TMX1

Summary

TMX1 (thioredoxin related transmembrane protein 1, HGNC:15487) is a protein-coding gene on chromosome 14q22.1, encoding Thioredoxin-related transmembrane protein 1 (Q9H3N1). Thiredoxin domain-containing protein that participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyze dithiol-disulfide exchange reactions.

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 ER-signal sequence, a catalytically active thioredoxin domain, and one transmembrane domain. Unlike most members of this gene family, it lacks a C-terminal ER-retention sequence. The mature membrane-bound protein can both oxidize and reduce disulfide bonds and acts selectively on membrane-associated polypeptides.

Source: NCBI Gene 81542 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 46 total
• Druggable target: yes
• MANE Select transcript: NM_030755

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15487
Approved symbol	TMX1
Name	thioredoxin related transmembrane protein 1
Location	14q22.1
Locus type	gene with protein product
Status	Approved
Aliases	TMX, PDIA11
Ensembl gene	ENSG00000139921
Ensembl biotype	protein_coding
OMIM	610527
Entrez	81542

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000457354, ENST00000555574, ENST00000556683, ENST00000898229, ENST00000898230, ENST00000911263

RefSeq mRNA: 1 — MANE Select: NM_030755 NM_030755

CCDS: CCDS41953

Canonical transcript exons

ENST00000457354 — 8 exons

Exon	Start	End
ENSE00000940750	51240247	51240444
ENSE00000940751	51243856	51243971
ENSE00000940752	51245313	51245358
ENSE00001672064	51254341	51257655
ENSE00003547421	51247092	51247220
ENSE00003572472	51249326	51249371
ENSE00003582649	51249468	51249569
ENSE00003655599	51249693	51249765

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.9831 / max 401.7352, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139516	72.9831	1822

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	98.34	gold quality
skin of hip	UBERON:0001554	97.23	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.16	gold quality
germinal epithelium of ovary	UBERON:0001304	96.88	gold quality
trabecular bone tissue	UBERON:0002483	96.82	gold quality
oral cavity	UBERON:0000167	96.81	gold quality
colonic mucosa	UBERON:0000317	96.70	gold quality
upper leg skin	UBERON:0004262	96.59	gold quality
jejunal mucosa	UBERON:0000399	96.48	gold quality
superficial temporal artery	UBERON:0001614	96.02	gold quality
esophagus squamous epithelium	UBERON:0006920	95.97	gold quality
secondary oocyte	CL:0000655	95.89	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.86	gold quality
tendon of biceps brachii	UBERON:0008188	95.75	gold quality
pigmented layer of retina	UBERON:0001782	95.63	gold quality
choroid plexus epithelium	UBERON:0003911	95.40	gold quality
monocyte	CL:0000576	95.36	gold quality
periodontal ligament	UBERON:0008266	95.27	gold quality
mononuclear cell	CL:0000842	95.25	gold quality
mammary duct	UBERON:0001765	95.20	gold quality
penis	UBERON:0000989	95.14	gold quality
calcaneal tendon	UBERON:0003701	95.09	gold quality
gingiva	UBERON:0001828	95.07	gold quality
seminal vesicle	UBERON:0000998	94.98	gold quality
leukocyte	CL:0000738	94.88	gold quality
epithelium of mammary gland	UBERON:0003244	94.87	gold quality
epithelium of nasopharynx	UBERON:0001951	94.86	gold quality
epithelium of esophagus	UBERON:0001976	94.85	gold quality
islet of Langerhans	UBERON:0000006	94.69	gold quality
gingival epithelium	UBERON:0001949	94.69	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	14.58
E-GEOD-75367	no	205.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

168 targeting TMX1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 10)

