GLRX5

Summary

GLRX5 (glutaredoxin 5, HGNC:20134) is a protein-coding gene on chromosome 14q32.13, encoding Glutaredoxin-related protein 5, mitochondrial (Q86SX6). Monothiol glutaredoxin involved in mitochondrial iron-sulfur (Fe/S) cluster transfer. It is a selective cancer dependency (DepMap: 53.7% of cell lines).

This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron-sulfur clusters, which are required for normal iron homeostasis. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory sideroblastic anemia.

Source: NCBI Gene 51218 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spasticity-ataxia-gait anomalies syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 140 total — 7 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 53
• Cancer dependency (DepMap): dependent in 53.7% of screened cell lines
• MANE Select transcript: NM_016417

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20134
Approved symbol	GLRX5
Name	glutaredoxin 5
Location	14q32.13
Locus type	gene with protein product
Status	Approved
Aliases	PR01238, GRX5
Ensembl gene	ENSG00000182512
Ensembl biotype	protein_coding
OMIM	609588
Entrez	51218

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000331334, ENST00000553672, ENST00000557731, ENST00000902982

RefSeq mRNA: 1 — MANE Select: NM_016417 NM_016417

CCDS: CCDS9936

Canonical transcript exons

ENST00000331334 — 2 exons

Exon	Start	End
ENSE00001305542	95543947	95544714
ENSE00001325931	95535050	95535384

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.0318 / max 3236.6397, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141292	59.0318	1823

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.17	gold quality
diaphragm	UBERON:0001103	98.77	gold quality
triceps brachii	UBERON:0001509	98.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.56	gold quality
vastus lateralis	UBERON:0001379	98.48	gold quality
biceps brachii	UBERON:0001507	98.42	gold quality
quadriceps femoris	UBERON:0001377	98.16	gold quality
adult organism	UBERON:0007023	97.97	gold quality
gluteal muscle	UBERON:0002000	97.94	gold quality
left ventricle myocardium	UBERON:0006566	97.94	gold quality
myocardium	UBERON:0002349	97.74	gold quality
endothelial cell	CL:0000115	97.72	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.61	gold quality
skeletal muscle tissue	UBERON:0001134	97.38	gold quality
heart right ventricle	UBERON:0002080	97.38	gold quality
bone marrow	UBERON:0002371	97.31	gold quality
nephron tubule	UBERON:0001231	97.30	gold quality
heart left ventricle	UBERON:0002084	97.18	gold quality
cardiac ventricle	UBERON:0002082	97.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.10	gold quality
muscle tissue	UBERON:0002385	96.94	gold quality
kidney epithelium	UBERON:0004819	96.89	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.87	gold quality
muscle organ	UBERON:0001630	96.85	gold quality
gastrocnemius	UBERON:0001388	96.79	gold quality
body of tongue	UBERON:0011876	96.79	gold quality
cardiac atrium	UBERON:0002081	96.77	gold quality
superficial temporal artery	UBERON:0001614	96.75	gold quality
right atrium auricular region	UBERON:0006631	96.72	gold quality
right adrenal gland	UBERON:0001233	96.71	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	1092.74
E-MTAB-7407	yes	293.24
E-HCAD-4	yes	149.27
E-HCAD-9	yes	11.82
E-MTAB-9388	yes	8.75
E-MTAB-9467	no	2.56
E-HCAD-10	no	2.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting GLRX5, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-15B-3P	97.85	66.68	974
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-5187-3P	97.28	67.10	1037

