GPX5

Summary

GPX5 (glutathione peroxidase 5, HGNC:4557) is a protein-coding gene on chromosome 6p22.1, encoding Epididymal secretory glutathione peroxidase (O75715). Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione.

This gene belongs to the glutathione peroxidase family. It is specifically expressed in the epididymis in the mammalian male reproductive tract, and is androgen-regulated. Unlike several other characterized glutathione peroxidases, this enzyme is not a selenoprotein, lacking the selenocysteine residue. Thus, it is selenium-independent, and has been proposed to play a role in protecting the membranes of spermatozoa from the damaging effects of lipid peroxidation and/or preventing premature acrosome reaction. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 2880 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_001509

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4557
Approved symbol	GPX5
Name	glutathione peroxidase 5
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000224586
Ensembl biotype	protein_coding
OMIM	603435
Entrez	2880

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000412168, ENST00000442674, ENST00000469384, ENST00000483784

RefSeq mRNA: 2 — MANE Select: NM_001509 NM_001509, NM_003996

CCDS: CCDS4652, CCDS4653

Canonical transcript exons

ENST00000412168 — 5 exons

Exon	Start	End
ENSE00001813382	28525881	28526100
ENSE00003518229	28531778	28531895
ENSE00003574455	28533961	28534955
ENSE00003575916	28532321	28532420
ENSE00003653076	28529451	28529604

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 61.50.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0134 / max 20.9311, expressed in 1 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66640	0.0062	1
66638	0.0046	1
66639	0.0027	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	61.50	gold quality
testis	UBERON:0000473	60.80	gold quality
left testis	UBERON:0004533	60.44	gold quality
sural nerve	UBERON:0015488	44.12	gold quality
bone marrow cell	CL:0002092	39.10	gold quality
ganglionic eminence	UBERON:0004023	37.36	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
granulocyte	CL:0000094	35.28	gold quality
superior frontal gyrus	UBERON:0002661	34.61	silver quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	33.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
prefrontal cortex	UBERON:0000451	31.17	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
leukocyte	CL:0000738	29.45	gold quality
monocyte	CL:0000576	29.08	silver quality
islet of Langerhans	UBERON:0000006	28.77	gold quality
prostate gland	UBERON:0002367	28.26	gold quality
duodenum	UBERON:0002114	28.14	gold quality
frontal cortex	UBERON:0001870	27.75	gold quality
endocervix	UBERON:0000458	27.69	silver quality
adult mammalian kidney	UBERON:0000082	27.64	gold quality
lymph node	UBERON:0000029	27.57	gold quality
primary visual cortex	UBERON:0002436	27.54	gold quality
blood	UBERON:0000178	27.51	silver quality
kidney	UBERON:0002113	27.38	gold quality
tonsil	UBERON:0002372	27.05	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETV4

miRNA regulators (miRDB)

43 targeting GPX5, 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-4481	100.00	66.42	1669
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-8078	98.32	65.73	361
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-676-3P	97.86	65.70	668
HSA-MIR-3614-3P	97.81	67.15	582
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4456	97.50	64.88	1678

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpx1b	ENSDARG00000006207
danio_rerio	gpx1a	ENSDARG00000018146
danio_rerio	gpx3	ENSDARG00000043342
danio_rerio	gpx4a	ENSDARG00000068478
drosophila_melanogaster	Gpxl	FBGN0034415
caenorhabditis_elegans		WBGENE00007516
caenorhabditis_elegans		WBGENE00007517
caenorhabditis_elegans		WBGENE00011045
caenorhabditis_elegans	gpx-8	WBGENE00018850
caenorhabditis_elegans		WBGENE00022377

Paralogs (7): GPX7 (ENSG00000116157), GPX8 (ENSG00000164294), GPX4 (ENSG00000167468), GPX2 (ENSG00000176153), GPX6 (ENSG00000198704), GPX3 (ENSG00000211445), GPX1 (ENSG00000233276)

Protein

Protein identifiers

Epididymal secretory glutathione peroxidase — O75715 (reviewed: O75715)

Alternative names: Epididymis-specific glutathione peroxidase-like protein, Glutathione peroxidase 5

All UniProt accessions (2): O75715, V9HWN8

UniProt curated annotations — full annotation on UniProt →

Function. Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-like protective system against peroxide damage in sperm membrane lipids.

Subcellular location. Secreted.

Tissue specificity. Epididymis.