• These results suggest a specific role for transmembrane thioredoxin-related protein TMX and its mechanism of action in redox-based ER quality control. (PMID:19741092)
• TMX1 is enriched on the mitochondria-associated membrane. Targeting TMX to the MAM requires palmitoylation of two membrane-proximal cytosolic cysteines. (PMID:22045338)
• the silencing of TMX in the prostatic cell line DU145 reduced the sensitivity of the cells to ricin intoxication further confirming a role for this enzyme in intracellular ricin activation. (PMID:22228764)
• We conclude that TMX plays a major role in host defense under the type of inflammatory conditions associated with oxidative stress. (PMID:22924822)
• Here we show that TMX1, one of the few transmembrane members of the family, forms functional complexes with the ER lectin calnexin and preferentially intervenes during maturation of cysteine-containing, membrane-associated proteins (PMID:26246604)
• TMX1 increases mitochondrial ATP production and apoptosis progression. (PMID:27502484)
• TMX1 selectively intervenes in clearance of membrane-tethered Endoplasmic Reticulum-Associated Degradation substrates. TMX1 preferentially acts on membrane-tethered folding-defective polypeptides essentially ignoring the same misfolded ectodomains, when not associated to the Endoplasmic Reticulum membrane. (PMID:29932915)
• Data show that TMX1 expression is upregulated in melanoma cell lines and patient samples. TMX knockdown altered mitochondrial organization, enhanced bioenergetics, and elevated mitochondrial- and NOX4-derived ROS. The TMX-knockdown-induced oxidative stress suppressed melanoma proliferation, migration, and xenograft tumor growth by inhibiting NFAT1. TMX1 is associated with poor disease outcome. (PMID:31304984)
• Thiol Isomerases Orchestrate Thrombosis and Hemostasis. (PMID:33940944)
• TMX family genes and their association with prognosis, immune infiltration, and chemotherapy in human pan-cancer. (PMID:38147024)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmx1	ENSDARG00000019487
mus_musculus	Tmx1	ENSMUSG00000021072
rattus_norvegicus	Tmx1	ENSRNOG00000057934
drosophila_melanogaster	ERp60	FBGN0033663
drosophila_melanogaster	Tmx3	FBGN0036579
drosophila_melanogaster	Pdi	FBGN0286818
caenorhabditis_elegans		WBGENE00003962
caenorhabditis_elegans		WBGENE00003963
caenorhabditis_elegans	pdi-3	WBGENE00003964
caenorhabditis_elegans	M04D5.1	WBGENE00014807
caenorhabditis_elegans	ZK973.11	WBGENE00022836

Paralogs (13): ERP44 (ENSG00000023318), PDIA5 (ENSG00000065485), TMX4 (ENSG00000125827), ERP27 (ENSG00000139055), PDIA6 (ENSG00000143870), TXNDC11 (ENSG00000153066), PDIA4 (ENSG00000155660), TMX3 (ENSG00000166479), PDIA3 (ENSG00000167004), PDILT (ENSG00000169340), PDIA2 (ENSG00000185615), P4HB (ENSG00000185624), TXNDC5 (ENSG00000239264)

Protein

Protein identifiers

Thioredoxin-related transmembrane protein 1 — Q9H3N1 (reviewed: Q9H3N1)

Alternative names: Protein disulfide-isomerase TMX1, Thioredoxin domain-containing protein 1, Transmembrane Trx-related protein

All UniProt accessions (2): Q9H3N1, G3V448

UniProt curated annotations — full annotation on UniProt →

Function. Thiredoxin domain-containing protein that participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyze dithiol-disulfide exchange reactions. Acts as a key inhibitor of the alternative triglyceride biosynthesis pathway by inhibiting the activity of TMEM68/DIESL at the endoplasmic reticulum, thereby restricting accumulation of triacylglycerol. The alternative triglyceride biosynthesis pathway mediates formation of triacylglycerol from diacylglycerol and membrane phospholipids. Acts as a protein disulfide isomerase by catalyzing formation or reduction of disulfide bonds. Specifically mediates formation of disulfide bonds of transmembrane proteins at the endoplasmic reticulum membrane. Involved in endoplasmic reticulum-associated degradation (ERAD) via its protein disulfide isomerase activity by acting on folding-defective polypeptides at the endoplasmic reticulum membrane. Acts as a negative regulator of platelet aggregation following secretion in the extracellular space. Acts as a regulator of endoplasmic reticulum-mitochondria contact sites via its ability to regulate redox signals. Regulates endoplasmic reticulum-mitochondria Ca(2+) flux.

