Gluthathione peroxidase deficiency

Summary

Gluthathione peroxidase deficiency (MONDO:0013601) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	gluthathione peroxidase deficiency
Mondo ID	MONDO:0013601
OMIM	614164
SNOMED CT	234590006
UMLS	C0398747
MedGen	473098
GARD	0024936
Is cancer (heuristic)	no

Also known as: glutathione peroxidase deficiency · gluthathione peroxidase deficiency · GPXD · hemolytic anaemia due to glutathione peroxidase deficiency · hemolytic anemia due to glutathione peroxidase deficiency

Data availability: 30 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › gluthathione peroxidase deficiency

Related subtypes (92): thiopurine metabolic disease, hypercalcemia, infantile, hypermanganesemia with dystonia, abdominal obesity-metabolic syndrome, plasma protein metabolism disease, inherited lipid metabolism disorder, lysosomal storage disease, striatonigral degeneration, inborn metal metabolism disorder, inborn vitamin metabolic disorder, chondrocalcinosis 2, Ehlers-Danlos syndrome, spondylodysplastic type, fish eye disease, aromatase excess syndrome, spondyloepiphyseal dysplasia with congenital joint dislocations, hypertriglyceridemia 1, autosomal dominant myoglobinuria, diastrophic dysplasia, hemolytic anemia due to diphosphoglycerate mutase deficiency, multiple epiphyseal dysplasia type 4, atelosteogenesis type II, inherited threoninemia, inborn glycerol kinase deficiency, achondrogenesis type IB, diabetes mellitus, noninsulin-dependent, 1, diabetes mellitus, noninsulin-dependent, 2, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, diabetes mellitus, noninsulin-dependent, 3, hypercholesterolemia, familial, 4, hypoalphalipoproteinemia, primary, 1, autosomal recessive proximal renal tubular acidosis, diabetes mellitus, noninsulin-dependent, 4, normophosphatemic familial tumoral calcinosis, apolipoprotein c-III deficiency, hypotonia-failure to thrive-microcephaly syndrome, chondrodysplasia with joint dislocations, gPAPP type, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diabetes mellitus, noninsulin-dependent, 5, congenital disorder of glycosylation, monogenic diabetes, 2-hydroxyglutaric aciduria, familial hypoparathyroidism, familial intrahepatic cholestasis, inborn aminoacylase deficiency, disorder of lysosomal-related organelles, inborn disorder of porphyrin metabolism, disorder of metabolite absorption and transport, autosomal dominant proximal renal tubular acidosis, neurodegeneration with brain iron accumulation, ferro-cerebro-cutaneous syndrome, familial hypocalciuric hypercalcemia, hypophosphatasia, hereditary amyloidosis, peroxisomal disease, inborn disorder of amino acid and other organic acid metabolism, inborn carbohydrate metabolic disorder, inborn disorder of energy metabolism, inborn disorder of biogenic amine metabolism and transport, inborn disorder of purine or pyrimidine metabolism, spondyloepimetaphyseal dysplasia, PAPSS2 type, hereditary lipodystrophy, hereditary recurrent myoglobinuria, DNA repair disease, 4-hydroxyphenylacetic aciduria, 5-nucleotidase syndrome, antigen-peptide-transporter 2 deficiency, APO A-i deficiency, cardiomyopathy hypogonadism metabolic anomalies, deficiency of coenzyme q cytochrome c reductase, defective apolipoprotein b-100, sulfide quinone oxidoreductase deficiency, congenital disorder of deglycosylation, hypoalphalipoproteinemia, primary, 2, uridine-cytidineuria, NAD(P)HX dehydratase deficiency, inborn disorder of aspartate family metabolism, weinstein kliman scully syndrome, glycoprotein metabolism disease, inherited thyroid metabolism disease, tumoral calcinosis, hyperphosphatemic, familial, 2, tumoral calcinosis, hyperphosphatemic, familial, 3, combined ApoA-I and ApoC-III deficiency, familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome, tumoral calcinosis, hyperphosphatemic, familial, 1, Waldenstrom macroglobulinemia, mucopolysaccharidosis or mucopolysaccharidosis-like disorder, disorder of peptide and amine metabolism, CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis, Lane Hamilton syndrome, SQSTM1-related multisystem proteinopathy, hypertriglyceridemia 2, autosomal dominant dopa-responsive dystonia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

