Persius/hicric huggingface dataset:
TFEB
Transcription factor EB is a protein that in humans is encoded by the TFEB gene.

# Function
TFEB is a master gene for lysosomal biogenesis. It encodes a transcription factor that coordinates expression of lysosomal hydrolases, membrane proteins and genes involved in autophagy. Upon nutrient depletion and under aberrant lysosomal storage conditions such as in lysosomal storage diseases, TFEB translocates from the cytoplasm to the nucleus, resulting in the activation of its target genes. TFEB overexpression in cultured cells induces lysosomal biogenesis, exocytosis and autophagy.  Viral-mediated TFEB overexpression in cellular and mouse models of lysosomal storage disorders and in common neurodegenerative diseases such as Huntington,  Parkinson and Alzheimer diseases, resulted in intracellular clearance of accumulating molecules and rescue of disease phenotypes. TFEB is activated by PGC1-alpha and promotes reduction of htt aggregation and neurotoxicity in a mouse model of Huntington disease.
TFEB overexpression has been found in patients with renal cell carcinoma and pancreatic cancer and was shown to promote tumorogenesis via induction of varius oncogenic signals.
Nuclear localization and activity of TFEB is inhibited by serine phosphorylation by mTORC1 and extracellular signalregulated kinase 2 (ERK2). 
mTORC1 phosphorylation of TFEB occurs at the lysosomal surface, both of which are localized there by interaction with the Rag GTPases. Phosphorylated TFEB is then retained in the cytosol by interaction with 14-3-3 proteins. These kinases are tuned to the levels of extracellular nutrients suggesting a coordination in regulation of autophagy and lysosomal biogenesis and partnership of two distinct cellular organelles. Nutrient depletion induces TFEB dephosphorylation and subsequent nuclear translocation via the phosphatase calcineurin. 
TFEB nuclear export is mediated by CRM1 and is dependent on phosphorylation. 
TFEB is also a target of the protein kinase AKT/PKB. AKT/PKB phosphorylates TFEB at serine 467 and inhibits TFEB nuclear translocation. Pharmacological inhibition of AKT/PKB activates TFEB, promotes lysosome biogenesis and autophagy, and ameliorates neuropathology in a mouse model of Juvenile Batten disease.
TFEB is activated in Trex1-deficient cells via inhibition of mTORC1 activity, resulting in an expanded lysosomal compartment.
TGM6
Transglutaminase 6 is a protein that in humans is encoded by the TGM6 gene.

# Function
The protein encoded by this gene belongs to the transglutaminase superfamily. It catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Mutations in this gene are associated with spinocerebellar ataxia type 35 (SCA35). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. .
Mutations in TGM6 cause                 acute myeloid leukaemia            .

# Model organisms
Model organisms have been used in the study of TGM6 function. A conditional knockout mouse line called Tgm6tm1a(KOMP)Wtsi 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
TLK1
Serine/threonine-protein kinase tousled-like 1 is an enzyme that in humans is encoded by the TLK1 gene.

# Function
The Tousled-like kinases, first described in Arabidopsis, are nuclear serine/threonine kinases that are potentially involved in the regulation of chromatin assembly.

# Interactions
TLK1 has been shown to interact with ASF1B, ASF1A and TLK2.
TLK2
Serine/threonine-protein kinase tousled-like 2 is an enzyme that in humans is encoded by the TLK2 gene.

# Function
The Tousled-like kinases, first described in Arabidopsis, are nuclear serine/threonine kinases that are potentially involved in the regulation of chromatin assembly. These are different from other "tousled" varieties, such as flock-of-seagulls, post-coitus, or the-Sean-Bean.

# Interactions
TLK2 has been shown to interact with TLK1, ASF1B and ASF1A.
TLR3
Toll-like receptor 3 (TLR3) also known as CD283 (cluster of differentiation 283) is a protein that in humans is encoded by the TLR3 gene. TLR3 is a member of the toll-like receptor family of pattern recognition receptors of the innate immune system.

# Function
TLR3 is a member of the toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of IRF3 and NF-B. Unlike other TLRs, TLR3 uses TRIF as the sole adaptor. IRF3 ultimately induces the production of type I interferons. It may thus play a role in host defense against viruses.
TLR3 recognizes double-stranded RNA, a form of genetic information carried by some viruses such as reoviruses. Additionally, an ephemeral form of double-stranded RNA exists as a replicative intermediate during virus replication. Upon recognition, TLR 3 induces the activation of IRF3 to increase production of type I interferons which signal other cells to increase their antiviral defenses. Double-stranded RNA is also recognised by the cytoplasmic receptors RIG-I and MDA-5.
TLR3 displays a protective role in mouse models of atherosclerosis, and activation of TLR3 signaling is associated with ischemic preconditioning-induced protection against brain ischemia and attenuation of reactive astrogliosis. Furthermore, TLR3 activation has been shown to promote hair follicle regeneration in skin wound healing. In addition, TLR3 activators show effects on human vascular cells.

