TAC1

Summary

TAC1 (tachykinin precursor 1, HGNC:11517) is a protein-coding gene on chromosome 7q21.3, encoding Protachykinin-1 (P20366). Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles.

This gene encodes four products of the tachykinin peptide hormone family, substance P and neurokinin A, as well as the related peptides, neuropeptide K and neuropeptide gamma. These hormones are thought to function as neurotransmitters which interact with nerve receptors and smooth muscle cells. They are known to induce behavioral responses and function as vasodilators and secretagogues. Substance P is an antimicrobial peptide with antibacterial and antifungal properties. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6863 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_003182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11517
Approved symbol	TAC1
Name	tachykinin precursor 1
Location	7q21.3
Locus type	gene with protein product
Status	Approved
Aliases	NPK
Ensembl gene	ENSG00000006128
Ensembl biotype	protein_coding
OMIM	162320
Entrez	6863

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000319273, ENST00000346867, ENST00000350485, ENST00000491437, ENST00000495916, ENST00000864055, ENST00000926836, ENST00000962701

RefSeq mRNA: 4 — MANE Select: NM_003182 NM_003182, NM_013996, NM_013997, NM_013998

CCDS: CCDS5649, CCDS5650, CCDS5651

Canonical transcript exons

ENST00000319273 — 7 exons

Exon	Start	End
ENSE00000918961	97733723	97733819
ENSE00000918962	97734248	97734292
ENSE00001039794	97739874	97740472
ENSE00001039798	97732604	97732735
ENSE00001957284	97732086	97732195
ENSE00003504502	97734826	97734849
ENSE00003633466	97736299	97736352

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 99.37.

FANTOM5 (CAGE): breadth broad, TPM avg 4.3450 / max 452.3702, expressed in 336 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79804	3.5411	297
79805	0.2238	103
79800	0.1973	94
79802	0.1906	62
79801	0.1087	43
79803	0.0835	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	99.37	gold quality
lateral globus pallidus	UBERON:0002476	98.25	gold quality
endothelial cell	CL:0000115	98.13	gold quality
putamen	UBERON:0001874	98.07	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.03	gold quality
caudate nucleus	UBERON:0001873	97.89	gold quality
nucleus accumbens	UBERON:0001882	97.57	gold quality
middle frontal gyrus	UBERON:0002702	97.24	gold quality
trigeminal ganglion	UBERON:0001675	94.16	gold quality
superior vestibular nucleus	UBERON:0007227	93.40	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.70	gold quality
tibial nerve	UBERON:0001323	91.55	gold quality
hypothalamus	UBERON:0001898	91.20	gold quality
prefrontal cortex	UBERON:0000451	90.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.86	gold quality
ventral tegmental area	UBERON:0002691	89.30	gold quality
CA1 field of hippocampus	UBERON:0003881	89.19	gold quality
cingulate cortex	UBERON:0003027	89.12	gold quality
anterior cingulate cortex	UBERON:0009835	89.06	gold quality
spleen	UBERON:0002106	88.75	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.29	gold quality
telencephalon	UBERON:0001893	88.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.24	gold quality
Brodmann (1909) area 10	UBERON:0013541	86.74	gold quality
frontal cortex	UBERON:0001870	86.29	gold quality
cerebral cortex	UBERON:0000956	86.09	gold quality
neocortex	UBERON:0001950	86.05	gold quality
Ammon’s horn	UBERON:0001954	86.05	gold quality
orbitofrontal cortex	UBERON:0004167	85.93	gold quality
inferior olivary complex	UBERON:0002127	85.90	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	8611.40
E-MTAB-8894	yes	2263.17
E-GEOD-81383	yes	1233.36
E-HCAD-5	yes	778.85
E-MTAB-7008	yes	96.51
E-HCAD-30	no	140.99
E-ANND-3	no	3.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CREB1, CREM, FOS, GATA1, GATA2, GLI3, JUN, MAX, MEF2C, NCOA1, NFKB1, NFKB, RELA, REST, SP1, TCF12, TFAP2A, TP53, TTF1, TXK, USF1, ZFPM1, ZNF335

miRNA regulators (miRDB)

48 targeting TAC1, 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-3646	100.00	73.56	5283
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-203A-3P	99.49	70.56	2806

Literature-anchored findings (GeneRIF, showing 40)

• We report on an HD phenocopy with selective loss of preprotachykinin (PPT) neurons, dysfunction of surviving PPT neurons, preservation of preproenkephalin (PPE) neurons within the striatum. (PMID:11921119)
• Involvement of the second extracellular loop (E2) of the neurokinin-1 receptor in the binding of substance P (PMID:11950831)
• The antimicrobial peptide substance P has activity against invasive bacteria and fungi. (PMID:12074933)
• Substance P up-regulates the TGF-beta 1 mRNA expression of human dermal fibroblasts in vitro (PMID:12382579)
• Substance P induced intracellular signalling in Caco-2 cells. It induced the activation of the mitogen-activated protein kinases in a time- and dose-dependent manner. (PMID:12383866)
• REVIEW: Substance p-fibronectin-cytokine interactions in myeloproliferative disorders with bone marrow fibrosis. (PMID:12486316)
• Substance P is expressed in human articular cartilage and is involved in chondrocyte mechanotransduction via the NK1 receptor in an autocrine and paracrine manner. (PMID:12528114)
• Substance P expressed in NT2-N neuronal cells is functionally involved in the regulation of macrophage inflammatory protein 1 beta and may play a major role in modulating neuronal functions related to immune regulatory activities within the CNS. (PMID:12548712)
• The release of substance P is higher during the first 12 hours after a cerebral ischemia attack, decreasing later but remaining high compared to controls. (PMID:12578734)
• a role for substance P and its receptor, neurokinin NK(1) receptor, in the brainstem nuclei in the development of emesis (review) (PMID:12686752)
• Expression of substance P was studied in neoplastic cells of childhood acute lymphocytic leukemia. It was detected in the cytoplasm of blasts in leukemias of the common and T-lymphocyte cell types. (PMID:12705477)
• correlation between SP levels and diarrhea severity in cryptosporidiosis; may imply that SP plays a role in diarrhea mediation (PMID:12854086)
• This review points out a distinct role for full-length peptide substance P by reducing excessive excitation in the activity-dependent modulation of cholinergic neurotransmission. (PMID:12871824)
• substance P receptor dimerization with micro-opioid receptor, sequestering MOR-1 via an endocytotic pathway with delayed recycling and resensitization kinetics. (PMID:14532289)
• Elevated substance P in nasal lavage fluid associated with increased cough sensitivity in patients with chronic nonproductive cough. Neurochemical abnormality in upper airway. (PMID:14564346)
• Presence of substance P within these nerves is strong evidence that these nerves have the potential to transmit signals of nociception. (PMID:14589248)
• Normal component of human tears. Levels might reflect denervation of eye surface. Catabolized by degradative enzymes in tears to maintain ocular surface by exerting trophic effects of substance P while avoiding undesirable effects. (PMID:14703707)
• The contents of plasma neurokinin A (NKA) were significantly higher during the asthma attack stage of children, and the higher was the level of NKA, the more severe the attack. (PMID:14749007)
• SP stimulates platelet aggregation, intracellular mobilization of calcium and degranulation. Platelets contain SP-like immunoreactivity that is secreted upon activation implicating SP-like substances in the autocrine/paracrine regulation of these cells. (PMID:15130944)
• certain bioactive peptides such as somatostatin and substance P directly interact with human P-glycoprotein as endogenous substrates for P-glycoprotein-mediated transport (PMID:15358539)
• data directly demonstrate the presence of both PPT-A mRNA and tachykinin immunoreactivity in inflammatory airway cells which are in direct contact to NK-1 receptor positive glandular myoepithelium (PMID:15544859)
• Preprotachykinin-I peptides mediate autocrine proliferation of the neuroblastoma cells through both NK-1 and NK-2 receptors. (PMID:15690122)
• Prresence in pituitary tumours is unknown but does not appear to be related to headache or endocrine activity of the tumour. (PMID:15761654)
• Bombesin/gastrin-releasing peptide and substance P are involved together with cytokines in the neuroimmunomodulation that occurs in the arthritic joint. (PMID:15899028)
• The increase in plasma SP concentrations, possibly driven by serum progesterone concentration, is certainly an important element of the hypothalamo-pituitary-gonadal system necessary for the full development of the preovulatory LH surge in the human. (PMID:16816831)
• Activation of STAT6 appears to be a key factor in P-selectin expression induced by substance P and IL-4 because treatment with STAT6 decoy oligodeoxynucleotides significantly inhibited P-selectin expression. (PMID:16877367)
• SST and TAC1 are involved in colon carcinogenesis. (PMID:16952549)
• SP, CGRP and VIP may play important roles in the pathophysiological mechanism of vasomotor rhinitis. (PMID:17087112)
• Increase in AngII and decrease in substance P after coronary artery bypass grafting may play role in occurrence of postoperative atrial fibrillation. (PMID:17257983)
• Possesses antiapoptotic effects in the colonic mucosa by activating Akt, which prevents apoptosis and mediates tissue recovery during colitis. (PMID:17264209)
• Nonneuronal substance P and its receptor NK-1 might have a role in psoriasis, also during chronic stress. (PMID:17370082)
• the TAC1 locus is not likely to play a major role in the development of autism. (PMID:17376622)
• NF-kappaB is involved in the repression of Tac1 at higher levels of SDF-1alpha in MCF12A. These results are relevant to dysfunction of Tac1 in breast cancer cells. (PMID:17409218)
• Substance P and Titanium particles acted synergistically to increase PGE2 and IL-6 secretion in fibroblasts from periprosthetic membrane. (PMID:17450584)
• We concluded that excessive daytime sleepiness seen in some of the obstructive sleep apnea syndrome patients might be associated with various pathophysiologic mechanisms including substance P levels. (PMID:17494790)
• These findings suggest the novel possible role of SP in blasts proliferation in childhood ALL of common (CD10) origin. (PMID:17588657)
• Substance P was elevated in obstructive sleep apnea. (PMID:17667845)
• there is synergism between REST and NFkappaB in the suppression of TAC1 in non-neuronal cells (PMID:17709376)
• neurotransmitter substance P is regulated by microRNAs in human mesenchymal stem cell-derived neuronal cells (PMID:17855557)
• there are two proposed mechanisms for severe hRSV disease: reduced local IFN-gamma response and SP mediated inflammation (PMID:17940602)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tac1	ENSDARG00000014490
danio_rerio	tac4	ENSDARG00000096234
mus_musculus	Tac1	ENSMUSG00000061762
rattus_norvegicus	Tac1	ENSRNOG00000078101