30 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2308960	NM_000581.4(GPX1):c.125T>C (p.Ile42Thr)	GPX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2362014	NM_000581.4(GPX1):c.395C>T (p.Ala132Val)	GPX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2378040	NM_000581.4(GPX1):c.568C>T (p.Pro190Ser)	GPX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2390646	NM_000581.4(GPX1):c.418G>T (p.Ala140Ser)	GPX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2432255	NM_000581.4(GPX1):c.592C>T (p.Gln198Ter)	GPX1	Uncertain significance	criteria provided, single submitter
2432256	NM_000581.4(GPX1):c.68C>A (p.Pro23Gln)	GPX1	Uncertain significance	criteria provided, single submitter
2432257	NM_000581.4(GPX1):c.21GGC[7] (p.Ala13_Gln14insAla)	GPX1	Uncertain significance	criteria provided, single submitter
2432258	NM_000581.4(GPX1):c.52G>T (p.Ala18Ser)	GPX1	Uncertain significance	criteria provided, single submitter
2432259	NM_000581.4(GPX1):c.302C>G (p.Pro101Arg)	GPX1	Uncertain significance	criteria provided, single submitter
2432261	NM_000581.4(GPX1):c.362G>C (p.Gly121Ala)	GPX1	Uncertain significance	criteria provided, single submitter
2432262	NM_000581.4(GPX1):c.564C>G (p.Ile188Met)	GPX1	Uncertain significance	criteria provided, single submitter
2432263	NM_000581.4(GPX1):c.164A>G (p.Asp55Gly)	GPX1	Uncertain significance	criteria provided, single submitter
2432264	NM_000581.4(GPX1):c.29C>T (p.Ala10Val)	GPX1	Uncertain significance	criteria provided, single submitter
2432265	NM_000581.4(GPX1):c.228C>A (p.Phe76Leu)	GPX1	Uncertain significance	criteria provided, single submitter
2689151	NM_000581.4(GPX1):c.439C>T (p.Pro147Ser)	GPX1	Uncertain significance	criteria provided, single submitter
2689152	NM_000581.4(GPX1):c.511C>T (p.Pro171Ser)	GPX1	Uncertain significance	criteria provided, single submitter
2689153	NM_000581.4(GPX1):c.8C>T (p.Ala3Val)	GPX1	Uncertain significance	criteria provided, single submitter
2689154	NM_000581.4(GPX1):c.85C>A (p.Pro29Thr)	GPX1	Uncertain significance	criteria provided, single submitter
2689155	NM_000581.4(GPX1):c.412G>A (p.Asp138Asn)	GPX1	Uncertain significance	criteria provided, single submitter
2689156	NM_000581.4(GPX1):c.223G>T (p.Gly75Cys)	GPX1	Uncertain significance	criteria provided, single submitter
4078835	NM_000581.4(GPX1):c.508G>A (p.Gly170Ser)	GPX1	Uncertain significance	criteria provided, single submitter
4078836	NM_000581.4(GPX1):c.512C>T (p.Pro171Leu)	GPX1	Uncertain significance	criteria provided, single submitter
4078837	NM_000581.4(GPX1):c.359C>T (p.Ala120Val)	GPX1	Uncertain significance	criteria provided, single submitter
4078838	NM_000581.4(GPX1):c.299G>A (p.Arg100Gln)	GPX1	Uncertain significance	criteria provided, single submitter
4078839	NM_000581.4(GPX1):c.68C>T (p.Pro23Leu)	GPX1	Uncertain significance	criteria provided, single submitter
4078840	NM_000581.4(GPX1):c.476A>G (p.Asp159Gly)	GPX1	Uncertain significance	criteria provided, single submitter
4078841	NM_000581.4(GPX1):c.110del (p.Gly37fs)	GPX1	Uncertain significance	criteria provided, single submitter
4078842	NM_000581.4(GPX1):c.440C>G (p.Pro147Arg)	GPX1	Uncertain significance	criteria provided, single submitter
4078843	NM_000581.4(GPX1):c.271G>A (p.Glu91Lys)	GPX1	Uncertain significance	criteria provided, single submitter
16082	NM_000581.4(GPX1):c.599C>T (p.Pro200Leu)	GPX1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GPX1	Limited	Autosomal recessive	gluthathione peroxidase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GPX1	HGNC:4553	ENSG00000233276	P07203	Glutathione peroxidase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GPX1	Glutathione peroxidase 1	Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GPX1	Enzyme (other)	yes	1.11.1.9	Glutathione_peroxidase, GPX_AS, GPX_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GPX1	134	ubiquitous	marker	monocyte, leukocyte, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GPX1	158