# Structure
The structure of TLR3 was reported in June 2005 by researchers at The Scripps Research Institute. TLR3 forms a large horseshoe shape that contacts with a neighboring horseshoe, forming a "dimer" of two horseshoes. Much of the TLR3 protein surface is covered with sugar molecules, making it a glycoprotein, but on one face (including the proposed interface between the two horseshoes), there is a large sugar-free surface. This surface also contains two distinct patches rich in positively charged amino acids, which may be a binding site for negatively charged double-stranded RNA.
Despite being a glycoprotein, TLR3 crystallises readily  a prerequisite for structural analysis by x-ray crystallography.
TLR7
Toll-like receptor 7, also known as TLR7, is a protein that in humans is encoded by the TLR7 gene.  Orthologs are found in mammals and birds. It is a member of the toll-like receptor (TLR) family and detects single stranded RNA.

# Function
The TLR family plays an important role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is predominantly expressed in lung, placenta, and spleen, and lies in close proximity to another family member, TLR8, on the human X chromosome.
TLR7 recognizes single-stranded RNA in endosomes, which is a common feature of viral genomes which are internalised by macrophages and dendritic cells. TLR7 recognizes single-stranded RNA of viruses such as HIV and HCV,. TLR7 can recognize GU-rich single-stranded RNA. However, the presence of GU-rich sequences in the single-stranded RNA is not sufficient to stimulate TLR7.

# Clinical significance
Imiquimod acts upon TLR7.
TLR7 has been shown to play a significant role in the pathogenesis of autoimmune disorders such as Systemic Lupus Erythematosus (SLE) as well as in the regulation of antiviral immunity. Although not yet fully elucidated, using an unbiased genome-scale screen with short hairpin RNA (shRNA), it has been demonstrated that the receptor TREML4 acts as an essential positive regulator of TLR7 signalling. In TREML4 -/- mice macrophages that are hyporesponsive to TLR7 agonists, macrophages fail to produce type I interferons due to impaired phosphorylation of the transcription factor STAT1 by the mitogen-activated protein kinase p38 and decreased recruitment of the adaptor MyD88 to TLR7. TREML4 deficiency reduced the production of inflammatory cytokines and autoantibodies in MRL/lpr mice, suggesting that TRL7 is a vital component of antiviral immunity and a predecessor factor in the pathogenesis of rheumatic diseases such as SLE. A TLR7 agonist, Aldara, an imidazoquinoline, has been approved for topical use in treating warts caused by papillomavirus and for actinic keratoses.
Due to their ability to induce robust production of anti-cancer cytokines such as interleukin-12, TLR7 agonists have been investigated for cancer immunotherapy. Recent examples include TMX-202 delivery via liposomal formulation, as well as the delivery of resiquimod via nanoparticles formed from beta-cyclodextrin.
TLR8
Toll-like receptor 8 is a protein that in humans is encoded by the TLR8 gene. TLR8 has also been designated as CD288 (cluster of differentiation 288). It is a member of the toll-like receptor (TLR) family.

# Function
TLR8 seems to function differently in humans and mice.  Until recently, TLR8 was believed to be nonfunctional in mice, but it seems to counteract TLR7 activity
The TLR family plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is predominantly expressed in lung and peripheral blood leukocytes, and lies in close proximity to another family member, TLR7, on chromosome X.
TLR8 can recognize GU-rich single-stranded RNA. However, the presence of GU-rich sequences in the single-stranded RNA is not sufficient to stimulate TLR8. TLR8 recognizes G-rich oligonucleotides.
TLR8 is an endosomal receptor that recognizes single stranded RNA (ssRNA), and can recognize ssRNA viruses such as Influenza, Sendai, and Coxsackie B viruses. TLR8 binding to the viral RNA recruits MyD88 and leads to activation of the transcription factor NF-B and an antiviral response. TLR8 recognizes single-stranded RNA of viruses such as HIV and HCV.

# Clinical significance
Genetic variants in TLR8 has recently been linked to susceptibility to pulmonary tuberculosis.

## As a drug target
TLR8 agonists (e.g. VTX-2337) have undergone clinical trials as immune stimulants in combination therapy for some cancers.
TMC1
Transmembrane channel-like protein 1 is a protein that in humans is encoded by the TMC1 gene. TMC1 contains six transmembrane domains with both the C and N termini on the endoplasmic side of the membrane, as well as a large loop between domains 4 and 5. This topology is similar to that of transient receptor potential channels (TRPs), a family of proteins involved in the perception of senses such as temperature, taste, pressure, and vision. TMC1 has been located in the post-natal mouse cochlea, and knockouts for TMC1 and TMC2 result in both auditory and vestibular deficits (hearing loss and balance issues) indicating TMC1 is a molecular part of auditory transduction.