Similarity. Belongs to the glutathione peroxidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75715-1	1	yes
O75715-2	2

RefSeq proteins (2): NP_001500, NP_003987 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000889	Glutathione_peroxidase	Family
IPR029759	GPX_AS	Active_site
IPR029760	GPX_CS	Conserved_site
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF00255

Enzyme classification (BRENDA):

• EC 1.11.1.9 — glutathione peroxidase (BRENDA: 58 organisms, 96 substrates, 65 inhibitors, 63 Km, 23 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
H2O2	0.0023–19.08	19
GSH	0.033–11.1	18
CUMENE HYDROPEROXIDE	0.006–7.8	6
TERT-BUTYL HYDROPEROXIDE	0.059–7.9	6
GLUTATHIONE	0.022–1.73	4
CUMENE PEROXIDE	0.09–0.42	2
L-ALPHA-PHOSPHATIDYLCHOLINE HYDROPEROXIDE	0.026–9.7	2
LINOLENIC ACID HYDROPEROXIDE	0.007–3.8	2
CHOLESTEROL 5ALPHA-HYDROPEROXIDE	0.004	1
CHOLESTEROL 7ALPHA-HYDROPEROXIDE	0.011	1
CHOLESTEROL 7BETA-HYDROPEROXIDE	0.003	1
TERT-BUTYLHYDROPEROXIDE	0.024	1

Catalyzed reactions (Rhea), 1 shown:

• 2 glutathione + H2O2 = glutathione disulfide + 2 H2O (RHEA:16833)

UniProt features (27 total): strand 10, helix 10, sequence variant 2, signal peptide 1, chain 1, active site 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2I3Y	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75715-F1	90.86	0.79

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 (1): 73

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3299685	Detoxification of Reactive Oxygen Species

MSigDB gene sets: 59 (showing top): GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_DETOXIFICATION, GATA1_04, GOBP_LIPID_METABOLIC_PROCESS, GOMF_ANTIOXIDANT_ACTIVITY, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PEROXIDE_AS_ACCEPTOR, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE, GOMF_GLUTATHIONE_PEROXIDASE_ACTIVITY, KEGG_GLUTATHIONE_METABOLISM, YOSHIMURA_MAPK8_TARGETS_UP, PILON_KLF1_TARGETS_UP, DE_YY1_TARGETS_UP, ATF2_UP.V1_UP, SRC_UP.V1_UP, REACTOME_DETOXIFICATION_OF_REACTIVE_OXYGEN_SPECIES

GO Biological Process (4): lipid metabolic process (GO:0006629), cellular response to oxidative stress (GO:0034599), response to oxidative stress (GO:0006979), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (3): glutathione peroxidase activity (GO:0004602), peroxidase activity (GO:0004601), oxidoreductase activity (GO:0016491)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular response to chemical stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
response to oxidative stress	1
cellular response to chemical stress	1
response to stress	1
cellular detoxification	1
peroxidase activity	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPX5	GSR	P00390	973
GPX5	TXN	P10599	895
GPX5	XDH	P47989	884
GPX5	SOD2	P04179	851
GPX5	F5H3C5	F5H3C5	850
GPX5	GLRX	P35754	841
GPX5	HMOX1	P09601	838
GPX5	TXNRD1	Q16881	822
GPX5	SOD1	P00441	816
GPX5	G6PD	P11413	804
GPX5	H6PD	O95479	804
GPX5	GPT	P24298	801
GPX5	NFE2L2	Q16236	796
GPX5	CASP3	P42574	764
GPX5	ACO2	Q99798	757

IntAct

3 interactions, top by confidence:

A	B	Type	Score
P		psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): GPX5 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A8M1N5Y4, A2A863, B0FYY4, B3SP85, E7E2N8, H9J9M0, O17861, O22925, O75715, O80977, P11584, P12606, P13284, P22297, P28714, P28826, P30710, P48980, P52717, P81628, P93026, P93484, Q08169, Q10RB4, Q27874, Q499T2, Q56H28, Q56NL1, Q56ZQ3, Q5RFN1, Q5XJN2, Q61847, Q64632, Q6AUC6, Q6P5E4, Q7PQD1, Q8L7E3, Q8R0I0, Q920A5, Q95RA9

Diamond homologs: A1KV41, A6QLY2, G9JJU2, O02621, O04922, O08368, O18994, O22448, O22850, O23814, O23968, O23970, O24031, O24296, O32770, O46607, O48646, O49069, O59858, O62327, O70325, O75715, P00435, P04041, P06610, P07203, P0A0T4, P0A0T5, P0C2T0, P11352, P11909, P18283, P21765, P22352, P28714, P30708, P30710, P35666, P36014, P36968

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

978 predictions. Top by Δscore:

Variant	Effect	Δscore
6:28529602:CTGG:C	donor_loss	0.9900
6:28529605:G:GG	donor_gain	0.9900
6:28529605:G:T	donor_loss	0.9900
6:28529606:T:G	donor_loss	0.9900
6:28531896:G:GG	donor_gain	0.9900
6:28533953:T:TA	acceptor_gain	0.9900
6:28529449:A:AG	acceptor_gain	0.9800
6:28529450:G:GG	acceptor_gain	0.9800
6:28529450:GAT:G	acceptor_gain	0.9800
6:28529449:AGAT:A	acceptor_gain	0.9700
6:28529450:GATG:G	acceptor_gain	0.9700
6:28526099:AGGTG:A	donor_loss	0.9600
6:28526100:GGTG:G	donor_loss	0.9600
6:28526101:G:C	donor_loss	0.9600
6:28526102:T:G	donor_loss	0.9600
6:28529386:TGAAA:T	acceptor_gain	0.9600
6:28529387:GAAAG:G	acceptor_gain	0.9600
6:28529388:AAAGA:A	acceptor_gain	0.9600
6:28529449:AGATG:A	acceptor_gain	0.9600
6:28529450:GATGG:G	acceptor_gain	0.9600
6:28533959:A:AG	acceptor_gain	0.9600
6:28533960:G:GG	acceptor_gain	0.9600
6:28532282:T:G	acceptor_gain	0.9500
6:28533954:G:A	acceptor_gain	0.9500
6:28533947:T:G	acceptor_gain	0.9400
6:28533960:GC:G	acceptor_gain	0.9400
6:28526097:GAAG:G	donor_gain	0.9300
6:28526101:G:GG	donor_gain	0.9300
6:28529445:TTCCA:T	acceptor_loss	0.9300
6:28529446:TCCA:T	acceptor_loss	0.9300

AlphaMissense

1462 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:28534048:T:C	F183L	0.997
6:28534050:T:A	F183L	0.997
6:28534050:T:G	F183L	0.997
6:28531846:T:C	F104L	0.996
6:28531848:T:A	F104L	0.996
6:28531848:T:G	F104L	0.996
6:28534047:C:A	N182K	0.995
6:28534047:C:G	N182K	0.995
6:28532416:T:C	L152S	0.994
6:28534090:C:A	R197S	0.994
6:28534091:G:C	R197P	0.994
6:28531831:T:C	F99L	0.993
6:28531833:T:A	F99L	0.993
6:28531833:T:G	F99L	0.993
6:28534058:T:C	F186S	0.993
6:28529567:C:A	N68K	0.992
6:28529567:C:G	N68K	0.992
6:28531839:C:G	C101W	0.992
6:28532420:G:C	K153N	0.992
6:28532420:G:T	K153N	0.992
6:28532406:T:C	F149L	0.991
6:28532408:C:A	F149L	0.991
6:28532408:C:G	F149L	0.991
6:28531847:T:G	F104C	0.990
6:28534048:T:A	F183I	0.990
6:28534093:T:A	W198R	0.990
6:28534093:T:C	W198R	0.990
6:28534095:G:C	W198C	0.990
6:28534095:G:T	W198C	0.990
6:28532329:G:C	R123P	0.989

dbSNP variants (sampled 300 via entrez): RS1000182346 (6:28530724 G>A,T), RS1000423731 (6:28531094 C>A,T), RS1000433964 (6:28529605 G>A,T), RS1000744226 (6:28524898 T>C,G), RS1000754995 (6:28532570 A>T), RS1000891627 (6:28529284 C>T), RS1001093030 (6:28525235 C>T), RS1001246976 (6:28528799 A>G), RS1001633056 (6:28528355 G>A), RS1002189036 (6:28534101 C>T), RS1002251123 (6:28530488 C>A), RS1002735235 (6:28528456 G>A,C), RS1002920991 (6:28526984 G>C), RS1003307310 (6:28530568 C>G), RS1003308668 (6:28526552 CAG>C)

Disease associations

OMIM: gene MIM:603435 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST003518_56	Daytime sleep phenotypes	2.000000e-07
GCST004521_112	Autism spectrum disorder or schizophrenia	3.000000e-26
GCST004521_166	Autism spectrum disorder or schizophrenia	4.000000e-24
GCST004521_212	Autism spectrum disorder or schizophrenia	5.000000e-14
GCST004521_43	Autism spectrum disorder or schizophrenia	2.000000e-27
GCST004521_7	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_73	Autism spectrum disorder or schizophrenia	8.000000e-11
GCST004521_77	Autism spectrum disorder or schizophrenia	1.000000e-19
GCST005212_37	Asthma	6.000000e-07
GCST006575_10	Takayasu arteritis	5.000000e-06
GCST006862_1	Asthma	5.000000e-09
GCST008921_4	Asthma and major depressive disorder	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs451774	Efficacy	3	carboplatin;cisplatin;gemcitabine	Non-Small Cell Lung Carcinoma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs451774	GPX5	3	2.75	1	carboplatin;cisplatin;gemcitabine

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Paraquat	affects cotreatment, increases expression	2
naringenin	increases expression, affects cotreatment	1
sodium arsenite	affects methylation	1
1,4-phenylenebis(methylene)selenocyanate	increases expression	1
bisphenol S	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression	1
Thioctic Acid	increases expression	1
Nitrogen Dioxide	increases expression	1
Quercetin	affects cotreatment, increases expression	1
Carbaryl	increases expression	1
Valproic Acid	decreases methylation	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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