GLRX3

protein-coding

glutaredoxin 3, the group of Glutaredoxin domain containing

Gene summary

This gene encodes a member of the glutaredoxin family. Glutaredoxins are oxidoreductase enzymes that reduce a variety of substrates using glutathione as a cofactor. The encoded protein binds to and modulates the function of protein kinase C theta. The encoded protein may also inhibit apoptosis and play a role in cellular growth, and the expression of this gene may be a marker for cancer. Pseudogenes of this gene are located on the short arm of chromosomes 6 and 9. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

Previous symbols:

TXNL2

MANE transcript

NM_006541.5

Inheritance

—

ClinVar variants

U:56B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr10:130,136,391-130,184,521

External References & Databases

Ensembl (ENSG00000108010)

Transcript & Mutation Effects

hg38 • Region Span ~48.1 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 GLRX3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006541.5. 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 clinvar	2
missense			49 clinvar	1 clinvar		50
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	56	1	1	58

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 97 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006541.5	RefSeq	NP_006532.2	11	MANE Select
ENST00000331244.10	Ensembl	ENSP00000330836.5	11	MANE Select
NM_001199868.2	RefSeq	NP_001186797.1	11	Standard
NM_001321980.2	RefSeq	NP_001308909.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
glrx3	Danio rerio	Structure: nucleate erythrocyte Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

glrx3

Danio rerio

Structure: nucleate erythrocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transport of small molecules
Iron uptake and transport

Biological Process

regulation of the force of heart contraction
cellular iron ion homeostasis
negative regulation of cardiac muscle hypertrophy
electron transport chain
[2Fe-2S] cluster assembly

Molecular Function

RNA binding
protein kinase C binding
protein binding
electron transfer activity
protein disulfide oxidoreductase activity

Cellular Component

nucleus
cytosol
cell cortex
Z disc
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368644
Coding exons: 11
Length: 48123
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.148	157	162	0.967	0.00000790	2173
Missense (PolyPhen)		39	51.808	0.75278		670
Synonymous	0.728	50	57.0	0.877	0.00000279	627
Loss of Function	3.36	5	22.0	0.227	0.00000117	268

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (PubMed:26613676, PubMed:27519415). Acts as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator (By similarity). Required for hemoglobin maturation (PubMed:23615448). Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity. {ECO:0000250|UniProtKB:Q9CQM9, ECO:0000269|PubMed:23615448, ECO:0000269|PubMed:26613676, ECO:0000269|PubMed:27519415}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.704
RVIS EVS: -0.07
RVIS percentile EVS: 48.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.673

Gene Damage Prediction

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