TXNDC5

Summary

TXNDC5 (thioredoxin domain containing 5, HGNC:21073) is a protein-coding gene on chromosome 6p24.3, encoding Thioredoxin domain-containing protein 5 (Q8NBS9). Protein disulfide isomerase of the endoplasmic reticulum lumen involved in the formation of disulfide bonds in proteins.

This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal endoplasmic reticulum (ER)-signal sequence, three catalytically active thioredoxin domains and a C-terminal ER-retention sequence. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S5 gene.

Source: NCBI Gene 81567 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 1 total
• Druggable target: yes
• MANE Select transcript: NM_030810

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21073
Approved symbol	TXNDC5
Name	thioredoxin domain containing 5
Location	6p24.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC3178, FLJ21353, FLJ90810, EndoPDI, Hcc-2, ERp46, PDIA15
Ensembl gene	ENSG00000239264
Ensembl biotype	protein_coding
OMIM	616412
Entrez	81567

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 retained_intron

ENST00000379757, ENST00000460138, ENST00000469459, ENST00000473453, ENST00000475802, ENST00000933220, ENST00000933221, ENST00000946227

RefSeq mRNA: 2 — MANE Select: NM_030810 NM_001145549, NM_030810

CCDS: CCDS4505, CCDS47369

Canonical transcript exons

ENST00000379757 — 10 exons

Exon	Start	End
ENSE00001482400	7910514	7910788
ENSE00003638410	7881517	7883266
ENSE00003715789	7889495	7889581
ENSE00003727657	7895106	7895202
ENSE00003729357	7888705	7888848
ENSE00003735674	7899576	7899681
ENSE00003736620	7891621	7891736
ENSE00003745146	7884359	7884488
ENSE00003749406	7885961	7886043
ENSE00003751092	7904574	7904723

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.4554 / max 2901.9130, expressed in 1817 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71635	64.9731	1814
71636	9.4823	1720

Top tissues by expression

138 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	99.07	gold quality
rectum	UBERON:0001052	99.03	gold quality
stromal cell of endometrium	CL:0002255	98.90	gold quality
vermiform appendix	UBERON:0001154	98.77	gold quality
lymph node	UBERON:0000029	98.60	gold quality
spleen	UBERON:0002106	98.52	gold quality
smooth muscle tissue	UBERON:0001135	98.44	gold quality
placenta	UBERON:0001987	98.41	gold quality
islet of Langerhans	UBERON:0000006	98.37	gold quality
body of pancreas	UBERON:0001150	98.20	gold quality
gall bladder	UBERON:0002110	98.11	gold quality
pancreas	UBERON:0001264	98.02	gold quality
saliva-secreting gland	UBERON:0001044	97.75	gold quality
minor salivary gland	UBERON:0001830	97.62	gold quality
endocervix	UBERON:0000458	97.45	gold quality
mucosa of transverse colon	UBERON:0004991	97.41	gold quality
ascending aorta	UBERON:0001496	97.22	gold quality
right coronary artery	UBERON:0001625	97.22	gold quality
thoracic aorta	UBERON:0001515	97.20	gold quality
body of stomach	UBERON:0001161	97.16	gold quality
right lobe of liver	UBERON:0001114	97.09	gold quality
transverse colon	UBERON:0001157	97.05	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.03	gold quality
right ovary	UBERON:0002118	97.01	gold quality
left coronary artery	UBERON:0001626	96.94	gold quality
left uterine tube	UBERON:0001303	96.90	gold quality
omental fat pad	UBERON:0010414	96.88	gold quality
upper lobe of left lung	UBERON:0008952	96.78	gold quality
descending thoracic aorta	UBERON:0002345	96.70	gold quality
left ovary	UBERON:0002119	96.69	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-GEOD-150728	yes	2523.63
E-MTAB-9467	yes	1184.31
E-GEOD-149689	yes	1103.23
E-MTAB-6386	yes	961.42
E-HCAD-32	yes	835.21
E-CURD-55	yes	711.67
E-CURD-88	yes	682.11
E-HCAD-9	yes	594.14
E-GEOD-124263	yes	548.14
E-HCAD-1	yes	345.40
E-CURD-77	yes	341.74
E-CURD-46	yes	86.15
E-HCAD-4	yes	72.94
E-MTAB-8410	yes	62.03
E-CURD-122	yes	58.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting TXNDC5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4716-3P	99.69	66.73	1022

