Persius/hicric huggingface dataset:
LARP1
La-related protein 1 (LARP1) is a 150 kDa protein that in humans is encoded by the LARP1 gene. LARP1 is a novel target of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, a circuitry often hyperactivated in cancer which regulates cell growth and proliferation primarily through the regulation of protein synthesis.

# Function
LARP1 is the largest of a 7 member family of LARP proteins (others are: LARP1B, LARP3 (aka genuine La or SSB), LARP4A, LARP4B, LARP6 and LARP7). All LARP proteins, including human LARPs, contain 2 conserved regions. The first conserved region shares homology with La proteins (called the La motif, see SSB) whereas the second conserved region (called the LA- motif) is restricted to LARP proteins. LARP1 and 1B also contain a conserved "DM15 region" within their C-terminus. This region is unique and has been shown to be required for RNA-binding. Mouse Larp1 is expressed in dorsal root ganglia and spinal cord, as well as in developing organs characterized by epithelial-mesenchymal interactions. Human LARP1 is present at low levels in normal, non-embryonic cells but is highly expressed in epithelial cancers (such as ovarian, colorectal, prostate, non-small cell lung, hepatocellular and cervical cancers). Some studies have shown that high levels of LARP1 protein correlate with worse prognosis in cancer patients.
LARP1 binds to and regulates the translation of terminal oligopyrimidine motif (TOP mRNAs) and can directly interact with the 5' cap of mRNAs. It has also been shown to interact with the 3' end and coding regions (CDS) of other genes. LARP1 protein colocalizes with stress granules and P-bodies, which function in RNA storage and degradation. It has been suggested that LARP1 functions in P-bodies to attenuate the abundance of conserved Ras-MAPK mRNAs. The cluster of LARP1 homologs may function to control the expression of key developmental regulators.
Several studies have demonstrated that LARP1 deficiency selectively affects the recruitment of TOP mRNAs to polysomes . In some cancer cells, LARP1 deficiency reduces proliferation and activates apoptotic cell death. Even though a decrease abundance of proteins encoded by TOP mRNAs has been reported in LARP1 silenced cells, some researchers believe that this can be explained simply by the reduced number of TOP mRNA transcripts in LARP1-deficient cells.
LEKTI
Lympho-epithelial Kazal-type-related inhibitor (LEKTI) also known as serine protease inhibitor Kazal-type 5 (SPINK5) is a protein that in humans is encoded by the SPINK5 gene.

# Structure and function
LEKTI is a large multidomain serine protease inhibitor expressed in stratified epithelial tissue. It consists of 15 domains that are cleaved into smaller, functional fragments by the protease furin. Only two of these domains (2 and 15) contain 6 evenly spaced cysteines responsible for 3 intramolecular disulfide bonds characteristic of Kazal-type related inhibitors. The remaining domains contain 4 cysteines. These disulfide bonds force the molecule into a rigid conformation that enables the protein to interact with a target protease via an extended beta-sheet. All domains (excepting 1, 2 and 15) contain an arginine at P1, indicating trypsin-like proteases are the likely targets.
In the epidermis, LEKTI is implicated in the regulation of desquamation via its ability to selectively inhibit KLK5, KLK7 and KLK14. Recombinant full length LEKTI inhibits the exogenous serine proteases trypsin, plasmin, subtilisin A, cathepsin G and human neutrophil elastase.
LEKTI may play a role in skin and hair morphogenesis and anti-inflammatory and/or antimicrobial protection of mucous epithelia.

# Gene
SPINK5 is a member of a gene family cluster located on chromosome 5q32, which encode inhibitors of serine proteases. This includes other epidermal proteins SPINK6 and LEKTI-2 (SPINK9). The SPINK5 gene is 61 kb in length and contains 33 exons. Alternative processing of SPINK5 results in the formation of three different gene products, which have been identified in differentiated keratinocytes.

