TXNRD2

thioredoxin reductase 2, the group of Selenoproteins

Basic information

Region (hg38): 22:19875516-19941820

Links

ENSG00000184470 ∙ NCBI:10587 ∙ OMIM:606448 ∙ HGNC:18155 ∙ Uniprot:Q9NNW7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• familial glucocorticoid deficiency (Supportive), mode of inheritance: AR
• dilated cardiomyopathy (Limited), mode of inheritance: AD
• glucocorticoid deficiency 5 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glucocorticoid deficiency 5	AR	Endocrine	Individuals have been described as having glucocorticoid deficiency, with poor cortisol response to ACTH stimulation, and required glucocorticoid replacement therapy	Endocrine	24601690

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TXNRD2 gene.

• Primary dilated cardiomyopathy (472 variants)
• Cardiovascular phenotype (307 variants)
• not provided (182 variants)
• not specified (58 variants)
• Glucocorticoid deficiency 5 (30 variants)
• Primary familial hypertrophic cardiomyopathy (6 variants)
• Inborn genetic diseases (6 variants)
• TXNRD2-related condition (4 variants)
• Cardiomyopathy (1 variants)
• TXNRD2-associated Cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TXNRD2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				131	5	136
missense			256	8	6	270
nonsense			8			8
start loss			2			2
frameshift			9			9
inframe indel			4			4
splice donor/acceptor (+/-2bp)			17			17
splice region			23	18		41
non coding			11	94	62	167
Total	0	0	307	233	73

Variants in TXNRD2

This is a list of pathogenic ClinVar variants found in the TXNRD2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-19875619-T-C			Benign (Jun 23, 2018)
22-19875633-TG-T			Benign (Jun 23, 2018)
22-19875633-T-TG			Likely benign (Mar 19, 2021)
22-19876812-G-A			Benign (Jun 23, 2018)
22-19877102-C-T		TXNRD2-related disorder	Likely benign (Feb 27, 2022)
22-19877105-T-G		Primary dilated cardiomyopathy	Uncertain significance (May 22, 2023)
22-19877107-A-G		Cardiovascular phenotype	Uncertain significance (Mar 09, 2020)
22-19877108-C-T		Primary dilated cardiomyopathy	Likely benign (Jul 19, 2022)
22-19877120-T-G		Primary dilated cardiomyopathy	Likely benign (Oct 24, 2022)
22-19877121-G-C		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Dec 06, 2022)
22-19877126-C-T		Primary dilated cardiomyopathy • Cardiovascular phenotype	Likely benign (Aug 09, 2022)
22-19877126-CG-C			Uncertain significance (Dec 07, 2022)
22-19877127-G-A		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Jan 06, 2024)
22-19877131-G-A		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Mar 05, 2024)
22-19877134-C-G		Primary dilated cardiomyopathy	Uncertain significance (Mar 08, 2021)
22-19877142-G-C			Uncertain significance (Apr 04, 2023)
22-19877145-C-T		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Nov 19, 2023)
22-19877146-G-A		Primary dilated cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Dec 08, 2022)
22-19877157-C-T		Cardiovascular phenotype • Primary dilated cardiomyopathy • TXNRD2-related disorder	Likely benign (Jan 04, 2024)
22-19877158-G-A		Primary dilated cardiomyopathy	Uncertain significance (Oct 10, 2021)
22-19877158-G-C		Primary dilated cardiomyopathy	Uncertain significance (Mar 08, 2022)
22-19877159-C-A		Cardiovascular phenotype	Likely benign (Dec 07, 2023)
22-19877165-G-A		Cardiovascular phenotype • Primary dilated cardiomyopathy	Likely benign (Oct 17, 2022)
22-19877166-A-G		Primary dilated cardiomyopathy	Uncertain significance (Nov 27, 2020)
22-19877166-A-T		Cardiovascular phenotype • Primary dilated cardiomyopathy	Uncertain significance (Feb 12, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TXNRD2	protein_coding	protein_coding	ENST00000400521	17	66302

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.47e-11	0.742	124688	0	215	124903	0.000861

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.636	296	328	0.901	0.0000219	3308
Missense in Polyphen		120	140.22	0.85579		1370
Synonymous	-0.601	146	137	1.07	0.00000976	1088
Loss of Function	1.60	21	30.5	0.687	0.00000159	336

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00116	0.00116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000111
Finnish	0.00	0.00
European (Non-Finnish)	0.000541	0.000521
Middle Eastern	0.000111	0.000111
South Asian	0.00392	0.00393
Other	0.000827	0.000823

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the control of reactive oxygen species levels and the regulation of mitochondrial redox homeostasis (PubMed:24601690). Maintains thioredoxin in a reduced state. May play a role in redox-regulated cell signaling. {ECO:0000269|PubMed:24601690}.
• Pathway: Selenocompound metabolism - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Selenium Micronutrient Network;Selenium Metabolism and Selenoproteins;Oxidative Stress;Detoxification of Reactive Oxygen Species;Cellular responses to stress;Pyrimidine metabolism;Cellular responses to external stimuli;thioredoxin pathway (Consensus)

Recessive Scores

• pRec: 0.337

Intolerance Scores

• loftool: 0.597
• rvis_EVS: 0.63
• rvis_percentile_EVS: 83.55

Haploinsufficiency Scores

• pHI: 0.145
• hipred: N
• hipred_score: 0.292
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Txnrd2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; liver/biliary system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: response to oxygen radical;electron transport chain;cellular response to oxidative stress;cell redox homeostasis;cellular oxidant detoxification
• Cellular component: cytoplasm;mitochondrion;mitochondrial matrix;cytosol
• Molecular function: thioredoxin-disulfide reductase activity;protein binding;electron transfer activity;flavin adenine dinucleotide binding