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 53.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• Mutations in GLRX5 is associated with sideroblastic-like microcytic anemia and iron overload (PMID:17485548)
• No GLRX5 mutations were found among sixty CSA probands examined (PMID:19731322)
• Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts (PMID:20364084)
• crystal structure of GLRX5 revealed a tetrameric organization with the [2Fe-2S] clusters buried in the interior and shielded from the solvent by the conserved beta1-alpha2 loop (PMID:21029046)
• Patients with GLRX5-associated variant nonketotic hyperglycemia had normal development with childhood-onset spastic paraplegia, spinal lesion, and optic atrophy. (PMID:24334290)
• GLRX5 rs1007814 showed a statistically marginally significant difference between cases and controls in genotype frequency (case/control: CC 1:6; CT 112:78; TT 752:505, P=0.049361), but no significant differences in allele distribution [odds ratio (OR)=0.852805]In men, we found a minor difference in the genotype frequency (case/control: CC 0:3; CT 72:36; TT 411:280, P=0.037370) and not in allele distribution (OR=1.142857) (PMID:27893590)
• A pathway for assembling 4Fe-4S clusters in mitochondrial iron-sulfur protein biogenesis. (PMID:31724821)
• Cluster exchange reactivity of [2Fe-2S]-bridged heterodimeric BOLA1-GLRX5. (PMID:32542995)
• Molecular Basis of Multiple Mitochondrial Dysfunctions Syndrome 2 Caused by CYS59TYR BOLA3 Mutation. (PMID:34063696)
• GLRX5-associated [Fe-S] cluster biogenesis disorder: further characterisation of the neurological phenotype and long-term outcome. (PMID:34732213)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	glrx5	ENSDARG00000043665
mus_musculus	Glrx5	ENSMUSG00000021102
rattus_norvegicus	Glrx5	ENSRNOG00000004206
drosophila_melanogaster	Grx5	FBGN0030584
caenorhabditis_elegans		WBGENE00013029

Paralogs (1): GLRX3 (ENSG00000108010)

Protein

Protein identifiers

Glutaredoxin-related protein 5, mitochondrial — Q86SX6 (reviewed: Q86SX6)

Alternative names: Monothiol glutaredoxin-5

All UniProt accessions (3): Q86SX6, A0A384MDT9, H0YJM6

UniProt curated annotations — full annotation on UniProt →

Function. Monothiol glutaredoxin involved in mitochondrial iron-sulfur (Fe/S) cluster transfer. Receives 2Fe/2S clusters from scaffold protein ISCU and mediates their transfer to apoproteins, to the 4Fe/FS cluster biosynthesis machinery, or export from mitochondrion. Required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1.

Subunit / interactions. Homodimer. Interacts with ISCU. Interacts with BOLA1.

Subcellular location. Mitochondrion matrix.

Disease relevance. Anemia, sideroblastic, 3, pyridoxine-refractory (SIDBA3) [MIM:616860] A form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA3 is refractory to treatment with vitamin B6, while iron chelation therapy may result in clinical improvement. SIDBA3 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Spasticity, childhood-onset, with hyperglycinemia (SPAHGC) [MIM:616859] An autosomal recessive disorder characterized by childhood-onset of spasticity, spinal lesions, leukodystrophy, optic atrophy in some patients, non-ketotic hyperglycinemia, and defective enzymatic glycine cleavage. Glycine levels in the cerebrospinal fluid are mildly increased in some but not all patients. The increase is less pronounced than in patients with classic non-ketotic hyperglycinemia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the glutaredoxin family. Monothiol subfamily.

RefSeq proteins (1): NP_057501* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002109	Glutaredoxin	Domain
IPR004480	Monothiol_GRX-rel	Family
IPR033658	GRX_PICOT-like	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF00462

UniProt features (25 total): helix 5, strand 5, binding site 5, sequence variant 4, modified residue 2, transit peptide 1, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2WUL	X-RAY DIFFRACTION	2.4
2MMZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SX6-F1	84.14	0.72

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 (5): 59; 67; 97–101; 109; 122–123

Post-translational modifications (2): 59, 156

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1362409	Mitochondrial iron-sulfur cluster biogenesis

MSigDB gene sets: 288 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GNF2_PRDX2, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GNF2_ANK1, GOBP_PROTEIN_MATURATION, GOBP_CELL_REDOX_HOMEOSTASIS, GGAANCGGAANY_UNKNOWN, GNF2_SPTA1, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOCC_NEURON_PROJECTION, RFX1_02, RGAGGAARY_PU1_Q6, SOX5_01

GO Biological Process (6): intracellular iron ion homeostasis (GO:0006879), iron-sulfur cluster assembly (GO:0016226), hemopoiesis (GO:0030097), [2Fe-2S] cluster assembly (GO:0044571), cell redox homeostasis (GO:0045454), protein maturation (GO:0051604)

