TXNDC11

Summary

TXNDC11 (thioredoxin domain containing 11, HGNC:28030) is a protein-coding gene on chromosome 16p13.13, encoding Thioredoxin domain-containing protein 11 (Q6PKC3). May act as a redox regulator involved in DUOX proteins folding.

Predicted to be located in endoplasmic reticulum membrane.

Source: NCBI Gene 51061 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 193 total
• Druggable target: yes
• MANE Select transcript: NM_015914

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28030
Approved symbol	TXNDC11
Name	thioredoxin domain containing 11
Location	16p13.13
Locus type	gene with protein product
Status	Approved
Aliases	EFP1
Ensembl gene	ENSG00000153066
Ensembl biotype	protein_coding
OMIM	617792
Entrez	51061

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000283033, ENST00000356957, ENST00000570917, ENST00000571882, ENST00000572732, ENST00000573174, ENST00000575349, ENST00000575591, ENST00000576969, ENST00000907105, ENST00000907106, ENST00000907107, ENST00000907108, ENST00000907109, ENST00000907110, ENST00000907111, ENST00000907112

RefSeq mRNA: 5 — MANE Select: NM_015914 NM_001303447, NM_001324022, NM_001324024, NM_001324025, NM_015914

CCDS: CCDS32387, CCDS76822

Canonical transcript exons

ENST00000283033 — 12 exons

Exon	Start	End
ENSE00001008624	11691290	11692082
ENSE00001105879	11730645	11730774
ENSE00002633581	11742477	11742857
ENSE00003462920	11688303	11688445
ENSE00003468802	11721577	11721670
ENSE00003483323	11736017	11736233
ENSE00003505745	11733982	11734079
ENSE00003515938	11684165	11684245
ENSE00003626303	11700452	11700564
ENSE00003629304	11679083	11679837
ENSE00003657349	11687857	11687966
ENSE00003675609	11698125	11698325

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 96.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.7454 / max 765.1624, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156305	13.3716	1808
156304	5.3738	1202

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	96.90	gold quality
right lobe of liver	UBERON:0001114	96.20	gold quality
right lobe of thyroid gland	UBERON:0001119	95.46	gold quality
left lobe of thyroid gland	UBERON:0001120	95.27	gold quality
body of pancreas	UBERON:0001150	95.15	gold quality
upper lobe of left lung	UBERON:0008952	95.06	gold quality
ileal mucosa	UBERON:0000331	94.72	gold quality
thyroid gland	UBERON:0002046	94.69	gold quality
right lung	UBERON:0002167	94.67	gold quality
upper lobe of lung	UBERON:0008948	94.61	gold quality
islet of Langerhans	UBERON:0000006	94.59	gold quality
mucosa of transverse colon	UBERON:0004991	94.32	gold quality
pancreas	UBERON:0001264	94.19	gold quality
body of stomach	UBERON:0001161	93.76	gold quality
minor salivary gland	UBERON:0001830	93.48	gold quality
gastrocnemius	UBERON:0001388	93.21	gold quality
rectum	UBERON:0001052	93.17	gold quality
spleen	UBERON:0002106	93.06	gold quality
metanephros cortex	UBERON:0010533	92.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.67	gold quality
adenohypophysis	UBERON:0002196	92.64	gold quality
transverse colon	UBERON:0001157	92.62	gold quality
liver	UBERON:0002107	92.61	gold quality
stomach	UBERON:0000945	92.59	gold quality
endocervix	UBERON:0000458	92.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.51	gold quality
muscle of leg	UBERON:0001383	92.34	gold quality
colonic epithelium	UBERON:0000397	92.28	gold quality
saliva-secreting gland	UBERON:0001044	92.28	gold quality
granulocyte	CL:0000094	92.02	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	79.43
E-MTAB-9467	yes	50.63
E-CURD-122	yes	50.43
E-MTAB-8410	yes	36.78
E-HCAD-1	yes	30.79
E-ANND-3	yes	27.17
E-HCAD-11	yes	19.59
E-GEOD-124858	no	90.46
E-MTAB-6142	no	71.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting TXNDC11, 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-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-6502-3P	97.86	65.43	569

Literature-anchored findings (GeneRIF, showing 4)

