Familial idiopathic steroid-resistant nephrotic syndrome
diseaseOn this page
Also known as familial idiopathic nephrotic syndrome
Summary
Familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006) is a disease (an umbrella term covering 14 Mondo subtypes) with 30 cohort genes. The dominant Reactome pathway is Postmitotic nuclear pore complex (NPC) reformation (7 cohort genes).
At a glance
- Prevalence: Unknown (Worldwide)
- Umbrella term: 14 Mondo subtypes
- Cohort genes: 30
- ClinVar variants: 8
- Phenotypes (HPO): 17
Clinical features
Signs & symptoms
Clinical features (HPO)
17 HPO clinical features (Orphanet curated; top 17 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000093 | Proteinuria | Obligate (100%) |
| HP:0000969 | Edema | Very frequent (80-99%) |
| HP:0000097 | Focal segmental glomerulosclerosis | Frequent (30-79%) |
| HP:0003774 | Stage 5 chronic kidney disease | Frequent (30-79%) |
| HP:0012622 | Chronic kidney disease | Frequent (30-79%) |
| HP:0100539 | Periorbital edema | Frequent (30-79%) |
| HP:0000737 | Irritability | Occasional (5-29%) |
| HP:0001945 | Fever | Occasional (5-29%) |
| HP:0001967 | Diffuse mesangial sclerosis | Occasional (5-29%) |
| HP:0002027 | Abdominal pain | Occasional (5-29%) |
| HP:0002315 | Headache | Occasional (5-29%) |
| HP:0003073 | Hypoalbuminemia | Occasional (5-29%) |
| HP:0011947 | Respiratory tract infection | Occasional (5-29%) |
| HP:0012579 | Minimal change glomerulonephritis | Occasional (5-29%) |
| HP:0031504 | Foamy urine | Occasional (5-29%) |
| HP:0000707 | Abnormality of the nervous system | Very rare (<1-4%) |
| HP:0002586 | Peritonitis | Very rare (<1-4%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | familial idiopathic steroid-resistant nephrotic syndrome |
| Mondo ID | MONDO:0019006 |
| Orphanet | 656 |
| ICD-11 | 1385860879 |
| SNOMED CT | 718141008 |
| UMLS | C4273714 |
| MedGen | 902527 |
| GARD | 0003946 |
| Is cancer (heuristic) | no |
Also known as: familial idiopathic nephrotic syndrome
Data availability: 8 ClinVar variants · 28 GenCC gene-disease records.
Disease family
An umbrella term covering 14 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › familial nephrotic syndrome › familial idiopathic steroid-resistant nephrotic syndrome
Related subtypes (17): congenital nephrotic syndrome, Finnish type, nephrotic syndrome, type 4, LAMB2-related infantile-onset nephrotic syndrome, immunoglobulin-mediated membranoproliferative glomerulonephritis, nephrotic syndrome, type 20, nephrotic syndrome, type 22, nephrotic syndrome, type 23, nephrotic syndrome, type 24, nephrotic syndrome, IIa 26, nephrotic syndrome, type 17, nephrotic syndrome, type 18, nephrotic syndrome, type 19, nephrotic syndrome, type 21, nephrotic syndrome 14, nephrotic syndrome 15, nephrotic syndrome 16, idiopathic multidrug-resistant nephrotic syndrome
Subtypes (14): nephrotic syndrome, type 2, focal segmental glomerulosclerosis 1, nephrotic syndrome, type 3, nephrotic syndrome, type 6, familial steroid-resistant nephrotic syndrome with sensorineural deafness, nephrotic syndrome, type 8, nephrotic syndrome, type 9, nephrotic syndrome, type 10, nephrotic syndrome, type 11, nephrotic syndrome, type 12, nephrotic syndrome, type 13, familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation, familial idiopathic steroid-resistant nephrotic syndrome with minimal changes, familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
8 retrieved; paginated sample, class counts are floors:
2 conflicting classifications of pathogenicity, 2 pathogenic, 2 pathogenic/likely pathogenic, 1 likely pathogenic, 1 uncertain significance
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 546072 | NM_173689.7(CRB2):c.2400C>G (p.Asn800Lys) | CRB2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 504890 | NM_014625.4(NPHS2):c.535-1G>T | NPHS2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3493 | NM_024426.6(WT1):c.1447+5G>A | WT1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3500 | NM_024426.6(WT1):c.1447+4C>T | WT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 222890 | NM_024426.6(WT1):c.1265G>T (p.Gly422Val) | WT1 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 180466 | NM_004646.4(NPHS1):c.3173C>T (p.Ser1058Leu) | NPHS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 222761 | NM_004646.4(NPHS1):c.2398C>T (p.Arg800Cys) | NPHS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3377412 | NM_005245.4(FAT1):c.748G>A (p.Ala250Thr) | FAT1 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 140 · Orphanet: 47 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| COQ8B | Definitive | Autosomal recessive | nephrotic syndrome, type 9 | 3 |
