GLRX

Summary

GLRX (glutaredoxin, HGNC:4330) is a protein-coding gene on chromosome 5q15, encoding Glutaredoxin-1 (P35754). Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase.

This gene encodes a member of the glutaredoxin family. The encoded protein is a cytoplasmic enzyme catalyzing the reversible reduction of glutathione-protein mixed disulfides. This enzyme highly contributes to the antioxidant defense system. It is crucial for several signalling pathways by controlling the S-glutathionylation status of signalling mediators. It is involved in beta-amyloid toxicity and Alzheimer’s disease. Multiple alternatively spliced transcript variants encoding the same protein have been identified.

Source: NCBI Gene 2745 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_001118890

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4330
Approved symbol	GLRX
Name	glutaredoxin
Location	5q15
Locus type	gene with protein product
Status	Approved
Aliases	GRX, GRX1
Ensembl gene	ENSG00000173221
Ensembl biotype	protein_coding
OMIM	600443
Entrez	2745

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000237858, ENST00000379979, ENST00000505427, ENST00000507412, ENST00000507605, ENST00000508780, ENST00000512469, ENST00000907620, ENST00000907621, ENST00000907622, ENST00000907623, ENST00000938002, ENST00000938003, ENST00000938004, ENST00000938005, ENST00000958151

RefSeq mRNA: 4 — MANE Select: NM_001118890 NM_001118890, NM_001243658, NM_001243659, NM_002064

CCDS: CCDS4078

Canonical transcript exons

ENST00000237858 — 3 exons

Exon	Start	End
ENSE00001483235	95813849	95814389
ENSE00002066532	95822456	95822726
ENSE00003677140	95816507	95816626

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 99.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8485 / max 465.3557, expressed in 1720 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62654	24.8453	1719
62653	0.9310	463
62652	0.5026	242
62656	0.3190	97
62655	0.2506	96

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.40	gold quality
decidua	UBERON:0002450	99.19	gold quality
stromal cell of endometrium	CL:0002255	99.12	gold quality
monocyte	CL:0000576	98.88	gold quality
mononuclear cell	CL:0000842	98.87	gold quality
leukocyte	CL:0000738	98.86	gold quality
placenta	UBERON:0001987	98.81	gold quality
ileal mucosa	UBERON:0000331	98.78	gold quality
upper leg skin	UBERON:0004262	98.78	gold quality
duodenum	UBERON:0002114	98.58	gold quality
oocyte	CL:0000023	98.43	gold quality
gastrocnemius	UBERON:0001388	98.41	gold quality
adult mammalian kidney	UBERON:0000082	98.39	gold quality
granulocyte	CL:0000094	98.37	gold quality
trabecular bone tissue	UBERON:0002483	98.36	gold quality
bone marrow	UBERON:0002371	98.29	gold quality
nephron tubule	UBERON:0001231	97.95	gold quality
muscle of leg	UBERON:0001383	97.90	gold quality
bone marrow cell	CL:0002092	97.75	gold quality
left adrenal gland	UBERON:0001234	97.70	gold quality
right adrenal gland	UBERON:0001233	97.69	gold quality
heart right ventricle	UBERON:0002080	97.66	gold quality
left adrenal gland cortex	UBERON:0035825	97.62	gold quality
epithelium of nasopharynx	UBERON:0001951	97.56	gold quality
adrenal cortex	UBERON:0001235	97.53	gold quality
right adrenal gland cortex	UBERON:0035827	97.44	gold quality
renal medulla	UBERON:0000362	97.32	gold quality
periodontal ligament	UBERON:0008266	97.27	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.13	gold quality
kidney epithelium	UBERON:0004819	97.09	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	4828.12
E-MTAB-10855	yes	1515.79
E-CURD-89	yes	953.21
E-CURD-11	yes	950.35
E-MTAB-3929	yes	113.13
E-HCAD-1	yes	78.55
E-GEOD-125970	yes	72.20
E-HCAD-4	yes	54.10
E-HCAD-6	yes	52.70
E-CURD-120	yes	45.10
E-MTAB-10042	yes	14.01
E-MTAB-9067	yes	13.44
E-MTAB-9801	yes	6.67
E-CURD-122	yes	4.83
E-GEOD-124858	no	449.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ESR2, IRF6, NFKB, PPARA, RELA

miRNA regulators (miRDB)