Literature-anchored findings (GeneRIF, showing 35)

• Member of the protein disulphide isomerase family and highly expressed in endothelial cells. Protects endothelial cells from apoptosis under hypoxia. (PMID:12963716)
• upregulation of TXNDC5 are involved in the early development of colorectal cancer (PMID:17895523)
• ERp46 has specificity towards peroxiredoxin-4, a thioredoxin peroxidase. (PMID:19887585)
• results suggest that TXNDC5 gene polymorphisms are associated with the development of nonsegmental vitiligo in the Korean population. (PMID:19906073)
• these results establish ERp46 as the first AdipoR1-specific interacting protein and suggest a role for ERp46 in adiponectin receptor biology and adiponectin signalling. (PMID:20074551)
• TXNDC5 can promote the growth and proliferation of gastric cells. Silencing of TXNDC5 can restrain the growth and proliferation of gastric cancer cells. (PMID:20157732)
• Overexpression of the TXNDC5 protein is associated with non-small cell lung carcinoma. (PMID:21617212)
• TXNDC5 has a genetic effect on the risk of rheumatoid arthritis and ankylosing spondylitis (PMID:21801346)
• crystal structure of the third catalytic domain of protein disulfide isomerase ERp46 (also known as protein disulfide isomerase A5 and TXNDC5) was determined to 2.0 A resolution (PMID:22505402)
• Hypoxia induced TXCNDC5 expression, which contributed to adiponectin expression, cytokine production and the cellular proliferation and migration of fibroblasts in rheumatoid arthritis. (PMID:23326410)
• Authors show that ERp46 is able to bind to a large pool of peptides containing aromatic and basic residues via all three of its catalytic domains (a(0), a and a’), though the a(0) domain may contain the primary binding site. (PMID:23376096)
• Hyperoxidized peroxiredoxin 2 interacts with the protein disulfide- isomerase ERp46. (PMID:23713588)
• results suggest that TXNDC5 polymorphisms could be related to the development of HCC in the Korean male population (PMID:24023338)
• TXNDC5 has increased expression in many tumors that is involved in the proliferation and migration of tumor cells, acting as a tumor-enhancing gene. (PMID:24100949)
• Endo-PDI is a novel, important mediator of AP-1-driven gene expression and endothelial angiogenic function. (PMID:24103565)
• Role of ERp46 in oxidative protein folding.Independent actions of ERp46 thioredoxin domains on folding substrates.Structure of thioredoxin ERp46 domains. (PMID:24462249)
• suggest that the tumorigenic properties of ERp46 in RCC cells are not related to an inhibitory modulation of AdipoR1 (PMID:24594673)
• we defined an important role of TXNDC5 in CRPC and further investigations are needed to screen TXNDC5 antagonists as a novel therapeutic approaches to treat PCa patients with Castration-resistant prostate cancer. (PMID:25500540)
• High TXNDC5 expression is associated with renal cell carcinoma. (PMID:26810069)
• Taken together, by linking HSC70 and NF-kappaB signaling, TXNDC5 plays a pro-inflammatory role in rheumatoid arthritis synovial fibroblasts, highlighting a potential approach to treat rheumatoid arthritis by blocking the TXNDC5/HSC70 interaction. (PMID:28603283)
• TXNDC5 is also closely associated with rheumatoid arthritis, diabetes, hepatic steatosis and vitiligo. [review] (PMID:28604976)
• TXNDC5 contributes to abnormal rheumatoid arthritis synovial fibroblast-like cells proliferation, migration and IL-6 production by inhibiting IGFBP1 expression. (PMID:29131315)
• These results strongly suggest that high levels of TXNDC5 in Rheumatoid Arthritis synovial tissues suppress CXCL10 and TNFSF10 expression. (PMID:29247155)
• TXNDC5 mRNA and protein were highly upregulated in failing human left ventricles. TXNDC5 mRNA and protein were increased in human cardiac fibroblasts under transforming growth factor beta1 stimulation in vitro.TXNDC5 knockdown attenuated TGFbeta1-induced activation and ECM protein upregulation independent of SMAD3, but increasing expression of TXNDC5 triggered activation and proliferation and increased ECM protein prod… (PMID:29535165)
• Hypoxia induces the expression of TXNDC5 via upregulating HIF-1alpha in colorectal cancer cells. (PMID:29749460)
• the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor alpha locus (TCRalpha), was reconstituted only when ERp46 had established a covalent interaction with EDEM3 (PMID:29784879)
• serum levels were elevated in both early-onset and late-onset pre-eclampsia (PMID:30522366)
• HERG1 contributes to poor prognosis in patients with esophageal squamous cell carcinoma (ESCC) by promoting ESCC cell proliferation, migration, and invasion via TXNDC5 through the PI3K/AKT signaling pathway. Our findings provided novel insights into the pathology of ESCC and role of HERG1 in tumor progression, suggesting that targeting HERG1 has potential diagnostic and therapeutic value for ESCC treatment. (PMID:31331361)
• Fibroblast-enriched endoplasmic reticulum protein TXNDC5 promotes pulmonary fibrosis by augmenting TGFbeta signaling through TGFBR1 stabilization. (PMID:32848143)
• Circ_0078710 promotes the development of liver cancer by upregulating TXNDC5 via miR-431-5p. (PMID:34606982)
• The role and mechanism of TXNDC5 in diseases. (PMID:35934705)
• The novel role of ER protein TXNDC5 in the pathogenesis of organ fibrosis: mechanistic insights and therapeutic implications. (PMID:36050716)
• Identification of thioredoxin domain containing family members’ expression pattern and prognostic value in diffuse gliomas via in silico analysis. (PMID:36106447)
• Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release. (PMID:38548704)
• The role and mechanism of TXNDC5 in disease progression. (PMID:38629066)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	txndc5	ENSDARG00000009342
mus_musculus	Txndc5	ENSMUSG00000038991
rattus_norvegicus	Txndc5	ENSRNOG00000013469
drosophila_melanogaster	prtp	FBGN0030329
caenorhabditis_elegans		WBGENE00003962
caenorhabditis_elegans	M04D5.1	WBGENE00014807

