QSOX1

Summary

QSOX1 (quiescin sulfhydryl oxidase 1, HGNC:9756) is a protein-coding gene on chromosome 1q25.2, encoding Sulfhydryl oxidase 1 (O00391). Catalyzes the oxidation of sulfhydryl groups in peptide and protein thiols to disulfides with the reduction of oxygen to hydrogen peroxide.

This gene encodes a protein that contains domains of thioredoxin and ERV1, members of two long-standing gene families. The gene expression is induced as fibroblasts begin to exit the proliferative cycle and enter quiescence, suggesting that this gene plays an important role in growth regulation. Two transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 5768 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 171 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002826

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9756
Approved symbol	QSOX1
Name	quiescin sulfhydryl oxidase 1
Location	1q25.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000116260
Ensembl biotype	protein_coding
OMIM	603120
Entrez	5768

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000367600, ENST00000367602, ENST00000392029, ENST00000443059

RefSeq mRNA: 2 — MANE Select: NM_002826 NM_001004128, NM_002826

CCDS: CCDS1337, CCDS30950

Canonical transcript exons

ENST00000367602 — 12 exons

Exon	Start	End
ENSE00000822660	180166491	180166591
ENSE00000822661	180175321	180175366
ENSE00000822662	180175931	180176033
ENSE00001344115	180194213	180194392
ENSE00001344126	180190433	180190580
ENSE00001445106	180196262	180204030
ENSE00001848814	180154869	180155172
ENSE00003584964	180186053	180186182
ENSE00003587633	180182174	180182319
ENSE00003657907	180189552	180189674
ENSE00003671396	180183916	180184050
ENSE00003675025	180178794	180178884

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 153.5404 / max 2826.9764, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6944	153.5404	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.93	gold quality
lower esophagus mucosa	UBERON:0035834	98.70	gold quality
gall bladder	UBERON:0002110	98.66	gold quality
right atrium auricular region	UBERON:0006631	98.57	gold quality
left testis	UBERON:0004533	98.50	gold quality
right testis	UBERON:0004534	98.46	gold quality
right ovary	UBERON:0002118	98.45	gold quality
upper lobe of left lung	UBERON:0008952	98.42	gold quality
left ovary	UBERON:0002119	98.33	gold quality
right lung	UBERON:0002167	98.21	gold quality
body of stomach	UBERON:0001161	98.15	gold quality
right coronary artery	UBERON:0001625	98.03	gold quality
upper lobe of lung	UBERON:0008948	97.94	gold quality
cardiac atrium	UBERON:0002081	97.59	gold quality
mucosa of stomach	UBERON:0001199	97.54	gold quality
left coronary artery	UBERON:0001626	97.49	gold quality
coronary artery	UBERON:0001621	97.40	gold quality
decidua	UBERON:0002450	97.31	gold quality
stomach	UBERON:0000945	97.27	gold quality
mucosa of urinary bladder	UBERON:0001259	97.25	gold quality
thoracic aorta	UBERON:0001515	97.24	gold quality
ascending aorta	UBERON:0001496	97.23	gold quality
descending thoracic aorta	UBERON:0002345	97.15	gold quality
esophagus mucosa	UBERON:0002469	97.06	gold quality
apex of heart	UBERON:0002098	96.95	gold quality
fundus of stomach	UBERON:0001160	96.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.69	gold quality
ovary	UBERON:0000992	96.65	gold quality
buccal mucosa cell	CL:0002336	96.60	gold quality
mucosa of transverse colon	UBERON:0004991	96.50	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	4346.77
E-MTAB-6678	yes	2741.59
E-CURD-114	yes	46.25
E-CURD-46	yes	23.64
E-GEOD-81547	yes	22.61
E-ANND-3	yes	20.41
E-GEOD-125970	yes	16.83
E-HCAD-9	yes	7.96
E-MTAB-10553	yes	5.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, HIF1A, NKX3-1

miRNA regulators (miRDB)