• EFP1 is a thioredoxin-related protein and partner of duox (PMID:15561711)
• EDEM2 stably disulfide-bonded to TXNDC11 catalyzes the first mannose trimming step in mammalian glycoprotein ERAD. (PMID:32065582)
• Expression analysis and functional characterization of thioredoxin domain-containing protein 11. (PMID:36152228)
• High Thioredoxin Domain-Containing Protein 11 Expression Is Associated with Tumour Progression in Glioma. (PMID:37686174)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	txndc11	ENSDARG00000101291
mus_musculus	Txndc11	ENSMUSG00000022498
rattus_norvegicus	Txndc11	ENSRNOG00000002452
drosophila_melanogaster	Tmx3	FBGN0036579
caenorhabditis_elegans		WBGENE00003962
caenorhabditis_elegans	M04D5.1	WBGENE00014807
caenorhabditis_elegans	ZK973.11	WBGENE00022836

Paralogs (13): ERP44 (ENSG00000023318), PDIA5 (ENSG00000065485), TMX4 (ENSG00000125827), ERP27 (ENSG00000139055), TMX1 (ENSG00000139921), PDIA6 (ENSG00000143870), PDIA4 (ENSG00000155660), TMX3 (ENSG00000166479), PDIA3 (ENSG00000167004), PDILT (ENSG00000169340), PDIA2 (ENSG00000185615), P4HB (ENSG00000185624), TXNDC5 (ENSG00000239264)

Protein

Protein identifiers

Thioredoxin domain-containing protein 11 — Q6PKC3 (reviewed: Q6PKC3)

Alternative names: EF-hand-binding protein 1

All UniProt accessions (4): Q6PKC3, I3L0Q4, I3L1A5, I3L2Z6

UniProt curated annotations — full annotation on UniProt →

Function. May act as a redox regulator involved in DUOX proteins folding. The interaction with DUOX1 and DUOX2 suggest that it belongs to a multiprotein complex constituting the thyroid H(2)O(2) generating system. It is however not sufficient to assist DUOX1 and DUOX2 in H(2)O(2) generation.

Subunit / interactions. Interacts with the cytoplasmic part of DUOX1 and DUOX2. Interacts with TPO and CYBA.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed at low level. Expressed at higher level in thyroid and prostate.

Similarity. Belongs to the protein disulfide isomerase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6PKC3-1	1	yes
Q6PKC3-2	2
Q6PKC3-3	3

RefSeq proteins (5): NP_001290376, NP_001310951, NP_001310953, NP_001310954, NP_056998* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013766	Thioredoxin_domain	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR052792	Thioredoxin_dom-contain_11	Family
IPR058777	TXNDC11_thioredoxin	Domain

Pfam: PF00085, PF26234

UniProt features (16 total): splice variant 3, disulfide bond 2, domain 2, region of interest 2, compositionally biased region 2, chain 1, transmembrane region 1, sequence variant 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PKC3-F1	72.06	0.28

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 (1): 828

Disulfide bonds (2): 469–472, 719–722

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-209968	Thyroxine biosynthesis

MSigDB gene sets: 112 (showing top): TGCGCANK_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, CHANDRAN_METASTASIS_DN, MELLMAN_TUT1_TARGETS_DN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, YANG_BCL3_TARGETS_UP, REACTOME_METABOLISM_OF_AMINE_DERIVED_HORMONES, REACTOME_THYROXINE_BIOSYNTHESIS, FOXD2_TARGET_GENES, FOXJ2_TARGET_GENES, HDAC4_TARGET_GENES, HES2_TARGET_GENES, HMG20B_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amine-derived hormones	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1878 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TXNDC11	EDEM2	Q9BV94	851
TXNDC11	EDEM3	Q9BZQ6	630
TXNDC11	SNN	O75324	557
TXNDC11	DNAJC10	Q8IXB1	521
TXNDC11	MAN1B1	Q9UKM7	490
TXNDC11	EDEM1	Q92611	474
TXNDC11	MYDGF	Q969H8	466
TXNDC11	TXNDC5	Q8NBS9	451
TXNDC11	UGGT1	Q9NYU2	445
TXNDC11	SNX29	Q8TEQ0	440
TXNDC11	ERLEC1	Q96DZ1	438
TXNDC11	SH3BGRL3	Q9H299	435
TXNDC11	PEX11G	Q96HA9	426
TXNDC11	TXN	P10599	420
TXNDC11	DEXI	O95424	411