Protein

Protein identifiers

Protachykinin-1 — P20366 (reviewed: P20366)

Alternative names: PPT

All UniProt accessions (1): P20366

UniProt curated annotations — full annotation on UniProt →

Function. Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles. Is a ligand for TACR1, and triggers G protein-coupled receptor signaling via activation of phosphatidylinositol hydrolysis by phospholipase C. Substance P binding to TACR1 also triggers signaling via activation of adenylate cyclase activity which results in increased intracellular levels of cyclic AMP (cAMP). Is also a TACR3 agonist with low receptor affinity. Basic secretagogue neuropeptide released from the terminals of specific sensory nerves. Acts as a ligand for MRGPRX2 receptor in mast cells, initiating a signaling that mediates neurogenic inflammation and pain. Neurogenic inflammation includes mast cell activation, recruitment of immune cells and release of inflammatory mediators, such as cytokines and chemokines. The inflammatory response can then activate or sensitize nociceptors, promoting pain. Is a ligand for TACR2, and triggers G protein-coupled receptor signaling via activation of G(q) and phosphatidylinositol hydrolysis by phospholipase C. Binding to TACR2 also triggers signaling via activation of adenylate cyclase activity which results in increased intracellular levels of cyclic AMP (cAMP).

Subcellular location. Secreted Secreted.

Post-translational modifications. The substance P form is cleaved at Pro-59 by the prolyl endopeptidase FAP (seprase) activity (in vitro). Substance P is also cleaved and degraded by Angiotensin-converting enzyme (ACE) and neprilysin (MME).

Similarity. Belongs to the tachykinin family.