# Clinical significance
Mutations in the SPINK5 gene may result in Netherton syndrome, a disorder characterized by ichthyosis, defective cornification, and atopy.
LETM1
Leucine zipper-EF-hand containing transmembrane protein 1 is a protein that in humans is encoded by the LETM1 gene.

# Structure
The LETM1 protein has a transmembrane domain and a casein kinase 2 and protein kinase C phosphorylation site.  The LETM1 gene is expressed in the mitochondria of many eukaryotes indicating that this is a conserved mitochondrial protein.

# Function
LETM1 is a eukaryotic protein that is expressed in the inner membrane of mitochondria. Experiments performed with human cells have been interpreted to indicate that it functions as a component of a Ca2+/H+ antiporter. Experimental results with yeast cells have been interpreted as suggesting that LETM1 functions as a component of a K+/H+ antiporter. The Drosophila melanogaster LETM1 protein has been shown to functionally substitute for the K+/H+ antiporter function in yeast cells.

# Clinical significance
Deletion of LETM1 is thought to be involved in the development of WolfHirschhorn syndrome in humans.
LIMK1
LIM domain kinase 1 is an enzyme that in humans is encoded by the LIMK1 gene.

# Function
There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs, a central PDZ domain, and a C-terminal protein kinase domain. LIMK1 is likely to be a component of an intracellular signaling pathway and may be involved in brain development.

# Clinical significance
LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome.

# Interactions
LIMK1 has been shown to interact with:
- CFL1,
- CDKN1C,
- NRG1,
- PAK1,
- PAK4, and
- YWHAZ.
LIMS1
LIM and senescent cell antigen-like-containing domain protein 1 is a protein that in humans is encoded by the LIMS1 gene.

# Function
The protein encoded by this gene is an adaptor protein which contains five LIM domains, or double zinc fingers. The protein is likely involved in integrin signaling through its LIM domain-mediated interaction with integrin-linked kinase, found in focal adhesion plaques. It is also thought to act as a bridge linking integrin-linked kinase to NCK adaptor protein 2, which is involved in growth factor receptor kinase signaling pathways. Its localization to the periphery of spreading cells also suggests that this protein may play a role in integrin-mediated cell adhesion or spreading.

# Interactions
LIMS1 has been shown to interact with Integrin-linked kinase and NCK2.
LIN28
Lin-28 homolog A is a protein that in humans is encoded by the LIN28 gene.
LIN28 encodes an RNA-binding protein that binds to and enhances the translation of the IGF-2 (insulin-like growth factor 2) mRNA. Lin28 binds to the let-7 pre-microRNA and blocks production of the mature let-7 microRNA in mouse embryonic stem cells. In pluripotent embryonal carcinoma cells, LIN28 is localized in the ribosomes, P-bodies and stress granules.

# Function

## Stem cell expression
LIN28 is thought to regulate the self-renewal of stem cells. In Caenorhabditis elegans, there is only one Lin28 gene that is expressed and in vertebrates, there are two paralogs present, Lin28a and Lin28b. In nematodes, the LIN28 homolog lin-28 is a heterochronic gene that determines the onset of early larval stages of developmental events in C. elegans, by regulating the self-renewal of nematode stem cells in the skin (called seam cells) and vulva (called VPCs) during development. In mice, LIN28 is highly expressed in mouse embryonic stem cells and during early embryogenesis.
LIN28 is highly expressed in human embryonic stem cells and can enhance the efficiency of the formation of induced pluripotent stem (iPS) cells from human fibroblasts.

