SQOR

Summary

SQOR (sulfide quinone oxidoreductase, HGNC:20390) is a protein-coding gene on chromosome 15q21.1, encoding Sulfide:quinone oxidoreductase, mitochondrial (Q9Y6N5). Catalyzes the oxidation of hydrogen sulfide with the help of a quinone, such as ubiquinone-10, giving rise to thiosulfate and ultimately to sulfane (molecular sulfur) atoms.

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.

Source: NCBI Gene 58472 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sulfide quinone oxidoreductase deficiency (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 76 total — 2 pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021199

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20390
Approved symbol	SQOR
Name	sulfide quinone oxidoreductase
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	CGI-44, SQR
Ensembl gene	ENSG00000137767
Ensembl biotype	protein_coding
OMIM	617658
Entrez	58472

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 41 protein_coding

ENST00000260324, ENST00000561493, ENST00000561735, ENST00000563296, ENST00000565227, ENST00000565997, ENST00000566934, ENST00000568606, ENST00000888093, ENST00000888094, ENST00000888095, ENST00000888096, ENST00000888097, ENST00000888098, ENST00000888099, ENST00000888100, ENST00000888101, ENST00000888102, ENST00000888103, ENST00000888104, ENST00000888105, ENST00000888106, ENST00000888107, ENST00000888108, ENST00000888109, ENST00000888110, ENST00000888111, ENST00000888112, ENST00000888113, ENST00000888114, ENST00000943739, ENST00000943740, ENST00000943741, ENST00000943742, ENST00000943743, ENST00000943744, ENST00000943745, ENST00000943746, ENST00000943747, ENST00000943748, ENST00000943749

RefSeq mRNA: 2 — MANE Select: NM_021199 NM_001271213, NM_021199

CCDS: CCDS10127

Canonical transcript exons

ENST00000260324 — 10 exons

Exon	Start	End
ENSE00000931286	45682478	45682661
ENSE00000942007	45688337	45688404
ENSE00000942008	45689039	45689217
ENSE00000942009	45690973	45691281
ENSE00001046927	45635029	45635108
ENSE00001120225	45676101	45676310
ENSE00003488246	45658907	45659157
ENSE00003526950	45669928	45669981
ENSE00003563131	45673607	45673801
ENSE00003686709	45661955	45662125

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 99.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.6753 / max 685.2201, expressed in 1622 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146479	49.5066	1612
146476	1.3880	714
146484	0.9440	114
146478	0.2610	112
146477	0.2161	71
146485	0.1914	89
146475	0.1681	77

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic mucosa	UBERON:0000317	99.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.38	gold quality
mucosa of transverse colon	UBERON:0004991	99.23	gold quality
rectum	UBERON:0001052	98.69	gold quality
esophagus squamous epithelium	UBERON:0006920	98.58	gold quality
epithelium of esophagus	UBERON:0001976	98.47	gold quality
tongue squamous epithelium	UBERON:0006919	98.29	gold quality
ileal mucosa	UBERON:0000331	98.22	gold quality
transverse colon	UBERON:0001157	98.12	gold quality
gluteal muscle	UBERON:0002000	97.84	gold quality
squamous epithelium	UBERON:0006914	97.82	gold quality
gingival epithelium	UBERON:0001949	97.73	gold quality
gingiva	UBERON:0001828	97.69	gold quality
oral cavity	UBERON:0000167	97.66	gold quality
pharyngeal mucosa	UBERON:0000355	97.58	gold quality
esophagus mucosa	UBERON:0002469	97.53	gold quality
monocyte	CL:0000576	97.49	gold quality
mononuclear cell	CL:0000842	97.42	gold quality
leukocyte	CL:0000738	97.37	gold quality
palpebral conjunctiva	UBERON:0001812	97.17	gold quality
triceps brachii	UBERON:0001509	97.03	gold quality
large intestine	UBERON:0000059	97.02	gold quality
colon	UBERON:0001155	96.94	gold quality
metanephric glomerulus	UBERON:0004736	96.91	gold quality
renal glomerulus	UBERON:0000074	96.86	gold quality
blood	UBERON:0000178	96.84	gold quality
lower esophagus mucosa	UBERON:0035834	96.82	gold quality
gastrocnemius	UBERON:0001388	96.75	gold quality
penis	UBERON:0000989	96.63	gold quality
nasal cavity epithelium	UBERON:0005384	96.61	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	45.88
E-MTAB-6142	no	167.35
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting SQOR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4680-5P	96.43	67.15	893
HSA-MIR-5591-3P	96.23	67.03	489