Isoforms (4)

UniProt ID	Names	Canonical?
P20366-1	Beta	yes
P20366-2	Alpha
P20366-3	Gamma
P20366-4	Delta

RefSeq proteins (4): NP_003173, NP_054702, NP_054703, NP_054704 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008215	Tachykinin_dom	Domain
IPR008216	Tachykinin_fam	Family
IPR013055	Tachy_Neuro_lke_CS	Conserved_site

Pfam: PF02202

UniProt features (27 total): peptide 6, helix 6, site 5, splice variant 3, modified residue 2, turn 2, signal peptide 1, propeptide 1, sequence conflict 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
4HOM	X-RAY DIFFRACTION	1.9
8U26	ELECTRON MICROSCOPY	2.5
7XWO	ELECTRON MICROSCOPY	2.7
7P00	ELECTRON MICROSCOPY	2.71
7P02	ELECTRON MICROSCOPY	2.87
8JBH	ELECTRON MICROSCOPY	2.9
7VDM	ELECTRON MICROSCOPY	2.98
7RMG	ELECTRON MICROSCOPY	3
7RMH	ELECTRON MICROSCOPY	3.1
2B19	SOLUTION NMR
2KS9	SOLUTION NMR
2KSA	SOLUTION NMR
2KSB	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20366-F1	67.06	0.09

Antibody-complex structures (SAbDab): 8 — 7P00, 7P02, 7RMG, 7RMH, 7VDM, 7XWO, 8JBH, 8U26

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 (5): 64–65 (cleavage; by mme); 65–66 (cleavage; by ace); 66–67 (cleavage; by ace and mme); 59–60 (cleavage; by fap); 63–64 (cleavage; by mme)

Post-translational modifications (2): 68, 107

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-380095	Tachykinin receptors bind tachykinins
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 384 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, AP1_01, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_COGNITION, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR

GO Biological Process (26): positive regulation of acute inflammatory response (GO:0002675), inflammatory response (GO:0006954), positive regulation of cytosolic calcium ion concentration (GO:0007204), tachykinin receptor signaling pathway (GO:0007217), neuropeptide signaling pathway (GO:0007218), cell-cell signaling (GO:0007267), chemical synaptic transmission (GO:0007268), insemination (GO:0007320), long-term memory (GO:0007616), regulation of blood pressure (GO:0008217), associative learning (GO:0008306), detection of abiotic stimulus (GO:0009582), response to hormone (GO:0009725), negative regulation of heart rate (GO:0010459), positive regulation of epithelial cell migration (GO:0010634), sensory perception of pain (GO:0019233), positive regulation of synaptic transmission, cholinergic (GO:0032224), positive regulation of synaptic transmission, GABAergic (GO:0032230), response to lipopolysaccharide (GO:0032496), positive regulation of action potential (GO:0045760), positive regulation of ossification (GO:0045778), response to pain (GO:0048265), positive regulation of lymphocyte proliferation (GO:0050671), positive regulation of stress fiber assembly (GO:0051496), cellular response to nerve growth factor stimulus (GO:1990090), positive regulation of corticosterone secretion (GO:2000854)

GO Molecular Function (1): substance P receptor binding (GO:0031835)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), axon (GO:0030424), neuronal cell body (GO:0043025), synapse (GO:0045202), neuronal dense core vesicle (GO:0098992)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of biological quality	2
G protein-coupled receptor signaling pathway	2
positive regulation of synaptic transmission	2
acute inflammatory response	1
regulation of acute inflammatory response	1
positive regulation of inflammatory response	1
defense response	1
cell communication	1
signaling	1
anterograde trans-synaptic signaling	1
copulation	1
multi-organism reproductive process	1
multi-multicellular organism process	1
multicellular organismal reproductive process	1
memory	1
blood circulation	1
learning	1
response to abiotic stimulus	1
detection of stimulus	1
response to endogenous stimulus	1
response to chemical	1
regulation of heart rate	1
negative regulation of heart contraction	1
epithelial cell migration	1
regulation of epithelial cell migration	1
positive regulation of cell migration	1
sensory perception	1
synaptic transmission, cholinergic	1
regulation of synaptic transmission, cholinergic	1
regulation of synaptic transmission, GABAergic	1
synaptic transmission, GABAergic	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
action potential	1
positive regulation of biological process	1
regulation of action potential	1
neurokinin receptor binding	1
cellular anatomical structure	1
neuron projection	1

Protein interactions and networks

STRING

3056 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAC1	TACR1	P25103	999
TAC1	TACR2	P21452	998
TAC1	TAC3	Q9UHF0	998
TAC1	GRP	P07491	995
TAC1	AGT	P01019	993
TAC1	TACR3	P29371	991
TAC1	KNG1	P01042	987
TAC1	NTS	P30990	970
TAC1	VIP	P01282	970
TAC1	SST	P01166	962
TAC1	GAL	P22466	945
TAC1	TRPV1	Q8NER1	939
TAC1	NPY	P01303	928
TAC1	PDYN	P01213	925
TAC1	TAC4	Q86UU9	898

IntAct

13 interactions, top by confidence:

A	B	Type	Score
FAP	TAC1	psi-mi:“MI:0194”(cleavage reaction)	0.440
TAC1	DPP4	psi-mi:“MI:0194”(cleavage reaction)	0.440
TAC1	PLEC	psi-mi:“MI:0915”(physical association)	0.400
CRELD2	TAC1	psi-mi:“MI:0915”(physical association)	0.370
CENPB	TAC1	psi-mi:“MI:0915”(physical association)	0.370
XRCC6	TAC1	psi-mi:“MI:0915”(physical association)	0.370
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
TAC1	BAG6	psi-mi:“MI:0915”(physical association)	0.000
TAC1	ARHGEF40	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): TACR2 (Reconstituted Complex), TACR1 (Reconstituted Complex), BAG6 (Two-hybrid), PLEC (Proximity Label-MS), TACR1 (Reconstituted Complex), TACR3 (Reconstituted Complex), TAC1 (Reconstituted Complex), TAC1 (Affinity Capture-MS), BAG6 (Two-hybrid), XRCC6 (Two-hybrid), CENPB (Two-hybrid)

ESM2 similar proteins: E2AJ76, E2ASG4, F1QQI2, I7C2V3, M9P2C1, O57312, O93464, P01263, P01289, P01355, P01356, P06298, P06299, P06307, P06767, P07660, P08435, P09240, P12760, P20366, P22923, P23362, P25421, P29007, P41520, P41539, P41540, P43306, P48645, P50144, P50145, P53366, P55099, P80344, P80345, P81872, P87352, Q04617, Q0VBW8, Q0VC44

Diamond homologs: M9P2C1, P01289, P06767, P20366, P25421, P41539, P41540, Q60541

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TAC1	up-regulates	TACR2	binding
TAC1	“up-regulates quantity”	OXT

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

945 predictions. Top by Δscore:

Variant	Effect	Δscore
7:97732193:GCA:G	donor_gain	1.0000
7:97732196:G:GG	donor_gain	1.0000
7:97732575:T:A	acceptor_gain	1.0000
7:97732660:GCT:G	acceptor_gain	1.0000
7:97732732:CAAG:C	donor_loss	1.0000
7:97732733:AAGG:A	donor_loss	1.0000
7:97732735:GGT:G	donor_loss	1.0000
7:97732736:G:A	donor_loss	1.0000
7:97732737:T:A	donor_loss	1.0000
7:97732191:TCGCA:T	donor_gain	0.9900
7:97732192:CGCAG:C	donor_loss	0.9900
7:97732193:GCAGT:G	donor_loss	0.9900
7:97732194:CA:C	donor_gain	0.9900
7:97732195:AGTAA:A	donor_loss	0.9900
7:97732196:GT:G	donor_loss	0.9900
7:97732197:TAAGT:T	donor_loss	0.9900
7:97732198:AAGT:A	donor_loss	0.9900
7:97732592:A:AG	acceptor_gain	0.9900
7:97732593:C:G	acceptor_gain	0.9900
7:97732659:A:AG	acceptor_gain	0.9900
7:97732660:G:GG	acceptor_gain	0.9900
7:97733825:A:G	donor_gain	0.9900
7:97734850:G:GG	donor_gain	0.9900
7:97732192:CGCA:C	donor_gain	0.9800
7:97732193:GCAG:G	donor_gain	0.9800
7:97732199:AGTG:A	donor_loss	0.9800
7:97733439:G:T	donor_gain	0.9800
7:97733719:CCA:C	acceptor_loss	0.9800
7:97733720:CAGGA:C	acceptor_loss	0.9800
7:97733721:A:AG	acceptor_gain	0.9800