Paralogs (13): ERP44 (ENSG00000023318), PDIA5 (ENSG00000065485), TMX4 (ENSG00000125827), ERP27 (ENSG00000139055), TMX1 (ENSG00000139921), PDIA6 (ENSG00000143870), TXNDC11 (ENSG00000153066), PDIA4 (ENSG00000155660), TMX3 (ENSG00000166479), PDIA3 (ENSG00000167004), PDILT (ENSG00000169340), PDIA2 (ENSG00000185615), P4HB (ENSG00000185624)

Protein

Protein identifiers

Thioredoxin domain-containing protein 5 — Q8NBS9 (reviewed: Q8NBS9)

Alternative names: Endoplasmic reticulum resident protein 46, Thioredoxin-like protein p46

All UniProt accessions (2): Q8NBS9, A0A024QZV0

UniProt curated annotations — full annotation on UniProt →

Function. Protein disulfide isomerase of the endoplasmic reticulum lumen involved in the formation of disulfide bonds in proteins. Can reduce insulin disulfide bonds.

Subcellular location. Endoplasmic reticulum lumen.

Similarity. Belongs to the protein disulfide isomerase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NBS9-1	1	yes
Q8NBS9-2	2

RefSeq proteins (2): NP_001139021, NP_110437* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005788	PDI_thioredoxin-like_dom	Domain
IPR013766	Thioredoxin_domain	Domain
IPR017937	Thioredoxin_CS	Conserved_site
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR051063	PDI	Family

Pfam: PF00085

Enzyme classification (BRENDA):

• EC 5.3.4.1 — protein disulfide-isomerase (BRENDA: 81 organisms, 481 substrates, 347 inhibitors, 35 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