Subunit / interactions. Interacts with ATP2A2.

Subcellular location. Endoplasmic reticulum membrane. Mitochondrion membrane. Secreted.

Tissue specificity. Ubiquitous. Highly expressed in kidney, liver, placenta and lung.

Post-translational modifications. Palmitoylated; palmitoylation is required for localization to mitochondria-associated endoplasmic reticulum membrane (MAM).

Miscellaneous. Mediates reduction of intermolecular disulfide bonds between chain A and B of Ricin toxin (Ricin A chain and Ricin B chain, respectively), thereby releasing and activating Ricin A chain.

RefSeq proteins (1): NP_110382* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013766	Thioredoxin_domain	Domain
IPR017937	Thioredoxin_CS	Conserved_site
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR052454	TMX_domain-containing	Family

Pfam: PF00085

UniProt features (37 total): helix 6, modified residue 5, strand 5, mutagenesis site 3, sequence conflict 3, lipid moiety-binding region 2, topological domain 2, turn 2, active site 2, signal peptide 1, chain 1, disulfide bond 1, transmembrane region 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1X5E	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3N1-F1	76.95	0.59

Functional residue map

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

Catalytic / active sites (2): 56 (nucleophile); 59 (nucleophile)

Post-translational modifications (7): 228, 247, 270, 274, 280, 205, 207

Disulfide bonds (1): 56–59

Mutagenesis-validated functional residues (3):

Position	Phenotype
56	loss of reductase activity and ability to inhibit tmem68/diesl; when associated with s-59.
59	loss of reductase activity and ability to inhibit tmem68/diesl; when associated with s-56.
205–207	abolished palmitoylation, leading to decreased localization to mitochondria-associated endoplasmic reticulum membrane (m

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 261 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, TAATAAT_MIR126, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_WOUND_HEALING, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_REGULATION_OF_COAGULATION, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PLATELET_ACTIVATION, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_PLATELET_ACTIVATION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (6): negative regulation of triglyceride biosynthetic process (GO:0010868), response to endoplasmic reticulum stress (GO:0034976), regulation of calcium ion transport (GO:0051924), negative regulation of platelet aggregation (GO:0090331), positive regulation of ERAD pathway (GO:1904294), triglyceride biosynthetic process (GO:0019432)

GO Molecular Function (6): protein disulfide isomerase activity (GO:0003756), enzyme inhibitor activity (GO:0004857), protein-disulfide reductase activity (GO:0015035), disulfide oxidoreductase activity (GO:0015036), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (8): extracellular region (GO:0005576), endoplasmic reticulum membrane (GO:0005789), endomembrane system (GO:0012505), mitochondrial membrane (GO:0031966), mitochondria-associated endoplasmic reticulum membrane contact site (GO:0044233), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

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
organelle membrane	2
cytoplasm	2
intracellular membrane-bounded organelle	2
regulation of triglyceride biosynthetic process	1
triglyceride biosynthetic process	1
negative regulation of lipid biosynthetic process	1
negative regulation of triglyceride metabolic process	1
cellular response to stress	1
calcium ion transport	1
regulation of metal ion transport	1
negative regulation of platelet activation	1
negative regulation of homotypic cell-cell adhesion	1
platelet aggregation	1
regulation of platelet aggregation	1
ERAD pathway	1
positive regulation of proteasomal protein catabolic process	1
regulation of ERAD pathway	1
positive regulation of response to endoplasmic reticulum stress	1
triglyceride metabolic process	1
acylglycerol biosynthetic process	1
intramolecular oxidoreductase activity, transposing S-S bonds	1
enzyme regulator activity	1
molecular function inhibitor activity	1
disulfide oxidoreductase activity	1
oxidoreductase activity, acting on a sulfur group of donors	1
binding	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vacuole	1
plasma membrane	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane contact site	1
endomembrane system	1