## Puberty
LIN28 overexpression in mice can cause gigantism and a delay in puberty onset, consistent with human genome-wide association studies suggesting that polymorphisms in the human LIN28B gene are associated with human height and puberty timing. Mutations in LIN28B are associated with precocious puberty.
LIN28 can regulate glucose homeostasis in mammals by increasing insulin-PI3K-mTOR signaling and insulin sensitivity, thereby promoting resistance to high fat diet-induced obesity and type 2 diabetes. Aberrant expression of LIN28 has been seen to regulate aerobic glycolysis to facilitate cancer proliferation

## Tissue regeneration
Mice genetically altered to produce LIN28 during their lifespan showed improved hair growth. and healthy tissue regeneration on added puncture wounds in later life stages. While the mice could regenerate limbs, they could not repair damaged heart tissue. Appropriate drugs replicated the regeneration in unaltered mice, using the same metabolic paths. The drugs increased the subjects' metabolic rates, evidently causing the body to heal at higher rates. The effects of Lin28a activation faded with age.

# Structure
Models of Lin28/let-7 complexes obtained through X-ray crystallography and NMR reveal that two folded domains of Lin28 recognize two distinct RNA regions. The domains are sufficient for inhibition of let-7 in vivo.

# Applications
LIN28 is a marker of undifferentiated human embryonic stem cells and has been used to enhance the efficiency of the formation of iPS cells from human fibroblasts.
LMAN1
Protein ERGIC-53 also known as ER-Golgi intermediate compartment 53 kDa protein or lectin mannose-binding 1 is a protein that in humans is encoded by the LMAN1 gene.

# Function
ERGIC-53 (also named LMAN1) is a type I integral membrane protein localized in the intermediate region (ERGIC) between the endoplasmic reticulum and the Golgi, presumably recycling between the two compartments. The protein is a mannose-specific lectin and is a member of a novel family of plant lectin homologs in the secretory pathway of animal cells. Mutations in the gene are associated with a coagulation defect. Using positional cloning, the gene was identified as the disease gene leading to combined deficiency of factor V-factor VIII, a rare, autosomal recessive disorder in which both coagulation factors V and VIII are diminished. MCFD2 is the second gene that leads to combined deficiency of factor V-factor VIII. ERGIC-53 and MCFD2  form a protein complex and serve as a cargo receptor to transport FV and FVIII from the ER to the ERGIC and then the Golgi,as illustrated here.

# Clinical significance
LMAN1 mutational inactivation is a frequent and early event potentially contributing to colorectal tumorigenesis.
LMTK2
Serine/threonine-protein kinase LMTK2 also known as Lemur tyrosine kinase 2 (LMTK2) is an enzyme that in humans is encoded by the LMTK2 gene.

# Function
The LMTK2 enzyme belongs to both the protein kinase and the tyrosine kinase families. It contains N-terminus transmembrane helices and a long C-terminal cytoplasmic tail with serine/threonine/tyrosine kinase activity.  This protein interacts with several other proteins, such as androgen receptor, inhibitor-2 (Inh2), protein phosphatase-1 (PP1C), p35, and myosin VI. It phosphorylates other proteins, and is itself also phosphorylated when interacting with cyclin-dependent kinase 5 (cdk5)/p35 complex. This protein is involved in nerve growth factor (NGF)-TrkA signalling, and also plays a critical role in endosomal membrane trafficking. Mouse studies suggested an essential role of this protein in spermatogenesis.

# Clinical significance
Loss of LMTK2 has been implicated to play a role in development of prostate cancer.

# Interactions
LMTK2 has been shown to interact with PPP1CA, Cyclin-dependent kinase 5 and PPP1R2.
LMX1B
LIM homeobox transcription factor 1-beta, also known as LMX1B, is a protein which in humans is encoded by the LMX1B gene.

# Function
LMX1B is a LIM homeobox transcription factor which plays a central role in dorso-ventral patterning of the vertebrate limb.

# Clinical significance
Mutations in the LMX1B gene are associated with the Nail-patella syndrome.
LONP1
Lon protease homolog, mitochondrial is an enzyme that in humans is encoded by the LONP1 gene.