35 targeting QSOX1, 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-6798-5P	100.00	65.77	699
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-619-3P	98.38	65.58	693
HSA-MIR-599	98.32	66.99	1037
HSA-MIR-432-5P	98.00	68.13	989
HSA-MIR-4421	97.99	64.89	701
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-5699-3P	97.81	65.00	861
HSA-MIR-490-3P	97.79	65.54	606
HSA-MIR-4786-5P	97.45	67.89	924

Literature-anchored findings (GeneRIF, showing 28)

• Data show that the longer version of human QSOX1 protein (hQSOX1a) is a transmembrane protein localized primarily to the Golgi apparatus, and that hQSOX1a can act in vivo as an oxidase. (PMID:17331072)
• internal redox steps studied by mutagenesis (PMID:18393449)
• In the plasma peptidome of patients with ductal adenocarcinoma of the pancreas (DAP), a prominent peptide was identified from the QSOX1 parent protein. This peptide was present in 16 of 23 DAP patients and 4 of 5 patients with IPMN. (PMID:19795908)
• A partial QSOX1 crystal structure reveals a single-chain pseudo-dimer mimicking the quaternary structure of Erv enzymes. (PMID:20211621)
• Data suggested that the C449-C452 motif was essential for the activity of human QSOX 1b; the C70-C73 motif was fundamental in electron transfer from thiol-containing substrate including reduced proteins, DTT, GSH. (PMID:21148546)
• Taken together, our results suggest that the mechanism of QSOX1-mediated tumor cell invasion is by activation of MMP-2 and MMP-9. (PMID:21989104)
• These results propose for the first time possible roles for QSOX1 in atherosclerosis. (PMID:22069028)
• crystal structure (PMID:22801504)
• QSOX1 is a potential new prognostic marker which may prove of use in the staging of breast tumours and the stratification of breast cancer patients. (PMID:23460839)
• High levels of QSOX1 RNA expression is associated with breast cancer. (PMID:23536962)
• these studies suggest that QSOX1 is a predictive biomarker for luminal cancers and that it may be a useful target for elusive luminal B disease (PMID:23680167)
• QSOX1 activity was required for incorporation of laminin into the extracellular matrix (ECM) synthesized by fibroblasts, and ECM produced without QSOX1 was defective in supporting cell-matrix adhesion. (PMID:23704371)
• Data suggest that isoenzyme QSOX1A is secreted from mammalian cells despite transmembrane domain; QSOX1A is cleaved at internal sites and processed within Golgi apparatus to yield soluble enzyme that forms dimer upon cleavage of C-terminal domain. (PMID:23713614)
• QSOX1 is induced by hypoxic stimuli and identified that QSOX1 is a direct target of HIF-1. (PMID:24008827)
• QSOX1 may be revealed as an important player in cancer detection and prognosis. Defining the mechanism(s) of QSOX1 activity in tumors and in in vivo models will provide important insights into how to target QSOX1 with anti-neoplastic agents. (PMID:24359107)
• Examination of the unusual kinetics of QSOX1 toward cysteine and glutathione at low micromolar concentrations suggests that circulating QSOX1 is unlikely to significantly contribute to the oxidation of these monothiols in plasma (PMID:24468475)
• QSOX1 may be involved in neuroblastoma differentiation and regression and may thus function as a biomarker for identifying risk groups for this neoplasm. (PMID:24704990)
• QSOX1 immunoexpression was observed in the non-neoplastic cerebellum samples and the medulloblastoma samples (PMID:25908093)
• Data indicate ebselen as an in vitro inhibitor of quiescin sulfhydryl oxidase 1 (QSOX1) enzymatic activity. (PMID:26158899)
• High QSOX1 expression is a strong and independent factor of reduced survival in breast cancer and may represent a biomarker for aggressive disease and a potential treatment target (PMID:27562495)
• Hypoxia-induced upregulation of QSOX1 and a consequent elevation in intracellular H2O2 increased apoptosis in placentae of pregnancies complicated by Preeclampsia. (PMID:29712536)
• This study provides a key example of the effect of glycosylation on Golgi exit and contributes to an understanding of late secretory sorting and quality control. (PMID:29757379)
• High QSOX1 expression correlates with tumor invasiveness (PMID:29804717)
• QSOX1 might be a lung cancer tissue-derived biomarker and be involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers. (PMID:30336636)
• mutation of a conserved cis-proline amino acid, analogous to a mutation used to trap substrates of a bacterial disulfide catalyst, has a dramatic effect on the physiological function of the mammalian disulfide catalyst QSOX1. (PMID:30367560)
• QSOX1 promotes mitochondrial apoptosis of hepatocellular carcinoma cells during anchorage-independent growth by inhibiting lipid synthesis. (PMID:32863002)
• Quiescin sulfhydryl oxidase 1 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by driving EGFR endosomal trafficking and inhibiting NRF2 activation. (PMID:33770521)
• Aberrant m5C hypermethylation mediates intrinsic resistance to gefitinib through NSUN2/YBX1/QSOX1 axis in EGFR-mutant non-small-cell lung cancer. (PMID:37161388)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	qsox1	ENSDARG00000039459
mus_musculus	Qsox1	ENSMUSG00000033684
rattus_norvegicus	Qsox1	ENSRNOG00000003649
drosophila_melanogaster	Qsox1	FBGN0033814
drosophila_melanogaster	Qsox3	FBGN0038918
drosophila_melanogaster	Qsox2	FBGN0038919
drosophila_melanogaster	Qsox4	FBGN0051413
caenorhabditis_elegans		WBGENE00020426

