SRXN1

Summary

SRXN1 (sulfiredoxin 1, HGNC:16132) is a protein-coding gene on chromosome 20p13, encoding Sulfiredoxin-1 (Q9BYN0). Contributes to oxidative stress resistance by reducing cysteine-sulfinic acid formed under exposure to oxidants in the peroxiredoxins PRDX1, PRDX2, PRDX3 and PRDX4.

Enables oxidoreductase activity, acting on a sulfur group of donors. Involved in response to oxidative stress. Located in cytosol.

Source: NCBI Gene 140809 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_080725

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16132
Approved symbol	SRXN1
Name	sulfiredoxin 1
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	Npn3, Srx, SRX1, YKL086W, dJ850E9.2
Ensembl gene	ENSG00000271303
Ensembl biotype	protein_coding
OMIM	617583
Entrez	140809

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000381962, ENST00000860831, ENST00000918016, ENST00000961979

RefSeq mRNA: 1 — MANE Select: NM_080725 NM_080725

CCDS: CCDS13005

Canonical transcript exons

ENST00000381962 — 2 exons

Exon	Start	End
ENSE00001490407	652976	653200
ENSE00003520801	646615	648917

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 98.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.1707 / max 732.7123, expressed in 1782 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185980	35.1707	1782

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	98.87	gold quality
adrenal tissue	UBERON:0018303	96.47	gold quality
lower esophagus mucosa	UBERON:0035834	95.57	gold quality
left adrenal gland	UBERON:0001234	94.69	gold quality
left adrenal gland cortex	UBERON:0035825	94.58	gold quality
right adrenal gland cortex	UBERON:0035827	94.42	gold quality
right adrenal gland	UBERON:0001233	94.18	gold quality
adrenal gland	UBERON:0002369	94.09	gold quality
esophagus mucosa	UBERON:0002469	93.88	gold quality
stromal cell of endometrium	CL:0002255	92.36	gold quality
heart left ventricle	UBERON:0002084	91.05	gold quality
right atrium auricular region	UBERON:0006631	91.05	gold quality
esophagus	UBERON:0001043	90.70	gold quality
gastrocnemius	UBERON:0001388	90.26	gold quality
heart	UBERON:0000948	89.98	gold quality
apex of heart	UBERON:0002098	89.95	gold quality
right frontal lobe	UBERON:0002810	89.74	gold quality
monocyte	CL:0000576	89.63	gold quality
leukocyte	CL:0000738	89.55	gold quality
anterior cingulate cortex	UBERON:0009835	89.10	gold quality
muscle of leg	UBERON:0001383	88.96	gold quality
body of stomach	UBERON:0001161	88.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.73	gold quality
left lobe of thyroid gland	UBERON:0001120	88.71	gold quality
pancreas	UBERON:0001264	88.65	gold quality
frontal cortex	UBERON:0001870	88.40	gold quality
adenohypophysis	UBERON:0002196	88.34	gold quality
superior frontal gyrus	UBERON:0002661	88.31	gold quality
right lobe of thyroid gland	UBERON:0001119	88.30	gold quality
descending thoracic aorta	UBERON:0002345	88.29	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	155.06
E-CURD-11	no	211.96
E-ANND-3	no	2.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, NFE2L2, NFKBIB

miRNA regulators (miRDB)

87 targeting SRXN1, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3153	99.55	67.59	2337

Literature-anchored findings (GeneRIF, showing 39)