# Structure
This gene encoded a mitochondrial matrix protein that is the subunit of a barrel-shaped homo-oligometric protein complex, the Lon protease.  Lon protease is a member of ATP-dependent proteases (AAA+ proteases). Mature and catalytically viable Human Lon protease complex contains a hexameric ring while other formations of complexes have been observed (e.g., heptameric ring in Saccharomyces cerevisiae). A single subunit of Lon protease contains three domains, N-Domain for protein substrate recognition, AAA + module for ATP binding and hydrolysis, and P-domain for protein proteolysis. A similar protease expressed in E. coli  regulates gene expression by targeting specific regulatory proteins for degradation. Lon protease binds a specific sequence in the light and heavy chain promoters of the mitochondrial genome which are involved in regulation of DNA replication and transcription.

# Function
Lon protease (LONP1) is a conserved serine peptidase identified from bacteria to eukaryotic cells. In mitochondrial matrix, a majority of damaged proteins is removed via proteolysis led by Lon protease, which is an essential mechanism for mitochondrial protein quality control (PQC).
For Lon protease-dependent degradation, protein substrates are first recognized and then unfolded if necessary in an ATP-dependent manner. The substrates are subsequently transferred through the pore of complex and into the proteolytic chamber of complex for degradation. ATP binding to the AAA module of the Lon complex results in a change in Lon conformation into a proteolytically active state. In general, Lon protease interacts with peptide regions(sequences) that are located within the hydrophobic core of substrates and rarely on the surface. These regions can be presented to Lon protease when proteins are damaged and lost their conformation integrity. In addition to misfolded proteins, several regulatory proteins can be processed by Lon protease by removing a degradable tag before they fully gain their biological functions.
LONP1 is also a DNA-binding protein that participates in mtDNA maintenance and gene expression regulation.  LONP1 degrades mitochondrial transcription factor A (TFAM) when substrate is modified by post-translational modifications (PTMs) such as phosphorylation, regulating mtDNA copy number and metabolism to maintain the TFAM/mtDNA ratio necessary to control replication and transcription.

# Clinical significance
Given the crucial role of LON protease in maintaining the control of mitochondrial function, its dynamics in expression under stress conditions has been found associating with human diseases and aging. For example, LONP1 expression levels are increased in different tumors and tumor cell lines. Downregulation of LONP1 in some tumor cells causes apoptosis and cell death, indicating a possible addiction of tumor cells to LONP1 function, as occurs with other intracellular proteases associated with cancer.
LOXL1
Lysyl oxidase homolog 1, also known as LOXL1, is an enzyme which in humans is encoded by the LOXL1 gene.

# Function
This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family.

# Clinical significance
Polymorphisms of the LOXL1 gene are associated with pseudoexfoliation syndrome, a disease where the extracellular matrix contains abnormal amounts of cross-linked, amyloid-like fibrillar material and glycoproteins. When this happens in the eye, exfoliation glaucoma results.

# Interactions
LOXL1 has been shown to interact with FBLN5.
LOXL2
Lysyl oxidase homolog 2 is an enzyme that in humans is encoded by the LOXL2 gene.

# Function
This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family.
LOXL2 can also crosslink collagen type IV and hence influence the sprouting of new blood vessels.

# Clinical significance
LOXL2 is an enzyme that is up-regulated in several types of cancer and is associated with a poorer prognosis. LOXL2 changes the structure of histones (proteins that are attached to DNA) and thus changes the shape of the cells, making it easier for the cancer cells to metastasize.
An antibody that inhibits the activity of LOXL2, simtuzumab and is currently in clinical trials for the treatment of several types of cancer and fibrotic diseases such as liver fibrosis.
LOXL3
Lysyl oxidase homolog 3 is an enzyme that in humans is encoded by the LOXL3 gene.
This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Alternatively spliced transcript variants of this gene have been reported but their full-length nature has not been determined.

