TXNDC16

Summary

TXNDC16 (thioredoxin domain containing 16, HGNC:19965) is a protein-coding gene on chromosome 14q22.1, encoding Thioredoxin domain-containing protein 16 (Q9P2K2).

Located in endoplasmic reticulum lumen.

Source: NCBI Gene 57544 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 142 total
• MANE Select transcript: NM_020784

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19965
Approved symbol	TXNDC16
Name	thioredoxin domain containing 16
Location	14q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000087301
Ensembl biotype	protein_coding
OMIM	616179
Entrez	57544

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000281741, ENST00000554399, ENST00000555312, ENST00000557374, ENST00000850587, ENST00000850588, ENST00000886893, ENST00000936707, ENST00000936708, ENST00000936709, ENST00000936710, ENST00000936711, ENST00000956219

RefSeq mRNA: 2 — MANE Select: NM_020784 NM_001160047, NM_020784

CCDS: CCDS32083

Canonical transcript exons

ENST00000281741 — 21 exons

Exon	Start	End
ENSE00000657360	52482822	52482965
ENSE00000657368	52511240	52511390
ENSE00000657370	52514880	52514970
ENSE00000854730	52482230	52482289
ENSE00001093416	52537599	52537672
ENSE00001093425	52542371	52542453
ENSE00001093428	52536719	52536793
ENSE00001093432	52519172	52519293
ENSE00001194882	52544264	52544371
ENSE00001194890	52543398	52543630
ENSE00003472394	52488363	52488486
ENSE00003486128	52490839	52491005
ENSE00003587629	52490391	52490451
ENSE00004282235	52439204	52439394
ENSE00004282236	52430596	52432587
ENSE00004282237	52552316	52552505
ENSE00004282238	52440564	52440724
ENSE00004282240	52470037	52470173
ENSE00004282241	52457090	52457174
ENSE00004282243	52455324	52455462
ENSE00004282244	52470512	52470680

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 93.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9697 / max 182.7254, expressed in 1545 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143251	8.9697	1545

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	93.34	gold quality
corpus epididymis	UBERON:0004359	91.27	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.66	gold quality
ganglionic eminence	UBERON:0004023	87.45	gold quality
ileal mucosa	UBERON:0000331	86.86	gold quality
cortical plate	UBERON:0005343	86.66	gold quality
calcaneal tendon	UBERON:0003701	86.28	gold quality
cauda epididymis	UBERON:0004360	85.88	gold quality
ventricular zone	UBERON:0003053	85.81	gold quality
secondary oocyte	CL:0000655	84.30	gold quality
cartilage tissue	UBERON:0002418	84.30	gold quality
postcentral gyrus	UBERON:0002581	84.13	gold quality
upper leg skin	UBERON:0004262	84.09	gold quality
tibia	UBERON:0000979	83.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.06	gold quality
pigmented layer of retina	UBERON:0001782	82.66	gold quality
corpus callosum	UBERON:0002336	82.57	gold quality
superior frontal gyrus	UBERON:0002661	82.56	gold quality
caput epididymis	UBERON:0004358	82.06	gold quality
prostate gland	UBERON:0002367	81.94	gold quality
parietal lobe	UBERON:0001872	81.82	gold quality
upper arm skin	UBERON:0004263	81.70	silver quality
entorhinal cortex	UBERON:0002728	81.57	gold quality
urethra	UBERON:0000057	81.53	gold quality
prefrontal cortex	UBERON:0000451	80.62	gold quality
germinal epithelium of ovary	UBERON:0001304	80.59	gold quality
skin of hip	UBERON:0001554	80.41	gold quality
cerebellar cortex	UBERON:0002129	80.02	gold quality
cerebellar hemisphere	UBERON:0002245	79.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting TXNDC16, 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-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
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-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-187-5P	99.74	70.26	1404

Literature-anchored findings (GeneRIF, showing 2)

• The function of ERp90 is related to substrate recruitment or delivery to the ERAD retrotranslocation machinery by ERFAD. (PMID:21359175)
• in addition to reported occurrence as a soluble endoplasmic reticulum-luminal glycoprotein, TXNDC16 shows endoplasmic reticulum-associated subcellular localization in cytosol, as confirmed by confocal microscopy, molecular mass shift, flow cytometry (PMID:25122923)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	txndc16	ENSDARG00000032256
mus_musculus	Txndc16	ENSMUSG00000021830
rattus_norvegicus	Txndc16	ENSRNOG00000006334

Protein

Protein identifiers

Thioredoxin domain-containing protein 16 — Q9P2K2 (reviewed: Q9P2K2)

All UniProt accessions (4): Q9P2K2, B7ZME4, G3V2S5, H0YJI6

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with FOXRED2.