| NPHS1 | Definitive | Autosomal recessive | congenital nephrotic syndrome, Finnish type | 6 |
| NPHS2 | Definitive | Autosomal recessive | nephrotic syndrome, type 2 | 7 |
| NUP93 | Definitive | Autosomal recessive | nephrotic syndrome, type 12 | 6 |
| PLCE1 | Definitive | Autosomal recessive | nephrotic syndrome, type 3 | 5 |
| ARHGDIA | Strong | Autosomal recessive | nephrotic syndrome, type 8 | 5 |
| EMP2 | Strong | Autosomal recessive | nephrotic syndrome, type 10 | 4 |
| MAGI2 | Strong | Autosomal recessive | nephrotic syndrome 15 | 5 |
| NUP107 | Strong | Autosomal recessive | nephrotic syndrome, type 11 | 11 |
| NUP133 | Strong | Autosomal recessive | nephrotic syndrome, type 18 | 8 |
| NUP160 | Strong | Autosomal recessive | nephrotic syndrome, type 19 | 4 |
| NUP205 | Strong | Autosomal recessive | nephrotic syndrome, type 13 | 4 |
| NUP85 | Strong | Autosomal recessive | nephrotic syndrome, type 17 | 5 |
| PTPRO | Strong | Autosomal recessive | nephrotic syndrome, type 6 | 4 |
| PTPRU | Strong | Autosomal recessive | nephrotic syndrome, type 6 | 4 |
| TBC1D8B | Strong | X-linked | nephrotic syndrome, type 20 | 4 |
| ACTN4 | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 4 |
| ANKFY1 | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 2 |
| ANLN | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 4 |
| ARHGAP24 | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 2 |
| CD2AP | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 3 |
| CRB2 | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 7 |
| GAPVD1 | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | |
| INF2 | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 7 |
| MYO1E | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 6 |
| NUP37 | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 2 |
| PAX2 | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 6 |
| TRPC6 | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 4 |
| WT1 | Supportive | Autosomal dominant | familial idiopathic steroid-resistant nephrotic syndrome | 7 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| WT1 | Orphanet:220 | Denys-Drash syndrome |
| WT1 | Orphanet:242 | 46,XY complete gonadal dysgenesis |
| WT1 | Orphanet:251510 | 46,XY partial gonadal dysgenesis |
| WT1 | Orphanet:3097 | Meacham syndrome |
| WT1 | Orphanet:347 | Frasier syndrome |
| WT1 | Orphanet:654 | Nephroblastoma |
| WT1 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| WT1 | Orphanet:83469 | Desmoplastic small round cell tumor |
| WT1 | Orphanet:893 | WAGR syndrome |
| NPHS2 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| CRB2 | Orphanet:443988 | Ventriculomegaly-cystic kidney disease |
| CRB2 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| NPHS1 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| NPHS1 | Orphanet:839 | Congenital nephrotic syndrome, Finnish type |
| TRPC6 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| ANLN | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| CD2AP | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| ACTN4 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| PLCE1 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| NUP133 | Orphanet:2065 | Galloway-Mowat syndrome |
| NUP133 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| NUP160 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| NUP205 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| MAGI2 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| COQ8B | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| COQ8B | Orphanet:791 | Retinitis pigmentosa |
| ANKFY1 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| GAPVD1 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| INF2 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| INF2 | Orphanet:93114 | Autosomal dominant intermediate Charcot-Marie-Tooth disease type E |
| TBC1D8B | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| ARHGAP24 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| NUP93 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| NUP107 | Orphanet:2065 | Galloway-Mowat syndrome |
| NUP107 | Orphanet:243 | 46,XX gonadal dysgenesis |
| NUP107 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| NUP37 | Orphanet:2512 | Autosomal recessive primary microcephaly |
| NUP37 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| EMP2 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| ARHGDIA | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| MYO1E | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| PAX2 | Orphanet:1475 | Renal coloboma syndrome |
| PAX2 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| PAX2 | Orphanet:97362 | Renal hypoplasia, bilateral |
| NUP85 | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
| NUP85 | Orphanet:808 | Seckel syndrome |
| PTPRO | Orphanet:656 | Hereditary steroid-resistant nephrotic syndrome |
Cohort genes → proteins
30 cohort genes, 30 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 30 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| WT1 | HGNC:12796 | ENSG00000184937 | P19544 | Wilms tumor protein | gencc,clinvar |
| NPHS2 | HGNC:13394 | ENSG00000116218 | Q9NP85 | Podocin | gencc,clinvar |
| CRB2 | HGNC:18688 | ENSG00000148204 | Q5IJ48 | Protein crumbs homolog 2 | gencc,clinvar |
| NPHS1 | HGNC:7908 | ENSG00000161270 | O60500 | Nephrin | gencc,clinvar |
| TRPC6 | HGNC:12338 | ENSG00000137672 | Q9Y210 | Short transient receptor potential channel 6 | gencc |
| ANLN | HGNC:14082 | ENSG00000011426 | Q9NQW6 | Anillin | gencc |
| CD2AP | HGNC:14258 | ENSG00000198087 | Q9Y5K6 | CD2-associated protein | gencc |
| ACTN4 | HGNC:166 | ENSG00000130402 | O43707 | Alpha-actinin-4 | gencc |
| PLCE1 | HGNC:17175 | ENSG00000138193 | Q9P212 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 | gencc |
| NUP133 | HGNC:18016 | ENSG00000069248 | Q8WUM0 | Nuclear pore complex protein Nup133 | gencc |
| NUP160 | HGNC:18017 | ENSG00000030066 | Q12769 | Nuclear pore complex protein Nup160 | gencc |
| NUP205 | HGNC:18658 | ENSG00000155561 | Q92621 | Nuclear pore complex protein Nup205 | gencc |
| MAGI2 | HGNC:18957 | ENSG00000187391 | Q86UL8 | Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 | gencc |
| COQ8B | HGNC:19041 | ENSG00000123815 | Q96D53 | Atypical kinase COQ8B, mitochondrial | gencc |
| ANKFY1 | HGNC:20763 | ENSG00000185722 | Q9P2R3 | Ankyrin repeat and FYVE domain-containing protein 1 | gencc |
| GAPVD1 | HGNC:23375 | ENSG00000165219 | Q14C86 | GTPase-activating protein and VPS9 domain-containing protein 1 | gencc |
| INF2 | HGNC:23791 | ENSG00000203485 | Q27J81 | Inverted formin-2 | gencc |
| TBC1D8B | HGNC:24715 | ENSG00000133138 | Q0IIM8 | TBC1 domain family member 8B | gencc |
| ARHGAP24 | HGNC:25361 | ENSG00000138639 | Q8N264 | Rho GTPase-activating protein 24 | gencc |
| NUP93 | HGNC:28958 | ENSG00000102900 | Q8N1F7 | Nuclear pore complex protein Nup93 | gencc |
| NUP107 | HGNC:29914 | ENSG00000111581 | P57740 | Nuclear pore complex protein Nup107 | gencc |
| NUP37 | HGNC:29929 | ENSG00000075188 | Q8NFH4 | Nucleoporin Nup37 | gencc |
| EMP2 | HGNC:3334 | ENSG00000213853 | P54851 | Epithelial membrane protein 2 | gencc |
| ARHGDIA | HGNC:678 | ENSG00000141522 | P52565 | Rho GDP-dissociation inhibitor 1 | gencc |
| MYO1E | HGNC:7599 | ENSG00000157483 | Q12965 | Unconventional myosin-Ie | gencc |
| PAX2 | HGNC:8616 | ENSG00000075891 | Q02962 | Paired box protein Pax-2 | gencc |
| NUP85 | HGNC:8734 | ENSG00000125450 | Q9BW27 | Nuclear pore complex protein Nup85 | gencc |
| PTPRO | HGNC:9678 | ENSG00000151490 | Q16827 | Receptor-type tyrosine-protein phosphatase O | gencc |
| PTPRU | HGNC:9683 | ENSG00000060656 | Q92729 | Receptor-type tyrosine-protein phosphatase U | gencc |
| FAT1 | HGNC:3595 | ENSG00000083857 | Q14517 | Protocadherin Fat 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| WT1 | Wilms tumor protein | Transcription factor that plays an important role in cellular development and cell survival. |
| NPHS2 | Podocin | Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton. |
| CRB2 | Protein crumbs homolog 2 | Apical polarity protein that plays a central role during the epithelial-to-mesenchymal transition (EMT) at gastrulation, when newly specified mesodermal cells move inside the embryo. |
| NPHS1 | Nephrin | Seems to play a role in the development or function of the kidney glomerular filtration barrier. |
| TRPC6 | Short transient receptor potential channel 6 | Forms a receptor-activated non-selective calcium permeant cation channel. |
| ANLN | Anillin | Required for cytokinesis. |
| CD2AP | CD2-associated protein | Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. |
| ACTN4 | Alpha-actinin-4 | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. |
| PLCE1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. |
| NUP133 | Nuclear pore complex protein Nup133 | Involved in poly(A)+ RNA transport. |
| NUP160 | Nuclear pore complex protein Nup160 | Functions as a component of the nuclear pore complex (NPC). |
| NUP205 | Nuclear pore complex protein Nup205 | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. |
| MAGI2 | Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 | Seems to act as a scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins. |
| COQ8B | Atypical kinase COQ8B, mitochondrial | Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration. |
| ANKFY1 | Ankyrin repeat and FYVE domain-containing protein 1 | Proposed effector of Rab5. |
| GAPVD1 | GTPase-activating protein and VPS9 domain-containing protein 1 | Acts both as a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF), and participates in various processes such as endocytosis, insulin receptor internalization or LC2A4/GLUT4 trafficking. |
| INF2 | Inverted formin-2 | Severs actin filaments and accelerates their polymerization and depolymerization. |
| TBC1D8B | TBC1 domain family member 8B | Involved in vesicular recycling, probably as a RAB11B GTPase-activating protein. |
| ARHGAP24 | Rho GTPase-activating protein 24 | Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization. |
| NUP93 | Nuclear pore complex protein Nup93 | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. |
| NUP107 | Nuclear pore complex protein Nup107 | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. |
| NUP37 | Nucleoporin Nup37 | Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). |
| EMP2 | Epithelial membrane protein 2 | Functions as a key regulator of cell membrane composition by regulating protein surface expression. |
| ARHGDIA | Rho GDP-dissociation inhibitor 1 | Controls Rho proteins homeostasis. |
| MYO1E | Unconventional myosin-Ie | Actin-based motor molecule with ATPase activity. |
| PAX2 | Paired box protein Pax-2 | Transcription factor that may have a role in kidney cell differentiation. |
| NUP85 | Nuclear pore complex protein Nup85 | Essential component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance. |
| PTPRO | Receptor-type tyrosine-protein phosphatase O | Possesses tyrosine phosphatase activity. |
| PTPRU | Receptor-type tyrosine-protein phosphatase U | Tyrosine-protein phosphatase which dephosphorylates CTNNB1. |
| FAT1 | Protocadherin Fat 1 | Plays an essential role for cellular polarization, directed cell migration and modulating cell-cell contact. |
Protein-family classification
Druggable: 7 · Difficult: 9 · Unknown: 14 · Druggable fraction: 0.23
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Scaffold/PPI | 6 | 3.5× | 0.053 |
| Phosphatase | 2 | 5.6× | 0.198 |
| Ion channel | 1 | 3.7× | 0.590 |
| Kinase | 2 | 1.9× | 0.590 |
| Antibody/Immunoglobulin | 1 | 1.0× | 0.927 |
| Other/Unknown | 14 | 0.8× | 0.927 |
| Transcription factor | 3 | 0.8× | 0.927 |
| Enzyme (other) | 1 | 0.4× | 0.927 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| WT1 | Transcription factor | no | Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf | |
| NPHS2 | Other/Unknown | no | Band_7, Stomatin_HflK_fam, Band_7/stomatin-like_CS | |
| CRB2 | Other/Unknown | no | EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G | |
| NPHS1 | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, FN3_dom | |
| TRPC6 | Ion channel | yes | Ankyrin_rpt, TRPC_channel, TRPC6_channel | |
| ANLN | Scaffold/PPI | no | PH_domain, PH-like_dom_sf, AHD | |
| CD2AP | Scaffold/PPI | no | SH3_domain, CD2AP_SH3_1, CD2AP_SH_2 | |
| ACTN4 | Other/Unknown | no | Actinin_actin-bd_CS, CH_dom, Spectrin_repeat | |
| PLCE1 | Enzyme (other) | yes | 3.1.4.11 | C2_dom, RA_dom, PLipase_C_PInositol-sp_X_dom |
| NUP133 | Scaffold/PPI | no | Nucleoporin_Nup133/Nup155_C, WD40/YVTN_repeat-like_dom_sf, Nup133-like | |
| NUP160 | Other/Unknown | no | Nucleoporin_Nup160, TPR_NUP160_M, TPR_NUP160_C | |
| NUP205 | Other/Unknown | no | Nup186/Nup192/Nup205 | |
| MAGI2 | Kinase | yes | WW_dom, PDZ, Guanylate_kin-like_dom | |
| COQ8B | Kinase | yes | ABC1_dom, Kinase-like_dom_sf, ADCK3_dom | |
| ANKFY1 | Transcription factor | no | BTB/POZ_dom, Znf_FYVE, Ankyrin_rpt | |
| GAPVD1 | Other/Unknown | no | RasGAP_dom, VPS9, Rho_GTPase_activation_prot | |
| INF2 | Other/Unknown | no | WH2_dom, FH3_dom, GTPase-bd | |
| TBC1D8B | Other/Unknown | no | Rab-GAP-TBC_dom, EF_hand_dom, GRAM | |
| ARHGAP24 | Scaffold/PPI | no | RhoGAP_dom, PH_domain, Rho_GTPase_activation_prot | |
| NUP93 | Other/Unknown | no | Nucleoporin_int_Nup93/Nic96 | |
| NUP107 | Other/Unknown | no | Nup84/Nup107 | |
| NUP37 | Scaffold/PPI | no | WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS | |
| EMP2 | Other/Unknown | no | EMP-2, PMP22/EMP/MP20/Claudin, PMP22_EMP_MP20 | |
| ARHGDIA | Other/Unknown | no | Rho_GDI, Ig_E-set, RhoGDI_dom_sf | |
| MYO1E | Scaffold/PPI | no | SH3_domain, Myosin_head_motor_dom-like, Myosin_TH1 | |
| PAX2 | Transcription factor | no | Paired_dom, Homeodomain-like_sf, Pax2_C | |
| NUP85 | Other/Unknown | no | Nucleoporin_Nup85 | |
| PTPRO | Phosphatase | yes | 3.1.3.48 | PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat |
| PTPRU | Phosphatase | yes | 3.1.3.48 | PTP_cat, Tyr_Pase_dom, MAM_dom |
| FAT1 | Other/Unknown | no | EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G |
Expression context
Cohort genes with no expression data: 0.
30 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 30 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| ventricular zone | 6 |
| metanephric glomerulus | 5 |
| renal glomerulus | 4 |
| oocyte | 4 |
| secondary oocyte | 4 |
| ganglionic eminence | 3 |
| corpus callosum | 3 |
| calcaneal tendon | 2 |
| sural nerve | 2 |
| metanephros cortex | 2 |
| renal medulla | 2 |
| germinal epithelium of ovary | 1 |
| kidney epithelium | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| body of pancreas | 1 |
| buccal mucosa cell | 1 |
| vena cava | 1 |
| lower esophagus | 1 |
| lower esophagus muscularis layer | 1 |
| right lung | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| WT1 | 168 | broad | marker | germinal epithelium of ovary, renal glomerulus, metanephric glomerulus |
| NPHS2 | 47 | tissue_specific | marker | renal glomerulus, metanephric glomerulus, kidney epithelium |
| CRB2 | 99 | broad | marker | ventricular zone, ganglionic eminence, male germ line stem cell (sensu Vertebrata) in testis |
| NPHS1 | 147 | tissue_specific | marker | buccal mucosa cell, body of pancreas, vena cava |
| TRPC6 | 180 | broad | marker | right lung, lower esophagus muscularis layer, lower esophagus |
| ANLN | 222 | ubiquitous | marker | corpus callosum, inferior vagus X ganglion, C1 segment of cervical spinal cord |
| CD2AP | 275 | ubiquitous | marker | jejunal mucosa, esophagus squamous epithelium, colonic mucosa |
| ACTN4 | 145 | ubiquitous | marker | popliteal artery, tibial artery, smooth muscle tissue |
| PLCE1 | 271 | broad | marker | renal glomerulus, metanephric glomerulus, ventricular zone |
| NUP133 | 297 | ubiquitous | marker | secondary oocyte, oocyte, ventricular zone |
| NUP160 | 278 | ubiquitous | marker | oocyte, mucosa of paranasal sinus, secondary oocyte |
| NUP205 | 265 | ubiquitous | marker | ventricular zone, ganglionic eminence, embryo |
| MAGI2 | 267 | ubiquitous | marker | calcaneal tendon, corpus callosum, Brodmann (1909) area 23 |
| COQ8B | 227 | ubiquitous | marker | right uterine tube, adenohypophysis, pituitary gland |
| ANKFY1 | 265 | ubiquitous | marker | skin of hip, parietal pleura, corpus callosum |
| GAPVD1 | 299 | ubiquitous | marker | bronchial epithelial cell, epithelium of bronchus, bronchus |
| INF2 | 260 | ubiquitous | marker | sural nerve, nerve, tibial nerve |
| TBC1D8B | 237 | ubiquitous | marker | right adrenal gland cortex, right adrenal gland, left adrenal gland cortex |
| ARHGAP24 | 263 | ubiquitous | marker | renal medulla, pons, metanephros cortex |
| NUP93 | 285 | ubiquitous | marker | ventricular zone, ganglionic eminence, left lobe of thyroid gland |
| NUP107 | 283 | ubiquitous | marker | secondary oocyte, oocyte, ventricular zone |
| NUP37 | 265 | ubiquitous | marker | oocyte, secondary oocyte, primordial germ cell in gonad |
| EMP2 | 273 | ubiquitous | marker | upper leg skin, upper arm skin, lower lobe of lung |
| ARHGDIA | 292 | ubiquitous | marker | granulocyte, colonic epithelium, mucosa of transverse colon |
| MYO1E | 235 | ubiquitous | marker | calcaneal tendon, sural nerve, gall bladder |
| PAX2 | 92 | broad | marker | metanephros cortex, renal medulla, adult mammalian kidney |
| NUP85 | 258 | ubiquitous | marker | cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum |
| PTPRO | 214 | broad | marker | renal glomerulus, metanephric glomerulus, cortical plate |
| PTPRU | 239 | ubiquitous | marker | endocervix, olfactory segment of nasal mucosa, ectocervix |
| FAT1 | 288 | ubiquitous | marker | choroid plexus epithelium, tibia, metanephric glomerulus |
Protein interactions among cohort
Intra-cohort edges: 84.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ANLN | 6,413 |
| WT1 | 3,938 |
| NUP107 | 3,524 |
| NUP133 | 3,453 |
| ACTN4 | 3,303 |
| MAGI2 | 3,246 |
| GAPVD1 | 3,119 |
| NUP93 | 3,031 |
| ANKFY1 | 2,929 |
| NUP205 | 2,881 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ACTN4 | ANLN | biogrid_interaction, string_interaction |
| ACTN4 | CD2AP | string_interaction |
| ACTN4 | INF2 | string_interaction |
| ACTN4 | MYO1E | string_interaction |
| ACTN4 | NPHS1 | string_interaction |
| ACTN4 | NPHS2 | string_interaction |
| ACTN4 | PLCE1 | string_interaction |
| ACTN4 | PTPRO | string_interaction |
| ACTN4 | TRPC6 | string_interaction |
| ANKFY1 | GAPVD1 | string_interaction |
| ANKFY1 | TBC1D8B | string_interaction |
| ANLN | CD2AP | string_interaction |
| ANLN | INF2 | intact, string_interaction |
| ANLN | MYO1E | intact, string_interaction |
| ARHGAP24 | ARHGDIA | string_interaction |
| ARHGAP24 | INF2 | string_interaction |
| ARHGAP24 | NPHS1 | string_interaction |
| ARHGAP24 | NPHS2 | string_interaction |
| CD2AP | FAT1 | string_interaction |
| CD2AP | INF2 | string_interaction |
| CD2AP | NPHS1 | string_interaction |
| CD2AP | NPHS2 | biogrid_interaction, string_interaction |
| CD2AP | PLCE1 | string_interaction |
| CD2AP | PTPRO | string_interaction |
| CD2AP | TRPC6 | string_interaction |
| COQ8B | EMP2 | string_interaction |
| COQ8B | INF2 | string_interaction |
| COQ8B | MYO1E | string_interaction |
| COQ8B | NPHS1 | string_interaction |
| COQ8B | NPHS2 | string_interaction |
| COQ8B | PLCE1 | string_interaction |
| EMP2 | NPHS1 | string_interaction |
| EMP2 | NPHS2 | string_interaction |
| EMP2 | PLCE1 | string_interaction |
| FAT1 | NPHS1 | string_interaction |
| FAT1 | NPHS2 | string_interaction |
| GAPVD1 | TBC1D8B | string_interaction |
| INF2 | MYO1E | string_interaction |
| INF2 | NPHS1 | string_interaction |
| INF2 | NPHS2 | string_interaction |
| INF2 | PLCE1 | string_interaction |
| INF2 | PTPRO | string_interaction |
| INF2 | TRPC6 | string_interaction |
| INF2 | WT1 | string_interaction |
| MYO1E | NPHS1 | string_interaction |
| MYO1E | NPHS2 | string_interaction |
| MYO1E | PLCE1 | string_interaction |
| MYO1E | PTPRO | string_interaction |
| MYO1E | TRPC6 | string_interaction |
| NPHS1 | NPHS2 | biogrid_interaction, string_interaction |
Structural data
PDB: 20 · AlphaFold-only: 10 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| WT1 | P19544 | 28 |
| ARHGDIA | P52565 | 21 |
| CD2AP | Q9Y5K6 | 12 |
| INF2 | Q27J81 | 10 |
| NUP133 | Q8WUM0 | 8 |
| NUP93 | Q8N1F7 | 7 |
| NUP107 | P57740 | 7 |
| TRPC6 | Q9Y210 | 6 |
| ACTN4 | O43707 | 5 |
| NUP205 | Q92621 | 5 |
| MAGI2 | Q86UL8 | 5 |
| NUP160 | Q12769 | 4 |
| NUP37 | Q8NFH4 | 4 |
| NUP85 | Q9BW27 | 4 |
| ANLN | Q9NQW6 | 3 |
| PLCE1 | Q9P212 | 3 |
| PTPRO | Q16827 | 2 |
| PTPRU | Q92729 | 2 |
| CRB2 | Q5IJ48 | 1 |
| NPHS1 | O60500 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| EMP2 | P54851 | 94.89 |
| ANKFY1 | Q9P2R3 | 86.98 |
| MYO1E | Q12965 | 80.46 |
| TBC1D8B | Q0IIM8 | 79.33 |
| COQ8B | Q96D53 | 77.00 |
| NPHS2 | Q9NP85 | 75.00 |
| ARHGAP24 | Q8N264 | 66.68 |
| GAPVD1 | Q14C86 | 63.17 |
| PAX2 | Q02962 | 61.52 |
| FAT1 | Q14517 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 78. Enrichment computed across 30 evidence-associated genes (25 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 25 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Postmitotic nuclear pore complex (NPC) reformation | 7 | 114.2× | 3e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| IPs transport between nucleus and cytosol | 7 | 106.6× | 3e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| IP3 and IP4 transport between cytosol and nucleus | 7 | 106.6× | 3e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| IP6 and IP7 transport between cytosol and nucleus | 7 | 106.6× | 3e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Transport of Ribonucleoproteins into the Host Nucleus | 7 | 99.9× | 3e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Regulation of Glucokinase by Glucokinase Regulatory Protein | 7 | 99.9× | 3e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC) | 7 | 99.9× | 3e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| NEP/NS2 Interacts with the Cellular Export Machinery | 7 | 96.9× | 4e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Nuclear import of Rev protein | 7 | 94.0× | 4e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Vpr-mediated nuclear import of PICs | 7 | 94.0× | 4e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Transport of the SLBP independent Mature mRNA | 7 | 91.4× | 4e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| SUMOylation of SUMOylation proteins | 7 | 91.4× | 4e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Transport of the SLBP Dependant Mature mRNA | 7 | 88.8× | 4e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Rev-mediated nuclear export of HIV RNA | 7 | 88.8× | 4e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Nuclear Pore Complex (NPC) Disassembly | 7 | 86.4× | 5e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| SUMOylation of ubiquitinylation proteins | 7 | 82.0× | 7e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| NS1 Mediated Effects on Host Pathways | 7 | 79.9× | 8e-12 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Transport of Mature mRNA Derived from an Intronless Transcript | 7 | 76.1× | 1e-11 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Viral Messenger RNA Synthesis | 7 | 72.7× | 1e-11 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| SUMOylation of DNA replication proteins | 7 | 69.5× | 2e-11 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| SUMOylation of RNA binding proteins | 7 | 66.6× | 2e-11 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| snRNP Assembly | 7 | 59.2× | 6e-11 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| tRNA processing in the nucleus | 7 | 55.1× | 9e-11 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| SUMOylation of chromatin organization proteins | 7 | 44.4× | 4e-10 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Transport of Mature mRNA derived from an Intron-Containing Transcript | 7 | 42.6× | 5e-10 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| ISG15 antiviral mechanism | 7 | 42.1× | 6e-10 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| SUMOylation of DNA damage response and repair proteins | 7 | 41.0× | 7e-10 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Regulation of HSF1-mediated heat shock response | 7 | 39.0× | 9e-10 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| Nephrin family interactions | 5 | 95.2× | 4e-09 | NPHS2, NPHS1, CD2AP, ACTN4, MAGI2 |
| HCMV Late Events | 7 | 27.6× | 1e-08 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 30 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| nucleocytoplasmic transport | 7 | 91.4× | 3e-10 | NUP133, NUP160, NUP205, NUP93, NUP107, NUP37, NUP85 |
| nephron development | 4 | 249.7× | 2e-07 | NUP133, NUP160, NUP107, NUP85 |
| glomerulus development | 4 | 172.8× | 6e-07 | WT1, PLCE1, MYO1E, PTPRO |
| nuclear pore complex assembly | 3 | 168.5× | 4e-05 | NUP205, NUP93, NUP107 |
| glomerular basement membrane development | 3 | 153.2× | 4e-05 | WT1, NPHS1, MYO1E |
| podocyte development | 3 | 153.2× | 4e-05 | NPHS1, MAGI2, MYO1E |
| podocyte differentiation | 3 | 140.4× | 5e-05 | WT1, CD2AP, PTPRO |
| slit diaphragm assembly | 2 | 561.7× | 1e-04 | NPHS1, PTPRO |
| mRNA export from nucleus | 4 | 39.4× | 1e-04 | NUP133, NUP160, NUP107, NUP85 |
| glomerular filtration | 3 | 93.6× | 1e-04 | NPHS2, TBC1D8B, MYO1E |
| regulation of glomerular filtration | 2 | 280.9× | 5e-04 | EMP2, PTPRO |
| metanephric epithelium development | 2 | 224.7× | 8e-04 | WT1, PAX2 |
| protein import into nucleus | 4 | 19.2× | 0.001 | NUP133, NUP93, NUP107, NUP85 |
| metanephric mesenchyme development | 2 | 160.5× | 0.001 | WT1, PAX2 |
| nuclear pore organization | 2 | 140.4× | 0.002 | NUP133, NUP205 |
| actin filament organization | 4 | 15.8× | 0.002 | CD2AP, EMP2, FAT1, MYO1E |
