Persius/hicric huggingface dataset:
TREM1
Triggering receptor expressed on myeloid cells 1 is a protein that in humans is encoded by the TREM1 gene.

# Function
Monocyte/macrophage- and neutrophil-mediated inflammatory responses can be stimulated through a variety of receptors, including G protein-linked 7-transmembrane receptors (e.g., FPR1), Fc receptors (see MIM 146790), CD14  and Toll-like receptors (e.g., TLR4), and cytokine receptors (e.g., IFNGR1; MIM 107470). Engagement of these receptors can also prime myeloid cells to respond to other stimuli. Myeloid cells express receptors belonging to the Ig superfamily, such as TREM1, or to the C-type lectin superfamily. Depending on their transmembrane and cytoplasmic sequence structure, these receptors have either activating (e.g., KIR2DS1; MIM 604952) or inhibitory functions (e.g., KIR2DL1). In granulocyte cells, TREM1 is activated by C/EBP independently from inflammatory response.

# Model organisms
Model organisms have been used in the study of TREM1 function. A conditional knockout mouse line called Trem1tm1(KOMP)Vlcg was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed:  - In-depth immunological phenotyping
TREM2
Triggering receptor expressed on myeloid cells 2 also known as TREM-2 is a protein that in humans is encoded by the TREM2 gene.

# Function
Monocyte/macrophage- and neutrophil-mediated inflammatory responses can be stimulated through a variety of receptors, including G protein-linked 7-transmembrane receptors (e.g., FPR1), Fc receptors, CD14  and Toll-like receptors (e.g., TLR4), and cytokine receptors (e.g., IFNGR1). Engagement of these receptors can also prime myeloid cells to respond to other stimuli. Myeloid cells express receptors belonging to the Immunoglobulin (Ig) superfamily, such as TREM2, or to the C-type lectin superfamily. Depending on their transmembrane and cytoplasmic sequence structure, these receptors have either activating (e.g., KIR2DS1) or inhibitory functions (e.g., KIR2DL1).

# Clinical significance
Homozygous mutations in TREM2 are known to cause rare, autosomal recessive forms of dementia with an early onset and presenting with or without bone cysts and fractures.
A rare missense mutation (rs75932628-T) in the gene encoding TREM2, (predicted to result in an R47H substitution), confers a significant risk of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, it is suspected of interfering with the brains ability to prevent the buildup of plaque. TREM2 mutations increase the risk of neurodegenerative conditions such as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. TREM2 interacts with DAP12 in microglia to trigger phagocytosis of amyloid beta peptide and apoptotic neurons without inflammation.  Mutations in TREM2 impair the normal proteolytic maturation of the protein which in turn interferes with phagocytosis and may therefore contribute to the pathogenesis of Alzheimer's disease.
Soluble TREM2 has been detected in human cerebrospinal fluid (CSF), where it was found to be elevated in CSF of patients with multiple sclerosis and other inflammatory neurological conditions in comparison to patients without inflammatory neurologic disorders.
TREX1
Three prime repair exonuclease 1 is an enzyme that in humans is encoded by the TREX1 gene.

# Function
This gene encodes the major 3'->5' DNA exonuclease in human cells. The protein is a non-processive exonuclease that may serve a proofreading function for a human DNA polymerase. It is also a component of the SET complex, and acts to rapidly degrade 3' ends of nicked DNA during granzyme A-mediated cell death. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, RVCL (Retinal Vasculopathy with Cerebral Leukodystrophy), and Cree encephalitis. Multiple transcript variants encoding different isoforms have been found for this gene.

