TXNIP

protein-coding

thioredoxin interacting protein, the group of Alpha arrestins

Gene summary

This gene encodes a thioredoxin-binding protein that is a member of the alpha arrestin protein family. Thioredoxin is a thiol-oxidoreductase that is a major regulator of cellular redox signaling which protects cells from oxidative stress. This protein inhibits the antioxidative function of thioredoxin resulting in the accumulation of reactive oxygen species and cellular stress. This protein also functions as a regulator of cellular metabolism and of endoplasmic reticulum (ER) stress. This protein may also function as a tumor suppressor. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

MANE transcript

NM_006472.6

Inheritance

—

ClinVar variants

U:64B:4

Top phenotype

—

Max pathogenic AF

—

Genomic locus

chr1:145,992,435-145,996,579

External References & Databases

Ensembl (ENSG00000265972)

Transcript & Mutation Effects

hg38 • Region Span ~4.1 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 TXNIP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006472.6. 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					2 clinvar	2
missense			64 clinvar		2 clinvar	66
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	64	0	4	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006472.6	RefSeq	NP_006463.3	8	MANE Select
ENST00000582401.6	Ensembl	ENSP00000462521.1	8	MANE Select
NM_001313972.2	RefSeq	NP_001300901.1	7	Standard
ENST00000425134.2	Ensembl	ENSP00000396322.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NOD-like receptor signaling pathway - Homo sapiens (human)
VEGFA-VEGFR2 Signaling Pathway
The NLRP3 inflammasome
Inflammasomes
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways

Biological Process

negative regulation of transcription by RNA polymerase II
protein import into nucleus
cell cycle
response to mechanical stimulus
response to glucose

Molecular Function

enzyme inhibitor activity
protein binding
ubiquitin protein ligase binding

Cellular Component

nucleus
cytoplasm
mitochondrial intermembrane space
cytosol

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over- expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1). {ECO:0000269|PubMed:12821938, ECO:0000269|PubMed:17603038, ECO:0000269|PubMed:18541147, ECO:0000269|PubMed:21460850}.;

Recessive Scores

pRec: 0.295

Intolerance Scores

LoFtool: 0.468
RVIS EVS: 0.08
RVIS percentile EVS: 60.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.607

Gene Damage Prediction

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