Paralogs (1): QSOX2 (ENSG00000165661)

Protein

Protein identifiers

Sulfhydryl oxidase 1 — O00391 (reviewed: O00391)

Alternative names: Quiescin Q6

All UniProt accessions (4): O00391, A0A140VKE5, A8MXT8, H0Y5Z8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidation of sulfhydryl groups in peptide and protein thiols to disulfides with the reduction of oxygen to hydrogen peroxide. Plays a role in disulfide bond formation in a variety of extracellular proteins. In fibroblasts, required for normal incorporation of laminin into the extracellular matrix, and thereby for normal cell-cell adhesion and cell migration.

Subunit / interactions. Monomer.

Subcellular location. Golgi apparatus membrane. Secreted Secreted.

Tissue specificity. Expressed in heart, placenta, lung, liver, skeletal muscle, pancreas and very weakly in brain and kidney.

Post-translational modifications. N-glycosylated. O-glycosylated on Thr and Ser residues.

Cofactor. Binds 1 FAD per subunit.

Induction. Induced in quiescent cells just as fibroblasts begin to leave the proliferative cycle and enter quiescence.

Miscellaneous. ‘Quiescin Q6’ means that it was the sixth clone to be found at a higher level of expression in quiescent fibroblasts.

Similarity. Belongs to the quiescin-sulfhydryl oxidase (QSOX) family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00391-1	1, a, QSOX-L	yes
O00391-2	2, b, QSOX-S

RefSeq proteins (2): NP_001004128, NP_002817* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013766	Thioredoxin_domain	Domain
IPR017905	ERV/ALR_sulphydryl_oxidase	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR036774	ERV/ALR_sulphydryl_oxid_sf	Homologous_superfamily
IPR039798	Sulfhydryl_oxidase	Family
IPR040986	QSOX_FAD-bd_dom	Domain
IPR041269	QSOX_Trx1	Domain
IPR042568	QSOX_FAD-bd_sf	Homologous_superfamily

Pfam: PF00085, PF04777, PF18108, PF18371

Enzyme classification (BRENDA):

• EC 1.8.3.2 — thiol oxidase (BRENDA: 39 organisms, 163 substrates, 41 inhibitors, 94 Km, 60 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
DITHIOTHREITOL	0.03–52.2	16
GLUTATHIONE	0.02–41.2	11
O2	0.0001–0.77	10
GSH	0.09–20	8
L-CYS	0.42–10.9	7
RNASE A	0.014–0.36	5
DTT	0.14–12.5	4
2-MERCAPTOETHANOL	7.9–54	3
CYSTEAMINE	1.25–30	3
D-CYS	1.33–13.1	3
N-ACETYL-L-CYS	1.13–3.85	3
REDUCED RIBONUCLEASE	0.0174–0.115	2
2-NITRO-5-THIOBENZOIC ACID	100	1
GLY-GLY-L-CYS	6.31	1
N-ACETYL-EAQCGTS	1.72	1