Literature-anchored findings (GeneRIF, showing 9)

• Sulfide:quinone oxidoreductase catalyzes the first step in hydrogen sulfide metabolism and produces a sulfane sulfur metabolite. (PMID:22852582)
• SQR is part of the human mitochondrial hydrogen sulfide oxidation pathway (PMID:25225291)
• The I264T SQRDL polymorphism is associaated with osteoporosis in Korean postmenopausal women. (PMID:26258864)
• Hydrogen Sulfide Oxidation Catalyzed by Human Sulfide Quinone Oxidoreductase (PMID:26318450)
• Therefore, this study reveals the reduction in SQR activity as one of the pathomechanisms associated with Coenzyme Q deficiency syndrome. (PMID:27856619)
• Data, including data from studies using recombinant SQR immobilized by embedding in nanodiscs, suggest that immobilized SQR exhibits enhanced catalytic performance; pre-steady-state kinetic characterization of immobilized SQR catalytic cycle indicates that glutathione serves as physiologically relevant sulfur acceptor during hydrogen sulfide oxidation. (PMID:28512131)
• The evidence supported the significant role of SQRDL in the etiology of postmenopausal osteoporosis and suggest that it may be a genetic risk factor for BMD and osteoporosis in Han Chinese postmenopausal women. (PMID:29855663)
• human SQOR contains unique features: an electropositive surface depression implicated as a binding site for sulfane sulfur acceptors and postulated to funnel negatively charged substrates to a hydrophilic H2S-oxidizing active site, which is connected to a hydrophobic internal tunnel that binds coenzyme Q (PMID:30905673)
• Pathogenic variants in SQOR encoding sulfide:quinone oxidoreductase are a potentially treatable cause of Leigh disease. (PMID:32160317)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sqor	ENSDARG00000017034
mus_musculus	Sqor	ENSMUSG00000005803
rattus_norvegicus	Sqor	ENSRNOG00000000172
drosophila_melanogaster	Sqor	FBGN0035515
caenorhabditis_elegans		WBGENE00008538
caenorhabditis_elegans		WBGENE00021183

Protein

Protein identifiers

Sulfide:quinone oxidoreductase, mitochondrial — Q9Y6N5 (reviewed: Q9Y6N5)

Alternative names: Sulfide dehydrogenase-like, Sulfide quinone oxidoreductase

All UniProt accessions (7): A0A1B0GXB4, Q9Y6N5, H3BMS6, H3BNP9, H3BT21, H3BUD7, H3BV36

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidation of hydrogen sulfide with the help of a quinone, such as ubiquinone-10, giving rise to thiosulfate and ultimately to sulfane (molecular sulfur) atoms. Requires an additional electron acceptor; can use sulfite, sulfide or cyanide (in vitro). It is believed the in vivo electron acceptor is glutathione.

Subcellular location. Mitochondrion.

Disease relevance. Sulfide:quinone oxidoreductase deficiency (SQORD) [MIM:619221] An autosomal recessive disorder of hydrogen sulfide metabolism characterized by a variable phenotype. Some patients present with encephalopathy, clinical manifestations of Leigh syndrome, and may have a fatal disease course. Others are asymptomatic. Additional features may include lactic acidosis and decreased mitochondrial respiratory chain complex IV activity in tissues. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 FAD per subunit.

Similarity. Belongs to the SQRD family.

RefSeq proteins (2): NP_001258142, NP_067022* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015904	Sulphide_quinone_reductase	Family
IPR023753	FAD/NAD-binding_dom	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily

Pfam: PF07992

Enzyme classification (BRENDA):

• EC 1.8.5.4 — bacterial sulfide:quinone reductase (BRENDA: 27 organisms, 51 substrates, 30 inhibitors, 84 Km, 50 kcat entries)
• EC 1.8.5.8 — eukaryotic sulfide quinone oxidoreductase (BRENDA: 7 organisms, 31 substrates, 13 inhibitors, 22 Km, 11 kcat entries)

Substrate kinetics (BRENDA)