GO Molecular Function (4): metal ion binding (GO:0046872), 2 iron, 2 sulfur cluster binding (GO:0051537), protein binding (GO:0005515), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), dendrite (GO:0030425), neuronal cell body (GO:0043025), iron-sulfur cluster assembly complex (GO:1990229)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
metallo-sulfur cluster assembly	1
cell development	1
iron-sulfur cluster assembly	1
cellular homeostasis	1
gene expression	1
protein metabolic process	1
cation binding	1
iron-sulfur cluster binding	1
binding	1
metal cluster binding	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1
protein-containing complex	1

Protein interactions and networks

STRING

1310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLRX5	ISCA2	Q86U28	947
GLRX5	SLC25A38	Q96DW6	940
GLRX5	BOLA3	Q53S33	929
GLRX5	GLRX	P35754	921
GLRX5	ISCA1	Q9BUE6	914
GLRX5	ALAS2	P22557	884
GLRX5	NFU1	Q9UMS0	842
GLRX5	BOLA1	Q9Y3E2	841
GLRX5	ACO1	P21399	834
GLRX5	HSCB	Q8IWL3	825
GLRX5	ABCB7	O75027	816
GLRX5	IBA57	Q5T440	811
GLRX5	NFS1	Q9Y697	810
GLRX5	ISCU	Q9H1K1	786
GLRX5	GLRX2	Q9NS18	766

IntAct

56 interactions, top by confidence:

A	B	Type	Score
BOLA3	GLRX5	psi-mi:“MI:0915”(physical association)	0.820
GLRX5	BOLA3	psi-mi:“MI:0407”(direct interaction)	0.820
BOLA3	GLRX5	psi-mi:“MI:0914”(association)	0.820
BOLA3	GLRX5	psi-mi:“MI:0407”(direct interaction)	0.820
HSCB	HSPA9	psi-mi:“MI:0914”(association)	0.740
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
HSCB	GLRX5	psi-mi:“MI:0915”(physical association)	0.620
	GLRX5	psi-mi:“MI:0407”(direct interaction)	0.560
BOLA1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
ISCA2	SLMAP	psi-mi:“MI:0914”(association)	0.530
MCEE	CLUH	psi-mi:“MI:0914”(association)	0.530
KEAP1	GLRX5	psi-mi:“MI:0915”(physical association)	0.370
	GLRX5	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
BOLA1	NME4	psi-mi:“MI:0914”(association)	0.350
BOLA3	NDUFS6	psi-mi:“MI:0914”(association)	0.350
FMC1	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NUDT19	psi-mi:“MI:0914”(association)	0.350
NDUFS3	ACOT7	psi-mi:“MI:0914”(association)	0.350
BOLA1	PMPCB	psi-mi:“MI:0914”(association)	0.350
FMC1	DNM1L	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): BOLA1 (Co-fractionation), BOLA3 (Co-fractionation), GLOD4 (Co-fractionation), GLRX5 (Co-fractionation), GLRX5 (Co-fractionation), GLRX5 (Co-fractionation), TXN (Co-fractionation), GLRX5 (Affinity Capture-MS), GLRX5 (Affinity Capture-MS), GLRX5 (Affinity Capture-MS), GLRX5 (Affinity Capture-MS), GLRX5 (Affinity Capture-MS), GLRX5 (Affinity Capture-MS), GLRX5 (Affinity Capture-MS), GLRX5 (Affinity Capture-MS)

ESM2 similar proteins: A1A4Q2, A6NEY8, B2RZ27, E9QI36, O06465, O75131, O76003, O81187, P0A155, P0A156, P12081, P19480, P35340, P55143, Q28EX9, Q28ID3, Q2KI84, Q2KJD7, Q3ZCL8, Q4I963, Q58DA7, Q5FWT7, Q5R4C4, Q5R4R2, Q5RAE1, Q5RC61, Q5XJ54, Q5ZJJ8, Q61035, Q641F1, Q6DBT3, Q6DI37, Q7KLV9, Q80T18, Q80Y14, Q86SX6, Q8BGR9, Q8CI33, Q8K3X2, Q8WVY7