Catalyzed reactions (Rhea), 1 shown:

• 2 R’C(R)SH + O2 = R’C(R)S-S(R)CR’ + H2O2 (RHEA:17357)

UniProt features (96 total): helix 27, strand 17, mutagenesis site 12, binding site 8, sequence variant 7, disulfide bond 5, turn 5, glycosylation site 3, splice variant 2, domain 2, active site 2, signal peptide 1, chain 1, modified residue 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3LLK	X-RAY DIFFRACTION	2
3LLI	X-RAY DIFFRACTION	2.05
3Q6O	X-RAY DIFFRACTION	2.05
4IJ3	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00391-F1	78.51	0.64

Antibody-complex structures (SAbDab): 1 — 4IJ3

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): 70 (nucleophile); 73 (nucleophile)

Ligand- & substrate-binding residues (8): 408; 412; 451; 455; 478–485; 500; 503; 401

Post-translational modifications (1): 426

Disulfide bonds (5): 70–73, 101–110, 393–405, 449–452, 509–512

Glycosylation sites (3): 130, 243, 575

Mutagenesis-validated functional residues (12):

Position	Phenotype
70–73	loss of catalytic activity. cannot prevent cell detachment after depletion of the endogenous protein.
70	reduces activity by 93%.
72	decreased protein stability and catalytic activity; when associated with s-119 or t-119.
73	reduces activity by 93%.
119	loss of catalytic activity. decreased protein stability and catalytic activity; when associated with a-72.
130	loss of glycosylation site.
243	loss of glycosylation site. abolishes secretion. no effect on catalytic activity.
276–282	decreased o-glycosylation.
449	reduces activity by 96%.
452	loss of activity.
509	no effect. reduces activity by 70%; when associated with s-512.
512	reduces activity by 40%. reduces activity by 70%; when associated with s-509.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-6798695	Neutrophil degranulation
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 248 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, MODULE_93, MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, CHIBA_RESPONSE_TO_TSA_UP, BOYAULT_LIVER_CANCER_SUBCLASS_G56_DN, LU_IL4_SIGNALING, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2

GO Biological Process (3): protein folding (GO:0006457), negative regulation of macroautophagy (GO:0016242), extracellular matrix assembly (GO:0085029)

GO Molecular Function (5): protein disulfide isomerase activity (GO:0003756), flavin-dependent sulfhydryl oxidase activity (GO:0016971), FAD binding (GO:0071949), oxidoreductase activity (GO:0016491), thiol oxidase activity (GO:0016972)

GO Cellular Component (10): Golgi membrane (GO:0000139), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), platelet alpha granule lumen (GO:0031093), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Metabolism of proteins	1
Innate Immune System	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
intracellular organelle lumen	2
secretory granule lumen	2
cellular process	1
protein maturation	1
negative regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
cellular component assembly	1
extracellular matrix organization	1
intramolecular oxidoreductase activity, transposing S-S bonds	1
catalytic activity, acting on a protein	1
protein-disulfide reductase activity	1
thiol oxidase activity	1
flavin adenine dinucleotide binding	1
catalytic activity	1
disulfide oxidoreductase activity	1
oxidoreductase activity, acting on a sulfur group of donors, oxygen as acceptor	1
Golgi apparatus	1
bounding membrane of organelle	1
endoplasmic reticulum	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
platelet alpha granule	1
specific granule	1
extracellular vesicle	1
tertiary granule	1

Protein interactions and networks

STRING

852 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
QSOX1	GFER	P55789	870
QSOX1	TXN	P10599	799
QSOX1	PRDX6	P30041	511
QSOX1	ERO1A	Q96HE7	510
QSOX1	CEP350	Q5VT06	509
QSOX1	TDRD5	Q8NAT2	492
QSOX1	TOR1AIP1	Q5JTV8	491
QSOX1	TGM4	P49221	476
QSOX1	VWF	P04275	472
QSOX1	TOR3A	Q9H497	472
QSOX1	PRDX4	Q13162	458
QSOX1	GAPDHS	O14556	450
QSOX1	CHCHD4	Q8N4Q1	433
QSOX1	ERO1B	Q86YB8	411
QSOX1	SOAT1	P35610	404
QSOX1	CES5A	Q6NT32	404

IntAct

76 interactions, top by confidence:

A	B	Type	Score
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
QSOX1	SLC4A1AP	psi-mi:“MI:0915”(physical association)	0.400
QSOX1	CCR1	psi-mi:“MI:0915”(physical association)	0.370
QSOX1	CCR6	psi-mi:“MI:0915”(physical association)	0.370
QSOX1	CHRM4	psi-mi:“MI:0915”(physical association)	0.370
QSOX1	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
QSOX1	BEGAIN	psi-mi:“MI:0915”(physical association)	0.370
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
NEK4	QSOX1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
TEFM	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (85): QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS)

ESM2 similar proteins: A4FUW8, D3Z2R5, H2N4I1, O00391, O14525, O75129, O88199, P0DV84, P97793, Q07105, Q08DV9, Q0VCN6, Q3U3D7, Q5F479, Q5R9Q9, Q60943, Q61137, Q68CR1, Q6IUU3, Q6L8S8, Q6L9W6, Q6PKC3, Q766D5, Q7LGC8, Q7T2L7, Q7TN22, Q80TS8, Q80Z10, Q86WK6, Q86XL3, Q8BND5, Q8C3I9, Q8HYZ0, Q8JZL1, Q8K099, Q8K2W3, Q8NFM7, Q91XN4, Q92179, Q98SV0

Diamond homologs: A0A8M1N5Y4, D3Z6P0, D4B2L8, G4NFB7, H2N4I1, O00391, O08841, O13704, O13811, O22263, O48773, P00275, P04785, P05307, P07237, P08003, P09102, P09103, P0A4L1, P0A4L2, P11598, P12243, P12865, P13667, P17967, P21195, P23400, P27773, P29828, P30101, P32474, P34329, P38657, P38658, P38659, P38660, P38661, P46843, P52230, P52588

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
cell chemotaxis	5	13.6×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	132
Likely benign	10
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
599187	NC_000001.10:g.172652343_183538289del10885947	Pathogenic

SpliceAI

1954 predictions. Top by Δscore:

Variant	Effect	Δscore
1:180155169:AAAGG:A	donor_loss	1.0000
1:180155170:AAGGT:A	donor_loss	1.0000
1:180155171:AGG:A	donor_loss	1.0000
1:180155172:GGTGA:G	donor_loss	1.0000
1:180155173:G:GA	donor_loss	1.0000
1:180155173:G:GG	donor_gain	1.0000
1:180155174:T:G	donor_loss	1.0000
1:180175319:A:AG	acceptor_gain	1.0000
1:180175320:G:GG	acceptor_gain	1.0000
1:180176034:G:GG	donor_gain	1.0000
1:180178861:G:GT	donor_gain	1.0000
1:180178881:AGAGG:A	donor_loss	1.0000
1:180178884:GGTGA:G	donor_loss	1.0000
1:180178885:G:T	donor_loss	1.0000
1:180178886:T:A	donor_loss	1.0000
1:180182318:GT:G	donor_gain	1.0000
1:180182320:G:GG	donor_gain	1.0000
1:180186033:A:AG	acceptor_gain	1.0000
1:180186034:T:G	acceptor_gain	1.0000
1:180186042:T:A	acceptor_gain	1.0000
1:180186043:G:A	acceptor_gain	1.0000
1:180186051:A:AG	acceptor_gain	1.0000
1:180186052:G:GT	acceptor_gain	1.0000
1:180186052:GCTC:G	acceptor_gain	1.0000
1:180186180:AAG:A	donor_loss	1.0000
1:180186181:AGGTG:A	donor_loss	1.0000
1:180186183:GTG:G	donor_loss	1.0000
1:180186184:T:G	donor_loss	1.0000
1:180189550:A:AG	acceptor_gain	1.0000
1:180189551:G:GT	acceptor_gain	1.0000

