Cell surface receptor that transfers passive humoral immunity from the mother to the newborn. Binds to the Fc region of monomeric immunoglobulin gamma and mediates its selective uptake from milk. IgG in the milk is bound at the apical surface of the intestinal epithelium. The resultant FcRn-IgG complexes are transcytosed across the intestinal epithelium and IgG is released from FcRn into blood or tissue fluids. Throughout life, contributes to effective humoral immunity by recycling IgG and extending its half-life in the circulation. Mechanistically, monomeric IgG binding to FcRn in acidic endosomes of endothelial and hematopoietic cells recycles IgG to the cell surface where it is released into the circulation. In addition of IgG, regulates homeostasis of the other most abundant circulating protein albumin ALB.; (Microbial infection) Acts as an uncoating receptor for a panel of echoviruses including Echovirus 5, 6, 7, 9, 11, 13, 25 and 29.
Cell surface receptor that transfers passive humoral immunity from the mother to the newborn. Binds to the Fc region of monomeric immunoglobulin gamma and mediates its selective uptake from milk. IgG in the milk is bound at the apical surface of the intestinal epithelium. The resultant FcRn-IgG complexes are transcytosed across the intestinal epithelium and IgG is released from FcRn into blood or tissue fluids. Throughout life, contributes to effective humoral immunity by recycling IgG and extending its half-life in the circulation. Mechanistically, monomeric IgG binding to FcRn in acidic endosomes of endothelial and hematopoietic cells recycles IgG to the cell surface where it is released into the circulation. In addition of IgG, regulates homeostasis of the other most abundant circulating protein albumin ALB.; (Microbial infection) Acts as an uncoating receptor for a panel of echoviruses including Echovirus 5, 6, 7, 9, 11, 13, 25 and 29.
Glucose-6-Phosphate 1-Dehydrogenase (G6PD) is a cytosolic enzyme that belongs to the glucose-6-phosphate dehydrogenase family. G6PD participates in the pentose phosphate pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). G6PD produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power. NADPH in turn maintains the level of glutathione in these cells that helps protect the red blood cells against oxidative damage. It is notable in humans that G6PD is remarkable for its genetic diversity. G6PD deficiency may cause neonatal jaundice, acute hemolysis, or severe chronic non-spherocytic hemolytic anemia.
Herpes simplex viruses (human herpesviruses types 1 and 2) commonly cause recurrent infection affecting the skin, mouth, lips, eyes, and genitals. Herpes simplex virus type 2 (HSV-2) infection is responsible for significant neurological morbidity, perhaps more than any other virus. Herpes simplex virus type 2–associated neurological disease may result from primary infection or reactivation of latent HSV-2. Common severe infections include encephalitis, meningitis, neonatal herpes, and, in immunocompromised patients, disseminated infection.
Fibroblast growth factor 16 (FGF16) is preferentially expressed in the heart after birth, suggesting its regulation is associated with tissue-specific chromatin remodeling and DNA-protein interactions. Mutation of the MEF2 site resulted in a blunting of FGF16 promoter activity in transfected neonatal rat cardiac myocytes, that chromatin remodeling and MEF2 binding in the FGF16 promoter contribute to expression in the postnatal heart. FGF16 involvement in the fine tuning of the human skeleton of the hand. Impaired FGF16 function may also be responsible for connective tissue symptoms in MF4 patients. FGF16 expression is markedly increased in ovarian tumors, and FGF16 in conjunction with Wnt pathway contributes to the cancer phenotype of ovarian cells and suggests that modulation of its expression in ovarian cells might be a promising therapeutic strategy for the treatment of invasive ovarian cancers.
The papain superfamily member bleomycin hydrolase (BLMH) is a cytoplasmic cysteine peptidase that is highly conserved through evolution. The only known activity of the enzyme is metabolic inactivation of the glycopeptide bleomycin (BLM), an essential component of combination chemotherapy regimens for cancer. The papain superfamily member bleomycin hydrolase (BLMH) is a neutral cysteine protease with structural similarity to a 20S proteasome. Bleomycin (BLM), a clinically used glycopeptide anticancer agent. BLMH is an essential protectant against BLM-induced death and has an important role in neonatal survival and in maintaining epidermal integrity. Sequencing revealed several putative sites phosphorylated by different types of protein kinases, but no signal sequence, transmembrane domain, N-linked glycosylation site or DNA-binding motif.
CD177 is polymorphic and has at least two alleles: PRV1 and NB1. Human PRV1 is a Glycosyl-Phosphatidylinositol (GPI)-linked cell surface glycoprotein that belongs to the uPAR CD59 Ly6 family of receptors. PRV1 is expressed by neutrophils and neutrophil precursors,and changes in expression serve as diagnostic markers for myeloproliferative disorders such as polycythemia vera and essential thrombocythemia. PRV1 may also be expressed by Erythroblasts, B cells, and Monocytes. NB1, a Glycosyl-Phosphatidylinositol (GPI)-linked cell surface glycoprotein, was first described in a case of neonatal alloimmune neutropenia. It is reported that CD177 functions as a novel heterophilic binding partner that engages PECAM-1 in membrane-proximal IgD6.
Fibroblast growth factor 10 (FGF10) regulates multiple stages of structural lung morphogenesis, cellular differentiation, and the response to injury. As a driver of lung airway branching morphogenesis, FGF10 signaling defects during development lead to neonatal lung disease. Lung diseases impact patients across the lifespan, from infants in the first minutes of life through the aged population. Congenital abnormalities of lung structure can cause lung disease at birth or make adults more susceptible to chronic disease.
INS (Insulin) is a Protein Coding gene. This gene encodes insulin, a peptide hormone that plays a vital role in the regulation of carbohydrate and lipid metabolism. After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. The binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. Diseases associated with INS include Hyperproinsulinemia and Maturity-Onset Diabetes Of The Young, Type 10. A multitude of mutant alleles with phenotypic effects has been identified, including insulin-dependent diabetes mellitus, permanent neonatal diabetes mellitus, maturity-onset diabetes of the young type 10, and hyperproinsulinemia.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy
Syntaxin-binding protein 1, also known as N-Sec1, Protein unc-18 homolog 1, MUNC18-1 and STXBP1, is a peripheral membrane protein that belongs to the STXBP unc-18 SEC1 family. STXBP1 is an evolutionally conserved neuronal Sec1 Munc-18 (SM) protein that is essential in synaptic vesicle release in several species. It may participate in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins. STXBP1 is essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. It can interact with syntaxins 1, 2, and 3 but not syntaxin 4. STXBP1 may also play a role in determining the specificity of intracellular fusion reactions. Defects in STXBP1 are the cause of epileptic encephalopathy early infantile type 4 (EIEE4). Affected individuals have neonatal or infantile onset of seizures, suppression-burst pattern on EEG, profound mental retardation, and MRI evidence of hypomyelination.
Erythropoietin (EPO) is a glycoprotein hormone that is principally known for its role in erythropoiesis, where it is responsible for stimulating proliferation and differentiation of erythroid progenitor cells. Erythropoietin is a member of the EPO TPO family. It is a secreted, glycosylated cytokine composed of four alpha helical bundles. The differentiation of CFU-E (Colony Forming Unit-Erythroid) cells into erythrocytes can only be accomplished in the presence of EPO. Physiological levels of EPO in adult mammals are maintained primarily by the kidneys, whereas levels in fetal or neonatal mammals are maintained by the liver. EPO also can exert various non-hematopoietic activities, including vascularization and proliferation of smooth muscle, neural protection during hypoxia, and stimulation of certain B cells. Genetic variation in erythropoietin is associated with susceptbility to microvascular complications of diabetes type 2. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy.
Triose-phosphate isomerase, also named Triose-phosphate isomerase, TPI and TIM, is an enzyme that catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate. TPI has been found in nearly every organism searched for the enzyme, including animals such as mammals and insects as well as in fungi, plants, and bacteria. However, some bacteria that do not perform glycolysis, like ureaplasmas, lack TPI. TPI plays an important role in glycolysis and is essential for efficient energy production. TPI deficiency is an autosomal recessive disorder and the most severe clinical disorder of glycolysis. Triose phosphate isomerase deficiency is associated with neonatal jaundice, chronic hemolytic anemia, progressive neuromuscular dysfunction, cardiomyopathy and increased susceptibility to infection and characterized by chronic hemolytic anemia.