15 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CYSTEINE	1–3	3
MYCOTHIOL-COUPLED HYDROXYETHYL DISULFIDE	0.46–33.69	3
RIBONUCLEASE	0.002–0.01	3
RNASE A	0.007–0.05	3
2-MERCAPTOETHANOL	0.2–0.8	2
DITHIOTHREITOL	0.003–0.0054	2
GSH	5–17	2
RNASE	0.028–0.063	2
SCRAMBLED RIBONUCLEASE	0.0011–0.0033	2
DENATURED-REDUCED LYSOZYME	0.0253	1
INSULIN	2.026	1
INSULIN-(SS)	0.005	1
SCRAMBLED REOXIDIZED LYSOZYME	0.0116	1
SCRAMBLED RNASE	0.02	1
SRNASE	—	0

UniProt features (45 total): strand 14, helix 12, turn 6, disulfide bond 3, domain 3, signal peptide 1, chain 1, splice variant 1, sequence conflict 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
3WGX	X-RAY DIFFRACTION	0.92
3WGE	X-RAY DIFFRACTION	0.95
3UVT	X-RAY DIFFRACTION	2
3WGD	X-RAY DIFFRACTION	2.5
3UJ1	X-RAY DIFFRACTION	2.65
8EKY	ELECTRON MICROSCOPY	3.47
2DIZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBS9-F1	81.89	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (3): 350–353, 89–92, 217–220

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-432720	Lysosome Vesicle Biogenesis
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 175 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, chr6p24, REACTOME_MEMBRANE_TRAFFICKING, SHAFFER_IRF4_TARGETS_IN_PLASMA_CELL_VS_MATURE_B_LYMPHOCYTE, GOBP_PROTEIN_MATURATION, GOBP_PROTEIN_FOLDING, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_DENDRITIC_CELL, MODULE_95, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, GOCC_LYSOSOMAL_LUMEN, GOCC_SECRETORY_VESICLE, GOCC_VESICLE_LUMEN, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, GOCC_VACUOLAR_LUMEN

GO Biological Process (2): protein folding (GO:0006457), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (5): protein disulfide isomerase activity (GO:0003756), protein-disulfide reductase activity (GO:0015035), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), isomerase activity (GO:0016853)

GO Cellular Component (9): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), azurophil granule lumen (GO:0035578), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), endomembrane system (GO:0012505), intracellular organelle lumen (GO:0070013)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	2
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
catalytic activity, acting on a protein	2
catalytic activity	2
vacuolar lumen	2
cellular process	1
protein maturation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
intramolecular oxidoreductase activity, transposing S-S bonds	1
disulfide oxidoreductase activity	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1
secretory granule lumen	1
azurophil granule	1
lysosome	1
extracellular vesicle	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1
intracellular organelle	1
organelle lumen	1

Protein interactions and networks

STRING

2642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TXNDC5	PRDX4	Q13162	891
TXNDC5	ERO1A	Q96HE7	748
TXNDC5	ADIPOR1	Q96A54	605
TXNDC5	TXNDC12	O95881	582
TXNDC5	ERP29	P30040	578
TXNDC5	ERO1B	Q86YB8	563
TXNDC5	BLOC1S5	Q8TDH9	541
TXNDC5	HSPA5	P11021	539
TXNDC5	UGGT1	Q9NYU2	534
TXNDC5	ERP27	Q96DN0	513
TXNDC5	HYOU1	Q9Y4L1	480
TXNDC5	EDEM3	Q9BZQ6	453
TXNDC5	TXNDC11	Q6PKC3	451
TXNDC5	AR	P10275	437
TXNDC5	EIF2AK3	Q9NZJ5	427

IntAct

95 interactions, top by confidence:

A	B	Type	Score
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
TXNDC5	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
TXNDC5		psi-mi:“MI:0915”(physical association)	0.550
DCAF7	CLASP2	psi-mi:“MI:0914”(association)	0.510
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
	BIN1	psi-mi:“MI:0914”(association)	0.460
Edem3	PDIA3	psi-mi:“MI:0914”(association)	0.460
TXNDC5	PRDX4	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
PRDX4	TXNDC5	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
ZNF780A	TXNDC5	psi-mi:“MI:0915”(physical association)	0.400
RNF20	TXNDC5	psi-mi:“MI:0915”(physical association)	0.400
NODAL	TXNDC5	psi-mi:“MI:0915”(physical association)	0.400
TXNDC5	E7	psi-mi:“MI:0915”(physical association)	0.370
TXNDC5	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.370
TXNDC5	GMPPB	psi-mi:“MI:0915”(physical association)	0.370
TXNDC5	KRT38	psi-mi:“MI:0915”(physical association)	0.370
ECE1	TXNDC5	psi-mi:“MI:0915”(physical association)	0.370
FOXN1	FOXN1	psi-mi:“MI:0914”(association)	0.350
RBPJ	SAMD1	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (275): TXNDC5 (Two-hybrid), TXNDC5 (Two-hybrid), TXNDC5 (Two-hybrid), TXNDC5 (Two-hybrid), TXNDC5 (Two-hybrid), TXNDC5 (Two-hybrid), TXNDC5 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-2 (Two-hybrid), LHX4 (Two-hybrid), KRT40 (Two-hybrid), ALS2CR12 (Two-hybrid), MGAT5B (Two-hybrid), TRIM42 (Two-hybrid), KRTAP10-7 (Two-hybrid)

ESM2 similar proteins: A2VE29, A6QLU8, D3Z6P0, H2N4I1, O00391, O08841, P04785, P05307, P07237, P08003, P09102, P09103, P13667, P21195, P30040, P38657, P38659, P57759, P81628, P97278, P97346, Q0VCM5, Q13087, Q14554, Q29052, Q2HWU2, Q2KIL5, Q499T2, Q4VIT4, Q503L9, Q5E936, Q5I0H9, Q5R5B6, Q5RCH2, Q5WA72, Q61702, Q67IX6, Q6DKJ4, Q6GM16, Q6IUU3

Diamond homologs: A0A8M1N5Y4, A3KPF5, D4B2L8, O13704, O13811, O22022, O22263, O48773, O83889, P05307, P07591, P07887, P08003, P09103, P0A4L1, P0A4L2, P0AGG4, P0AGG5, P0AGG6, P0AGG7, P11598, P12243, P12865, P13667, P17967, P21195, P23400, P27773, P30101, P33791, P34329, P37395, P38657, P38658, P38659, P38660, P38661, P46843, P50254, P50338

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by BRAF and RAF1 fusions	5	10.8×	8e-03
MAPK family signaling cascades	7	9.1×	3e-03
RAF/MAP kinase cascade	9	7.0×	3e-03
Signaling by Receptor Tyrosine Kinases	9	5.9×	4e-03
Diseases of signal transduction by growth factor receptors and second messengers	8	5.8×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
insulin receptor signaling pathway	6	13.9×	2e-03
myelination	5	13.1×	6e-03
epidermal growth factor receptor signaling pathway	5	12.9×	6e-03
positive regulation of epithelial cell proliferation	5	12.7×	6e-03
cell surface receptor protein tyrosine kinase signaling pathway	6	10.9×	4e-03
protein phosphorylation	8	5.7×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1975 predictions. Top by Δscore:

Variant	Effect	Δscore
6:7884368:G:A	donor_gain	1.0000
6:7884484:CACAC:C	acceptor_gain	1.0000
6:7884486:CAC:C	acceptor_gain	1.0000
6:7884487:ACC:A	acceptor_loss	1.0000
6:7884487:ACCTA:A	acceptor_loss	1.0000
6:7884489:CTAAG:C	acceptor_loss	1.0000
6:7885954:CACTT:C	donor_loss	1.0000
6:7885955:ACTTA:A	donor_loss	1.0000
6:7885956:CTTAC:C	donor_loss	1.0000
6:7885957:TTA:T	donor_loss	1.0000
6:7885958:T:TG	donor_loss	1.0000
6:7885958:TACCA:T	donor_loss	1.0000
6:7885959:A:AC	donor_gain	1.0000
6:7885959:A:C	donor_loss	1.0000
6:7885959:A:T	donor_loss	1.0000
6:7885960:C:CC	donor_gain	1.0000
6:7886043:CCT:C	acceptor_loss	1.0000
6:7886044:C:A	acceptor_loss	1.0000
6:7886044:CTTCA:C	acceptor_loss	1.0000
6:7886045:T:G	acceptor_loss	1.0000
6:7886047:C:CT	acceptor_gain	1.0000
6:7886048:A:T	acceptor_gain	1.0000
6:7888700:CCCA:C	donor_loss	1.0000
6:7888701:CCA:C	donor_loss	1.0000
6:7888702:CA:C	donor_loss	1.0000
6:7888703:ACCT:A	donor_loss	1.0000
6:7888704:C:G	donor_loss	1.0000
6:7888704:C:T	donor_loss	1.0000
6:7888847:ACC:A	acceptor_loss	1.0000
6:7888848:CCT:C	acceptor_loss	1.0000

