TXNDC9

Summary

TXNDC9 (thioredoxin domain containing 9, HGNC:24110) is a protein-coding gene on chromosome 2q11.2, encoding Thioredoxin domain-containing protein 9 (O14530). Significantly diminishes the chaperonin TCP1 complex ATPase activity, thus negatively impacts protein folding, including that of actin or tubulin. It is a selective cancer dependency (DepMap: 11.0% of cell lines).

The protein encoded by this gene is a member of the thioredoxin family. The exact function of this protein is not known but it is associated with cell differentiation.

Source: NCBI Gene 10190 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 28 total
• Cancer dependency (DepMap): dependent in 11.0% of screened cell lines
• MANE Select transcript: NM_005783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24110
Approved symbol	TXNDC9
Name	thioredoxin domain containing 9
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	APACD
Ensembl gene	ENSG00000115514
Ensembl biotype	protein_coding
OMIM	612564
Entrez	10190

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264255, ENST00000409434, ENST00000409705, ENST00000422767, ENST00000434323, ENST00000438680, ENST00000463385, ENST00000465183, ENST00000477337, ENST00000863431, ENST00000863432, ENST00000863433, ENST00000863434, ENST00000915055, ENST00000959454, ENST00000959455

RefSeq mRNA: 1 — MANE Select: NM_005783 NM_005783

CCDS: CCDS2044

Canonical transcript exons

ENST00000264255 — 5 exons

Exon	Start	End
ENSE00001038773	99318982	99319799
ENSE00001580663	99336239	99336333
ENSE00002467726	99333022	99333242
ENSE00003605252	99321955	99322209
ENSE00003663371	99327535	99327653

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 95.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.5830 / max 709.1135, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29881	48.5830	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.85	gold quality
epithelium of nasopharynx	UBERON:0001951	95.01	gold quality
nasopharynx	UBERON:0001728	95.00	gold quality
hair follicle	UBERON:0002073	94.28	gold quality
endothelial cell	CL:0000115	93.81	gold quality
secondary oocyte	CL:0000655	93.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.55	gold quality
oral cavity	UBERON:0000167	93.52	gold quality
cervix squamous epithelium	UBERON:0006922	93.35	gold quality
skin of hip	UBERON:0001554	93.31	gold quality
islet of Langerhans	UBERON:0000006	93.05	gold quality
heart right ventricle	UBERON:0002080	92.75	gold quality
corpus epididymis	UBERON:0004359	92.65	gold quality
colonic mucosa	UBERON:0000317	92.63	gold quality
palpebral conjunctiva	UBERON:0001812	92.61	gold quality
gingiva	UBERON:0001828	92.56	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.44	gold quality
gingival epithelium	UBERON:0001949	92.41	gold quality
oviduct epithelium	UBERON:0004804	92.32	gold quality
squamous epithelium	UBERON:0006914	92.24	gold quality
periodontal ligament	UBERON:0008266	92.15	gold quality
nasal cavity epithelium	UBERON:0005384	92.10	gold quality
cervix epithelium	UBERON:0004801	92.06	gold quality
rectum	UBERON:0001052	92.04	gold quality
bronchial epithelial cell	CL:0002328	91.99	gold quality
esophagus squamous epithelium	UBERON:0006920	91.91	gold quality
nasal cavity mucosa	UBERON:0001826	91.68	gold quality
epithelium of esophagus	UBERON:0001976	91.66	gold quality
endometrium	UBERON:0001295	91.62	gold quality
tongue squamous epithelium	UBERON:0006919	91.60	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.60
E-MTAB-6379	no	2337.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting TXNDC9, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• antagonistic actions of PhLP3 and prefoldin serve to modulate CCT activity and play a key role in establishing a functional cytoskeleton in vivo (PMID:16415341)
• PhLP3 is important for the maintenance of beta-tubulin levels in mammalian cells. (PMID:22174782)
• These findings suggest that TXNDC9 gene may function in colorectalcancer development (PMID:23210642)
• TXNDC9 promotes hepatocellular carcinoma progression by positive regulation of MYC-mediated transcriptional network. (PMID:30382079)
• these studies demonstrate that the TXNDC9-PRDX1 axis plays an important role for ROS to activate AR functions. It provides a proof-of-principle that co-targeting AR and PRDX1 may be more effective to control prostate cancer (PCa) growth. (PMID:31477836)
• Thioredoxin domain-containing protein 9 (TXNDC9) contributes to oxaliplatin resistance through regulation of autophagy-apoptosis in colorectal adenocarcinoma. (PMID:32029274)
• High level of TXNDC9 predicts poor prognosis and contributes to the NF-kappaB-regulated metastatic potential in gastric cancer. (PMID:34846159)
• TXNDC9 knockdown inhibits lung adenocarcinoma progression by targeting YWHAG. (PMID:35485284)
• Thioredoxin domain-containing protein 9 protects cells against UV-B-provoked apoptosis via NF-kappaB/p65 activation in cutaneous squamous cell carcinoma. (PMID:37303736)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	txndc9	ENSDARG00000069853
mus_musculus	Txndc9	ENSMUSG00000058407
rattus_norvegicus	Txndc9	ENSRNOG00000018593
drosophila_melanogaster	CG4511	FBGN0037843
caenorhabditis_elegans		WBGENE00006515