83 targeting GLRX, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-433-3P	99.98	69.37	1203
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4267	99.96	66.53	2368
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805

Literature-anchored findings (GeneRIF, showing 40)

• Glutaredoxin-dependent peroxiredoxin from poplar: protein-protein interaction and catalytic mechanism (PMID:11832487)
• Results suggest that glutaredoxin plays an important role during implantation, while Trx levels remained constant during the secretory phase. (PMID:12029072)
• role of GRX in oxidative stress-induced signaling and cytotoxicity in glucose-deprived human cancer cells (PMID:12244106)
• facilitates GS-radical scavenging and S-glutathionylation of redox signal mediators, consistent with a critical role in redox signal transduction and cellular regulation (PMID:12556467)
• role in metabolic oxidative stress-induced activation of apoptosis signal-regulating kinase 1 (PMID:12723971)
• secretion of Grx1 and its presence in plasma suggests extracellular functions as found for mammalian thioredoxin 1 (PMID:15184054)
• Lung cells can synthesize Grx1 mRNA and protein. Grx1 is expressed in alveolar macrophages of healthy lung. (PMID:15297967)
• Grx1(as) cDNA is an alternatively spliced human Grx1 cDNA and the Grx1(as) 3’-untranslated region may have a role in stabilizing mRNA (PMID:15637068)
• Abeta neurotoxicity might be mediated by oxidation of GRX1 or TRX1 and subsequent activation of the ASK1 cascade. (PMID:16311508)
• We propose that GRX1 is essential for ATPase function and catalyses either the reduction of intramolecular disulphide bonds or the deglutathionylation of the cysteine residues within the CxxC motifs to facilitate copper-binding for subsequent transport. (PMID:16884690)
• GRX plays an important role in PDGF-BB-dependent cell proliferation by regulating the redox state of LMW-PTP (PMID:16893901)
• Grx1 is a potential redox modulatory protein regulating the intracellular as well as extracellular homeostasis of glutathionylated proteins and GSH in human lung. (PMID:17064412)
• A novel mechanism of caspase-3 regulation by glutaredoxin is demonstrated in tumor necrosis factor-alpha-induced apoptosis. (PMID:17185628)
• In this review, reversible glutathiolation of procaspase-3 by glutaredoxin provides further mechanistic insight into the role of reactive oxygen species in TNF-alpha-induced apoptosis. (PMID:17272816)
• Deglutathionylation of IRF3 is necessary for efficient interaction of IRF3 with CREBBP. (PMID:18309294)
• downregulation of Grx1 leads to mitochondrial dysfunction through oxidative modification of the outer membrane protein, VDAC, providing support for the critical role of Grx1 in maintenance of mitochondrial membrane potential (PMID:18560520)
• NO increased the S-glutathiolation of SERCA, and adenoviral overexpression of glutaredoxin-1 prevented both the HNO-stimulated oxidative modification of SERCA and its activation. (PMID:19265039)
• Role of glutaredoxin1 and glutathione in regulating the activity of the copper-transporting P-type ATPases, ATP7A and ATP7B. (PMID:20566629)
• findings reveal another signalling molecule affected by S-glutathionylation and uncover a crucial role for GRX-1 in the TRAF6-dependent activation of NF-kappaB by IL-1R/TLRs. (PMID:21078302)
• Microsecond-millisecond motions in glutaredoxin result from substrate binding and not from crossing of the transition state energy barrier of product formation. Instead substrate binding induces a conformational change. (PMID:21323311)
• These results showed that cigarette smoke can modulate glutaredoxin 1, not only at the expression level, but can also directly modify glutaredoxin 1 itself, decreasing its activity. (PMID:21454804)
• Data show that glutaredoxin acts as a reductant for methionine sulfoxide reductases A and B (MsrA and MsrB) with or without resolving cysteine. (PMID:22634633)