# Clinical relevance
TREX1 helps HIV1 to evade cytosolic sensing by degrading viral cDNA in the cytoplasm
TRIB1
Tribbles homolog 1 is a protein kinase that in humans is encoded by the TRIB1 gene.  Orthologs of this protein pseudokinase (pseudoenzyme) can be found almost ubiquitously throughout the animal kingdom. It exerts its biological functions through binding to signalling proteins of the MAPKK level of the MAPK pathway, therefore eliciting a regulatory role in the function of this pathway which mediates proliferation, apoptosis and differentiation in cells. Tribbles-1 is encoded by the trib1 gene, which in humans can be found on chromosome 8 at position 24.13 on the longest arm (q). Recent crystal structures show that Tribbles 1 has an unusual 3D structure, containing a 'broken' C-helix region, a binding site for ubiquitinated substrates such as C/EBPalpha and a key regulatory  C-tail region. Like TRIB2 and TRIB3, TRIB1 has recently been considered as a potential allosteric drug target 

# Function
Tribbles-1 is one of three members of the Tribbles subfamily, which is a part of the CAMK Ser/Thr protein kinase family, of the protein kinase superfamily. The Tribbles subfamily is one of the pseudokinases, meaning that while expressing putative kinase regions in its structure, it is non-catalytic. The Tribbles subfamily lacks a functional ATP binding pocket, and therefore cannot phosphorylate its substrates; instead, Tribbles proteins function as scaffold proteins, which bind their substrates to localize them to or from their function 
Expression of Tribbles-1 is highly variable, constantly changing with respect to time and cell-type, which suggests a large amount of regulation that exists in the cell. The protein's primary structure contains a PEST region, indicative of proteins that are highly susceptible to degradation in the cell; Tribbles-1 plays a role in regulating its own expression by binding to its substrate, which not only produces its function on the MAPK pathway, but also works to protect it from degradation whilst binding. This, in part, creates a positive feedback loop in the function of Tribbles-1, as the function of Tribbles-1 directly aids in the increase of the amount of it. As positive feedback loops are often seen throughout biology in circumstances that require the alleviation of an external stimulus, the positive feedback loop exhibited by Tribbles-1 suggests that it plays a functional role in cell response.

# Clinical significance
Tribbles-1 is an inflammatory regulator.
Tribbles-1 is associated with Acute Myeloid Leukemia (AML).
Tribbles-1 has been implicated in atherosclerosis.
TRIP6
Thyroid receptor-interacting protein 6 is a protein that in humans is encoded by the TRIP6 gene.

# Function
This gene is a member of the zyxin family and encodes a protein with three LIM zinc-binding domains. This protein localizes to focal adhesion sites and along actin stress fibers. Recruitment of this protein to the plasma membrane occurs in a lysophosphatidic acid (LPA)-dependent manner and it regulates LPA-induced cell migration. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.

# Interactions
TRIP6 has been shown to interact with LPAR2, BCAR1 and HOXA9.
TRPC1
Transient receptor potential channel 1 (TRPC1) is a protein that in humans is encoded by the TRPC1 gene.

# Function
TRPC1 is an ion channel located on the plasma membrane of numerous human and animal cell types.
It is a nonspecific cation channel, which means that both sodium and calcium ions can pass through it. TRPC1 is thought to mediate calcium entry in response to depletion of endoplasmic calcium stores or activation of receptors coupled to the phospholipase C system. In HEK293 cells the unitary current-voltage relationship of endogenous TRPC1 channels is almost linear, with a slope conductance of about 17 pS. The extrapolated reversal potential of TRPC1 channels is +30 mV. 
The TRPC1 protein is widely expressed throughout the mammalian brain and has a similar corticolimbic expression pattern as TRPC4 and TRPC5.
 The highest density of TRPC1 protein is found in the lateral septum, an area with dense TRPC4 expression, and hippocampus and prefrontal cortex, areas with dense TRPC5 expression.

# History
TRPC1 was the first mammalian Transient Receptor Potential channel to be identified. In 1995 it was cloned when the research groups headed by Craig Montell and Lutz Birnbaumer were searching for proteins similar to the TRP channel in Drosophila. Together with TRPC3 they became the founding members of the TRPC ion channel family.