Paralogs (4): PDCL3 (ENSG00000115539), PDC (ENSG00000116703), PDCL (ENSG00000136940), PDCL2 (ENSG00000163440)

Protein

Protein identifiers

Thioredoxin domain-containing protein 9 — O14530 (reviewed: O14530)

Alternative names: ATP-binding protein associated with cell differentiation, Protein 1-4

All UniProt accessions (5): B8ZZX4, O14530, F8WBV5, F8WCJ3, G3XAJ4

UniProt curated annotations — full annotation on UniProt →

Function. Significantly diminishes the chaperonin TCP1 complex ATPase activity, thus negatively impacts protein folding, including that of actin or tubulin.

Subunit / interactions. Forms ternary complexes with the chaperonin TCP1 complex, spanning the cylindrical chaperonin cavity and contacting at least 2 subunits.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome. Midbody.

Isoforms (2)

UniProt ID	Names	Canonical?
O14530-1	1	yes
O14530-2	2

RefSeq proteins (1): NP_005774* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013766	Thioredoxin_domain	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF00085

UniProt features (11 total): sequence conflict 3, modified residue 3, sequence variant 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14530-F1	84.48	0.64

Functional residue map

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

Post-translational modifications (3): 188, 221, 223

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 143 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOCC_MICROTUBULE_ORGANIZING_CENTER, WEI_MYCN_TARGETS_WITH_E_BOX, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOCC_CENTROSOME, GARY_CD5_TARGETS_DN, SCHLOSSER_SERUM_RESPONSE_DN, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, GOCC_MIDBODY, BLALOCK_ALZHEIMERS_DISEASE_DN, WANG_TUMOR_INVASIVENESS_UP, chr2q11, GOMF_CELL_ADHESION_MOLECULE_BINDING, GOMF_CADHERIN_BINDING, PUIFFE_INVASION_INHIBITED_BY_ASCITES_DN

GO Biological Process (1): microtubule cytoskeleton organization (GO:0000226)

GO Molecular Function (2): cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), midbody (GO:0030496), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoskeleton organization	1
microtubule-based process	1
cell adhesion molecule binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2844 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TXNDC9	INSR	P06213	953
TXNDC9	KRT17	Q04695	897
TXNDC9	YWHAG	P35214	863
TXNDC9	HTT	P42858	863
TXNDC9	YWHAE	P29360	845
TXNDC9	SFN	P31947	845
TXNDC9	YWHAH	Q04917	833
TXNDC9	YWHAB	P31946	821
TXNDC9	YWHAZ	P29213	771
TXNDC9	ESR1	P03372	757
TXNDC9	DDX1	Q92499	745
TXNDC9	TP53	P04637	737
TXNDC9	BECN1	Q14457	735
TXNDC9	TXN	P10599	721
TXNDC9	YWHAQ	P27348	697