IntAct

134 interactions, top by confidence:

A	B	Type	Score
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
HTT	TXNDC11	psi-mi:“MI:0915”(physical association)	0.670
TXNDC11	HTT	psi-mi:“MI:0915”(physical association)	0.670
PRPF18	TXNDC11	psi-mi:“MI:0915”(physical association)	0.560
ZNF417	TXNDC11	psi-mi:“MI:0915”(physical association)	0.560
TXNDC11	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
MKRN3	TXNDC11	psi-mi:“MI:0915”(physical association)	0.560
KLHL38	TXNDC11	psi-mi:“MI:0915”(physical association)	0.560
TXNDC11	ZNF417	psi-mi:“MI:0915”(physical association)	0.560
TXNDC11	RAB2B	psi-mi:“MI:0915”(physical association)	0.560
TXNDC11		psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
FGG	KDM1A	psi-mi:“MI:0914”(association)	0.530
ANGPTL7	TCP1	psi-mi:“MI:0914”(association)	0.530
DCT	CANX	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
PBXIP1	KCNN4	psi-mi:“MI:0914”(association)	0.530

BioGRID (122): TXNDC11 (Affinity Capture-RNA), TXNDC11 (Affinity Capture-RNA), TXNDC11 (Affinity Capture-RNA), TXNDC11 (Affinity Capture-MS), TXNDC11 (Affinity Capture-MS), CREBBP (Affinity Capture-MS), TXLNA (Affinity Capture-MS), RBL2 (Affinity Capture-MS), ZNF703 (Affinity Capture-MS), USO1 (Affinity Capture-MS), CCDC102A (Affinity Capture-MS), RBL1 (Affinity Capture-MS), PCNT (Affinity Capture-MS), HAUS4 (Affinity Capture-MS), TXNDC11 (Affinity Capture-MS)

ESM2 similar proteins: A0JPE1, A0JPH4, A2VDJ0, A4D0V7, A4IH36, A6H684, O75129, O88199, O95170, P16047, P23352, P33005, P97793, Q05004, Q08DV9, Q3U095, Q3U3D7, Q52KP5, Q5NDE4, Q5XI89, Q60943, Q68CR1, Q6L8S8, Q6L9W6, Q6PKC3, Q6Q2W4, Q6UWF7, Q7LFX5, Q7T2L7, Q7TN22, Q7Z443, Q80TS8, Q8CHI9, Q8JZL1, Q8K2W3, Q8N323, Q8N6G5, Q8NFM7, Q90369, Q91XQ5

Diamond homologs: A4FUW8, O22263, P08003, P11598, P13667, P27773, P30101, P34329, P38657, P38661, P52588, P52589, P80284, P92981, Q00002, Q10057, Q29RV1, Q43116, Q4VIT4, Q53LQ0, Q5RDG4, Q6PKC3, Q75M08, Q8JG64, Q8K2W3, Q942L2, Q9FF55, Q9MAU6, Q9R6P9, Q9XI01, A0A8M1N5Y4, D3Z6P0, D4B2L8, O13704, O13811, O48773, O96952, P04785, P05307, P07237

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 127 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
ER-Phagosome pathway	6	10.2×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	8	14.3×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	164
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2453 predictions. Top by Δscore:

Variant	Effect	Δscore
16:11687853:TTACC:T	donor_loss	1.0000
16:11687854:TA:T	donor_loss	1.0000
16:11687855:A:AC	donor_gain	1.0000
16:11687855:AC:A	donor_gain	1.0000
16:11687855:ACCT:A	donor_loss	1.0000
16:11687856:C:CA	donor_loss	1.0000
16:11687856:C:CC	donor_gain	1.0000
16:11687856:CC:C	donor_gain	1.0000
16:11687856:CCTTG:C	donor_gain	1.0000
16:11687962:ACGTC:A	acceptor_gain	1.0000
16:11687963:CGTC:C	acceptor_gain	1.0000
16:11687963:CGTCC:C	acceptor_gain	1.0000
16:11687964:GTC:G	acceptor_gain	1.0000
16:11687965:TC:T	acceptor_gain	1.0000
16:11687966:CC:C	acceptor_gain	1.0000
16:11687967:C:CC	acceptor_gain	1.0000
16:11687968:T:A	acceptor_loss	1.0000
16:11698119:TCTTA:T	donor_loss	1.0000
16:11698120:CTTA:C	donor_loss	1.0000
16:11698121:TTACC:T	donor_loss	1.0000
16:11698122:TAC:T	donor_loss	1.0000
16:11698124:C:A	donor_loss	1.0000
16:11698124:CCT:C	donor_gain	1.0000
16:11698322:AGAC:A	acceptor_gain	1.0000
16:11730782:C:CT	acceptor_gain	1.0000
16:11730783:A:T	acceptor_gain	1.0000
16:11733976:TCTTA:T	donor_loss	1.0000
16:11733977:CTTA:C	donor_loss	1.0000
16:11733978:TTA:T	donor_loss	1.0000
16:11733979:TACCT:T	donor_loss	1.0000

AlphaMissense

6262 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:11736080:C:A	W136C	0.999
16:11736080:C:G	W136C	0.999
16:11736082:A:G	W136R	0.999
16:11736082:A:T	W136R	0.999
16:11734056:A:C	C165W	0.998
16:11734059:G:C	N164K	0.998
16:11734059:G:T	N164K	0.998
16:11679784:A:G	L790P	0.997
16:11687927:A:G	C722R	0.997
16:11687956:A:G	L712P	0.997
16:11734057:C:T	C165Y	0.997
16:11734058:A:G	C165R	0.997
16:11736168:A:T	V107D	0.997
16:11698275:C:A	W346C	0.996
16:11698275:C:G	W346C	0.996
16:11698277:A:G	W346R	0.996
16:11698277:A:T	W346R	0.996
16:11734036:C:G	C172S	0.996
16:11734037:A:G	C172R	0.996
16:11734037:A:T	C172S	0.996
16:11734053:C:A	W166C	0.996
16:11734053:C:G	W166C	0.996
16:11736069:G:A	S140F	0.996
16:11679825:A:C	S776R	0.995
16:11679825:A:T	S776R	0.995
16:11679827:T:G	S776R	0.995
16:11687896:A:G	L732P	0.995
16:11687925:A:C	C722W	0.995
16:11721658:C:A	G238W	0.995
16:11734006:G:T	P182H	0.995

dbSNP variants (sampled 300 via entrez): RS1000022319 (16:11702470 C>A), RS1000038569 (16:11742190 A>C), RS1000091654 (16:11707451 C>T), RS1000130010 (16:11707296 G>A), RS1000164885 (16:11706432 G>A,C), RS1000274296 (16:11738889 T>C), RS1000349308 (16:11726107 T>C), RS1000405966 (16:11731476 C>T), RS1000426892 (16:11707611 G>A), RS1000447140 (16:11733426 C>A,G,T), RS1000479711 (16:11733518 C>T), RS1000507884 (16:11740087 G>A), RS1000545418 (16:11721983 C>T), RS1000576467 (16:11721656 C>G,T), RS1000583731 (16:11738984 G>A)

Disease associations

OMIM: gene MIM:617792 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002318_162	Rheumatoid arthritis	9.000000e-09
GCST002318_163	Rheumatoid arthritis	4.000000e-08
GCST006043_1	Plasma renin activity levels	3.000000e-07
GCST006959_115	Rheumatoid arthritis	6.000000e-07
GCST006959_77	Rheumatoid arthritis	5.000000e-07
GCST008152_154	Weight	6.000000e-06
GCST010244_76	Triglyceride levels	2.000000e-09
GCST90002396_578	Mean reticulocyte volume	5.000000e-10
GCST90002397_231	Mean spheric corpuscular volume	7.000000e-11
GCST90002404_335	Red cell distribution width	5.000000e-10
GCST90011900_121	Serum alkaline phosphatase levels	1.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006828	plasma renin activity measurement
EFO:0004338	body weight
EFO:0004530	triglyceride measurement
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630840 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3784921	Efficacy	3	hydrochlorothiazide	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3784921	TXNDC11	3	2.75	1	hydrochlorothiazide

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tunicamycin	increases expression	2
Zinc	affects cotreatment, increases expression	2
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
CGP 52608	increases reaction, affects binding	1
PCI 5002	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4606088	Binding	Activation of TXNDC11 (unknown origin)	Degradation versus Inhibition: Development of Proteolysis-Targeting Chimeras for Overcoming Statin-Induced Compensatory Upregulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase. — J Med Chem

Clinical trials (associated diseases)

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