• The reduction of the cysteine sulfinic acid moiety within the active site of the peroxiredoxin by sulfiredoxin involves novel sulfur chemistry and the use of ATP and Mg(2+). (PMID:15952770)
• analysis of the reduction of cysteine sulfinic acid of peroxiredoxin to cysteine by mammalian sulfiredoxin (PMID:16565085)
• Actin and protein tyrosine phosphatase 1B were identified in vitro as targets of sulfiredoxin 1 (Srx1)-dependent deglutathionylation. (PMID:16818657)
• Aspartate-187 of peroxiredoxin (Prx) I is the catalytic residue responsible for ATP hydrolysis in the cysteinesulfinic acid reduction of Prx by human sulfiredoxin. (PMID:17176052)
• 2.6 A crystal structure of the human Srx-PrxI complex [Srx] (PMID:18172504)
• Reduction of cysteine sulfinic acid in peroxiredoxin by sulfiredoxin proceeds directly through a sulfinic phosphoryl ester intermediate (PMID:18579529)
• analysis of a protein thiosulfinate intermediate in the reduction of cysteine sulfinic acid in peroxiredoxin by human sulfiredoxin (PMID:18593714)
• decreased expression in lungs from patients with chronic obstructive pulmonary disorder (PMID:19027064)
• The current study identifies Sulfiredoxin as a unique target of activator protein-1 (AP-1) activation and TAM67 inhibition. (PMID:19057013)
• Deglutathionylation of 2-Cys Prx is specifically catalyzed by Srx. (PMID:19561357)
• Studies present the 2.1 A crystal structure of human Srx in complex with PrxI, ATP, and Mg(2+). (PMID:19812042)
• sulfiredoxin 1 is associatd with the pathogenesis of human pulmonary fibrosis. (PMID:20718723)
• Srx-Prx IV axis is critical for lung cancer maintenance and metastasis, suggesting that targeting the Srx-Prx IV axis may provide unique effective strategies for cancer prevention and treatment. (PMID:21487000)
• Real-time PCR validated that up-regulation of sulphiredoxin 1 homolog (SRXN1), hemeoxygenase 1 (HMOX1), and breast carcinoma amplified sequence 3 (BCAS3) were consistently modulated. (PMID:21742584)
• Smokers and ex-smokers had significantly more sulfiredoxin expression in their tumors and in patients receiving cytostatic drugs or radiation therapy, sulfiredoxin expression predicted a poor prognosis. (PMID:21943684)
• Srx functions as a novel component to maintain the balance between H2O2 production and elimination (PMID:22086924)
• Gemfibrozil, a lipid-lowering drug, increases myelin genes in human oligodendrocytes via peroxisome proliferator-activated receptor-beta. (PMID:22879602)
• SRX forms a complex with S100A4 (and has stronger affinity for S-glutathionylated S100A4), regulates its activity, and mediates redox regulation of the interaction of S100A4 with nonmuscle myosin heavy chain II-A. (PMID:22934964)
• NRF2 and SRXN1 genetic polymorphisms are associated with breast cancer risk and survival (PMID:22964583)
• This review will highlight the cumulative effects of sulfiredoxin in various systemic disorders with a strong emphasis on its target activity and the factors influencing its expression in such conditions. (PMID:25460739)
• This review will summarize the molecular basis of differences in the affinity of Srx for individual Prx and the role of individual component of the Srx-Prx system in tumor progression and metastasis. (PMID:26170166)
• Study shows that Srx plays a critical oncogenic role to promote cell invasion and metastasis, which is at least partially due to its stimulation of the MAPK pathway through EGFR deacetylation. (PMID:26290602)
• rs6053666 of SRXN1 is associated with cerebrovascular disease in a Finnish cohort (PMID:27226772)
• The analysis of SXR polymorphism is a promising tool to predict both the favourable response to corticosteroids and the risk of developing steroid resistance (PMID:27377607)
• Study identify a role for Srxn1 as a denitrosylase for neuronal Prx2. Finding points to the NO/Srxn1 pair in a previously unrecognized redox cycle that modulates Prx2 peroxidase activity. (PMID:27821734)
• Increased expression of Srx protects peroxiredoxins against hyperoxidation in the early stage of hyperglycaemia. (PMID:28202395)
• The up-regulated expression of Srx was significantly associated with lymph node metastasis, infiltration of vessels, and the depth of cancer invasion. (PMID:28274319)
• We silenced Srx by short hairpin RNA in HeLa and SiHa cells. Diminished Srx expression upregulated E-cadherin expression. The cell invasion and migration activity in the ShSrx group were obviously decreased in HeLa and SiHa cells. (PMID:28351308)
• Wnt/beta-catenin pathway was stimulated by sulfiredoxin in tumor cell line, with activation of CD44-its target genes-resulting in the promotion of invasion and migration in cervical cancer cell lines. (PMID:28448437)
• NRF2, DJ1 and SRNX1 are commonly expressed in diffusely infiltrating astrocytomas and they can be used in predicting patient prognosis. (PMID:29441509)
• Srx expression, MDA levels, and ROS levels in BGC823 cells were markedly inhibited upon treatment with diallyl trisulfide (DATS), a major constituent of garlic oil with proven anticancer effects. These results suggest that Srx may be an oxidative stress marker. Antioxidation may account for the anticancer potential of garlic. (PMID:30863778)
• Sulfiredoxin exhibits an increased association with TXNDC5, facilitating the retention of Srx in the endoplasmic reticulum. The cellular levels of Srx and TXNDC5 may be useful as biomarkers to predict the survival of individuals with lung cancer. (PMID:31000628)
• Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer. (PMID:32411320)
• SRXN1 stimulates hepatocellular carcinoma tumorigenesis and metastasis through modulating ROS/p65/BTG2 signalling. (PMID:32746503)
• Sulfiredoxin-1 is a promising novel prognostic biomarker for hepatocellular carcinoma. (PMID:32955798)
• CircABCA13 acts as a miR-4429 sponge to facilitate esophageal squamous cell carcinoma development by stabilizing SRXN1. (PMID:37017121)
• Antioxidative stress protein SRXN1 can be used as a radiotherapy prognostic marker for prostate cancer. (PMID:37726767)
• Unraveling the role of sulfiredoxin-1 in early-onset preeclampsia: A key player in trophoblast ferroptosis. (PMID:38852489)
• Sulfiredoxin-1 promotes the growth of hepatocellular carcinoma by inhibiting TFEB-mediated autophagy and lysosome biogenesis. (PMID:39029574)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	srxn1	ENSDARG00000079160
mus_musculus	Srxn1	ENSMUSG00000032802
rattus_norvegicus	Srxn1	ENSRNOG00000031167
drosophila_melanogaster	Srx	FBGN0030876

Protein

Protein identifiers

Sulfiredoxin-1 — Q9BYN0 (reviewed: Q9BYN0)

All UniProt accessions (1): Q9BYN0

UniProt curated annotations — full annotation on UniProt →

Function. Contributes to oxidative stress resistance by reducing cysteine-sulfinic acid formed under exposure to oxidants in the peroxiredoxins PRDX1, PRDX2, PRDX3 and PRDX4. Does not act on PRDX5 or PRDX6. May catalyze the reduction in a multi-step process by acting both as a specific phosphotransferase and a thioltransferase.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed with highest levels in kidney, lung, spleen and thymus.

Similarity. Belongs to the sulfiredoxin family.

RefSeq proteins (1): NP_542763* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003115	ParB_N	Domain
IPR016692	Sulfiredoxin	Family
IPR036086	ParB/Sulfiredoxin_sf	Homologous_superfamily

Pfam: PF02195

Enzyme classification (BRENDA):

• EC 1.8.98.2 — sulfiredoxin (BRENDA: 7 organisms, 54 substrates, 8 inhibitors, 8 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.03–0.125	2
PEROXIREDOXIN-(S-HYDROXY-S-OXOCYSTEINE)	0.029–0.079	2
GAMMA-S-ATP	0.13	1
GSH	1.8	1
THIOREDOXIN 1	0.0012	1

Catalyzed reactions (Rhea), 1 shown:

• S-hydroxy-S-oxy-L-cysteinyl-[peroxiredoxin] + [protein]-dithiol + ATP = S-hydroxy-L-cysteinyl-[peroxiredoxin] + [protein]-disulfide + ADP + phosphate (RHEA:17545)

