Table 1.
Genes mutated in SRNS/FSGS
| Gene | Chromosome | Protein | Inheritance | Age of onset | Eventual syndromic forms |
|---|---|---|---|---|---|
| Slight diaphragm proteins | |||||
| NPHS1 | 19q13.1 | Nephrin | AR | Congenital nephrotic syndrome; childhood FSGS | |
| NPHS2 | 1q25.2 | Podocin | AR | Early childhood, adolescence or adulthood | |
| CD2AP | 6p12 | CD2-associated protein | AD; rarely AR | Childhood or adulthood | |
| CRB2 | 9q33.4 | Crumbs homolog 2 | AR | Childhood FSGS | Association with cerebral ventriculomegaly |
| PLCE1 | 10q23.33 | Phospholipase C ε 1 | AR | Early-onset childhood | |
| TRPC6 | 11q22.1 | Transient receptor potential cation channel 6 | AD | Adulthood, rarely childhood | |
| Cytoskeleton structural and regulatory proteins | |||||
| ACTN4 | 19q13 | α-Actinin-4 | AD | Adulthood | |
| MYO1E | 15q22.2 | Non-muscle myosin 1E | AR | Childhood | |
| MYH9 | 22q12.3 | Myosin heavy chain 9 | AD | Childhood | Epstein–Fechtner syndrome (FSGS, deafness, cataracts, macrothrombocytopenia, leukocyte inclusions) |
| INF2 | 14q32.33 | Inverted formin 2 | AD | Adulthood | Association with Charcot–Marie–Tooth disease |
| ANLN | 7p15-p14 | Anillin | AD | Adulthood | |
| ARHGDIA | 17q25.3 | Rho GDP dissociation inhibitor α | AR | Congenital nephrotic syndrome/early childhood | |
| ARHGAP24 | 4q21.23 | RhoGTPase activating protein 24 | AD | Early childhood | |
| KANK 1 | 9p24.3 | Kidney ankyrin repeat- containing protein 1 | AR | Early adulthood | Association with intellectual disability |
| KANK 2 | 19p13.2 | Kidney ankyrin repeat- containing protein 2 | AR | Early childhood | |
| KANK 4 | 1p31.3 | Kidney ankyrin repeat- containing protein 4 | AR | Early childhood | Association with intellectual disability, facial dysmorphism and atrial septal defect |
| Adhesion proteins | |||||
| ITGA3 | 17q21.33 | Integrin α3 | AR | Early childhood | Association with epidermolysis bullosa and interstitial lung disease |
| ITGB4 | 17q11 | Integrin β4 | AR | Early childhood | Association with epidermolysis bullosa and pyloric atresia |
| LAMB2 | 3p21 | Laminin β2 | AR | Early childhood onset DMS or FSGS | Pierson syndrome (microcoria, neuromuscular junction defects) |
| Glomerular basement membrane proteins | |||||
| COL4A3 | 2q36-q37 | α3 type IV collagen | AR | Childhood, adulthood | Alport syndrome or familial/sporadic FSGS |
| COL4A4 | 2q35-q37 | α4 type IV collagen | AR | Childhood, adulthood | Alport syndrome or familial/sporadic FSGS |
| COL4A5 | Xq22 | α5 type IV collagen | X linked | Childhood, adulthood | Alport syndrome or familial/sporadic FSGS |
| LAMA 5 | 20q13.2-q13.3 | Laminin alpha 5 | AD | Adulthood | |
| Nuclear transcription factors | |||||
| LMX1B | 9q34 | LIM homeobox transcription factor 1β | AD | Familial FSGS | Nail–Patella syndrome (hypoplastic or absent patella, dysplasia of elbows, nail abnormalities) |
| WT1 | 11p13 | Wilms tumor 1 | AD | Childhood, adolescence | Frasier syndrome (FSGS, male pseudohermaphroditism, gonadoblastoma), Deny–Drash syndrome (DMS, male pseudohermaphroditism, Wilms tumor) |
| SMARCAL1 | 2q34-36 | SMARCA-like protein | AR | Childhood | Schimke immuno-osseous dysplasia (immunodeficiency, skeletal dysplasia) |
| NXF5 | Xq22 | Nuclear RNA export factor 5 | X linked | Adulthood | Association with cardiac conduction disorders |
| Nuclear pore complex proteins | |||||
| NUP93 | 16q13 | Nucleoporin 93 kDa | AR | Childhood | |
| NUP205 | 7q33 | Nucleoporin 205 kDa | AR | Childhood | |
| XPO5 | 6p21.1 | Exportin 5 | AR | Childhood | |
| NUP107 | 12q15 | Nucleoporin 107 kDa | AR | Childhood | Association with microcephaly |
| Coenzyme Q10 biosynthesis | |||||
| ADCK4 | 19q13.2 | aarF domain containing kinase 4 | AR | Childhood, early adulthood | |
| COQ2 | 4q21.23 | Coenzyme Q2 hydroxybenzoate-polyprenyl transferase | AR | Childhood | Association with encephalopathy |
| COQ6 | 14q24.3 | Coenzyme Q6 monooxygenase | AR | Early childhood | Association with deafness |
| PDSS2 | 6q21 | Prenyl (decaprenyl) diphosphate synthase | AR | Congenital SRNS | Association with encephalomyopathy |
| Other | |||||
| MTTL1 | mtDNA | Mitochondrially encoded tRNA leucine 1 | Maternal | Adulthood | MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) |
| SCARB2 | 4q13-21 | Scavenger receptor class B member 2 | AR | Early adulthood | Action myoclonus-renal failure syndrome (ataxia, myoclonus, collapsing FSGS) |
| CUBN | 10p12.31 | Cubilin | AR | Childhood | Association megaloblastic anemia |
| DGKE | 17q22 | Diacylglycerol kinase | AR | Childhood | |
| PTRO | 12p13-p12 | Protein tyrosine phosphatase, receptor type O | AR | Childhood | |
| PMM2 | 16p13.3 | Phosphomannomutase 2 | AR | Childhood | |
| WDR73 | 15q22 | WD repeat domain 73 | AR | Childhood | Galloway–Mowat syndrome (microcephaly and developmental delay) |
| ALG1 | 16p13.3 | Asparagine-linked glycosylation 1 | AR | Congenital nephrotic syndrome | |
AR, autosomic recessive; AD, autosomic dominant; DMS, diffuse mesangial sclerosis; mtDNA, mitochondrial DNA.