AlphaMissense

2790 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:7889526:G:T	P263H	0.999
6:7891693:G:C	C220W	0.999
6:7891694:C:A	C220F	0.999
6:7891694:C:T	C220Y	0.999
6:7891705:C:A	W216C	0.999
6:7891705:C:G	W216C	0.999
6:7891712:G:T	A214D	0.999
6:7904577:G:T	P137H	0.999
6:7904624:G:C	C121W	0.999
6:7904625:C:T	C121Y	0.999
6:7904690:C:A	W99C	0.999
6:7904690:C:G	W99C	0.999
6:7904692:A:G	W99R	0.999
6:7904692:A:T	W99R	0.999
6:7904711:G:C	C92W	0.999
6:7904712:C:A	C92F	0.999
6:7904712:C:T	C92Y	0.999
6:7904713:A:G	C92R	0.999
6:7904721:C:A	C89F	0.999
6:7904721:C:T	C89Y	0.999
6:7904722:A:G	C89R	0.999
6:7889573:A:C	C247W	0.998
6:7889574:C:T	C247Y	0.998
6:7891672:C:A	W227C	0.998
6:7891672:C:G	W227C	0.998
6:7891674:A:G	W227R	0.998
6:7891674:A:T	W227R	0.998
6:7891695:A:G	C220R	0.998
6:7891703:C:A	C217F	0.998
6:7891703:C:T	C217Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000068689 (6:7903909 C>G), RS1000137385 (6:7893124 A>G), RS1000328051 (6:7892554 T>C), RS1000436882 (6:7887730 C>T), RS1000476100 (6:7908934 T>C), RS1000711574 (6:7899032 C>G), RS1000718968 (6:7883571 G>T), RS1000816495 (6:7888104 C>T), RS1000817670 (6:7898447 G>T), RS1000867747 (6:7884570 T>C), RS1000890562 (6:7896573 A>C,G), RS1001012120 (6:7910025 G>A,C), RS1001077576 (6:7909880 C>G,T), RS1001240967 (6:7903435 T>C), RS1001243213 (6:7909737 G>A)

Disease associations

OMIM: gene MIM:616412 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006585_6	Blood protein levels	2.000000e-12
GCST008941_2	High chromosomal aberration frequency (chromatid type)	3.000000e-07
GCST010174_11	Pelvic organ prolapse	3.000000e-06
GCST90002390_559	Mean corpuscular hemoglobin	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009862	chromatid-type aberration frequency
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4739698 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.30	Kd	496.2	nM	CHEMBL5653589
6.30	ED50	496.2	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 5 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149693: Binding affinity to human TXNDC5 incubated for 45 mins by Kinobead based pull down assay	kd	0.4962	uM

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
cobaltous chloride	decreases abundance, increases expression, decreases expression	2
1,1-bis(3’-indolyl)-1-(4-hydroxyphenyl)methane	decreases reaction, increases expression, affects binding, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
p-carboxymethylphenyl 1,1-bis(3’-indolyl)-1-(p-carboxymethylphenyl)methane	decreases expression	1
2,4,6-tribromophenol	increases expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	increases expression	1
quinoline	decreases expression	1
leptomycin B	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	increases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	increases expression	1
thifluzamide	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Antimycin A	increases expression	1
Arsenic	increases abundance, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4682780	Binding	Inhibition of TXNDC5 (unknown origin)	Tuning isoform selectivity and bortezomib sensitivity with a new class of alkenyl indene PDI inhibitor. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3KD	Abcam HEK293T TXNDC5 KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.