UniProt features (21 total): strand 6, helix 6, modified residue 3, chain 1, region of interest 1, compositionally biased region 1, binding site 1, disulfide bond 1, mutagenesis site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
1XW3	X-RAY DIFFRACTION	1.65
3CYI	X-RAY DIFFRACTION	1.8
1XW4	X-RAY DIFFRACTION	2
3HY2	X-RAY DIFFRACTION	2.1
2RII	X-RAY DIFFRACTION	2.6
7LJ1	X-RAY DIFFRACTION	2.97
1YZS	SOLUTION NMR
2B6F	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYN0-F1	86.00	0.74

Functional residue map

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

Ligand- & substrate-binding residues (1): 98–101

Post-translational modifications (3): 11, 16, 32

Disulfide bonds (1): 99

Mutagenesis-validated functional residues (1):

Position	Phenotype
99	no effect on association with prdx1, prdx2, prdx3 or prdx4.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711123	Cellular response to chemical stress
R-HSA-9755511	KEAP1-NFE2L2 pathway
R-HSA-9759194	Nuclear events mediated by NFE2L2

MSigDB gene sets: 188 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, PATIL_LIVER_CANCER, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_DETOXIFICATION, SANSOM_APC_TARGETS_DN, GOMF_ANTIOXIDANT_ACTIVITY, ONGUSAHA_TP53_TARGETS, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE, ACEVEDO_LIVER_CANCER_UP, BURTON_ADIPOGENESIS_2, SARTIPY_NORMAL_AT_INSULIN_RESISTANCE_UP

GO Biological Process (3): response to oxidative stress (GO:0006979), cellular response to oxidative stress (GO:0034599), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (7): ATP binding (GO:0005524), oxidoreductase activity, acting on a sulfur group of donors (GO:0016667), sulfiredoxin activity (GO:0032542), nucleotide binding (GO:0000166), protein binding (GO:0005515), antioxidant activity (GO:0016209), oxidoreductase activity (GO:0016491)

GO Cellular Component (3): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Nuclear events mediated by NFE2L2	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Cellular response to chemical stress	1
KEAP1-NFE2L2 pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
response to stress	1
response to oxidative stress	1
cellular response to chemical stress	1
cellular detoxification	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
oxidoreductase activity	1
antioxidant activity	1
oxidoreductase activity, acting on a sulfur group of donors	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
molecular_function	1
cellular oxidant detoxification	1
catalytic activity	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1

Protein interactions and networks

STRING

1512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRXN1	PRDX1	P35703	943
SRXN1	TXNRD1	Q16881	852
SRXN1	PRDX2	P31945	847
SRXN1	TXN	P10599	784
SRXN1	NQO1	P15559	768
SRXN1	GCLM	P48507	754
SRXN1	GCLC	P48506	725
SRXN1	GDPD5	Q8WTR4	719
SRXN1	GSR	P00390	709
SRXN1	PRDX3	P30048	696
SRXN1	PRDX4	Q13162	683
SRXN1	GLRX	P35754	674
SRXN1	GPX2	P18283	645
SRXN1	KEAP1	Q14145	640
SRXN1	PRDX5	P30044	627

IntAct

10 interactions, top by confidence:

A	B	Type	Score
FGL1	LCMT2	psi-mi:“MI:0914”(association)	0.640
SRXN1	PRDX1	psi-mi:“MI:0407”(direct interaction)	0.620
	SHTN1	psi-mi:“MI:0914”(association)	0.350
TRIOBP	SKAP2	psi-mi:“MI:0914”(association)	0.350
KCNQ3	AKT2	psi-mi:“MI:0914”(association)	0.350
SRXN1	DCAF10	psi-mi:“MI:0914”(association)	0.350
RSPH1	SRXN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (54): CFL1 (Co-fractionation), SRXN1 (Co-fractionation), SRXN1 (Co-fractionation), SRXN1 (Biochemical Activity), SRXN1 (Affinity Capture-MS), SRXN1 (Affinity Capture-MS), SRXN1 (Affinity Capture-MS), CCDC102A (Affinity Capture-MS), SRXN1 (Affinity Capture-MS), DCAF10 (Affinity Capture-MS), SRXN1 (Proximity Label-MS), SRXN1 (Affinity Capture-RNA), SRXN1 (Two-hybrid), SRXN1 (Reconstituted Complex), SRXN1 (Affinity Capture-MS)

