 2020. The SQOR gene encodes sulfide quinone oxidoreductase, an enzyme that breaks down hydrogen sulfide which, when accumulated, inhibits complex IV. The SQOR gene was first reported in relation to autosomal recessive Leigh syndrome spectrum in 2020 (PMID: 32160317). Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included two variants identified in two cases from one publication (PMID: 32160317). Of note, there was much debate among this Expert Panel if Subject II-3 from Family B should be scored as the variant was also found to be homozygous in two healthy siblings. However, after extensive discussion within the Expert Panel, it was decided to score this case but downgrade the score. No segregation data were available. Loss of function is implicated as the mechanism of disease. This gene-disease association is also supported by biochemical function and expression (PMIDs: 27977873, 22067608). In summary, there is limited evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the NICHD U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on November 23, 2020 (SOP Version 7).
Inheritance Pattern: AR
Disease ID:MONDO:0030982
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Neurologic
Intervention: Biochemical
Rationale: The condition can involve neurometabolic sequelae, and adequate caloric intake with fasting avoidance has been recommended; Medical management. (eg, with hydroxycobalamin and methylene blue) has been suggested as potentially beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SQOR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021199.4. 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 | 3 | 1 | 4 | |||
| missense | 1 | 58 | 3 | 62 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 2 | 0 | 62 | 4 | 0 | 68 |
Highest pathogenic variant AF is 0.0000024783456
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067022.1 | 9 | MANE Select | |
| Ensembl | ENSP00000260324.7 | 9 | MANE Select | |
| RefSeq | NP_001258142.1 | 9 | Standard | |
| Ensembl | ENSP00000457937.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sulfur metabolism - Homo sapiens (human)
- Sulfide oxidation to sulfate
- Degradation of cysteine and homocysteine
- Metabolism of amino acids and derivatives
- Metabolism
Biological Process
- sulfide oxidation, using sulfide:quinone oxidoreductase
- hydrogen sulfide metabolic process
Molecular Function
- quinone binding
- sulfide:quinone oxidoreductase activity
- FAD binding
Cellular Component
- mitochondrial inner membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000260324
- Coding exons
- 9
- Length
- 60147
- Individuals with no LoFs
- 125669
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 79
- Defined
- 125748
- p
- 0.000314
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.532 | 225 | 249 | 0.905 | 0.0000131 | 2906 |
| Missense (PolyPhen) | 99 | 106.64 | 0.92838 | 1199 | ||
| Synonymous | -0.557 | 102 | 95.1 | 1.07 | 0.00000540 | 898 |
| Loss of Function | 0.920 | 17 | 21.6 | 0.786 | 0.00000117 | 252 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00059 | 0.00055 | rare |
| Latino/Admixed American | 0.00096 | 0.00093 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.000054 | 0.000046 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00040 | 0.00039 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the oxidation of hydrogen sulfide with the help of a quinone, such as ubiquinone, giving rise to thiosulfate and ultimately to sulfane (molecular sulfur) atoms. Requires an additional electron acceptor; can use sulfite, sulfide or cyanide (in vitro). {ECO:0000269|PubMed:22852582}.;
Recessive Scores
- pRec
- 0.253
Intolerance Scores
- RVIS EVS
- 0.44
- RVIS percentile EVS
- 77.85
Essentials
- Essential (gene trap)
- N