Table 3.
Genetic FSGS: Genetic variants with syndromes with Mendelian and mitochondrial inheritance
| Cell Matrix | Slit Diaphragm Complex | Cytoskeleton and Related | Mitochondria Function | DNA Repair, Transcription, Nuclear Transport | Cell Signaling | Lysosome | Cilia |
|---|---|---|---|---|---|---|---|
| Nonsyndromic | |||||||
| COL4A3 | NPHS (nephrin) | ACTN4 | INF2 | WT 1 (Denys–Drash, Frasier) | PLCE1 | TTC21B | |
| COL4A4 | NPHS2 (podocin) | INF2 | NUP95 | TRPC6 | |||
| COL4A5 | CD2AP | AHRGP24 | NUP203 | ||||
| PTPRO (GLEPP1) | AHRGDIA | XP05 (exportin 5) | |||||
| MYO1E | NXF5 (nuclear export factor 5) | ||||||
| PAX2 | |||||||
| Syndromic | |||||||
| ITGB4 (epidermolysiss bullosa) | MYH9 (Esptein, Fechtner) | INF2 (Charcot–Marie–Tooth) | WT1 (Denys–Drash, Frasier) | KANK4 | SCARB2 (action myoclonus) | ||
| LAMB2 (Pearson) | MT-TL1, MT-TL2 tRNA leucine (MELAS)a | LMX1B (Nail-patella) | |||||
| MT-TY, tRNA tyrosine (MELAS)a | |||||||
| COQ2 | SMARCAL1 (Schimke immune-osseous dysplasia) | ||||||
| COQ6 | NXF5 | ||||||
| PDSS2 (Leigh) | EYA1 (Branchio-oto-renal) | ||||||
| ADCK | WDR73 (Galloway–Mowat, nephrocerebellar syndrome) | ||||||
| LMNA (partial lipodystrophy) | |||||||
| 5 | 5 | 5 | 7 | 11 | 3 | 1 | 1 |
Genetic FSGS can be categorized as susceptibility genes (not shown; e.g., APOL1) and genes with Mendelian and mitochondrial inheritance (38 genes shown above); genes for which casual evidence is not yet entirely convincing or associations are with unbiopsied nephrotic syndrome are omitted. These gene products are located in various podocyte cell compartments, although some proteins are present in more than one location (the number of genes in each compartment are tabulated in the last row). Nonsyndromic genes are those in which mutations are associated with manifestations only in the kidney; syndromic genes are those in which mutations are also associated with extrarenal manifestations, in some cases with variable penetrance (some individuals with certain mutations may have a purely renal phenotype). For some diseases, eponyms or syndromic names are provided in parentheses. Most genes affecting mitochondrial function are encoded by nuclear genes. MELAS, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes.
The two MELAS genes are encoded by mitochondrial DNA and show mitochondrial inheritance.