Diamond homologs: B7ZFT1, O05957, O23420, O30824, O74790, O76003, P0AC62, P0AC63, P0AC64, P0AC69, P0AC70, P0AC71, P0AC72, P32642, P35754, P45085, P51384, P57284, P73056, Q02784, Q03835, Q0IWL9, Q0JM76, Q0JQ97, Q19297, Q1RHJ0, Q1XDA3, Q28ID3, Q2QX01, Q48833, Q4QLD2, Q4UK94, Q54EX7, Q555C8, Q58DA7, Q5XJ54, Q68W05, Q68XG4, Q6PBM1, Q6YFE4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GLRX5	“form complex”	“Mitochondrial BOLA1-GLRX5 iron-sulfur cluster assembly complex”	binding
GLRX5	“form complex”	“Mitochondrial BOLA3-GLRX5 iron-sulfur cluster assembly complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Complex I biogenesis	6	33.1×	4e-06
Mitochondrial protein import	5	28.0×	5e-05
Mitochondrial protein degradation	5	19.0×	3e-04
Aerobic respiration and respiratory electron transport	6	17.7×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
iron-sulfur cluster assembly	6	86.0×	2e-08
proton motive force-driven mitochondrial ATP synthesis	5	31.4×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	62
Likely benign	51
Benign	12

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1252035	NM_016417.3(GLRX5):c.197A>C (p.Gln66Pro)	Pathogenic
1606	NM_016417.3(GLRX5):c.294A>G (p.Gln98=)	Pathogenic
224510	NM_016417.3(GLRX5):c.301A>C (p.Lys101Gln)	Pathogenic
224511	NM_016417.3(GLRX5):c.443T>C (p.Leu148Ser)	Pathogenic
224513	NM_016417.3(GLRX5):c.86_93dup (p.Ala32fs)	Pathogenic
915891	NM_016417.3(GLRX5):c.200G>A (p.Cys67Tyr)	Pathogenic
915892	NM_016417.3(GLRX5):c.383T>A (p.Met128Lys)	Pathogenic
224512	NM_016417.3(GLRX5):c.148AAG[1] (p.Lys51del)	Likely pathogenic
4056445	NM_016417.3(GLRX5):c.367G>C (p.Asp123His)	Likely pathogenic

SpliceAI

283 predictions. Top by Δscore:

Variant	Effect	Δscore
14:95543942:CATA:C	acceptor_loss	1.0000
14:95543944:TAGG:T	acceptor_loss	1.0000
14:95543945:A:AG	acceptor_gain	1.0000
14:95543945:AG:A	acceptor_gain	1.0000
14:95543945:AGG:A	acceptor_loss	1.0000
14:95543946:G:GA	acceptor_gain	1.0000
14:95543946:GG:G	acceptor_gain	1.0000
14:95543946:GGC:G	acceptor_gain	1.0000
14:95534648:G:GT	donor_gain	0.9900
14:95534746:A:T	donor_gain	0.9900
14:95535381:CAAG:C	donor_loss	0.9900
14:95535382:AAGG:A	donor_loss	0.9900
14:95535383:AG:A	donor_loss	0.9900
14:95535384:GGTCA:G	donor_loss	0.9900
14:95535385:G:GA	donor_loss	0.9900
14:95535386:T:G	donor_loss	0.9900
14:95537037:GAGGA:G	donor_gain	0.9900
14:95543943:A:AG	acceptor_gain	0.9900
14:95543943:ATAG:A	acceptor_gain	0.9900
14:95543946:GGCA:G	acceptor_gain	0.9900
14:95543946:GGCAT:G	acceptor_gain	0.9900
14:95534852:G:GG	donor_gain	0.9800
14:95535391:C:T	donor_gain	0.9800
14:95537046:C:G	donor_gain	0.9800
14:95543944:T:G	acceptor_gain	0.9800
14:95534742:G:GT	donor_gain	0.9700
14:95537079:G:GT	donor_gain	0.9700
14:95537039:GGA:G	donor_gain	0.9600
14:95537040:GAG:G	donor_gain	0.9600
14:95543942:CATAG:C	acceptor_gain	0.9600