Protein interactions and networks

STRING

1934 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMX1	TXN	P10599	818
TMX1	CANX	P27824	718
TMX1	TMX2	Q9Y320	678
TMX1	TXNDC15	Q96J42	533
TMX1	TXNDC12	O95881	489
TMX1	ERP27	Q96DN0	486
TMX1	PDILT	Q8N807	457
TMX1	CCDC90B	Q9GZT6	456
TMX1	AGR3	Q8TD06	453
TMX1	TRMT1L	Q7Z2T5	430
TMX1	TXNL1	O43396	426
TMX1	TRAM2	Q15035	413
TMX1	INS	P01308	413
TMX1	PACS2	Q86VP3	412
TMX1	ERP29	P30040	409

IntAct

187 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
GET3	TMX1	psi-mi:“MI:0915”(physical association)	0.560
GIMAP1	TMX1	psi-mi:“MI:0915”(physical association)	0.560
FKBP8	TMX1	psi-mi:“MI:0915”(physical association)	0.560
LHFPL5	TMX1	psi-mi:“MI:0915”(physical association)	0.560
BCL2L2	TMX1	psi-mi:“MI:0915”(physical association)	0.560
GIMAP5	TMX1	psi-mi:“MI:0915”(physical association)	0.560
CCR1	TMX1	psi-mi:“MI:0915”(physical association)	0.560
PMP22	TMX1	psi-mi:“MI:0915”(physical association)	0.560
SOD1	TMX1	psi-mi:“MI:0915”(physical association)	0.560
MMP14	TIMP2	psi-mi:“MI:0914”(association)	0.560
TMX1	NRP1	psi-mi:“MI:0914”(association)	0.530
LYPD6	PLXNB2	psi-mi:“MI:0914”(association)	0.530
SNN	MTDH	psi-mi:“MI:0914”(association)	0.530
BTN2A1	POTEF	psi-mi:“MI:0914”(association)	0.530
TSPAN3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
VASN	AP3B1	psi-mi:“MI:0914”(association)	0.530
IGSF8	CLGN	psi-mi:“MI:0914”(association)	0.530
IL27RA	B4GALT5	psi-mi:“MI:0914”(association)	0.530
IZUMO1	ADCY3	psi-mi:“MI:0914”(association)	0.530
OCLN	DNAJC13	psi-mi:“MI:0914”(association)	0.530
COLEC12	CSPG5	psi-mi:“MI:0914”(association)	0.530

BioGRID (360): TMX1 (Affinity Capture-MS), LMAN1 (Co-fractionation), SSR1 (Co-fractionation), TMX1 (Co-fractionation), TXN (Co-fractionation), VDAC1 (Co-fractionation), VDAC2 (Co-fractionation), VDAC3 (Co-fractionation), TMX1 (Proximity Label-MS), TMX1 (Proximity Label-MS), TMX1 (Proximity Label-MS), TMX1 (Proximity Label-MS), TMX1 (Proximity Label-MS), TMX1 (Proximity Label-MS), TMX1 (Proximity Label-MS)

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 200 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
DAP12 signaling	6	15.6×	3e-04
Synthesis of PC	5	14.4×	1e-03
Transport of vitamins, nucleosides, and related molecules	7	13.4×	3e-04
Signaling by SCF-KIT	6	10.5×	1e-03
SLC-mediated transmembrane transport	10	4.2×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
sodium-independent organic anion transport	6	38.5×	8e-06
transmembrane transport	9	8.7×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1282 predictions. Top by Δscore:

Variant	Effect	Δscore
14:51240440:GAATT:G	donor_gain	1.0000
14:51240445:G:GG	donor_gain	1.0000
14:51243854:A:AG	acceptor_gain	1.0000
14:51243855:G:GG	acceptor_gain	1.0000
14:51243855:GTT:G	acceptor_gain	1.0000
14:51243855:GTTAT:G	acceptor_gain	1.0000
14:51243972:GTACT:G	donor_gain	1.0000
14:51245307:TTGTA:T	acceptor_loss	1.0000
14:51245308:TGTAG:T	acceptor_loss	1.0000
14:51245309:GTA:G	acceptor_loss	1.0000
14:51245310:TA:T	acceptor_loss	1.0000
14:51245311:A:AC	acceptor_loss	1.0000
14:51245312:GGACT:G	acceptor_gain	1.0000
14:51245359:G:GG	donor_gain	1.0000
14:51247090:A:AG	acceptor_gain	1.0000
14:51247091:G:GG	acceptor_gain	1.0000
14:51247091:GTT:G	acceptor_gain	1.0000
14:51247216:GTTCT:G	donor_gain	1.0000
14:51247217:TTCT:T	donor_gain	1.0000
14:51247218:TCT:T	donor_gain	1.0000
14:51247219:CT:C	donor_gain	1.0000
14:51247220:TG:T	donor_loss	1.0000
14:51247221:G:GG	donor_gain	1.0000
14:51247221:G:T	donor_loss	1.0000
14:51247222:T:G	donor_loss	1.0000
14:51247223:AAGTA:A	donor_loss	1.0000
14:51247224:A:AC	donor_loss	1.0000
14:51247225:G:C	donor_loss	1.0000
14:51249462:TTTTA:T	acceptor_loss	1.0000
14:51249463:TTTAG:T	acceptor_loss	1.0000

AlphaMissense

1820 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:51243868:G:C	W55C	1.000
14:51243868:G:T	W55C	1.000
14:51243901:G:C	W66C	1.000
14:51243901:G:T	W66C	1.000
14:51240443:T:C	F51L	0.999
14:51243856:T:A	F51L	0.999
14:51243856:T:G	F51L	0.999
14:51243866:T:A	W55R	0.999
14:51243866:T:C	W55R	0.999
14:51243869:T:C	C56R	0.999
14:51243879:G:A	C59Y	0.999
14:51243899:T:A	W66R	0.999
14:51243899:T:C	W66R	0.999
14:51245327:T:C	F95L	0.999
14:51245328:T:C	F95S	0.999
14:51245329:T:A	F95L	0.999
14:51245329:T:G	F95L	0.999
14:51245343:T:A	L100H	0.999
14:51245345:C:A	P101T	0.999
14:51245345:C:T	P101S	0.999
14:51245346:C:A	P101H	0.999
14:51243861:C:A	A53D	0.998
14:51243869:T:A	C56S	0.998
14:51243870:G:A	C56Y	0.998
14:51243870:G:C	C56S	0.998
14:51243871:C:G	C56W	0.998
14:51243878:T:C	C59R	0.998
14:51243879:G:T	C59F	0.998
14:51243880:T:G	C59W	0.998
14:51243957:T:A	V85D	0.998

dbSNP variants (sampled 300 via entrez): RS1000023351 (14:51247477 C>T), RS1000052998 (14:51249727 C>T), RS1000135242 (14:51253415 A>G), RS1000166520 (14:51238852 G>A,C), RS1000236620 (14:51241241 A>T), RS1000242540 (14:51247593 G>A), RS1000292016 (14:51243533 T>C), RS1000484461 (14:51253117 C>A,G), RS1000840950 (14:51241778 T>G), RS1001011710 (14:51246040 A>G), RS1001027231 (14:51252136 A>G), RS1001092015 (14:51251568 T>C), RS1001272294 (14:51250212 C>G), RS1001343188 (14:51254770 T>C), RS1001544731 (14:51251919 A>G)

Disease associations

OMIM: gene MIM:610527 | 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
GCST003445_12	Response to cyclophosphamide in systemic lupus erythematosus with lupus nephritis	7.000000e-06
GCST004088_11	Nonsyndromic cleft lip with or without cleft palate	2.000000e-07
GCST004088_12	Nonsyndromic cleft lip with or without cleft palate	7.000000e-10
GCST005275_24	Cancer	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003959	cleft lip

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295941 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Air Pollutants	increases abundance, decreases expression, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
kojic acid	decreases expression	1
quercitrin	decreases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Coumestrol	increases expression, affects cotreatment	1
Dietary Carbohydrates	increases expression	1
Doxorubicin	decreases expression	1
Environmental Pollutants	affects expression	1
Estradiol	increases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118784	Binding	Binding affinity to TMX1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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