Subcellular location. Secreted. Endoplasmic reticulum lumen.

Post-translational modifications. Glycosylated.

Domain organisation. Contains a masked and non-functional KDEL endoplasmic reticulum retrieval motif.

RefSeq proteins (2): NP_001153519, NP_065835* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013766	Thioredoxin_domain	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR040090	TXNDC16	Family
IPR057639	TXNDC16_N	Domain
IPR057642	TXNDC16_2nd	Domain
IPR057645	TXNDC16_3rd	Domain

Pfam: PF00085, PF13848, PF24508, PF24509, PF24510

UniProt features (12 total): sequence variant 3, signal peptide 1, chain 1, sequence conflict 1, domain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2K2-F1	80.51	0.51

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 (1): 449–456

Glycosylation sites (1): 460

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 165 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, MODULE_503, MODULE_195, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, MODULE_147, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_0, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, MODULE_356, BURTON_ADIPOGENESIS_9, MODULE_332, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, NIKOLSKY_BREAST_CANCER_14Q22_AMPLICON, MCBRYAN_PUBERTAL_BREAST_4_5WK_UP, WONG_ADULT_TISSUE_STEM_MODULE

GO Biological Process (0):

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

GO Cellular Component (5): endoplasmic reticulum lumen (GO:0005788), extracellular exosome (GO:0070062), extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
endoplasmic reticulum	1
intracellular organelle lumen	1
extracellular vesicle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1267 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TXNDC16	FOXRED2	Q8IWF2	748
TXNDC16	GPR137C	Q8N3F9	640
TXNDC16	STYX	Q8WUJ0	576
TXNDC16	DDHD1	Q8NEL9	524
TXNDC16	PSMC6	P49719	478
TXNDC16	NIPAL2	Q9H841	476
TXNDC16	DNAJC10	Q8IXB1	464
TXNDC16	SEL1L	Q9UBV2	462
TXNDC16	STXBP4	Q6ZWJ1	460
TXNDC16	RTRAF	Q9Y224	455
TXNDC16	ERLEC1	Q96DZ1	438
TXNDC16	HOXD1	Q9GZZ0	437
TXNDC16	OS9	Q13438	436
TXNDC16	KHK	P50053	418
TXNDC16	PABIR3	Q6P4D5	412

IntAct

55 interactions, top by confidence:

A	B	Type	Score
TXNDC16	FOXRED2	psi-mi:“MI:0914”(association)	0.730
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
PRG3	ZNF324	psi-mi:“MI:0914”(association)	0.530
FOXRED2	TOMM40	psi-mi:“MI:0914”(association)	0.530
SCGB1D4	EGFR	psi-mi:“MI:0914”(association)	0.530
FOXRED2	CLGN	psi-mi:“MI:0914”(association)	0.530
TXNDC16	DLD	psi-mi:“MI:0915”(physical association)	0.400
EXOSC4	RPS3	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
SUSD4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350
GGH	TGOLN2	psi-mi:“MI:0914”(association)	0.350
INSL5	LAMA5	psi-mi:“MI:0914”(association)	0.350
LYZL2	MANBA	psi-mi:“MI:0914”(association)	0.350
DNASE2B		psi-mi:“MI:0914”(association)	0.350
CALR3	CLN5	psi-mi:“MI:0914”(association)	0.350
FOXRED2	CASK	psi-mi:“MI:0914”(association)	0.350
TXNDC16	FLNA	psi-mi:“MI:0914”(association)	0.350
TXNDC16	ENO1	psi-mi:“MI:0914”(association)	0.350
	PLOD2	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): TXNDC16 (Affinity Capture-MS), FLNA (Affinity Capture-MS), RPL35 (Affinity Capture-MS), PPIB (Affinity Capture-MS), ENO1 (Affinity Capture-MS), HNRNPU (Affinity Capture-MS), HNRNPA2B1 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), MCM2 (Affinity Capture-MS), TAGLN2 (Affinity Capture-MS), FOXRED2 (Affinity Capture-MS), MARCKS (Affinity Capture-MS), TXNDC16 (Affinity Capture-MS), TXNDC16 (Affinity Capture-MS), TXNDC16 (Proximity Label-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: Q7TN22, Q9P2K2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	6	19.8×	3e-04
positive regulation of cell migration	7	7.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4128 predictions. Top by Δscore:

Variant	Effect	Δscore
14:52432583:AATTG:A	acceptor_gain	1.0000
14:52432584:ATTG:A	acceptor_gain	1.0000
14:52432585:T:TC	acceptor_gain	1.0000
14:52432585:TTG:T	acceptor_loss	1.0000
14:52432586:TG:T	acceptor_gain	1.0000
14:52432587:GC:G	acceptor_loss	1.0000
14:52432588:C:CC	acceptor_gain	1.0000
14:52432588:C:T	acceptor_loss	1.0000
14:52439197:AACTT:A	donor_loss	1.0000
14:52439198:ACTT:A	donor_loss	1.0000
14:52439199:CTTAC:C	donor_loss	1.0000
14:52439200:TTA:T	donor_loss	1.0000
14:52439201:TACTG:T	donor_loss	1.0000
14:52439202:A:AC	donor_gain	1.0000
14:52439202:ACTGA:A	donor_loss	1.0000
14:52439203:C:CA	donor_gain	1.0000
14:52439203:C:G	donor_loss	1.0000
14:52439203:CT:C	donor_gain	1.0000
14:52439203:CTG:C	donor_gain	1.0000
14:52439203:CTGA:C	donor_gain	1.0000
14:52439203:CTGAT:C	donor_gain	1.0000
14:52439319:C:CT	acceptor_gain	1.0000
14:52439391:CTTT:C	acceptor_gain	1.0000
14:52439395:C:CC	acceptor_gain	1.0000
14:52440558:A:AC	donor_gain	1.0000
14:52440558:ACT:A	donor_loss	1.0000
14:52440559:C:CC	donor_gain	1.0000
14:52440559:CTTA:C	donor_gain	1.0000
14:52440560:TTACA:T	donor_loss	1.0000
14:52440561:T:TG	donor_loss	1.0000

AlphaMissense

5426 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:52490894:C:G	A290P	0.983
14:52482822:A:G	W418R	0.982
14:52482822:A:T	W418R	0.982
14:52470530:A:G	L488P	0.979
14:52536732:C:G	A127P	0.978
14:52470627:A:G	C456R	0.977
14:52536722:A:G	L130P	0.977
14:52440702:A:G	L622P	0.976
14:52470625:A:C	C456W	0.976
14:52470646:A:C	C449W	0.976
14:52514946:G:T	A180D	0.976
14:52470648:A:G	C449R	0.974
14:52470626:C:G	C456S	0.973
14:52470627:A:T	C456S	0.973
14:52482288:C:A	W418C	0.973
14:52482288:C:G	W418C	0.973
14:52482836:A:G	L413P	0.973
14:52514918:A:C	F189L	0.973
14:52514918:A:T	F189L	0.973
14:52514920:A:G	F189L	0.973
14:52542399:A:G	L72P	0.973
14:52470599:G:T	P465H	0.972
14:52536741:C:G	A124P	0.972
14:52542420:A:G	L65P	0.972
14:52514950:C:G	A179P	0.971
14:52470626:C:T	C456Y	0.970
14:52432538:A:C	F748L	0.968
14:52432538:A:T	F748L	0.968
14:52432540:A:G	F748L	0.968
14:52470599:G:C	P465R	0.968

dbSNP variants (sampled 300 via entrez): RS1000012538 (14:52458013 A>G), RS1000053779 (14:52510513 T>A), RS1000058716 (14:52492742 C>A), RS1000063079 (14:52465449 G>A,C), RS1000076652 (14:52435721 G>A,C), RS1000080834 (14:52509575 T>C), RS1000085420 (14:52458279 C>G), RS1000176890 (14:52447532 C>T), RS1000195458 (14:52527933 A>G), RS1000211031 (14:52464408 T>G), RS1000242678 (14:52527755 T>G), RS1000254805 (14:52515997 T>A,G), RS1000287004 (14:52519951 T>A), RS1000309508 (14:52505396 C>T), RS1000315868 (14:52521839 A>C)

Disease associations

OMIM: gene MIM:616179 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001442_15	Orofacial clefts	8.000000e-07
GCST001942_15	Prostate cancer	2.000000e-14
GCST002361_27	Smooth-surface caries	2.000000e-06
GCST011346_26	Total cholesterol levels	3.000000e-09
GCST011347_46	Low density lipoprotein cholesterol levels	3.000000e-09
GCST012020_144	Serum metabolite levels	5.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Valproic Acid	affects expression, increases expression	3
Acetaminophen	increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
methylmercuric chloride	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression	1
Azathioprine	decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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