| mesenchymal to epithelial transition | 2 | 102.1× | 0.003 | WT1, PAX2 |
| nerve growth factor signaling pathway | 2 | 86.4× | 0.004 | CD2AP, MAGI2 |
| poly(A)+ mRNA export from nucleus | 2 | 44.9× | 0.015 | NUP133, NUP93 |
| septin ring assembly | 1 | 561.7× | 0.021 | ANLN |
| establishment of epithelial cell apical/basal polarity involved in camera-type eye morphogenesis | 1 | 561.7× | 0.021 | FAT1 |
| positive regulation of ion transmembrane transporter activity | 1 | 561.7× | 0.021 | TRPC6 |
| ingression involved in gastrulation with mouth forming second | 1 | 561.7× | 0.021 | CRB2 |
| optic chiasma development | 1 | 561.7× | 0.021 | PAX2 |
| negative regulation of metanephric glomerular mesangial cell proliferation | 1 | 561.7× | 0.021 | WT1 |
| positive regulation of optic nerve formation | 1 | 561.7× | 0.021 | PAX2 |
| protein localization to cell surface | 2 | 33.0× | 0.021 | EMP2, PTPRU |
| actin filament polymerization | 2 | 32.1× | 0.021 | CD2AP, INF2 |
| optic cup morphogenesis involved in camera-type eye development | 1 | 280.9× | 0.022 | PAX2 |
| regulation of animal organ formation | 1 | 280.9× | 0.022 | WT1 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 5 · Undrugged: 25
Druggability breadth: 14 of 30 evidence-associated genes (47%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| COQ8B | FEDRATINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| COQ8B | 9 | 4 |
| TRPC6 | 1 | 2 |
| ACTN4 | 1 | 2 |
| NUP205 | 1 | 2 |
| NUP93 | 1 | 2 |
| WT1 | 0 | 0 |
| NPHS2 | 0 | 0 |
| CRB2 | 0 | 0 |
| NPHS1 | 0 | 0 |
| ANLN | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| FEDRATINIB | 4 | COQ8B |
| VANDETANIB | 4 | COQ8B |
| ERLOTINIB | 4 | COQ8B |
| CRIZOTINIB | 4 | COQ8B |
| CANERTINIB | 3 | COQ8B |
| CLEMIZOLE | 2 | TRPC6 |
| MOLIBRESIB | 2 | ACTN4, NUP205, NUP93 |
| TG100-115 | 2 | COQ8B |
| R-406 | 2 | COQ8B |
| PELITINIB | 2 | COQ8B |
| BMS-387032 | 1 | COQ8B |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| COQ8B | 77 | Binding:77 |
| TRPC6 | 30 | Binding:30 |
| ACTN4 | 7 | Binding:7 |
| NUP205 | 7 | Binding:7 |
| NUP93 | 7 | Binding:7 |
| PTPRO | 7 | Binding:7 |
| ARHGDIA | 2 | Binding:2 |
| CD2AP | 1 | Binding:1 |
| NUP160 | 1 | Binding:1 |
| GAPVD1 | 1 | Binding:1 |
| INF2 | 1 | Binding:1 |
| PAX2 | 1 | Binding:1 |
| PTPRU | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PLCE1 | 3.1.4.11 | phosphoinositide phospholipase C |
| PTPRO | 3.1.3.48 | protein-tyrosine-phosphatase |
| PTPRU | 3.1.3.48 | protein-tyrosine-phosphatase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 30; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
11 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| FEDRATINIB | 4 | COQ8B |
| VANDETANIB | 4 | COQ8B |
| ERLOTINIB | 4 | COQ8B |
| CRIZOTINIB | 4 | COQ8B |
| CANERTINIB | 3 | COQ8B |
| CLEMIZOLE | 2 | TRPC6 |
| MOLIBRESIB | 2 | ACTN4, NUP205, NUP93 |
| TG100-115 | 2 | COQ8B |
| R-406 | 2 | COQ8B |
| PELITINIB | 2 | COQ8B |
| BMS-387032 | 1 | COQ8B |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | COQ8B |
| B | Phased (≥1) drug, not yet approved | 4 | TRPC6, ACTN4, NUP205, NUP93 |
| C | Druggable family + PDB, no drug | 5 | NPHS1, PLCE1, MAGI2, PTPRO, PTPRU |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 20 | WT1, NPHS2, CRB2, ANLN, CD2AP, NUP133, NUP160, ANKFY1, GAPVD1, INF2 (+10 more) |
Undrugged target profiles
25 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| NPHS2 | 0 | TRPC6 |
| PLCE1 | 0 | TRPC6 |
| INF2 | 1 | ACTN4 |
| EMP2 | 0 | COQ8B |
| MYO1E | 0 | ACTN4 |
| WT1 | 0 | — |
| CRB2 | 0 | — |
| NPHS1 | 0 | — |
| ANLN | 0 | — |
| CD2AP | 1 | — |
| NUP133 | 0 | — |
| NUP160 | 1 | — |
| MAGI2 | 0 | — |
| ANKFY1 | 0 | — |
| GAPVD1 | 1 | — |
| TBC1D8B | 0 | — |
| ARHGAP24 | 0 | — |
| NUP107 | 0 | — |
| NUP37 | 0 | — |
| ARHGDIA | 2 | — |
| PAX2 | 1 | — |
| NUP85 | 0 | — |
| PTPRO | 7 | — |
| PTPRU | 1 | — |
| FAT1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.