• Studies show that the glutaredoxin system with glutathione plays a backup role to keep oxidized thioredoxin 1 (Trx1) reduced in cells with loss of thioredoxin reductase 1 (TrxR1) activity. (PMID:22977247)
• sputum glutaredoxin-1 may have a role in asthma, while protein S may have a role in better lung function (PMID:23370801)
• Thioredoxin 1 is inactivated due to oxidation induced by peroxiredoxin under oxidative stress and reactivated by the glutaredoxin system. (PMID:24062305)
• Levels of GLRX in the cerebrospinal fluid increase significantly in the early stages of Alzheimer’s disease. (PMID:24270206)
• Glrx overexpression increased soluble VEGF receptor 1 (sFlt) in endothelial cells via NF-kappaB-dependent Wnt5a production. (PMID:24482236)
• Human Grx1 can catalyse reduction of Atox1 by glutathione but only in the presence of Cu(I). (PMID:24522867)
• A new function for GRX1 in neuronal copper homeostasis and in protection from copper-mediated oxidative injury. (PMID:24816595)
• Glutaredoxin 1 protects human retinal pigment epithelial cells from oxidative damage by preventing AKT glutathionylation. (PMID:25788646)
• The results demonstrate that the antiproliferative effect of NO is hampered by Trx1 and Grx1 and support the strategy of weakening the thiolic antioxidant defenses when designing new antitumoral therapies. (PMID:26210445)
• Prx2 glutathionylation is a favorable reaction that can occur in cells under oxidative stress and may have a role in redox signaling. GSH/Grx1 provide an alternative mechanism to thioredoxin and thioredoxin reductase for Prx2 recycling. (PMID:26601956)
• Glrx ablation stabilizes HIF-1alpha by increasing GSH adducts on Cys(520) promoting in vivo HIF-1alpha stabilization, VEGF-A production, and revascularization in the ischemic muscles. (PMID:27162359)
• Our results indicate that Grx1 upregulation promotes neuroinflammation and consequent neuronal cell death in vitro, and synergizes with proinflammatory insults to promote DA loss in vivo. (PMID:27224303)
• Glutaredoxin desensitizes lens to oxidative stress by connecting and integrating specific signaling and transcriptional regulation for antioxidant response. (PMID:27744453)
• Based on the roGFP2-hGrx1 signals, glutathione-dependent redox potentials of -267mV and -328mV, respectively, were obtained. Employing these novel tools, initial studies on the effects of redox-active agents and clinically employed antimalarial drugs were carried out on both organelles. (PMID:28062360)
• Overexpression of NOS3 increased the levels and activities of proteins of the redoxin systems, Trx1, Grx1, TrxR1 and TxnIP, and the levels of signaling proteins (Akt1, pAkt1(-)Ser473, MapK, pMapK, Stat3, Fas). (PMID:28162284)
• GRX1 overexpression constrains oxidative stress and apoptosis in osteoarthritis chondrocytes by regulating CREB/HO-1, providing a novel insight into the molecular mechanism and potential treatment of osteoarthritis. (PMID:28843170)
• Reduction potentials of protein disulfides and catalysis of glutathionylation and deglutathionylation by glutaredoxin enzymes (PMID:28963348)
• Research on Grx and its potential roles in Parkinson’s disease (PD) presents a complex situation where Grx1 likely plays a primary neuroprotective role in dopaminergic neurons but a proinflammatory role in microglia. Midbrain PD samples showed decreased Grx1 specifically within dopaminergic neurons. Increased GLRX copy number in PD patients was associated with earlier onset.[review] (PMID:29183158)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	glrx	ENSDARG00000028106
mus_musculus	Glrx	ENSMUSG00000021591
rattus_norvegicus	Glrx	ENSRNOG00000012183
rattus_norvegicus	Glrx-ps16	ENSRNOG00000050229
rattus_norvegicus		ENSRNOG00000078740
caenorhabditis_elegans	glrx-10	WBGENE00021331

Protein

Protein identifiers

Glutaredoxin-1 — P35754 (reviewed: P35754)

Alternative names: Thioltransferase-1

All UniProt accessions (1): P35754

UniProt curated annotations — full annotation on UniProt →

Function. Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins.

Subcellular location. Cytoplasm.

Similarity. Belongs to the glutaredoxin family.

RefSeq proteins (4): NP_001112362, NP_001230587, NP_001230588, NP_002055 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002109	Glutaredoxin	Domain
IPR011767	GLR_AS	Active_site
IPR011899	Glutaredoxin_euk/vir	Domain
IPR014025	Glutaredoxin_subgr	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR047185	GLRX1	Family

Pfam: PF00462

UniProt features (19 total): helix 5, strand 4, modified residue 2, disulfide bond 2, initiator methionine 1, chain 1, turn 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4RQR	X-RAY DIFFRACTION	1.08
1B4Q	SOLUTION NMR
1JHB	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35754-F1	97.08	0.98

Functional residue map

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

Post-translational modifications (2): 2, 9

Disulfide bonds (2): 23–26, 79–83

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-499943	Interconversion of nucleotide di- and triphosphates

MSigDB gene sets: 437 (showing top): MODULE_93, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WALLACE_PROSTATE_CANCER_RACE_UP, CHIBA_RESPONSE_TO_TSA_UP, MCLACHLAN_DENTAL_CARIES_UP, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, SWEET_KRAS_ONCOGENIC_SIGNATURE, MODULE_45, HALMOS_CEBPA_TARGETS_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, KYNG_DNA_DAMAGE_DN, MODULE_16, MODULE_503, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_DN

GO Biological Process (2): nucleobase-containing small molecule interconversion (GO:0015949), positive regulation of membrane potential (GO:0045838)

GO Molecular Function (4): glutathione disulfide oxidoreductase activity (GO:0015038), sodium channel regulator activity (GO:0017080), protein binding (GO:0005515), disulfide oxidoreductase activity (GO:0015036)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
nucleobase-containing small molecule metabolic process	1
regulation of membrane potential	1
disulfide oxidoreductase activity	1
sodium channel activity	1
ion channel regulator activity	1
binding	1
oxidoreductase activity, acting on a sulfur group of donors	1
intracellular membrane-bounded organelle	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2765 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLRX	GSR	P00390	967
GLRX	TXN	P10599	959
GLRX	GLRX5	Q86SX6	921
GLRX	TXNRD1	Q16881	866
GLRX	GLRX3	O76003	859
GLRX	HPGDS	O60760	854
GLRX	GPX2	P18283	850
GLRX	GPX3	P22352	847
GLRX	GPX7	Q96SL4	842
GLRX	GPX6	P59796	841
GLRX	GPX5	O75715	841
GLRX	GPX8	Q8TED1	841
GLRX	GRXCR1	A8MXD5	839
GLRX	PTGES2	Q9H7Z7	824
GLRX	GSTO1	P78417	814

IntAct

32 interactions, top by confidence:

A	B	Type	Score
CFAP298	PEX7	psi-mi:“MI:0914”(association)	0.620
GLRX	TRIM62	psi-mi:“MI:0915”(physical association)	0.560
GLRX	rep	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.560
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
GLRX		psi-mi:“MI:0570”(protein cleavage)	0.440
GLRX	AQP5	psi-mi:“MI:0915”(physical association)	0.370
CASP3	GLRX	psi-mi:“MI:0915”(physical association)	0.370
MMP23B	GLRX	psi-mi:“MI:0915”(physical association)	0.370
GLRX	GOT2	psi-mi:“MI:0915”(physical association)	0.370
MAD2L2		psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
TAGLN	LOC392647	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
CHURC1	NMT2	psi-mi:“MI:0914”(association)	0.350
GLRX	HPRT1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
ATF2	PLOD2	psi-mi:“MI:0914”(association)	0.350
CEBPA	MYO1C	psi-mi:“MI:0914”(association)	0.350
ERBB2	DNM1L	psi-mi:“MI:0914”(association)	0.350
MYB	A2ML1	psi-mi:“MI:0914”(association)	0.350
MYC	AP3B1	psi-mi:“MI:0914”(association)	0.350
STAT3	IDH3B	psi-mi:“MI:0914”(association)	0.350
GLRX	TRIM62	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): GLRX (Affinity Capture-MS), GLRX (Co-fractionation), GLRX (Co-fractionation), GLRX (Co-fractionation), GLRX (Co-fractionation), GLRX (Co-fractionation), GLRX (Co-fractionation), GLRX (Co-fractionation), GLRX (Co-fractionation), GLRX (Co-fractionation), GLRX (Co-fractionation), NIT1 (Co-fractionation), GLRX (Affinity Capture-MS), GLRX (Two-hybrid), GLRX (Two-hybrid)

ESM2 similar proteins: B7ZFT1, C9K7C5, O14463, O17486, O36032, O74790, O81187, O96952, P0AC62, P0AC63, P0AC64, P12309, P12864, P17695, P22803, P25373, P29429, P29445, P29447, P29448, P29449, P32642, P34723, P35754, P44758, P55142, P73492, P79764, Q03835, Q07090, Q0IWL9, Q1RQI9, Q1RQJ0, Q39239, Q39362, Q43636, Q54GP8, Q54KN7, Q6XHI1, Q7KQL8

Diamond homologs: A0A7H0DN48, O36032, P0DOQ9, P0DOR0, P10575, P12309, P12864, P35754, P38068, P68690, P68691, P68692, P79764, Q32L67, Q5RC53, Q6AXW1, Q6RZN3, Q76ZV3, Q775X4, Q77TL9, Q80E01, Q8JLF5, Q8QMY9, Q8V2V1, Q923X4, Q9ESH6, Q9FVX1, Q9JVU9, Q9JY15, Q9NS18, Q9QUH0, Q9UTI2, B7ZFT1, O05957, O23417, O23419, O23420, O23421, O81187, O82255

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2518 predictions. Top by Δscore:

Variant	Effect	Δscore
5:95763616:GAAAG:G	donor_gain	1.0000
5:95763619:AGG:A	donor_loss	1.0000
5:95763621:G:C	donor_loss	1.0000
5:95763621:G:GG	donor_gain	1.0000
5:95779148:A:G	donor_gain	1.0000
5:95783795:AGCT:A	acceptor_gain	1.0000
5:95783795:AGCTG:A	acceptor_gain	1.0000
5:95783796:GCT:G	acceptor_gain	1.0000
5:95783796:GCTG:G	acceptor_gain	1.0000
5:95783796:GCTGG:G	acceptor_gain	1.0000
5:95783959:CCAAG:C	donor_loss	1.0000
5:95783960:CAAG:C	donor_loss	1.0000
5:95783964:G:GA	donor_loss	1.0000
5:95783965:T:A	donor_loss	1.0000
5:95822451:CTCA:C	donor_loss	1.0000
5:95822452:TCACC:T	donor_loss	1.0000
5:95822453:CACCG:C	donor_loss	1.0000
5:95822454:A:AC	donor_gain	1.0000
5:95822454:ACC:A	donor_loss	1.0000
5:95822455:C:CC	donor_gain	1.0000
5:95822455:C:CG	donor_loss	1.0000
5:95822455:CCGTT:C	donor_gain	1.0000
5:95752237:A:AG	acceptor_gain	0.9900
5:95752238:G:GG	acceptor_gain	0.9900
5:95755389:A:AG	acceptor_gain	0.9900
5:95755390:A:G	acceptor_gain	0.9900
5:95755394:A:AG	acceptor_gain	0.9900
5:95755395:G:GG	acceptor_gain	0.9900
5:95763506:A:AG	acceptor_gain	0.9900
5:95763506:AG:A	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000142234 (5:95816335 A>G), RS1000744010 (5:95817787 A>G), RS1000847829 (5:95824207 A>G), RS1000877628 (5:95823917 G>A,C), RS1001301014 (5:95823130 T>C), RS1001382855 (5:95813515 G>A), RS1002587241 (5:95818557 T>C), RS1003001998 (5:95813581 A>C), RS1003455857 (5:95815487 A>T), RS1003912434 (5:95821726 G>A,T), RS1004593169 (5:95817393 C>T), RS1004679206 (5:95823516 A>G), RS1004916346 (5:95823203 G>A), RS1005040110 (5:95819635 C>A), RS1005524369 (5:95815900 G>A)