# Interactions
TRPC1 has been shown to interact with:
- HOMER3,
- Polycystic kidney disease 2,
- RHOA
- TRPC3,
- TRPC4, and
- TRPC5.
TRPC3
Short transient receptor potential channel 3 (TrpC3) also known as transient receptor protein 3 (TRP-3) is a protein that in humans is encoded by the TRPC3 gene. The TRPC3/6/7 subfamily are implicated in the regulation of vascular tone, cell growth, proliferation and pathological hypertrophy. These are diacylgylcerol-sensitive cation channels known regulate intracellular calcium via activation of the phospholipase C (PLC) pathway and/or by sensing Ca2+ store depletion. Together, their role in calcium homeostasis has made them potential therapeutic targets for a variety of central and peripheral pathologies.

# Function
Non-specific cation conductance elicited by the activation of TrkB by BDNF is TRPC3-dependent in the CNS. TRPC channels are almost always co-localized with mGluR1-expressing cells and likely play a role in mGluR-mediated EPSPs.
The TRPC3 channel has been shown to be preferentially expressed in non-excitable cell types, such as oligodendrocytes. However, evidence suggests that active TRPC3 channels in basal ganglia (BG) output neurons are responsible for maintaining a tonic inward depolarizing current that regulates resting membrane potential and promotes regular neuronal firing. Conversely, inhibiting TRPC3 promotes cellular hyperpolarization, which can lead to slower and more irregular neuronal firing.  While it's unclear if TRPC3 channels have equal expression, other members of the TRPC family have been localized to the axon hillock, cell body, and dendritic processes of dopamine-expressing cells.
The neuromodulator, substance P, activates TRPC3/7 channels inducing cellular currents that underlie rhythmic pacemaker activity in the brainstem, enhancing the regularity and frequency of respiratory rhythms, showing homology to the mechanism described in BG neurons. Transgenic cardiomyocytes expressing TRPC3 show prolonged action potential duration when exposed to a TRPC3 agonist. The same cardiomyocytes also increase their firing rate with agonist exposure under a current-clamp tetanus protocol suggesting that they may play a role in cardiac arrhythmogenesis.

# Modulators
A small molecule agonist is GSK1702934A and antagonists are GSK417651A and GSK2293017A. A commercially available inhibitor is available in the form of a pyrazole compound, Pyr3 TRPC3 has been shown to specifically interact with TRPC1 and TRPC6.
TRPC4
The short transient receptor potential channel 4 (TrpC4), also known as Trp-related protein 4, is a protein that in humans is encoded by the TRPC4 gene.

# Function
TrpC4 is a member of the transient receptor potential cation channels. This protein forms a non-selective calcium-permeable cation channel that is activated by Gi-coupled receptors, Gq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation.

# Tissue distribution
The nonselective cation channel TrpC4 has been shown to be present in high abundance in the cortico-limbic regions of the brain. In addition, TRPC4 mRNA is present in midbrain dopaminergic neurons in the ventral tegmental area and the substantia nigra.

# Roles
Deletion of the trpc4 gene decreases levels of sociability in a social exploration task. These results suggest that TRPC4 may play a role in regulating social anxiety in a number of different disorders.  However deletion of the trpc4 gene had no impact on basic or complex strategic learning.  Given that the trpc4 gene is expressed in a select population of midbrain dopamine neurons it has been proposed that is may have an important role in dopamine related processes including addiction and attention.

# Clinical significance
Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity.

# Interactions
TRPC4 has been shown to interact with ITPR1, TRPC1,  and TRPC5.
TRPC5
Short transient receptor potential channel 5 (TrpC5) also known as transient receptor protein 5 (TRP-5) is a protein that in humans is encoded by the TRPC5 gene. TrpC5 is subtype of the TRPC family of mammalian transient receptor potential ion channels.