# Function
This gene is considered a member of a gene family predicted to encode transmembrane proteins. Until recently, the specific function of this gene was relatively unknown; it was only known to be required for normal function of cochlear hair cells. However, new research suggests that TMC1 interacts with Tip link proteins protocadherin 15 and cadherin 23 indicating that TMC1, along with TMC2, are necessary proteins for hair cell mechanotransduction. Specifically, TMC1 and TMC2 may be two pore-forming subunits of the channel that responds to tip link deflection in hair cells.
Due to its implication in cochlear hair cell function and its interaction with hair cell tip links, TMC1 is being mutated and manipulated in order to better understand the receptor while at the same time producing a molecular model for deafness. While deafness can arise at any stage of auditory processing, DFNA36 (a type of progressive hearing loss) and DFNB7/B11 (congenital hearing loss) have been specifically shown to arise from TMC1 mutations. DFNA36 results from a dominant missense mutation and DFNB7/B11 results from a recessive mutation. Both have been modeled in mice, known as the Beethoven model and the dn model respectively. The TMC1 gene is located on chromosome 9q31-q21, and the dominant mutation associated with DFNA36 occurs at amino acid 572 which suggests the importance of this amino acid in the overall function of TMC1. Now that TMC1 has been shown to interact with the tip link proteins PCDH15 and CDH23, the next question may be whether or not amino acid 572 is necessary for TMC1 tip link interactions.
Researchers reported in 2015 that genetically deaf mice treated with TMC1 gene therapy recovered some of their hearing.

# Clinical significance
Mutations in this gene have been associated with progressive postlingual hearing loss,                 non syndromic deafness             and profound prelingual deafness. TMC1 mutations are not associated with other symptoms or abnormalities, which is known as Nonsyndromic hearing loss and indicates that TMC1 functions mainly in auditory sensation. Additionally, recessive mutations of the gene result in both a loss of TMC1 function as well as profound deafness indicating TMC1 function is necessary for the processing of auditory signals.
TMC2
Transmembrane channel-like protein 2 is a protein that in humans is encoded by the TMC2 gene.

# Function
This gene is considered a member of a gene family predicted to encode transmembrane proteins. The specific function of this gene is unknown; however, expression in the inner ear suggests that it may be crucial for normal auditory function.

# Clinical significance
Mutations in this gene may underlie hereditary disorders of balance and hearing.
TMC8
Transmembrane channel-like 8 is a protein which in humans is encoded by the TMC8 gene.

# Function
The protein encoded by this gene is an integral membrane protein that localize to the endoplasmic reticulum and is predicted to form transmembrane channels. This gene encodes a transmembrane channel-like protein with 8 predicted transmembrane domains and 3 leucine zipper motifs.

# Clinical significance
Mutations in the TMC8 gene are associated with epidermodysplasia verruciformis (EV), an autosomal recessive dermatosis characterized by abnormal susceptibility to human papillomaviruses (HPVs) and a high rate of progression to squamous cell carcinoma on sun-exposed skin.
TNIK
TRAF2 and NCK-interacting protein kinase is an enzyme that in humans is encoded by the TNIK gene.

# Function
Germinal center kinases (GCKs), such as TNIK, are characterized by an N-terminal kinase domain and a C-terminal GCK domain that serves a regulatory function.

# Interactions
TNIK has been shown to interact with KIAA0090, although the significance is unclear. TNIK has been shown to phosphorylate Gelsolin, a protein involved in F-actin depolymerisation thus inducing cytoskeletal changes.
TNK2
Activated CDC42 kinase 1, also known as ACK1, is an enzyme that in humans is encoded by the TNK2 gene.
TNK2 gene encodes a non-receptor tyrosine kinase, ACK1, that binds to multiple receptor tyrosine kinases e.g. EGFR, MERTK, AXL, HER2 and insulin receptor (IR). ACK1 also interacts with Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined.

# Interactions
ACK1 or TNK2 has been shown to interact with AKT, Androgen receptor or AR, a tumor suppressor WWOX, FYN and Grb2. ACK1 interaction with its substrates resulted in their phosphorylation at specific tyrosine residues. ACK1 has been shown to directly phosphorylate AKT at tyrosine 176, AR at Tyrosine 267 and 363, and WWOX at tyrosine 287 residues, respectively. ACK1-AR signaling has also been reported to regulate ATM levels,

# Clinical relevance
ACK1 is a survival kinase and shown to be associated with tumor cell survival, proliferation, hormone-resistance and radiation resistance. The activation of ACK1 has been observed in prostate, breast, pancreatic, lung and ovarian cancer cells. ACK1 transgenic mice, expressing activated ACK1 specifically in prostate gland has been reported; these mice develop prostatic intraepithelial neoplasia (PINs).