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GPX1	P07203	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of 15-eicosatetraenoic acid derivatives	1	1903.3×	0.001	GPX1
Synthesis of 12-eicosatetraenoic acid derivatives	1	1631.4×	0.001	GPX1
Synthesis of 5-eicosatetraenoic acids	1	1268.9×	0.001	GPX1
Detoxification of Reactive Oxygen Species	1	300.5×	0.003	GPX1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of supramolecular fiber organization	1	16852.0×	0.003	GPX1
endothelial cell development	1	4213.0×	0.003	GPX1
response to symbiotic bacterium	1	2808.7×	0.003	GPX1
response to vitamin E	1	2808.7×	0.003	GPX1
regulation of mammary gland epithelial cell proliferation	1	2808.7×	0.003	GPX1
biological process involved in interaction with symbiont	1	2808.7×	0.003	GPX1
response to folic acid	1	2407.4×	0.003	GPX1
response to hydroperoxide	1	1685.2×	0.003	GPX1
angiogenesis involved in wound healing	1	1685.2×	0.003	GPX1
lipoxygenase pathway	1	1532.0×	0.003	GPX1
response to selenium ion	1	1404.3×	0.003	GPX1
blood vessel endothelial cell migration	1	1404.3×	0.003	GPX1
myoblast proliferation	1	1404.3×	0.003	GPX1
UV protection	1	1203.7×	0.003	GPX1
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1	936.2×	0.003	GPX1
skeletal muscle tissue regeneration	1	887.0×	0.003	GPX1
intrinsic apoptotic signaling pathway in response to oxidative stress	1	842.6×	0.003	GPX1
myoblast differentiation	1	842.6×	0.003	GPX1
negative regulation of release of cytochrome c from mitochondria	1	802.5×	0.003	GPX1
heart contraction	1	766.0×	0.003	GPX1
regulation of proteasomal protein catabolic process	1	766.0×	0.003	GPX1
hydrogen peroxide catabolic process	1	674.1×	0.003	GPX1
temperature homeostasis	1	648.1×	0.003	GPX1
negative regulation of inflammatory response to antigenic stimulus	1	601.9×	0.003	GPX1
response to gamma radiation	1	581.1×	0.003	GPX1
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	581.1×	0.003	GPX1
skeletal muscle fiber development	1	543.6×	0.003	GPX1
arachidonate metabolic process	1	481.5×	0.003	GPX1
response to hydrogen peroxide	1	468.1×	0.003	GPX1
triglyceride metabolic process	1	443.5×	0.003	GPX1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GPX1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	GPX1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GPX1	17	Binding:17

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GPX1	1.11.1.9	glutathione peroxidase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	GPX1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	GPX1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.