ESM2 similar proteins: A3KMV1, A4IFA8, A8ID74, A8INQ0, A8JBB2, B4FR29, D3ZKV9, F5A894, O60292, P46062, P97287, Q07820, Q2KIL7, Q2QNS6, Q2T9W0, Q3TQF0, Q4VBF2, Q4VC12, Q53JI9, Q566Q8, Q580W5, Q5E9N0, Q5QD03, Q5XUX0, Q60764, Q69T21, Q6NWH0, Q6P7W2, Q6R2V6, Q6Z690, Q750K9, Q7YRZ9, Q8HYS5, Q8JZP9, Q8N8M0, Q8R4R9, Q8R4S0, Q8TAE6, Q8TBC3, Q8VD62

Diamond homologs: P36077, Q54RQ8, Q9BYN0, Q9D975, Q9URV9, Q9VX10, A8XSV3, E7FAW3, E9Q2M9, F4HZB2, F4I9T0, F4IG73, F4JD14, F4JHT3, F4JY12, O35242, P25356, P50851, P97412, Q19317, Q54PP7, Q54U63, Q55AV3, Q55DM1, Q562E7, Q6VNB8, Q6ZNJ1, Q6ZQA0, Q6ZS30, Q6ZS81, Q7LKZ7, Q86JF2, Q8GY89, Q8IZQ1, Q8NFP9, Q92636, Q99698, Q9EPN1, Q9ESE1, Q9TTK4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

343 predictions. Top by Δscore:

Variant	Effect	Δscore
20:648916:TCCTG:T	acceptor_loss	1.0000
20:648917:CCTGG:C	acceptor_loss	1.0000
20:648918:C:A	acceptor_loss	1.0000
20:648918:C:CC	acceptor_gain	1.0000
20:648919:T:A	acceptor_loss	1.0000
20:648913:TCCTC:T	acceptor_gain	0.9900
20:648914:CCTCC:C	acceptor_gain	0.9900
20:648915:CTC:C	acceptor_gain	0.9900
20:652962:C:CA	donor_gain	0.9900
20:652963:C:A	donor_gain	0.9900
20:652970:CCTCA:C	donor_loss	0.9900
20:652972:TCA:T	donor_loss	0.9900
20:652974:AC:A	donor_gain	0.9900
20:652975:CC:C	donor_gain	0.9900
20:648916:TC:T	acceptor_gain	0.9800
20:648917:CC:C	acceptor_gain	0.9800
20:650012:TGAA:T	donor_gain	0.9800
20:652974:A:AC	donor_gain	0.9800
20:652975:C:CC	donor_gain	0.9800
20:652969:GCCTC:G	donor_loss	0.9500
20:652975:CCCGG:C	donor_gain	0.9300
20:652926:C:A	donor_gain	0.9200
20:652943:C:A	donor_gain	0.9200
20:652833:G:A	donor_gain	0.9000
20:652996:TCTG:T	donor_gain	0.8900
20:652997:CTGC:C	donor_gain	0.8900
20:652998:TG:T	donor_gain	0.8900
20:649620:TGA:T	donor_gain	0.8800
20:653168:T:TA	donor_gain	0.8800
20:649582:A:C	donor_gain	0.8500