Disease associations

OMIM: gene MIM:600443 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST004611_78	High light scatter reticulocyte count	1.000000e-44
GCST004611_79	High light scatter reticulocyte count	6.000000e-28
GCST004612_74	High light scatter reticulocyte percentage of red cells	6.000000e-44
GCST004612_75	High light scatter reticulocyte percentage of red cells	3.000000e-27
GCST004619_199	Reticulocyte fraction of red cells	1.000000e-49
GCST004619_96	Reticulocyte fraction of red cells	4.000000e-31
GCST004622_181	Reticulocyte count	5.000000e-49
GCST004622_182	Reticulocyte count	9.000000e-31
GCST004628_73	Immature fraction of reticulocytes	9.000000e-21
GCST004628_74	Immature fraction of reticulocytes	8.000000e-12
GCST009391_163	Metabolite levels	6.000000e-06
GCST012127_1	hemolysis of donated blood (oxidative)	5.000000e-08
GCST012134_2	hemolysis of donated blood (oxidative)	1.000000e-12
GCST90002385_342	High light scatter reticulocyte count	4.000000e-116
GCST90002385_343	High light scatter reticulocyte count	1.000000e-50
GCST90002386_37	High light scatter reticulocyte percentage of red cells	9.000000e-119
GCST90002386_38	High light scatter reticulocyte percentage of red cells	7.000000e-54
GCST90002387_304	Immature fraction of reticulocytes	2.000000e-70
GCST90002387_305	Immature fraction of reticulocytes	3.000000e-31
GCST90002405_71	Reticulocyte count	9.000000e-91
GCST90002405_72	Reticulocyte count	1.000000e-38
GCST90002406_179	Reticulocyte fraction of red cells	4.000000e-96
GCST90002406_180	Reticulocyte fraction of red cells	2.000000e-43

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0010487	glutamate measurement
EFO:0009473	hemolysis

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	6
sodium arsenite	increases expression, affects expression, increases abundance	5
Benzo(a)pyrene	increases methylation, decreases expression, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	4
Cadmium Chloride	increases phosphorylation, affects activity, decreases reaction, increases glutathionylation, decreases expression (+3 more)	4
trichostatin A	increases expression	3
Acetaminophen	decreases expression	3
Copper	decreases abundance, decreases response to substance, decreases uptake, increases expression, affects binding	3
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
Tretinoin	increases expression	3
arsenite	increases expression, decreases reaction, increases abundance	2
Vorinostat	increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Glutathione	increases reduction, affects binding, decreases reaction, increases reaction, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
urushiol	increases expression	1
methylmercuric chloride	decreases activity, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
glycidyl methacrylate	decreases expression	1
sodium arsenate	affects cotreatment, increases reduction	1
cinnamaldehyde	affects localization, increases expression, affects activity, decreases reaction, increases glutathionylation (+1 more)	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
tetrahydropalmatine	decreases expression	1
sulforaphane	increases expression	1
1,2-dielaidoylphosphatidylethanolamine	decreases expression	1
nickel chloride	increases expression	1
perfluorooctanoic acid	increases expression	1

Clinical trials (associated diseases)

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