FSGS: Diagnosis and Diagnostic Work-Up

Table 1

Genetic defects associated with FSGS.

	Gene	Inheritance	Location	Function of the encoded protein
Slit diaphragm proteins
(i) Nephrin	NPHS1	AR	19q13.1	Member of the immunoglobulin family, cell adhesion molecules
(ii) Podocin	NPHS2	AR	1q25 31	Regulation of glomerular permeability
(iii) CD2 associated protein	CD2AP	AD (AR)	6p12	Scaffolding molecule that regulates the actin cytoskeleton
Cell membrane associated proteins
(i) Transient receptor potential cation channel 6	TRPC6	AD	11q21 22	Receptor-activated calcium channel in the cell membrane
(ii) Protein tyrosine phosphatase receptor type O	PTPRO	AR	12p22	Member of the R3 subtype family of protein tyrosine phosphatases at the apical surface of polarized cells
(iii) Laminin 2	LAMB2	AR	3p21	Family of extracellular matrix glycoproteins in the basement membranes
(iv) 4 integrin	ITGB4	AR	17q11	Transmembrane glycoprotein receptors
(v) Tetraspanin CD151	CD151	AR	11p15	Member of the transmembrane 4 superfamily, cell-surface proteins
(vi) LIM homeobox transcription factor 1β	LMX1B	AD	9q33.3	Member of LIM-homeodomain family, transcription factor
Cytosolic or cytoskeletal proteins
(i) Actinin 4	ACTN4	AD	19q13	Member of the spectrin gene superfamily, cytoskeletal proteins
(ii) Phospholipase C1	PLCE1	AR	10q23 24	Member of the apolipoprotein C1 family, role in HDL and VLDL metabolism
(iii) Myosin heavy chain 9	MYH9	AD	22q12.3	Nonmuscle myosin, involved in cytokinesis, cell motility, and maintenance of cell shape
(iv) Inverted formin 2	INF2	AD	14q32	Member of the formin family, function in de- and polymerization of actin filaments
(v) Myosin 1E	MYO1E	AR	15q21 26	Member of the nonmuscle class I myosins, involved in intracellular movement and membrane trafficking
(vi) Rho GDP-dissociation inhibitor 1	ARHGDIA	AR	17q25	Key role in the regulation of signaling through Rho GTPases
Nuclear proteins
(i) Wilms tumor 1	WT1	AD	11p13	Transcription factor, role in the normal development of the urogenital system
(ii) SMARCA-like protein	SMARCAL1	AR	2q34 36	Member of the SWI/SNF family, transcription factor
Mitochondrial components
(i) tRNAleu	mtDNA A3243G	Maternal	mtDNQ	Function unknown
(ii) Parahydroxybenzoate polyprenyltransferase	COQ2	AR	4q21 22	Functions in the final steps in the biosynthesis of CoQ
(iii) Coenzyme Q10 biosynthesis monooxygenase 6	COQ6	AR	14q24.3	Member of the ubiH/COQ6 family, required for the biosynthesis of coenzyme Q10
(iv) Decaprenyl diphosphate synthase subunit 2	PDSS2	AR	6q21	Enzyme that synthesizes the prenyl side chain of coenzyme Q or ubiquinone
(v) AarF domain-containing protein kinase 4	ADCK4	AR	19q13.2	Precise function unknown (possible protein kinase activity)
Lysosomal proteins
(i) Lysosomal integral membrane protein type 2	SCARB2	AR	4q13 21	Type III glycoprotein located in limiting membranes of lysosomes and endosomes
Unknown cellular location
(i) Apolipoprotein L1	APOL1	AR	22q12	Secreted high density lipoprotein, involved in the formation of cholesteryl esters and efflux of cholesterol from cells