AlphaMissense

860 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:648886:A:T	V81D	0.994
20:648848:A:C	Y94D	0.993
20:648840:A:C	F96L	0.992
20:648840:A:T	F96L	0.992
20:648842:A:G	F96L	0.992
20:648817:G:T	A104D	0.990
20:648830:G:C	H100D	0.987
20:648892:A:T	I79N	0.985
20:648827:G:T	R101S	0.984
20:653003:C:A	K61N	0.984
20:653003:C:G	K61N	0.984
20:648790:A:T	I113N	0.982
20:648784:G:T	A115D	0.981
20:648848:A:T	Y94N	0.981
20:648754:A:G	L125P	0.980
20:648877:A:T	I84N	0.980
20:648841:A:G	F96S	0.979
20:648877:A:C	I84S	0.979
20:653040:A:T	L49H	0.978
20:648883:A:G	L82P	0.975
20:648838:C:T	G97E	0.974
20:648901:A:T	V76E	0.973
20:652992:A:G	L65P	0.973
20:648877:A:G	I84T	0.972
20:648754:A:T	L125Q	0.971
20:648841:A:C	F96C	0.971
20:648739:C:T	G130E	0.970
20:648785:C:G	A115P	0.970
20:648826:C:G	R101P	0.969
20:648828:G:C	H100Q	0.969

dbSNP variants (sampled 300 via entrez): RS1000264528 (20:651763 A>G), RS1000701461 (20:651315 A>C), RS1001033636 (20:647593 GAGGAGAACCA>G), RS1001083475 (20:652078 G>A), RS1001087636 (20:647633 C>T), RS1001169053 (20:647654 T>C), RS1001413693 (20:653395 C>G,T), RS1001705190 (20:647919 A>C), RS1002139350 (20:648490 G>C), RS1002288624 (20:654106 CA>C), RS1003053047 (20:654472 C>A), RS1003085617 (20:654824 T>C), RS1003246647 (20:649931 G>A), RS1003247746 (20:648732 G>A,C), RS1003322216 (20:655171 C>T)

Disease associations

OMIM: gene MIM:617583 | 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
GCST003542_24	Night sleep phenotypes	4.000000e-07
GCST90020025_1652	Waist-to-hip ratio adjusted for BMI	7.000000e-10
GCST90020027_323	Waist-hip index	8.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	9
Benzo(a)pyrene	increases methylation, decreases expression, increases expression	8
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Cyclosporine	increases expression	6
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	5
Tobacco Smoke Pollution	increases expression	5
Aflatoxin B1	affects expression, increases expression, increases methylation, affects cotreatment, decreases expression	5
Particulate Matter	increases abundance, increases expression, increases response to substance, affects cotreatment	5
diethyl maleate	affects reaction, decreases reaction, increases reaction, affects cotreatment, decreases expression (+1 more)	4
Acetaminophen	increases expression	4
bisphenol A	affects cotreatment, decreases expression, affects expression, increases expression	3
sulforaphane	decreases expression, increases expression	3
bardoxolone methyl	decreases expression, increases expression, increases reaction	3
Arsenic Trioxide	increases expression, decreases reaction	3
Air Pollutants	increases abundance, increases expression	3
Cisplatin	affects cotreatment, increases expression	3
Estradiol	affects expression, increases expression	3
beauvericin	decreases expression, affects cotreatment	2
methylmercuric chloride	decreases expression, increases expression	2
arsenite	affects binding, increases reaction, increases expression, affects reaction	2
cobaltous chloride	increases expression	2
ochratoxin A	affects cotreatment, decreases expression, increases expression	2
nickel sulfate	decreases expression, increases expression	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	2
mercuric bromide	increases expression, affects cotreatment	2
enniatins	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Rosiglitazone	increases expression	2
Aerosols	increases expression	2
Ampicillin	decreases expression	2

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TQ50	HAP1 SRXN1 (-) 1	Cancer cell line	Male
CVCL_XT86	HAP1 SRXN1 (-) 2	Cancer cell line	Male
CVCL_XT87	HAP1 SRXN1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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