Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development (PubMed:12138111, PubMed:16357870, PubMed:30478443). DNA methylation is coordinated with methylation of histones (PubMed:12138111, PubMed:16357870, PubMed:30478443). It modifies DNA in a non-processive manner and also methylates non-CpG sites (PubMed:12138111, PubMed:16357870, PubMed:30478443). May preferentially methylate DNA linker between 2 nucleosomal cores and i

NucleusChromosomeCytoplasm

Tatton-Brown-Rahman syndrome

An overgrowth syndrome characterized by a distinctive facial appearance, tall stature and intellectual disability. Facial gestalt is characterized by a round face, heavy horizontal eyebrows and narrow palpebral fissures. Less common features include atrial septal defects, seizures, umbilical hernia, and scoliosis.

Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) (PubMed:26925370, PubMed:27604842). SDH also oxidizes malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate (By similarity). Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerized into keto-oxaloacetate (By similarity)

Mitochondrion inner membrane

Pheochromocytoma/paraganglioma syndrome 4

A form of pheochromocytoma/paraganglioma syndrome, a tumor predisposition syndrome characterized by the development of neuroendocrine tumors, usually in adulthood. Pheochromocytomas are catecholamine-producing tumors that arise from chromaffin cells in the adrenal medulla. Paragangliomas develop from sympathetic paraganglia in the thorax, abdomen, and pelvis, as well as from parasympathetic paraganglia in the head and neck. PPGL4 inheritance is autosomal dominant.

Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) (PubMed:20064382, PubMed:20616503, PubMed:20702524, PubMed:21357690, PubMed:21454698, PubMed:24560924, PubMed:28846097, PubMed:28846099, PubMed:28953886, PubMed:31118272). In contrast to most receptor tyrosine kinases, RET requires not onl

Cell membraneEndosome membrane

Hirschsprung disease 1

A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child.

Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier.

NucleusNucleus speckle

Erythrocytosis, familial, 4

An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts.

Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) (PubMed:10482792, PubMed:9533030). SDH also oxidizes malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate (By similarity). Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerized into keto-oxaloacetate

Mitochondrion inner membrane

Pheochromocytoma/paraganglioma syndrome 1

A form of pheochromocytoma/paraganglioma syndrome, a tumor predisposition syndrome characterized by the development of neuroendocrine tumors, usually in adulthood. Pheochromocytomas are catecholamine-producing tumors that arise from chromaffin cells in the adrenal medulla. Paragangliomas develop from sympathetic paraganglia in the thorax, abdomen, and pelvis, as well as from parasympathetic paraganglia in the head and neck. PPGL1 inheritance is autosomal dominant.

Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:10944113, PubMed:17981124, PubMed:19584355). Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions (PubMed:10944113, PubMed:17981124). Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases (PubMed:10944113, PubMed:1

CytoplasmCell membraneEndoplasmic reticulumNucleus

Pheochromocytoma

A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.