# Function
TrpC5 is one of the seven mammalian TRPC (transient receptor potential canonical) proteins. TrpC5 is a multi-pass membrane protein and is thought to form a receptor-activated non-selective calcium permeant cation channel. The protein is active alone or as a heteromultimeric assembly with TRPC1, TRPC3, and TRPC4. It also interacts with multiple proteins including calmodulin, CABP1, enkurin, Na+H+ exchange regulatory factor (NHERF), interferon-induced GTP-binding protein (MX1), ring finger protein 24 (RNF24), and SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).
TRPC4 and TRPC5 have been implicated in the mechanism of mercury toxicity and neurological behavior.

# Activation
Homomultimeric TRPC5 and heteromultimeric TRPC5-TRPC1 channels are activated by extracellular reduced thioredoxin. This channel has also been found to be involved in the action of anaesthetics such as chloroform, halothane and propofol.

# Interactions
TRPC5 has been shown to interact with STMN3, TRPC1, and TRPC4.
TRPM1
Transient receptor potential cation channel subfamily M member 1 is a protein that in humans is encoded by the TRPM1 gene.

# Function
The protein encoded by this gene is a member of the transient receptor potential (TRP) family of non-selective cation channels. It is expressed in the retina, in a subset of bipolar cells termed ON bipolar cells. These cells form synapses with either rods or cones, collecting signals from them. In the dark, the signal arrives in the form of the neurotransmitter glutamate, which is detected by a G protein-coupled receptor (GPCR) signal transduction cascade. Detection of glutamate by the GPCR Metabotropic glutamate receptor 6 results in closing of the TRPM1 channel. At the onset of light, glutamate release is halted and mGluR6 is deactivated; this results in opening of the TRPM1 channel, influx of sodium and calcium, and depolarization of the bipolar cell.
In addition to the retina, TRPM1 is also expressed in melanocytes, which are melanin-producing cells in the skin. The expression of TRPM1 is inversely correlated with melanoma aggressiveness, suggesting that it might suppress melanoma metastasis. However, subsequent work showed that a microRNA located in an intron of the TRPM1 gene, rather than the TRPM1 protein itself, is responsible for the tumor suppressor function. The expression of both TRPM1 and the microRNA are regulated by the Microphthalmia-associated transcription factor.

# Clinical significance
Mutations in TRPM1 are associated with congenital stationary night blindness in humans  and  coat spotting patterns in Appaloosa horses.
TRPM2
Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the TRPM2 gene.

# Function
The TRPM2 gene is highly expressed in the brain and was implicated by both genetic linkage studies in families and then by case control or trio allelic association studies in the genetic aetiology of bipolar affective disorder (Manic Depression).
The physiological role of TRPM2 is not well understood. It was shown to be involved in insulin secretion. In the immune cells it mediates parts of the responses to TNF-alpha. A role has been suggested for TRPM2 in activation of NLRP3 inflammasome, the dysregulation of which is strongly associated with a number of auto inflammatory and metabolic diseases, such as gout, obesity and diabetes. In the brain it is involved in the toxicity of amyloid beta, a protein associated with Alzheimer's disease.. In 2016, TRPM2 channel was strongly implicated in the detection of non-painful warm stimuli. Chun-Hsiang Tan and Peter McNaughton studied the responses of actual sensory neurons to thermal stimuli, then used an RNA-sequencing strategy to identify TRPM2 as genetically required for warmth detection in the non-noxious range of 3338 C.

# Structure
The protein encoded by this gene is a non-selective calcium-permeable cation channel and is part of the Transient Receptor Potential ion channel super family. The closest relative is the cold and menthol activated TRPM8 ion channel. While TRPM2 is not cold sensitive it is activated by heat. The TRPM2 ion channel is activated by free intracellular ADP-ribose in synergy with free intracellular calcium. ADP-Ribose is produced to by the enzyme PARP in response to oxidative stress and confers susceptibility to cell death. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.
TRPM3
Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.