# ACK1 inhibitors
Ack1 has emerged as a new cancer target and multiple small molecule inhibitors have been reported.
 All of these inhibitors are currently in the pre-clinical stage.
TOX3
TOX high mobility group box family member 3, also known as TOX3, is a human gene.
The protein encoded by this gene is a member of a subfamily of transcription factors that also includes TOX, TOX2, and TOX4 that share almost identical HMG-box DNA-binding domains which function to modify chromatin structure.

# Disease linkage
Mutations in the TOX3 gene are associated with an increased risk of breast cancer.
TP63
Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 (also known as the  p63) gene.
The TP63 gene was discovered 20 years after the discovery of the p53 tumor suppressor gene and along with p73 constitutes the p53 gene family based on their structural similarity.  Despite being discovered significantly later than p53, phylogenetic analysis of p53, p63 and p73, suggest that p63 was the original member of the family from which p53 and p73 evolved.

# Function
Tumor protein p63 is a member of the p53 family of transcription factors. p63 -/- mice have several developmental defects which include the lack of limbs and other tissues, such as teeth and mammary glands, which develop as a result of interactions between mesenchyme and epithelium. TP63 encodes for two main isoforms by alternative promoters (TAp63 and Np63). Np63 is involved in multiple functions during skin development and in adult stem/progenitor cell regulation. In contrast, TAp63 has been mostly restricted to its apoptotic function and more recently as the guardian of oocyte integrity. Recently, two new functions have been attributed to TAp63 in heart development and premature aging.

# Clinical significance
TP63 mutations underlie several malformation syndromes that include cleft lip and/or palate as a hallmark feature. Mutations in the TP63 gene are associated with ectrodactyly-ectodermal dysplasia-cleft syndrome in which a midline cleft lip is a common feature, cleft lip/palate syndrome 3 (EEC3); ectrodactyly (also known as split-hand/foot malformation 4 (SHFM4)); ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) or HayWells syndrome in which a midline cleft lip is also a common feature, Acrodermatounguallacrimaltooth syndrome (ADULT); limb-mammary syndrome; Rap-Hodgkin syndrome (RHS); and orofacial cleft 8.
Both cleft lip with or without a cleft palate and cleft palate only features have been seen to segregate within the same family with a TP63 mutation. Recently, induced pluripotent stem cells have been produced from patients affected by EEC syndromes by cell reprogramming. The defective epithelial commitment could be partially rescued by a small therapeutic compound.<

# Diagnostic utility
p63 immunostaining has utility for head and neck squamous cell carcinomas, differentiating prostatic adenocarcinoma (the most common type of prostate cancer) and benign prostatic tissue; normal prostatic glands stain with p63 (as they have basal cells), while the malignant glands in prostatic adenocarcinoma (which lacks these cells) do not.
P63 is also helpful in distinguishing poorly differentiated squamous cell carcinoma from small cell carcinoma or adenocarcinoma. P63 should be strongly stained in poorly differentiated squamous cell, but negative in small cell or adenocarcinoma.

# Interactions
TP63 has been shown to interact with HNRPAB.
It also activates IRF6 transcription through the IRF6 enhancer element.

# Regulation
There is some evidence that the expression of p63 is regulated by the microRNA miR-203.
TPBG
Trophoblast glycoprotein, also known as TPBG, 5T4, Wnt-Activated Inhibitory Factor 1 or WAIF1, is a human protein encoded by a TPBG gene. TPBG is an antagonist of Wnt/-catenin signalling pathway.

# Clinical significance
5T4 is an antigen expressed in a number of carcinomas. It is an N-glycosylated transmembrane 72 kDa glycoprotein containing eight leucine-rich repeats. 5T4 is often referred to as an oncofetal antigen due to its expression in foetal trophoblast (where it was first discovered) or trophoblast glycoprotein (TPBG).
5T4 is found in tumors including the colorectal, ovarian, and gastric. Its expression is used as a prognostic aid in these cases. It has very limited expression in normal tissue but is widespread in malignant tumours throughout their development. One study found that 5T4 was present in 85% of a cohort of 72 colorectal carcinomas and in 81% of a cohort of 27 gastric carcinomas.
Its confined expression appears to give 5T4 the potential to be a target for T cells in cancer immunotherapy. There has been extensive research into its role in antibody-directed immunotherapy through the use of the high-affinity murine monoclonal antibody, mAb5T4, to deliver response modifiers (such as staphylococcus aureus superantigen) accurately to a tumor.
5T4 is also the target of the cancer vaccine TroVax which is in clinical trials for the treatment of a range of different solid tumour types.

# Interactions
TPBG has been shown to interact with GIPC1.