Table 3.
Functions and medical conditions associated with the main putative targets of NHLH2
| NHLH2 targets | Gene product function | Diseases and medical conditions |
|---|---|---|
| Lhx5 | Regulation of neuronal differentiation and migration | Scapuloperoneal spinal muscular atrophy and scapuloperoneal myopathy |
| Nr5a2 | Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis, and triglyceride synthesis | Hepatitis B, maturity-onset diabetes of the young, and cholestasis and benign recurrent intrahepatic |
| Nr4a2 | Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development | Parkinson's disease, late-onset and arthritis |
| Rxfp1 | The activity of this receptor is mediated by G proteins leading to stimulation of adenylate cyclase and an increase of cAMP | Placenta accreta and endometriosis |
| Slc17a6 | Mediates the uptake of glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells | Amelogenesis imperfecta and arthrogryposis |
| Pdyn | Plays a role in a number of physiologic functions, including pain perception and responses to stress | Spinocerebellar ataxia 23 and drug dependence |
| Sphkap | Acts as a converging factor linking cAMP and sphingosine signaling pathways; plays a regulatory role in the modulation of SPHK1 | Renal cell carcinoma and papillary |
| Tmem35 | A soluble peptide released by shedding may interact with NGFR and modulate neurite outgrowth | Schizophrenia and Alzheimer's disease |
| Laptm4b | Blocks EGF-stimulated EGFR intraluminal sorting and degradation; plays a role as negative regulator of TGFB1 production in regulatory T cells; binds ceramide and facilitates its exit from late endosome in order to control cell death pathways | Mucolipidosis and gallbladder sarcoma |
| Tacr3 | Receptor for the tachykinin neuropeptide neuromedin-K; associated with G proteins that activate a phosphatidylinositol-calcium second messenger system | Hypogonadotropic hypogonadism 11 with or without anosmia and normosmic congenital hypogonadotropic hypogonadism |
| Rasd1 | Negatively regulates the transcription regulation activity of the APBB1/FE65-APP complex via its interaction with APBB1/FE65 | Malt Worker's lung and prostate leiomyosarcoma |
| Sox14 | Acts as a negative regulator of transcription; SRY-related HMG box gene 14, predominantly expressed in fetal brain, spinal cord, thymus, potentially involved in regulation of nervous system development, modulator of LINE retroposon promoter activity SOX14 | Blepharophimosis and moebius syndrome |
| Lhfpl1 | Lipoma HMGIC (high mobility Group I C protein) fusion partner like gene 1 | Branchiootic syndrome |
| Pcsk1 | Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues; substrates include POMC, renin, enkephalin, dynorphin, somatostatin, insulin, and AGRP | Proprotein convertase 1/3 deficiency and body mass index quantitative trait locus 12 |
| Pomc | Stimulates the adrenal glands to release cortisol; anorexigenic peptide; increases the pigmentation of skin by increasing melanin production in melanocytes; increases the pigmentation of skin by increasing melanin production in melanocytes; endogenous orexigenic opiate | Obesity, early-onset, with adrenal insufficiency and red hair and body mass index quantitative trait locus 11 |
| Vgll3 | May act as a specific coactivator for the mammalian TEFs | Juxtacortical osteosarcoma and malignant inflammatory fibrous histiocytoma |
| Golim4 | Plays a role in endosome to Golgi protein trafficking; mediates protein transport along the late endosome-bypass pathway from the early endosome to the Golgi | Spinal muscular atrophy, distal, autosomal recessive and immunodeficiency |
| App | Increased levels during neuronal differentiation | Cerebral amyloid angiopathy, app-related, and Alzheimer's disease |
| Npr3 | May function as a clearance receptor for NPPA, NPPB, and NPPC, regulating their local concentrations and effects; regulates diuresis, blood pressure, and skeletal development | Functional diarrhea and hypertension |
| Pcdh11x | Potential calcium-dependent cell-adhesion protein | Dyslexia and schizoaffective disorder |
| Pcdh19 | Potential calcium-dependent cell-adhesion protein | Epileptic encephalopathy, early infantile and childhood absence epilepsy |
| Rap2c | Plays a role in cytoskeletal rearrangements and regulates cell spreading through activation of the effector TNIK; may play a role in SRE-mediated gene transcription | Pathologic nystagmus |
| Enox2 | May be involved in cell growth | Suppressor of tumorigenicity 3 and variegate porphyria |
| Inhbb | Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland; inhibins appear to oppose the functions of activins | Eclampsia and pre-eclampsia |
| Rbms3 | Binds poly(A) and poly(U) oligoribonucleotides | Mental retardation with language impairment and with or without autistic features and Heimler syndrome 2 |
| Kcnk2 | Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward rectifying potassium channel in a phosphorylation-dependent manner | Posterolateral myocardial infarction and dentin sensitivity |
| Fgf13 | Plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus; required for the development of axonal initial segment-targeting inhibitory GABAergic synapses made by chandelier neurons | Borjeson-Forssman-Lehmann syndrome and X-linked congenital generalized hypertrichosis |