AlphaMissense

4828 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:180155126:C:G	C73W	0.995
1:180194291:T:G	F456C	0.995
1:180155125:G:A	C73Y	0.993
1:180190469:T:A	C393S	0.993
1:180190470:G:C	C393S	0.993
1:180155125:G:T	C73F	0.992
1:180190516:G:C	W408C	0.992
1:180190516:G:T	W408C	0.992
1:180155116:G:T	C70F	0.991
1:180155134:T:G	F76C	0.991
1:180196293:G:C	K500N	0.991
1:180196293:G:T	K500N	0.991
1:180196300:T:A	W503R	0.991
1:180196300:T:C	W503R	0.991
1:180196302:G:C	W503C	0.991
1:180196302:G:T	W503C	0.991
1:180155117:C:G	C70W	0.990
1:180155145:T:A	W80R	0.990
1:180155145:T:C	W80R	0.990
1:180155147:G:C	W80C	0.990
1:180155147:G:T	W80C	0.990
1:180155116:G:A	C70Y	0.989
1:180166528:T:G	C101W	0.989
1:180166553:T:A	C110S	0.989
1:180166554:G:C	C110S	0.989
1:180190469:T:C	C393R	0.989
1:180194290:T:C	F456L	0.989
1:180194292:C:A	F456L	0.989
1:180194292:C:G	F456L	0.989
1:180194370:C:A	N482K	0.989

dbSNP variants (sampled 300 via entrez): RS1000011175 (1:180165960 C>T), RS1000093223 (1:180180030 C>T), RS1000099301 (1:180198140 C>T), RS1000125978 (1:180158962 A>C), RS1000170006 (1:180196725 G>A,T), RS1000200653 (1:180187692 G>A), RS1000241219 (1:180158596 A>C), RS1000306285 (1:180182515 G>A,C), RS1000339032 (1:180190473 A>G), RS1000454369 (1:180155367 C>T), RS1000486820 (1:180153663 G>A), RS1000614938 (1:180187993 A>G), RS1000631651 (1:180193811 C>T), RS1000675750 (1:180189107 C>A,G,T), RS1000689665 (1:180183677 G>A)

Disease associations

OMIM: gene MIM:603120 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001961_12	Anorexia nervosa	9.000000e-06
GCST006629_77	Pulse pressure	2.000000e-13
GCST007269_41	Pulse pressure	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523117 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 13,237 (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
CHEMBL51085	EBSELEN	3	13,237

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.27	IC50	5400	nM	EBSELEN

PubChem BioAssay actives

2 with measured affinity, of 5 total; 1 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-phenyl-1,2-benzoselenazol-3-one	1527050: Inhibition of N-terminal poly-histidine tagged recombinant QSOX1 (33 to 546 residues) (unknown origin) expressed in Rosetta-gami B (DE3) cells using using reduced denatured RNAse A substrate by ROS-Glo assay	ic50	5.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	decreases expression, decreases response to substance	2
Estradiol	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Genistein	increases expression	2
graphene oxide	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	affects expression	1
methoxyacetic acid	increases expression, increases reaction	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
tetrabromobisphenol A	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
cupric chloride	increases expression	1
acetochlor	affects methylation, increases abundance	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
NSC 689534	increases expression, affects binding	1
Gefitinib	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4323653	Binding	Inhibition of N-terminal poly-histidine tagged recombinant QSOX1 (33 to 546 residues) (unknown origin) expressed in Rosetta-gami B (DE3) cells using using reduced denatured RNAse A substrate by ROS-Glo assay	Development and Therapeutic Potential of Selenazo Compounds. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TH92	HAP1 QSOX1 (-) 1	Cancer cell line	Male
CVCL_TH93	HAP1 QSOX1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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