# Function
The product of this gene belongs to the family of transient receptor potential (TRP) channels. TRP channels are cation-selective channels important for cellular calcium signaling and homeostasis. The protein encoded by this gene mediates calcium entry, and this entry is potentiated by calcium store depletion. Alternatively spliced transcript variants encoding different isoforms have been -identified.
TRPM3 was shown to be activated by the neurosteroid pregnenolone sulphate in pancreatic beta cell. The activation causes calcium influx and subsequent insulin release, therefore it is suggested that TRPM3 modulates glucose homeostasis.

# TRPM3 Ligands

## Channel Blockers
- Mefenamic acid
- Citrus fruit flavonoids, E.g. Naringenin and hesperetin, as well as Ononetin (a deoxybenzoin).

## Agonist
- CIM0216
TRPM5
Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the TRPM5 gene.

# Function
TRPM5 is a calcium-activated non-selective cation channel that induces depolarization upon increases in intracellular calcium, it is a signal mediator in chemosensory cells.  Channel activity is initiated by a rise in the intracellular calcium, and the channel permeates monovalent cations as K+ and Na+.
TRPM5 is a key component of taste transduction in the gustatory system of bitter, sweet and umami tastes being activated by high levels of intracellular calcium. It has also been targeted as a possible contributor to fat taste signaling. The calcium dependent opening of TRPM5 produces a depolarizing generator potential which leads to an action potential.
TRPM5 is expressed in pancreatic -cells where it is involved in the signaling mechanism for insulin secretion. The potentiation of TRPM5 in the -cells leads to increased insulin secretion and protects against the development of type 2 diabetes in mice. Further expression of TRPM5 can be found in tuft cells, solitary chemosensory cells and several other cell types in the body that have a sensory role.

# Drugs modulating TRPM5
The role of TRPM5 in the pancreatic -cell makes it a target for the development of novel antidiabetic therapies.

## Agonists
- Steviol glycosides, the sweet compounds in the leaves of the Stevia rebaudiana plant, potentiate the calcium-induced activity of TRPM5. In this way they stimulate the glucose-induced insulin secretion from the pancreatic -cell.
- Rutamarin, a phytochemical found in Ruta graveolens has been identified as an activator of several TRP channels, including TRPM5 and TRPV1 and inhibits the activity of TRPM8.

## Antagonists
Selective blocking agents of TRPM5 ion channels can be used to identify TRPM5 currents in primary cells. Most identified compounds show, however, a poor selectivity between TRPM4 and TRPM5 or other ion channels.
- TPPO or TriPhenylPhosphineOxide is the most selective blocker of TRPM5 however, its application suffers due to a poor solubility.
- Ketoconazole is an antifungal drug that inhibits TRPM5 activity.
- Flufenamic Acid is a NSAID drug that inhibits the activity of TRPM5 or TRPM4.
- Clotrimazole is an antifungal drug and reduces the currents through TRPM5.
- Nicotine inhibits the TRPM5 channel. Through the inhibition of TRPM5, the taste loss observed in people with a smoking habit can be explained.
TRPM7
Transient receptor potential cation channel, subfamily M, member 7, also known as TRPM7, is a human gene encoding a protein of the same name.

# Function
TRPs, mammalian homologs of the Drosophila transient receptor potential (trp) protein, are ion channels that are thought to mediate capacitative calcium entry into the cell. TRP-PLIK is a protein that is both an ion channel and a kinase. As a channel, it conducts calcium and monovalent cations to depolarize cells and increase intracellular calcium. As a kinase, it is capable of phosphorylating itself and other substrates. The kinase activity is necessary for channel function, as shown by its dependence on intracellular ATP and by the kinase mutants.

# Interactions
TRPM7 has been shown to interact with PLCB1 and PLCB2.

# Clinical relevance
Defects in this gene have been associated to magnesium deficiency in human microvascular endothelial cells.