GLRX

protein-coding

glutaredoxin, the group of Glutaredoxin domain containing

Gene summary

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. [provided by RefSeq, Aug 2011]

MANE transcript

NM_001118890.2

Inheritance

—

ClinVar variants

U:14B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.52

Max pathogenic AF

—

Genomic locus

chr5:95,751,319-95,822,726

External References & Databases

Ensembl (ENSG00000173221)

Transcript & Mutation Effects

hg38 • Region Span ~71.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GLRX variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001118890.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			13 clinvar	1 clinvar		14
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	14	1	0	15

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001118890.2	RefSeq	NP_001112362.1	2	MANE Select
ENST00000237858.11	Ensembl	ENSP00000237858.6	2	MANE Select
NM_001243658.2	RefSeq	NP_001230587.1	2	Standard
NM_001243659.2	RefSeq	NP_001230588.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

One Carbon Metabolism
Metabolism of nucleotides
Interconversion of nucleotide di- and triphosphates
Metabolism
arsenate detoxification I (glutaredoxin)

Biological Process

nucleobase-containing small molecule interconversion
electron transport chain
cell redox homeostasis
positive regulation of membrane potential
protein deglutathionylation

Molecular Function

electron transfer activity
glutathione disulfide oxidoreductase activity
protein N-terminus binding
glutathione oxidoreductase activity

Cellular Component

nucleus
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379979
Coding exons: 2
Length: 71687
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125747
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.484	47	57.3	0.820	0.00000291	687
Missense (PolyPhen)		5	11.339	0.44095		172
Synonymous	0.356	21	23.2	0.906	0.00000121	211
Loss of Function	-1.10	8	5.28	1.52	2.92e-7	52

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00055	0.00055	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

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

Recessive Scores

pRec: 0.342

Intolerance Scores

LoFtool: 0.858
RVIS EVS: -0.21
RVIS percentile EVS: 38.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.659

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium