GeneBe

TXN2

protein-coding

thioredoxin 2

Gene summary

This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012473.4

Inheritance

AR

ClinVar variants

P:1U:39B:20

Top phenotype

Combined oxidative phosphorylation deficiency 29

gnomAD constraint

pLI —, LoF o/e 0.98

Max pathogenic AF

—

Genomic locus

chr22:36,467,046-36,481,640

External References & Databases

Ensembl (ENSG00000100348)NCBI Gene (25828)OMIM (609063)HGNC:17772GenCCUniProt (Q99757)AlphaFoldClinVar (TXN2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~14.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

combined oxidative phosphorylation deficiency 29LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014781

Submitter: Labcorp Genetics (formerly Invitae)

combined oxidative phosphorylation defect type 29SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0033187

Submitter: Orphanet

combined oxidative phosphorylation deficiency 29MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014781

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Combined oxidative phosphorylation deficiency 29AR

Manifestation: Biochemical; Neurologic

Intervention: Biochemical

Rationale: Medical management (with coenzyme Q10) has been described as beneficial

Refs: 26626369Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TXN2 variants in ClinVar

4 Conditions Cataloged
not providedTotal: 51
not specifiedTotal: 18
Combined oxidative phosphorylation deficiency 29Total: 3
TXN2-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012473.4. 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.

EffectPLPVUSLBBSum
synonymous
18
clinvar
1
clinvar
 19
missense
37
clinvar
1
clinvar
 38
nonsense
1
clinvar
1
clinvar
 2
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total103919160

Highest pathogenic variant AF is 0.0000150555825

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_012473.4RefSeqNP_036605.23MANE Select
ENST00000216185.7EnsemblENSP00000216185.23MANE Select
ENST00000403313.5EnsemblENSP00000385393.13Standard
ENST00000403313.6EnsemblENSP00000385393.13Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • NOD-like receptor signaling pathway - Homo sapiens (human)
  • Fluid shear stress and atherosclerosis - Homo sapiens (human)
  • miR-targeted genes in epithelium - TarBase
  • miR-targeted genes in leukocytes - TarBase
  • miR-targeted genes in lymphocytes - TarBase

Biological Process

  • sulfur amino acid catabolic process
  • response to hypoxia
  • glycerol ether metabolic process
  • response to oxidative stress
  • response to hormone

Molecular Function

  • protein binding
  • peptide-methionine (S)-S-oxide reductase activity
  • protein disulfide oxidoreductase activity
  • peptide-methionine (R)-S-oxide reductase activity
  • protein-containing complex binding

Cellular Component

  • nucleolus
  • mitochondrion
  • mitochondrial matrix
  • dendrite
  • neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000216185
Coding exons
3
Length
14995
Individuals with no LoFs
125729
Homozygous LoFs
0
Heterozygous LoFs
18
Defined
125747
p
0.0000716
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6157995.90.8230.000004991078
Missense (PolyPhen)1730.7160.55347371
Synonymous-0.6244439.01.130.00000219345
Loss of Function0.050877.150.9794.65e-767

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.000120.00011rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Important for the control of mitochondrial reactive oxygen species homeostasis, apoptosis regulation and cell viability. Possesses a dithiol-reducing activity. {ECO:0000269|PubMed:12032145, ECO:0000269|PubMed:12080052, ECO:0000269|PubMed:26626369}.;

Intolerance Scores

LoFtool
0.605
RVIS EVS
-0.36
RVIS percentile EVS
28.63

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.539

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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