24 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SULFIDE	0.002–1.95	33
DECYLUBIQUINONE	0.002–0.036	20
SULFIDE	0.005–0.35	8
DUROQUINONE	0.0274–0.0419	4
NA2S	0.155–0.34	4
UBIQUINONE-1	0.0054–0.0199	4
CYANIDE	0.65–2.6	3
GLUTATHIONE	0.008–22	3
HYDROGEN SULFIDE	0.0029–2	3
SULFITE	0.19–0.26	3
COENZYME Q	0.014–0.019	2
PLASTOQUINONE-1	0.031–0.04	2
SULFITE	0.174	2
UBIQUINONE-4	0.0016	2
UBIQUINONE-9	0.0064	2

Catalyzed reactions (Rhea), 3 shown:

• ubiquinone-10 + hydrogen sulfide + sulfite + 2 H(+) = ubiquinol-10 + thiosulfate (RHEA:38359)
• a quinone + hydrogen sulfide + glutathione + H(+) = S-sulfanylglutathione + a quinol (RHEA:55156)
• ubiquinone-10 + hydrogen sulfide + glutathione + H(+) = S-sulfanylglutathione + ubiquinol-10 (RHEA:62608)

UniProt features (64 total): strand 23, helix 19, turn 7, binding site 6, modified residue 2, sequence variant 2, active site 2, transit peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6OIB	X-RAY DIFFRACTION	2.03
6OIC	X-RAY DIFFRACTION	2.21
6WH6	X-RAY DIFFRACTION	2.25
8DHK	X-RAY DIFFRACTION	2.3
6OI6	X-RAY DIFFRACTION	2.56
6MO6	X-RAY DIFFRACTION	2.59
6OI5	X-RAY DIFFRACTION	2.81
6MP5	X-RAY DIFFRACTION	2.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6N5-F1	93.42	0.90

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 201 (cysteine persulfide intermediate); 379 (cysteine persulfide intermediate)

Ligand- & substrate-binding residues (6): 53–54; 75; 83; 118; 336; 344–347

Post-translational modifications (2): 173, 343

Disulfide bonds (1): 201–379

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1614517	Sulfide oxidation to sulfate
R-HSA-1430728	Metabolism
R-HSA-1614558	Degradation of cysteine and homocysteine
R-HSA-1614635	Sulfur amino acid metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 288 (showing top): HONMA_DOCETAXEL_RESISTANCE, MODULE_255, KENNY_CTNNB1_TARGETS_UP, MODULE_317, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, PETRETTO_HEART_MASS_QTL_CIS_DN, GOCC_MITOCHONDRIAL_ENVELOPE, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOUYER_TUMOR_INVASIVENESS, ABBUD_LIF_SIGNALING_1_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, BERENJENO_TRANSFORMED_BY_RHOA_UP, GOCC_ORGANELLE_INNER_MEMBRANE, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, GOMF_QUINONE_BINDING

GO Biological Process (2): obsolete sulfide oxidation, using sulfide:quinone oxidoreductase (GO:0070221), sulfur compound metabolic process (GO:0006790)

GO Molecular Function (6): quinone binding (GO:0048038), sulfide:quinone oxidoreductase activity (GO:0070224), FAD binding (GO:0071949), glutathione-dependent sulfide quinone oxidoreductase activity (GO:0106436), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Degradation of cysteine and homocysteine	1
Sulfur amino acid metabolism	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on a sulfur group of donors, quinone or similar compound as acceptor	2
metabolic process	1
small molecule binding	1
flavin adenine dinucleotide binding	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1

Protein interactions and networks

STRING

2064 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SQOR	ETHE1	O95571	929
SQOR	SUOX	P51687	845
SQOR	TST	Q16762	812
SQOR	MPST	P25325	758
SQOR	CTH	P32929	741
SQOR	P0DN79	P0DN79	684
SQOR	H7C2H4	H7C2H4	674
SQOR	CRYZ	Q08257	636
SQOR	SDHA	P31040	602
SQOR	SDHB	P21912	545
SQOR	NDUFA5	Q16718	544
SQOR	COQ4	Q9Y3A0	535
SQOR	CHDH	Q8NE62	521
SQOR	COQ9	O75208	519
SQOR	COQ5	Q5HYK3	516

IntAct

126 interactions, top by confidence:

A	B	Type	Score
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.960
RAD51D	RAD51B	psi-mi:“MI:0914”(association)	0.850
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
E7	RB1	psi-mi:“MI:0914”(association)	0.700
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
FAM174A	GAK	psi-mi:“MI:0914”(association)	0.640
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
SMAD2	FAM83G	psi-mi:“MI:0915”(physical association)	0.400
SMAD3	FAM83G	psi-mi:“MI:0915”(physical association)	0.400
CABP5	SQOR	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
ZWINT	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
Bmpr1a	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
NCSTN	ESYT2	psi-mi:“MI:0914”(association)	0.350
Bod1	SPTBN2	psi-mi:“MI:0914”(association)	0.350
Tapt1	DERL1	psi-mi:“MI:0914”(association)	0.350
MATR3	BCLAF3	psi-mi:“MI:0914”(association)	0.350
TENT5A	GOLGA8R	psi-mi:“MI:0914”(association)	0.350
TUBG1	DPM1	psi-mi:“MI:0914”(association)	0.350
Junb	RGPD3	psi-mi:“MI:0914”(association)	0.350
XRCC3	DERL1	psi-mi:“MI:0914”(association)	0.350
HAUS2	SCAMP3	psi-mi:“MI:0914”(association)	0.350
CFTR	SNHG32	psi-mi:“MI:0914”(association)	0.350
E7	AP2A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (131): SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS), SQRDL (Affinity Capture-MS)

ESM2 similar proteins: A0PJE2, A5PJM4, A7YVH9, B4F6I3, B5FXE5, D3ZDM7, D4A2H2, O15269, O35296, O35469, O35704, O54695, O64489, O88736, P09367, P11172, P13439, P20132, P24815, P26439, P31228, P31754, P56937, Q2KIJ5, Q3TMV7, Q3TY86, Q5R514, Q5R9T5, Q5REJ2, Q60555, Q60HD1, Q62904, Q64421, Q68FS6, Q6GLW8, Q6IQS6, Q6PBT5, Q80SY6, Q8BUE4, Q8CCT7

Diamond homologs: O94284, Q54DK1, Q9R112, Q9Y6N5, O05267

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

76 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	58
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1012234	NM_021199.4(SQOR):c.637G>A (p.Glu213Lys)	Pathogenic
1012235	NM_021199.4(SQOR):c.446del (p.Leu149fs)	Pathogenic

SpliceAI

1996 predictions. Top by Δscore:

Variant	Effect	Δscore
15:45632016:G:GG	donor_gain	1.0000
15:45658905:A:AG	acceptor_gain	1.0000
15:45658906:G:GG	acceptor_gain	1.0000
15:45662121:AGAAG:A	donor_loss	1.0000
15:45662122:GAAG:G	donor_gain	1.0000
15:45662122:GAAGG:G	donor_loss	1.0000
15:45662123:AAG:A	donor_loss	1.0000
15:45662123:AAGG:A	donor_loss	1.0000
15:45662124:AG:A	donor_loss	1.0000
15:45662124:AGGTA:A	donor_loss	1.0000
15:45662125:GG:G	donor_loss	1.0000
15:45662126:G:A	donor_loss	1.0000
15:45662126:G:GA	donor_loss	1.0000
15:45662127:T:A	donor_loss	1.0000
15:45662127:T:G	donor_loss	1.0000
15:45669979:AAG:A	donor_loss	1.0000
15:45669980:AG:A	donor_loss	1.0000
15:45669981:GGTAC:G	donor_loss	1.0000
15:45669982:G:T	donor_loss	1.0000
15:45669982:GTACC:G	donor_loss	1.0000
15:45669983:T:A	donor_loss	1.0000
15:45673599:T:TA	acceptor_gain	1.0000
15:45673602:TGCA:T	acceptor_loss	1.0000
15:45673604:CA:C	acceptor_loss	1.0000
15:45673605:A:AG	acceptor_gain	1.0000
15:45673605:AG:A	acceptor_loss	1.0000
15:45673606:G:GA	acceptor_gain	1.0000
15:45673606:GA:G	acceptor_gain	1.0000
15:45673606:GAT:G	acceptor_gain	1.0000
15:45673606:GATT:G	acceptor_gain	1.0000

AlphaMissense

2939 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:45673748:T:C	C201R	0.999
15:45676155:T:C	F237L	0.999
15:45676157:C:A	F237L	0.999
15:45676157:C:G	F237L	0.999
15:45689099:T:C	F393L	0.999
15:45689101:T:A	F393L	0.999
15:45689101:T:G	F393L	0.999
15:45689057:T:C	C379R	0.998
15:45689058:G:A	C379Y	0.998
15:45689059:T:G	C379W	0.998
15:45689094:C:A	A391D	0.998
15:45673745:A:G	K200E	0.997
15:45673747:G:C	K200N	0.997
15:45673747:G:T	K200N	0.997
15:45673750:T:G	C201W	0.997
15:45682617:G:A	G335E	0.997
15:45682619:G:C	D336H	0.997
15:45682645:G:C	K344N	0.997
15:45682645:G:T	K344N	0.997
15:45682653:C:A	A347D	0.997
15:45689046:G:A	G375D	0.997
15:45689097:A:T	E392V	0.997
15:45689100:T:G	F393C	0.997
15:45676183:T:C	L246P	0.996
15:45682617:G:T	G335V	0.996
15:45682620:A:T	D336V	0.996
15:45682624:C:G	C337W	0.996
15:45682647:C:T	T345I	0.996
15:45682650:C:A	A346D	0.996
15:45689046:G:T	G375V	0.996

dbSNP variants (sampled 300 via entrez): RS1000012732 (15:45650323 T>C,G), RS1000078805 (15:45649308 C>G), RS1000081506 (15:45673039 A>G), RS1000149160 (15:45669510 C>A,G), RS1000168194 (15:45683785 A>G), RS1000265395 (15:45669849 C>A,G,T), RS1000275239 (15:45664539 G>A), RS1000347779 (15:45658473 A>C), RS1000374543 (15:45643416 C>G), RS1000427778 (15:45676418 G>A), RS1000432604 (15:45636863 C>G,T), RS1000459509 (15:45662689 G>A), RS1000506037 (15:45657208 C>T), RS1000518325 (15:45688436 A>G), RS1000641076 (15:45630046 C>A)

Disease associations

OMIM: gene MIM:617658 | disease phenotypes: MIM:619221

GenCC curated gene-disease

Disease	Classification	Inheritance
sulfide quinone oxidoreductase deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Leigh syndrome	Limited	AR

Mondo (1): sulfide quinone oxidoreductase deficiency (MONDO:0030982)

Orphanet (0):

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001259	Coma
HP:0002076	Migraine
HP:0003128	Lactic acidosis
HP:0003236	Elevated circulating creatine kinase concentration
HP:0006846	Acute encephalopathy
HP:0012707	Elevated brain lactate level by MRS
HP:0032792	Tonic seizure

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000837_4	Weight	5.000000e-06
GCST000838_6	Waist circumference	7.000000e-06
GCST001762_138	Obesity-related traits	8.000000e-06
GCST002482_4	Carotid plaque burden (smoking interaction)	9.000000e-06
GCST002875_113	Diisocyanate-induced asthma	5.000000e-06
GCST006483_37	Lung function (FVC)	2.000000e-08
GCST006483_38	Lung function (FVC)	2.000000e-06
GCST009217_6	Corpus callosum Mid-posterior volume	4.000000e-06
GCST011039_9	Parkinson’s disease progression (composite)	3.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight
EFO:0004626	IGFBP-3 measurement
EFO:0006501	carotid plaque build
EFO:0006995	response to diisocyanate
EFO:0004312	vital capacity
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523512 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 39,644 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1697725	AUROTHIOGLUCOSE	4
CHEMBL460499	CARMOFUR	2	39,644

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

28 potent at pChembl≥5 of 34 total, top 28 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.68	IC50	2.1	nM	CHEMBL5082385
8.26	IC50	5.5	nM	CHEMBL5075881
8.06	IC50	8.7	nM	CHEMBL5079537
8.03	IC50	9.4	nM	CHEMBL5080702
7.85	IC50	14	nM	CHEMBL5078297
7.60	IC50	25	nM	CHEMBL5074290
7.54	IC50	29	nM	CHEMBL5088404
7.52	IC50	30	nM	CHEMBL5078802
7.44	IC50	36	nM	CHEMBL5081359
7.37	IC50	43	nM	CHEMBL5092002
7.28	IC50	53	nM	CHEMBL5085735
7.12	IC50	75	nM	CHEMBL5078095
7.00	IC50	100	nM	CHEMBL5080718
6.97	IC50	108	nM	CHEMBL5078475
6.92	IC50	121	nM	CHEMBL5089512
6.91	IC50	123	nM	CHEMBL5084456
6.88	IC50	132	nM	CHEMBL5077205
6.82	IC50	153	nM	CHEMBL5084987
6.67	IC50	213	nM	CHEMBL5077063
6.60	IC50	252	nM	CHEMBL5088677
6.36	IC50	437	nM	CHEMBL5074864
6.27	IC50	541	nM	CHEMBL5079117
6.07	IC50	850	nM	CHEMBL5084810
6.03	IC50	925	nM	AUROTHIOGLUCOSE
6.03	IC50	924.7	nM	AUROTHIOGLUCOSE
5.87	IC50	1360	nM	CHEMBL5075924
5.24	Kd	5786	nM	CHEMBL5653589
5.24	ED50	5786	nM	CHEMBL5653589

