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Arylsulfatase A (ARSA) hydrolyzes cerebrosidesulfate to cerebroside and sulfate. ARSA is inhibited by phosphate. The phosphate develops a covalent bond with the active site 3-oxoalanine. ARSA gene defects cause metachromatic leucodystrophy (MLD), a progressive demyelination disease which results in various neurological symptoms and ultimately death.

PAPPA is a large zinc binding protein, which acts as a metalloprotease and specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. PAPP-A can also act as a regulator of IGF bioactivity in a number of biological systems, including the human ovary and cardiovascular systems. It was shown that PAPP A levels are elevated in patients with unstable angina or acute myocardial infarction. Furthermore, PAPPA is believed to be involved in local proliferative processes such as wound healing and bone remodeling. Moreover, PAPP-A is produced in high concentrations during pregnancy and is released into the maternal circulation. In placenta, PAPP A is expressed in X cells in septa and anchoring villi, and in syncytiotrophoblasts in the chorionic villi.
Lower levels of PAPPA are found in an array of other tissues including kidney, myometrium, endometrium, ovaries, breast, prostate, bone marrow, colon, fibroblasts and osteoblasts. PAPP-A is present in serum and placenta during pregnancy; with levels increasing throughout pregnancy. Low levels of PAPP A are associated with a number of foetal chromosomal abnormalities, as well as pre-eclampsia and stillbirth.
PAPPA levels may be a potentially highly specific marker for heart disease.
PAPP-A proteolytic activity is inhibited by targeting substrate exosite binding.

BPI encodes a lipopolysaccharide binding protein. BPI is related to human neutrophil granules and has bactericidal activity on gram-negative organisms.

Threonyl-tRNA Synthetase is a member of the aminoacyl-tRNA synthetase family, key enzymes of protein biosynthesis which charge tRNA molecules with the respective amino acids. This 83 kDa protein is an autoantigen recognized by PL-7 antibodies which occur in a subset of patients with polymyositis and dermatomyositis. Preliminary data suggest that PL-7 antibodies (similar to Jo-1 antibodies) indicate an increased risk for lung involvement, but this needs to be confirmed for a larger number of cases.

C9orf103 is a member of the gluconokinase gntK/gntV family. C9orf103 takes part in carbohydrate acid metabolism and D-gluconate degradation.

CBR4 is a member of the short-chain dehydrogenase/reductase family. CBR4 has a role in biosynthesis of fatty acids in the mitochondria and a broad substrate specificity and reduces 9,10-phenanthrenequinone, 1,4-benzoquinone and a range of other o-quinones and p-quinones (in vitro). CBR4 formation of a heteroteramer with HSD17B8 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity for o- and p-quinones.

Chitinase 3-Like 2 (CHI3L2) is similar to bacterial chitinases but lacks chitinase activity. CHI3L2 protein is secreted and is involved in cartilage biogenesis. CHI3L2 is a lectin, which binds chitooligosaccharides and other glycans with high affinity, but not heparin.

Uromodulin is the most abundant protein in normal urine. Its secretion in urine follows proteolytic cleavage of the ectodomain of its glycosyl phosphatidylinosital-anchored counterpart that is situated on the luminal cell surface of the loop of Henle. Uromodulin plays a role as a constitutive inhibitor of calcium crystallization in renal fluids. Secretion of uromodulin in urine provides protection against urinary tract infections caused by uropathogenic bacteria. Defects in Uromodulin expression are associated with the autosomal dominant renal disorders medullary cystic kidney disease-2 (MCKD2) and familial juvenile hyperuricemic nephropathy (FJHN). These disorders are characterized by juvenile onset of hyperuricemia, gout, and progressive renal failure. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. UMOD is involved in regulating the circulating activity of cytokines as it binds to il-1, il-2 and tnf with high affinity.

Pyrroline-5-Carboxylate Reductase Like (PYCRL) is a member of the pyrroline-5-carboxylate reductase family and acts as a homodecamer. PYCRL plays a key role in proline bio-synthesis. Proline serves as a non-enzymatic antioxidant to reduce damage caused by reactive oxygen species (ROS) in microorganisms, animals and plants. In the final stage of proline biosynthesis, PYCRL catalyzes the reduction of aldehyde dehydrogenase 4A1 (ALDH4A1) to proline with NAD(P)H as the cofactor.

Ornithine Aminotransferase is a mitochondrial enzyme which is an important factor that converts arginine and ornithine into the major excitatory and inhibitory neurotransmitters glutamate and GABA. Ornithine Aminotransferase mutations result in a deficiency that cause the autosomal recessive eye disease Gyrate Atrophy.

Interleukin-1 ra is a member of the interleukin 1 cytokine family. IL1RAinhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. IL1RAand five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer.

Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1a and MIP-1b that are now officially named CCL3 and CCL4 respectively. Both are major factors produced by macrophages after they are stimulated with bacterial endotoxins. They activate human granulocytes (neutrophils, eosinophils and basophils) which can lead to acute neutrophilic inflammation. They also induce the synthesis and release of other pro-inflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-a from fibroblasts and macrophages. The genes for CCL3 and CCL4 are both located on human chromosome 17.