IntAct

172 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
TUBA1C	TXNDC9	psi-mi:“MI:0914”(association)	0.730
TXNDC9	EXOSC8	psi-mi:“MI:0915”(physical association)	0.720
EXOSC8	TXNDC9	psi-mi:“MI:0915”(physical association)	0.720
MYOG	TXNDC9	psi-mi:“MI:0915”(physical association)	0.670
MAGEA6	TXNDC9	psi-mi:“MI:0915”(physical association)	0.670
TXNDC9	MYOG	psi-mi:“MI:0915”(physical association)	0.670
MPPED1	TXNDC9	psi-mi:“MI:0914”(association)	0.640
TUBA1B	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT2	PPP6C	psi-mi:“MI:0914”(association)	0.640
PDCL3	PEX7	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640

BioGRID (182): TXNDC9 (Affinity Capture-MS), TXNDC9 (Two-hybrid), TXNDC9 (Two-hybrid), TXNDC9 (Two-hybrid), TXNDC9 (Two-hybrid), TXNDC9 (Two-hybrid), EXOSC8 (Two-hybrid), CEP76 (Two-hybrid), C1orf94 (Two-hybrid), DYDC1 (Two-hybrid), CCDC172 (Two-hybrid), C3orf62 (Two-hybrid), TXNDC9 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT3 (Affinity Capture-MS)

ESM2 similar proteins: O01757, O14530, O18883, O64628, O94267, P87115, Q04004, Q0VA16, Q11183, Q13371, Q2HJA9, Q32LB0, Q32LN3, Q3TWF6, Q4HYB8, Q5E9R3, Q5EB92, Q5RBP4, Q63737, Q641Z6, Q6GPP0, Q6NPL9, Q71A37, Q71A38, Q78Y63, Q8IRG6, Q8K581, Q8LCV1, Q8MR62, Q8N4E4, Q8R491, Q8VWG7, Q920B9, Q9CQ79, Q9DBX2, Q9EQP2, Q9H223, Q9H4M9, Q9M2Q4, Q9NW82

Diamond homologs: O14095, O14096, O14530, O18883, O64628, Q04004, Q11183, Q6NPL9, Q71A37, Q8K581, Q8LCV1, Q9CQ79, Q9VGV8, C9K7C5, P37395, Q32LN3, Q42403, Q71A38, Q78Y63, Q8N4E4, P25372, Q58DA7, Q9CQM9, Q9JLZ1, P47370, Q1RQJ1, Q9CAS1, Q9MAH1, Q0VCW8, Q12017, Q4KLJ8, Q5RB77, Q6P268, Q71A39, Q8BVF2, Q8MR62, Q9H2J4, Q9Y7L1, P19632, Q13371

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 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
Formation of tubulin folding intermediates by CCT/TriC	15	111.3×	2e-26
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	15	107.3×	2e-26
Prefoldin mediated transfer of substrate to CCT/TriC	14	96.7×	5e-24
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	10	95.4×	4e-17
Transport of connexons to the plasma membrane	10	95.4×	4e-17
Gap junction trafficking and regulation	10	83.5×	2e-16
Gap junction trafficking	10	83.5×	2e-16
Post-chaperonin tubulin folding pathway	10	83.5×	2e-16

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	5	45.2×	6e-06
mitotic spindle organization	7	23.5×	2e-06
mitotic cell cycle	12	19.8×	4e-10
microtubule cytoskeleton organization	12	18.0×	6e-10
protein folding	7	8.9×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1583 predictions. Top by Δscore:

Variant	Effect	Δscore
2:99319798:CA:C	acceptor_gain	1.0000
2:99319798:CACT:C	acceptor_gain	1.0000
2:99319800:C:CC	acceptor_gain	1.0000
2:99319801:T:C	acceptor_gain	1.0000
2:99319801:T:TC	acceptor_gain	1.0000
2:99327649:CATTC:C	acceptor_gain	1.0000
2:99327651:TTCC:T	acceptor_loss	1.0000
2:99327652:TCCTA:T	acceptor_loss	1.0000
2:99327653:CCTA:C	acceptor_loss	1.0000
2:99327655:T:C	acceptor_loss	1.0000
2:99332982:A:AC	donor_gain	1.0000
2:99332983:C:CC	donor_gain	1.0000
2:99333020:A:AC	donor_gain	1.0000
2:99333021:C:CC	donor_gain	1.0000
2:99333042:T:TA	donor_gain	1.0000
2:99333047:AGTG:A	donor_gain	1.0000
2:99333050:G:A	donor_gain	1.0000
2:99333239:GGTG:G	acceptor_gain	1.0000
2:99333241:TG:T	acceptor_gain	1.0000
2:99333243:C:CC	acceptor_gain	1.0000
2:99319797:CCA:C	acceptor_gain	0.9900
2:99319797:CCACT:C	acceptor_gain	0.9900
2:99322206:ACACC:A	acceptor_loss	0.9900
2:99322207:CAC:C	acceptor_gain	0.9900
2:99322210:C:CC	acceptor_gain	0.9900
2:99322210:C:G	acceptor_loss	0.9900
2:99322211:T:G	acceptor_loss	0.9900
2:99322505:ACAG:A	acceptor_gain	0.9900
2:99322505:ACAGG:A	acceptor_loss	0.9900
2:99322507:A:AG	acceptor_gain	0.9900

AlphaMissense

1509 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:99322186:A:G	L111P	0.996
2:99327565:A:T	V93D	0.996
2:99327563:A:G	C94R	0.995
2:99322119:G:C	F133L	0.994
2:99322119:G:T	F133L	0.994
2:99322121:A:G	F133L	0.994
2:99322208:A:G	C104R	0.994
2:99322081:A:G	L146P	0.993
2:99322150:A:G	F123S	0.993
2:99321994:A:G	L175S	0.992
2:99322039:C:T	G160E	0.992
2:99322045:A:T	V158D	0.992
2:99322087:G:T	P144H	0.992
2:99322141:A:G	L126P	0.992
2:99322036:A:G	F161S	0.991
2:99322008:G:C	F170L	0.990
2:99322008:G:T	F170L	0.990
2:99322010:A:G	F170L	0.990
2:99322035:A:C	F161L	0.990
2:99322035:A:T	F161L	0.990
2:99322037:A:G	F161L	0.990
2:99322206:A:C	C104W	0.990
2:99327556:A:G	F96S	0.990
2:99327561:G:C	C94W	0.990
2:99321982:A:T	L179H	0.989
2:99322027:A:G	L164P	0.989
2:99327555:G:C	F96L	0.989
2:99327555:G:T	F96L	0.989
2:99327557:A:G	F96L	0.989
2:99321982:A:G	L179P	0.988

dbSNP variants (sampled 300 via entrez): RS1000014715 (2:99320235 T>C,G), RS1000057524 (2:99318695 G>C), RS1000185159 (2:99324856 C>T), RS1000215981 (2:99325050 T>C), RS1000428311 (2:99318459 G>C), RS1000482077 (2:99320700 A>C,G), RS1000493400 (2:99331806 G>A), RS1000503271 (2:99307521 T>C), RS1000512719 (2:99323630 G>A), RS1000553633 (2:99323876 C>G), RS1000702379 (2:99313297 C>T), RS1000706701 (2:99329794 C>G,T), RS1000782430 (2:99331526 A>T), RS1000865113 (2:99318741 G>A), RS1000867978 (2:99326118 G>A)

Disease associations

OMIM: gene MIM:612564 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001241_13	Bipolar disorder	3.000000e-06
GCST006979_15	Heel bone mineral density	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Air Pollutants	decreases expression, increases abundance	2
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
apocarotenal	increases expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
jinfukang	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Bortezomib	increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cisplatin	decreases expression, decreases reaction	1
Diuron	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Nicotine	increases expression	1
Piroxicam	decreases expression, decreases reaction	1
Smoke	decreases expression, increases abundance	1
Thimerosal	increases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases expression	1
beta Carotene	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2K1	Abcam HeLa TXNDC9 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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