PubChem BioAssay actives

25 with measured affinity, of 29 total; 25 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-methoxy-4-phenyl-5H-indeno[1,2-b]pyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.0021	uM
4-(4-fluorophenyl)-2-prop-2-enoxy-6-pyridin-2-ylpyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.0055	uM
4-(4-fluorophenyl)-2-methoxy-6-(3-methyl-2-pyridinyl)pyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.0087	uM
2-ethoxy-4-(4-fluorophenyl)-5H-indeno[1,2-b]pyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.0094	uM
4-(4-fluorophenyl)-2-methoxy-6-pyridin-2-ylpyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.0140	uM
4-(4-fluorophenyl)-2-methoxy-6-phenylpyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.0250	uM
4-(4-aminophenyl)-2-methoxy-6-(3-methyl-2-pyridinyl)pyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.0290	uM
ethyl 2-[(3-cyano-4,6-diphenyl-2-pyridinyl)oxy]acetate	1807937: Inhibition of human SQOR	ic50	0.0300	uM
4-(4-fluorophenyl)-6-(3-methyl-2-pyridinyl)-2-(pyridin-3-ylmethoxy)pyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.0360	uM
tert-butyl 4-[2-[[3-cyano-4-(4-fluorophenyl)-6-(3-methyl-2-pyridinyl)-2-pyridinyl]oxy]ethyl]piperazine-1-carboxylate	1807937: Inhibition of human SQOR	ic50	0.0430	uM
2-methoxy-4,6-diphenylpyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.0530	uM
4-(4-fluorophenyl)-2-methoxy-6-(2-methoxyphenyl)pyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.0750	uM
4,6-diphenyl-2-phenylmethoxypyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.1000	uM
4-(4-fluorophenyl)-2-methoxy-6-(3-methoxyphenyl)pyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.1080	uM
4-ethoxy-2,6-diphenylpyrimidine-5-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.1210	uM
4-(4-fluorophenyl)-2-(2-methoxyethoxy)-6-phenylpyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.1230	uM
2-ethylsulfanyl-4,6-diphenylpyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.1320	uM
6-tert-butyl-4-(4-fluorophenyl)-2-methoxypyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.1530	uM
4-(4-fluorophenyl)-2-methoxy-6-pyridin-3-ylpyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.2130	uM
4-(4-chlorophenyl)-2-methoxy-6-phenylpyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.2520	uM
2-methoxy-3-methyl-4,6-diphenylpyridine	1807937: Inhibition of human SQOR	ic50	0.4370	uM
2-methoxy-6-phenyl-4-pyridin-4-ylpyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.5410	uM
4-tert-butyl-2-methoxy-6-pyridin-2-ylpyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	0.8500	uM
4-(4-fluorophenyl)-2-methoxy-6-(4-methoxyphenyl)pyridine-3-carbonitrile	1807937: Inhibition of human SQOR	ic50	1.3600	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149478: Binding affinity to human SQRDL incubated for 45 mins by Kinobead based pull down assay	kd	5.7856	uM

CTD chemical–gene interactions

71 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression	6
Benzo(a)pyrene	decreases methylation, increases expression	4
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	3
Cyclosporine	increases expression	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Resveratrol	decreases expression, increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Hydrogen Peroxide	affects expression	2
Tetrachlorodibenzodioxin	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
hydroxyhydroquinone	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	decreases expression	1
gossypol acetic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
cupric chloride	increases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
chromium hexavalent ion	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418447	Binding	Inhibition of SQOR (unknown origin) using sodium sulfide, sodium sulfite and coenzyme Q1 by UV absorbance method	Alkyl-, acyl-, urea-, and aza-uracil sulfide:quinone oxidoreductase inhibitors

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8W6	Ubigene HCT 116 SQOR KO	Cancer cell line	Male
CVCL_TQ33	HAP1 SQRDL (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.