Interferon Alpha and Beta Receptor Subunit 2 or IFNAR2 is a protein, part of the class II cytokine receptor family. When different innate immune signaling transduction are activated, there is a rapid induction of type I IFNs because it has an intronless gene source. IFNAR2 is the main ligand and binds to the receptor. Once bind, stabilization occurs and a signaling compelx recptor is formed. IFNAR2 also takes part in the activation process of STAT proteins.

Acetoacetyl-CoA thiolase (ACAT1) is an enzyme member of the membrane-bound acyltransferase family and Sterol o-acyltransferase subfamily. The ACAT1 enzyme catalyzes the reversible formation of acetoacetyl-CoA from 2 molecules of acetyl-CoA. ACAT1 plays a part in lipoprotein compilation and dietary cholesterol absorption. Added to its acyltransferase activity, ACAT1 acts as a ligase.

ACAT2 enzyme participates in lipid metabolism. ACAT2 takes part in lipoprotein assembly, catalyzing cholesterol esterification in mammalian cells. ACAT2 is an integral membrane protein that localizes to the endoplasmic reticulum of human intestinal cells. ACAT2 deficiency contributes to severe mental retardation and hypotonus.

Acyl-CoA Thioesterase 7 (ACOT7) belongs to the acyl coenzyme family. ACOT7 hydrolyzes the CoA thioester of palmitoyl-CoA and other long-chain fatty acids. Decreased expression of the ACOT7 protein may be linked to mesial temporal lobe epilepsy.

Myeloid/Lymphoid Leukemia Translocated To 11 (MLLT11) is a part of the Mixed-Lineage Leukemia protein family. MLLT11 which takes part in leukemogenesis and in the progression of severe monocytic leukemia (AML) is located on chromosome 11q23. MLLT11 which is also expressed in embryonic brain cortex is upregulated during neuronal differentiation and is taking part in the evolution of the central nervous system.

Cathepsin-L also known as CTSL is a member of the peptidase C1 family. CTSL, is a dimer composed of disulfide-linked heavy and light chains, both formed from a single protein precursor. Furthermore, CTSL is a lysosomal cysteine proteinase which takes a main part in intracellular protein catabolism. CTSL substrates include collagen and elastin, as well as alpha-1 protease inhibitor, which is the most important controlling element of neutrophil elastase activity. CTSL has been implicated in a number of pathologic processes, including myofibril necrosis in myopathies and in myocardial ischemia, and in the renal tubular response to proteinuria. Multiple alternatively spliced transcript variants have been found for CTSL.

ADP-ribosylhydrolase like 2 (ADPRHL2) belongs to the ADP-ribosylglycohydrolase family. ADPRHL2 catalyzes the removal of ADP-ribose from ADP-ribosylated proteins. ADPRHL2, which is ubiquitously expressed, uses magnesium as a cofactor to catalyze the hydrolysis of poly (ADP-ribose) that is synthesized after DNA damage. Furthermore, ADPRHL2 has an essential role in the maintenance of normal neuronal cell function. The ADPRHL2 enzyme localizes to the mitochondria, in addition to the nucleus and cytoplasm.

AKR7A2 participates in the detoxification of aldehydes and ketones. AKR7A2 catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. AKR7A2 is involved in producing the neuromodulator gamma-hydroxybutyrate (GHB). AKR7A2 has extensive substrate specificity. AKR7A2 shows NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). AKR7A2 reduces 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). AKR7A2 reduces the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. AKR7A2 takes part in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen.

ALDOB is a tetrameric glycolytic enzyme which catalyzes the reversible cleavage of fructose 1-phosphate into dihydroxyacetone phosphate and glyceraldehyde. Fructose-bisphosphate aldolase B (ALDOB) is one of 3 known aldolase isoenzymes, and is located in the kidney and the small adult intestine where it is linked with aldolases A or C. ALDOB is regulated by Insulin and glucagon and is implicated in hereditary fructose intolerance disease.

Aldolase C Fructose-Bisphosphate (ALDOC) belongs to the class I fructose-bisphosphate aldolase family. ALDOC is a glycolytic enzyme which catalyzes the reversible aldol cleavage of fructose-1,6-biphosphate and fructose 1-phosphate to dihydroxyacetone phosphate and either glyceraldehyde-3-phosphate or glyceraldehydes respectively. ALDOC is expressed exclusively in the hippocampus and Purkinje cells of the brain.

Single-strand-selective monofunctional uracil-DNA glycosylase (SMUG1) is an enzyme responsible for recognizing base lesions in the genome and initiating base excision DNA repair. SMUG1 participates in base excision repair by removing uracil from single- and double-stranded DNA. SMUG1 serves as a monofunctional DNA glycosylase specific for uracil (U) residues in DNA and has inclination for single-stranded DNA substrates. SMUG1 activity is greater against mismatches (U/G) than against matches (U/A).

Aspartic Peptidase, Retroviral-Like 1 (ASPRV1) is a protein which contains one peptidase A2 domain. ASPRV1 undergoes autocleavage which is essential for activation of the protein. ASPRV1 is expressed mostly in the granular layer of the epidermis and inner root sheath of hair follicles and localized to membrane region. In the psoriatic skin, ASPRV1 is expressed throughout the stratum corneum. In the ulcerated skin, ASPRV1 is expressed in the stratum granulosum of intact epidermis; however it is virtually nonexistent from ulcerated regions. In addition, ASPRV1 is expressed in differentiated areas of squamous cell carcinomas but not in the undifferentiated tumors.