# Clinical significance
An autosomal recessive mutation (missense variant) in the LOXL3 gene is one of the causes of Stickler syndrome, a disease where collagen is not crosslinked properly. Common features are high myopia and cleft palate due to arthropathy (joint pathology) and vitreoretinopathy (pathology of the eye).
LPAR6
Lysophosphatidic acid receptor 6 also known as LPA6, P2RY5, and GPR87, is a protein that in humans is encoded by the LPAR6 gene. LPA6 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).
The protein encoded by this gene belongs to the family of G-protein coupled receptors, that are preferentially activated by adenosine and uridine nucleotides. This gene aligns with an internal intron of the retinoblastoma susceptibility gene in the reverse orientation.

# Role in hair growth/loss
In February 2008 researchers at the University of Bonn announced they have found the genetic basis of two distinct forms of inherited hair loss, opening a broad path to treatments for baldness. They found that mutations in the gene P2RY5 causes a rare, inherited form of hair loss called Hypotrichosis simplex. It is the first receptor in humans known to play a role in hair growth. The fact that any receptor plays a specific role in hair growth was previously unknown to scientists and with this new knowledge a focus on finding more of these genes may be able to lead to therapies for many different types of hair loss.
LPIN1
Lipin-1 is a protein that in humans is encoded by the LPIN1 gene.

# Function
Lipin-1 has phosphatidate phosphatase activity. The nuclear localization of Lipin 1 is regulated by the mammalian Target Of Rapamycin protein kinase and links mTORC1 activity to the regulation of Sterol regulatory element-binding proteins (SREBP)-dependent gene transcription.

# Clinical significance
This gene represents a candidate gene for human lipodystrophy, characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. Mouse studies suggest that this gene functions during normal adipose tissue development and may also play a role in human triglyceride metabolism.
LQT10

# Overview
Only one mutation in one patient of this Long QT syndrome subtype has been found.

# LQT10
This novel susceptibility gene for LQT is SCN4B encoding the protein NaV4, an auxiliary subunit to the pore-forming NaV1.5 (gene:  SCN5A) subunit of the voltage-gated sodium channel of the heart.  The mutation leads to a positive shift in inactivation of the sodium current, thus increasing sodium current.  Only one mutation in one patient has so far been found.

## History and Symptoms
- Seizures - due to oxygen deprivation that occurs during arrhythmia.
- Fainting - fainting or syncope is the most common symptom LQTS.
- A prodrome may occur before losing consciousness, which may consist of lightheadedness, heart palpitations, blurred vision or weakness.
- Sudden death - a fatal arrhythmia that is not quickly intervened on, may cause sudden death.

## Therapy
- Beta-blockers are the first line treatment in LQTS, even in asymptomatic carriers, as they reduce the incidence of syncope and sudden cardiac death.
- Other medications to control non-malignant arrhythmias.
- Electrolytes should be repleted as neccesary.
- Avoidance of triggers (drugs, supplements, loud noises, exercise).
- LQTs is one of the few diseases where genetic testing can provide important guidance, such as in whom to place an AICD (defibrillator) for the primary prevention of cardiac events. 
- Placement of a pacemaker may be indicated.
- Left stellectomy is not a cure, but is a second line therapy to reduce the risk of sudden cardiac death and is indicated if the patient does not tolerate beta blockers, as well as in young patients under the age of 12 where beta blockers are not deemed protective enough and AICD is not appropriate.
- Patients with long QT syndrome should undergo secondary prevention with AICD implantation if they sustain an aborted cardiac arrest or sudden cardiac death.
LRIG1
Leucine-rich repeats and immunoglobulin-like domains protein 1 is a protein that in humans is encoded by the LRIG1 gene.
It encodes a transmembrane protein that has been shown to interact with receptor tyrosine kinases of the EGFR-family
, MET and RET.

# Model organisms
Model organisms have been used in the study of LRIG1 function. A conditional knockout mouse line, called Lrig1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on homozygous mutant mice and ten significant abnormalities were observed, including decreased body weight and total body fat, scaly skin, abnormal hair shedding, a moderate degree of hearing impairment, vertebral fusion, abnormal plasma chemistry and an increased susceptibility to bacterial infection (with both Salmonella and Citrobacter).