AlphaMissense

845 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:97736331:G:T	G108C	0.990
7:97736331:G:C	G108R	0.989
7:97736316:T:C	F103L	0.988
7:97736318:T:A	F103L	0.988
7:97736318:T:G	F103L	0.988
7:97736323:G:A	G105E	0.986
7:97736322:G:A	G105R	0.985
7:97736322:G:C	G105R	0.985
7:97736326:T:C	L106P	0.984
7:97736330:G:A	M107I	0.984
7:97736330:G:C	M107I	0.984
7:97736330:G:T	M107I	0.984
7:97736332:G:T	G108V	0.983
7:97736339:A:C	R110S	0.982
7:97736339:A:T	R110S	0.982
7:97736332:G:A	G108D	0.980
7:97736317:T:G	F103C	0.979
7:97736326:T:A	L106Q	0.976
7:97733804:G:T	G69C	0.974
7:97733789:T:C	F64L	0.973
7:97733791:C:A	F64L	0.973
7:97733791:C:G	F64L	0.973
7:97733796:G:A	G66E	0.969
7:97733803:G:A	M68I	0.968
7:97733803:G:C	M68I	0.968
7:97733803:G:T	M68I	0.968
7:97736317:T:C	F103S	0.968
7:97733804:G:C	G69R	0.966
7:97736329:T:C	M107T	0.966
7:97733805:G:T	G69V	0.963

dbSNP variants (sampled 300 via entrez): RS1000216824 (7:97731858 G>A), RS1000337271 (7:97739857 C>A,T), RS1000397686 (7:97740191 A>G), RS1000479778 (7:97739965 G>A,C,T), RS1000672101 (7:97732053 G>A), RS1001048157 (7:97734633 ATT>A), RS1001278667 (7:97732069 G>A,C), RS1001340401 (7:97737766 T>A), RS1001392194 (7:97738248 G>C), RS1001447704 (7:97738667 G>A), RS1001615254 (7:97730103 G>A), RS1001708594 (7:97731675 A>AT), RS1002400025 (7:97736073 C>T), RS1003403502 (7:97734068 C>G), RS1003826930 (7:97737075 T>TA)

Disease associations

OMIM: gene MIM:162320 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001291_2	Response to platinum-based agents	5.000000e-07
GCST002034_1	Adverse response to radiation therapy	4.000000e-06
GCST004750_19	Squamous cell lung carcinoma	4.000000e-06
GCST006585_873	Blood protein levels	6.000000e-06
GCST006922_15	Regular attendance at a religious group	9.000000e-09
GCST006948_49	Feeling nervous	1.000000e-09
GCST007324_159	Adventurousness	4.000000e-12
GCST007325_149	General risk tolerance (MTAG)	3.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009592	social interaction measurement
EFO:0009597	feeling nervous measurement
EFO:0008579	risk-taking behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10486003	TAC1		0.00	0

Binding affinities (BindingDB)

6 measured of 8 human assays (15 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-one	KI	1.9 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	2.92 nM
cid_3396	KI	56 nM
1-[2-[4-[5-chloro-1-(4-fluorophenyl)-indol-3-yl]-1-piperidyl]ethyl]imidazolidin-2-one	KI	1050 nM
CAS_1893-33-0	KI	2770 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases reaction, increases expression, increases secretion, decreases expression	8
Acetaminophen	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases methylation, increases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
trichostatin A	affects cotreatment, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	decreases expression, increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Capsaicin	decreases expression, increases secretion	2
Histamine	decreases reaction, increases secretion	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
triptolide	decreases reaction, increases expression	1
urushiol	increases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	increases expression	1
arsenite	increases methylation	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression, increases expression	1
ferrous chloride	increases expression	1
triadimefon	increases expression	1
batimastat	increases secretion, decreases reaction, increases activity, increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
RTKI cpd	increases activity, increases phosphorylation, decreases reaction	1
rofecoxib	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	increases expression	1
quinocetone	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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