AlphaMissense

1006 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:95535266:G:C	K59N	1.000
14:95535266:G:T	K59N	1.000
14:95535294:T:C	F69L	1.000
14:95535296:C:A	F69L	1.000
14:95535296:C:G	F69L	1.000
14:95543954:A:C	K101N	1.000
14:95543954:A:T	K101N	1.000
14:95535259:T:C	F57S	0.999
14:95535267:G:A	G60R	0.999
14:95535267:G:C	G60R	0.999
14:95535267:G:T	G60W	0.999
14:95535268:G:A	G60E	0.999
14:95535268:G:T	G60V	0.999
14:95535294:T:A	F69I	0.999
14:95535294:T:G	F69V	0.999
14:95535295:T:C	F69S	0.999
14:95535295:T:G	F69C	0.999
14:95535297:A:C	S70R	0.999
14:95535298:G:T	S70I	0.999
14:95535299:C:A	S70R	0.999
14:95535299:C:G	S70R	0.999
14:95543967:T:A	W106R	0.999
14:95543967:T:C	W106R	0.999
14:95543969:G:C	W106C	0.999
14:95543969:G:T	W106C	0.999
14:95543980:C:A	P110Q	0.999
14:95544004:T:C	F118S	0.999
14:95544010:G:A	G120E	0.999
14:95544019:A:C	D123A	0.999
14:95544019:A:G	D123G	0.999

dbSNP variants (sampled 300 via entrez): RS1000028361 (14:95536866 C>G,T), RS1000068845 (14:95543127 G>A,C), RS1000146475 (14:95542365 G>A), RS1000421667 (14:95543392 G>A), RS1000809258 (14:95538445 C>A), RS1001017162 (14:95545014 T>TAGA), RS1001098753 (14:95540355 G>A), RS1001377976 (14:95533162 T>A,C), RS1001512598 (14:95543882 A>G), RS1001632508 (14:95544219 G>A), RS1001824318 (14:95533080 C>A), RS1001876577 (14:95533401 A>T), RS1002154882 (14:95533896 T>C), RS1003155925 (14:95534968 G>A,T), RS1003377239 (14:95534875 G>A)

Disease associations

OMIM: gene MIM:609588 | disease phenotypes: MIM:616860, MIM:616859

GenCC curated gene-disease

Disease	Classification	Inheritance
spasticity-ataxia-gait anomalies syndrome	Strong	Autosomal recessive
sideroblastic anemia 3	Strong	Autosomal recessive

Mondo (2): sideroblastic anemia 3 (MONDO:0014804), spasticity-ataxia-gait anomalies syndrome (MONDO:0014803)

Orphanet (2): Adult-onset autosomal recessive sideroblastic anemia (Orphanet:255132), Childhood-onset spasticity with hyperglycinemia (Orphanet:401866)

HPO phenotypes

53 total (30 of 53 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000736	Short attention span
HP:0000737	Irritability
HP:0000952	Jaundice
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001264	Spastic diplegia
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001394	Cirrhosis
HP:0001433	Hepatosplenomegaly
HP:0001712	Left ventricular hypertrophy
HP:0001744	Splenomegaly
HP:0001903	Anemia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002151	Increased circulating lactate concentration
HP:0002154	Hyperglycinemia
HP:0002191	Progressive spasticity
HP:0002240	Hepatomegaly
HP:0002317	Unsteady gait
HP:0002376	Developmental regression

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001762_211	Obesity-related traits	2.000000e-06
GCST002337_155	Amyotrophic lateral sclerosis (sporadic)	1.000000e-06
GCST002875_90	Diisocyanate-induced asthma	1.000000e-06
GCST004602_208	Mean corpuscular volume	2.000000e-10
GCST004630_154	Mean corpuscular hemoglobin	5.000000e-10
GCST010002_159	Refractive error	9.000000e-11
GCST90002390_276	Mean corpuscular hemoglobin	4.000000e-31
GCST90002392_463	Mean corpuscular volume	1.000000e-29
GCST90002396_572	Mean reticulocyte volume	1.000000e-11
GCST90002397_369	Mean spheric corpuscular volume	9.000000e-16

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005115	metabolic rate measurement
EFO:0006995	response to diisocyanate
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression, affects expression	4
Valproic Acid	increases methylation, affects expression, increases expression	3
bisphenol A	affects expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
chloropicrin	decreases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Ivermectin	decreases expression	1
Lead	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Isotretinoin	decreases expression	1
Palmitic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1Y5	HAP1 GLRX5 (-) 2	Cancer cell line	Male
CVCL_XP18	HAP1 GLRX5 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford