Nephronophthisis 2
diseaseOn this page
Also known as INVS nephronophthisis (disease)nephronophthisis (disease) caused by mutation in INVSnephronophthisis 2, infantilenephronophthisis type 2NPH2NPHP2
Summary
Nephronophthisis 2 (MONDO:0011190) is a disease caused by INVS (GenCC Definitive), with 9 cohort genes.
At a glance
- Prevalence: Unknown (Europe) [Orphanet-validated]
- Causal gene: INVS (GenCC Definitive)
- Cohort genes: 9
- ClinVar variants: 292
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | nephronophthisis 2 |
| Mondo ID | MONDO:0011190 |
| MeSH | C566582 |
| OMIM | 602088 |
| Orphanet | 93591 |
| DOID | DOID:0111113 |
| UMLS | C1865872 |
| MedGen | 355574 |
| GARD | 0018182 |
| Is cancer (heuristic) | no |
Also known as: INVS nephronophthisis (disease) · nephronophthisis (disease) caused by mutation in INVS · nephronophthisis 2 · nephronophthisis 2, infantile · nephronophthisis type 2 · NPH2 · NPHP2
Data availability: 292 ClinVar variants · 10 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › nephronophthisis › nephronophthisis 2
Related subtypes (17): nephronophthisis 1, nephronophthisis 3, nephronophthisis 4, nephronophthisis 7, nephronophthisis-like nephropathy 1, nephronophthisis 11, nephronophthisis 12, nephronophthisis 9, nephronophthisis 13, nephronophthisis 14, nephronophthisis 15, nephronophthisis 16, nephronophthisis 18, nephronophthisis 19, nephronophthisis 20, late-onset nephronophthisis, nephronophthisis-like nephropathy 2
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
292 retrieved; paginated sample, class counts are floors:
183 uncertain significance, 28 conflicting classifications of pathogenicity, 24 likely pathogenic, 18 pathogenic/likely pathogenic, 14 pathogenic, 11 likely benign, 9 benign/likely benign, 5 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2498123 | NM_014425.5(INVS):c.[796+5G>A;805_806del] | Pathogenic | criteria provided, single submitter | |
| 1067538 | NM_014425.5(INVS):c.2786+1G>A | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1069181 | NM_014425.5(INVS):c.497_512dup (p.His171fs) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179160 | GRCh37/hg19 9q31.1(chr9:103059178-103060312) | INVS | Pathogenic | no assertion criteria provided |
| 11959 | NM_014425.5(INVS):c.1807C>T (p.Arg603Ter) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 11961 | NM_014425.5(INVS):c.2719C>T (p.Arg907Ter) | INVS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 11962 | NM_014425.5(INVS):c.2695C>T (p.Arg899Ter) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 11963 | NM_014425.5(INVS):c.1453del (p.Gln485fs) | INVS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1252044 | NM_014425.5(INVS):c.753T>G (p.Tyr251Ter) | INVS | Pathogenic | criteria provided, single submitter |
| 1355469 | NM_014425.5(INVS):c.1186C>T (p.Arg396Ter) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1458571 | NM_014425.5(INVS):c.2501_2502del (p.Lys834fs) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1459019 | NM_014425.5(INVS):c.1760del (p.Gln587fs) | INVS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2498124 | NM_014425.5(INVS):c.805_806del (p.Gln269fs) | INVS | Pathogenic | criteria provided, single submitter |
| 2584431 | NM_014425.5(INVS):c.325C>T (p.Gln109Ter) | INVS | Pathogenic | criteria provided, single submitter |
| 2751391 | NM_014425.5(INVS):c.2614C>T (p.Gln872Ter) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2779386 | NM_014425.5(INVS):c.648G>A (p.Trp216Ter) | INVS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2783208 | NM_014425.5(INVS):c.1367del (p.Gly456fs) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2793597 | NM_014425.5(INVS):c.2449dup (p.Glu817fs) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2900307 | NM_014425.5(INVS):c.766C>T (p.Arg256Ter) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2977398 | NM_014425.5(INVS):c.2225dup (p.Lys743fs) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3019143 | NM_014425.5(INVS):c.1726C>T (p.Arg576Ter) | INVS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3020908 | NM_014425.5(INVS):c.833del (p.Asn278fs) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3596174 | NM_014425.5(INVS):c.2160del (p.Ser721fs) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4277275 | NM_014425.5(INVS):c.2790C>A (p.Tyr930Ter) | INVS | Pathogenic | criteria provided, single submitter |
| 567470 | NM_014425.5(INVS):c.2887C>T (p.Gln963Ter) | INVS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 591520 | NM_014425.5(INVS):c.2786+2T>C | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 660098 | NM_014425.5(INVS):c.1078+1G>A | INVS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 690376 | NM_014425.5(INVS):c.1789C>T (p.Arg597Ter) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 834292 | NM_014425.5(INVS):c.2972C>G (p.Ser991Ter) | INVS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 974395 | NM_014425.5(INVS):c.1484G>A (p.Trp495Ter) | INVS | Pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 66 · Orphanet: 19 · 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 |
|---|---|---|---|---|
| ANKS6 | Definitive | Autosomal recessive | nephronophthisis 16 | 5 |
| CEP83 | Definitive | Autosomal recessive | nephronophthisis 18 | 5 |
| INVS | Definitive | Autosomal recessive | nephronophthisis 2 | 5 |
| NPHP3 | Definitive | Autosomal recessive | nephronophthisis | 10 |
| NEK8 | Strong | Autosomal recessive | nephronophthisis 9 | 10 |
| NEK9 | Strong | Autosomal recessive | nephronophthisis 9 | 14 |
| TTC21B | Strong | Autosomal recessive | nephronophthisis 12 | 8 |
| ZNF423 | Strong | Autosomal recessive | nephronophthisis 14 | 9 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| INVS | Orphanet:3156 | Senior-Loken syndrome |
| INVS | Orphanet:93591 | Infantile nephronophthisis |
| TTC21B | Orphanet:474 | Jeune syndrome |
| TTC21B | Orphanet:93591 | Infantile nephronophthisis |
| NEK8 | Orphanet:294415 | Renal-hepatic-pancreatic dysplasia |
| NEK8 | Orphanet:730 | Autosomal dominant polycystic kidney disease |
| NEK8 | Orphanet:93591 | Infantile nephronophthisis |
| ZNF423 | Orphanet:2318 | Joubert syndrome with oculorenal defect |
| ZNF423 | Orphanet:93591 | Infantile nephronophthisis |
| CEP83 | Orphanet:93591 | Infantile nephronophthisis |
| NEK9 | Orphanet:464366 | NEK9-related lethal skeletal dysplasia |
| NEK9 | Orphanet:64754 | Nevus comedonicus syndrome |
| ANKS6 | Orphanet:93591 | Infantile nephronophthisis |
| ANKS6 | Orphanet:93592 | Juvenile nephronophthisis |
| NPHP3 | Orphanet:294415 | Renal-hepatic-pancreatic dysplasia |
| NPHP3 | Orphanet:3032 | NPHP3-related Meckel-like syndrome |
| NPHP3 | Orphanet:3156 | Senior-Loken syndrome |
| NPHP3 | Orphanet:93589 | Late-onset nephronophthisis |
| NPHP3 | Orphanet:93591 | Infantile nephronophthisis |
Cohort genes → proteins
9 cohort genes, 9 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 9 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| INVS | HGNC:17870 | ENSG00000119509 | Q9Y283 | Inversin | gencc,clinvar |
| TTC21B | HGNC:25660 | ENSG00000123607 | Q7Z4L5 | Tetratricopeptide repeat protein 21B | gencc,clinvar |
| NEK8 | HGNC:13387 | ENSG00000160602 | Q86SG6 | Serine/threonine-protein kinase Nek8 | gencc |
| ZNF423 | HGNC:16762 | ENSG00000102935 | Q2M1K9 | Zinc finger protein 423 | gencc |
| CEP83 | HGNC:17966 | ENSG00000173588 | Q9Y592 | Centrosomal protein of 83 kDa | gencc |
| NEK9 | HGNC:18591 | ENSG00000119638 | Q8TD19 | Serine/threonine-protein kinase Nek9 | gencc |
| ANKS6 | HGNC:26724 | ENSG00000165138 | Q68DC2 | Ankyrin repeat and SAM domain-containing protein 6 | gencc |
| NPHP3 | HGNC:7907 | ENSG00000113971 | Q7Z494 | Nephrocystin-3 | gencc |
| ERP44 | HGNC:18311 | ENSG00000023318 | Q9BS26 | Endoplasmic reticulum resident protein 44 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| INVS | Inversin | Required for normal renal development and establishment of left-right axis. |
| TTC21B | Tetratricopeptide repeat protein 21B | Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs). |
| NEK8 | Serine/threonine-protein kinase Nek8 | Required for renal tubular integrity. |
| ZNF423 | Zinc finger protein 423 | Transcription factor that can both act as an activator or a repressor depending on the context. |
| CEP83 | Centrosomal protein of 83 kDa | Component of the distal appendage region of the centriole involved in the initiation of primary cilium assembly. |
| NEK9 | Serine/threonine-protein kinase Nek9 | Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation. |
| ANKS6 | Ankyrin repeat and SAM domain-containing protein 6 | Required for renal function. |
| NPHP3 | Nephrocystin-3 | Required for normal ciliary development and function. |
| ERP44 | Endoplasmic reticulum resident protein 44 | Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif. |
Protein-family classification
Druggable: 2 · Difficult: 3 · Unknown: 4 · Druggable fraction: 0.22
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 |
|---|---|---|---|
| Kinase | 2 | 6.2× | 0.158 |
| Scaffold/PPI | 2 | 3.8× | 0.184 |
| Transcription factor | 1 | 0.9× | 0.847 |
| Other/Unknown | 4 | 0.8× | 0.847 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| INVS | Scaffold/PPI | no | IQ_motif_EF-hand-BS, Ankyrin_rpt, Ankyrin_rpt-contain_sf | |
| TTC21B | Other/Unknown | no | TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B | |
| NEK8 | Kinase | yes | Reg_chr_condens, Prot_kinase_dom, Ser/Thr_kinase_AS | |
| ZNF423 | Transcription factor | no | Znf_C2H2_type, Znf_C2H2_sf | |
| CEP83 | Other/Unknown | no | Centro_Cilium_Assembly | |
| NEK9 | Kinase | yes | Reg_chr_condens, Prot_kinase_dom, Ser/Thr_kinase_AS | |
| ANKS6 | Scaffold/PPI | no | SAM, Ankyrin_rpt, SAM/pointed_sf | |
| NPHP3 | Other/Unknown | no | TPR-like_helical_dom_sf, TPR_rpt, P-loop_NTPase | |
| ERP44 | Other/Unknown | no | Thioredoxin_domain, Thioredoxin-like_sf, ERp44_PDI_b_2 |
Expression context
Cohort genes with no expression data: 0.
8 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) | 9 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| calcaneal tendon | 3 |
| right uterine tube | 3 |
| sural nerve | 2 |
| cerebellar hemisphere | 2 |
| left ovary | 2 |
| adrenal tissue | 1 |
| buccal mucosa cell | 1 |
| left lobe of thyroid gland | 1 |
| metanephros cortex | 1 |
| biceps brachii | 1 |
| cartilage tissue | 1 |
| skeletal muscle tissue of biceps brachii | 1 |
| tibia | 1 |
| cerebellar cortex | 1 |
| right hemisphere of cerebellum | 1 |
| layer of synovial tissue | 1 |
| superficial temporal artery | 1 |
| decidua | 1 |
| parotid gland | 1 |
| type B pancreatic cell | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| INVS | 215 | ubiquitous | yes | calcaneal tendon, adrenal tissue, sural nerve |
| TTC21B | 179 | ubiquitous | marker | right uterine tube, calcaneal tendon, cerebellar hemisphere |
| NEK8 | 196 | ubiquitous | marker | buccal mucosa cell, metanephros cortex, left lobe of thyroid gland |
| ZNF423 | 252 | broad | marker | skeletal muscle tissue of biceps brachii, biceps brachii, cartilage tissue |
| CEP83 | 233 | ubiquitous | marker | right uterine tube, calcaneal tendon, sural nerve |
| NEK9 | 296 | ubiquitous | marker | tibia, right uterine tube, left ovary |
| ANKS6 | 202 | ubiquitous | marker | cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum |
| NPHP3 | 254 | ubiquitous | marker | superficial temporal artery, layer of synovial tissue, left ovary |
| ERP44 | 297 | ubiquitous | marker | type B pancreatic cell, decidua, parotid gland |
Protein interactions among cohort
Intra-cohort edges: 11.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| NEK9 | 2,341 |
| ERP44 | 2,309 |
| NPHP3 | 2,275 |
| INVS | 2,099 |
| CEP83 | 1,941 |
| TTC21B | 1,588 |
| ZNF423 | 1,526 |
| ANKS6 | 1,262 |
| NEK8 | 926 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ANKS6 | INVS | string_interaction |
| ANKS6 | NEK8 | biogrid_interaction, intact, string_interaction |
| ANKS6 | NEK9 | string_interaction |
| ANKS6 | NPHP3 | string_interaction |
| INVS | NEK8 | string_interaction |
| INVS | NEK9 | string_interaction |
| INVS | NPHP3 | string_interaction |
| NEK8 | NEK9 | biogrid_interaction |
| NEK8 | NPHP3 | string_interaction |
| NEK8 | ZNF423 | string_interaction |
| NEK9 | NPHP3 | string_interaction |
Structural data
PDB: 6 · AlphaFold-only: 3 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| ERP44 | Q9BS26 | 5 |
| TTC21B | Q7Z4L5 | 3 |
| NEK9 | Q8TD19 | 2 |
| ZNF423 | Q2M1K9 | 1 |
| ANKS6 | Q68DC2 | 1 |
| NPHP3 | Q7Z494 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| NEK8 | Q86SG6 | 85.23 |
| CEP83 | Q9Y592 | 81.90 |
| INVS | Q9Y283 | 70.76 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 9 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Trafficking of myristoylated proteins to the cilium | 1 | 380.7× | 0.036 | NPHP3 |
| Activation of NIMA Kinases NEK9, NEK6, NEK7 | 1 | 237.9× | 0.036 | NEK9 |
| Nuclear Envelope Breakdown | 1 | 76.1× | 0.055 | NEK9 |
| Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 | 1 | 63.4× | 0.055 | ZNF423 |
| Mitotic Prophase | 1 | 61.4× | 0.055 | NEK9 |
| Nuclear Pore Complex (NPC) Disassembly | 1 | 51.4× | 0.055 | NEK9 |
| Intraflagellar transport | 1 | 33.4× | 0.070 | TTC21B |
| Hedgehog ‘off’ state | 1 | 29.7× | 0.070 | TTC21B |
| Anchoring of the basal body to the plasma membrane | 1 | 18.8× | 0.092 | CEP83 |
| Cilium Assembly | 1 | 18.1× | 0.092 | CEP83 |
| EML4 and NUDC in mitotic spindle formation | 1 | 15.5× | 0.097 | NEK9 |
| Mitotic Prometaphase | 1 | 11.5× | 0.106 | NEK9 |
| Organelle biogenesis and maintenance | 1 | 11.0× | 0.106 | CEP83 |
| M Phase | 1 | 11.0× | 0.106 | NEK9 |
| Cell Cycle, Mitotic | 1 | 8.0× | 0.134 | NEK9 |
| Cell Cycle | 1 | 6.0× | 0.165 | NEK9 |
| Neutrophil degranulation | 1 | 3.9× | 0.234 | ERP44 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| determination of left/right symmetry | 3 | 85.1× | 3e-04 | NEK8, ANKS6, NPHP3 |
| kidney development | 3 | 46.8× | 9e-04 | INVS, ANKS6, NPHP3 |
| protein localization to cilium | 2 | 89.2× | 0.003 | TTC21B, ZNF423 |
| cilium assembly | 3 | 24.5× | 0.003 | TTC21B, CEP83, NPHP3 |
| determination of intestine left/right asymmetry | 1 | 1872.4× | 0.005 | NPHP3 |
| determination of stomach left/right asymmetry | 1 | 1872.4× | 0.005 | NPHP3 |
| protein localization to ciliary inversin compartment | 1 | 1872.4× | 0.005 | INVS |
| convergent extension involved in gastrulation | 1 | 936.2× | 0.007 | NPHP3 |
| regulation of intraciliary retrograde transport | 1 | 936.2× | 0.007 | TTC21B |
| convergent extension | 1 | 624.1× | 0.010 | NPHP3 |
| protein localization to non-motile cilium | 1 | 468.1× | 0.011 | TTC21B |
| determination of pancreatic left/right asymmetry | 1 | 374.5× | 0.011 | NPHP3 |
| maintenance of animal organ identity | 1 | 374.5× | 0.011 | NPHP3 |
| regulation of Wnt signaling pathway, planar cell polarity pathway | 1 | 374.5× | 0.011 | NPHP3 |
| determination of liver left/right asymmetry | 1 | 312.1× | 0.011 | NPHP3 |
| ureter development | 1 | 312.1× | 0.011 | NPHP3 |
| negative regulation of eating behavior | 1 | 312.1× | 0.011 | TTC21B |
| negative regulation of canonical Wnt signaling pathway | 2 | 26.2× | 0.011 | INVS, NPHP3 |
| Wnt signaling pathway | 2 | 22.2× | 0.011 | INVS, NPHP3 |
| regulation of hippo signaling | 1 | 267.5× | 0.012 | NEK8 |
| atrial septum development | 1 | 234.1× | 0.012 | NPHP3 |
| forebrain dorsal/ventral pattern formation | 1 | 234.1× | 0.012 | TTC21B |
| kidney morphogenesis | 1 | 208.1× | 0.013 | NPHP3 |
| establishment of centrosome localization | 1 | 187.2× | 0.014 | CEP83 |
| heart development | 2 | 17.5× | 0.014 | NEK8, ANKS6 |
| Bergmann glial cell differentiation | 1 | 170.2× | 0.014 | TTC21B |
| epithelial cilium movement involved in determination of left/right asymmetry | 1 | 144.0× | 0.016 | NPHP3 |
| glycoprotein metabolic process | 1 | 124.8× | 0.017 | ERP44 |
| intraciliary retrograde transport | 1 | 124.8× | 0.017 | TTC21B |
| cerebellar Purkinje cell differentiation | 1 | 117.0× | 0.018 | TTC21B |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 8
Druggability breadth: 3 of 9 evidence-associated genes (33%) 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 |
|---|---|
| NEK9 | MOMELOTINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| NEK9 | 21 | 4 |
| INVS | 0 | 0 |
| TTC21B | 0 | 0 |
| NEK8 | 0 | 0 |
| ZNF423 | 0 | 0 |
| CEP83 | 0 | 0 |
| ANKS6 | 0 | 0 |
| NPHP3 | 0 | 0 |
| ERP44 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| MOMELOTINIB | 4 | NEK9 |
| FEDRATINIB | 4 | NEK9 |
| DABRAFENIB | 4 | NEK9 |
| PACRITINIB | 4 | NEK9 |
| FOSTAMATINIB | 4 | NEK9 |
| CRIZOTINIB | 4 | NEK9 |
| DOVITINIB | 3 | NEK9 |
| LESTAURTINIB | 3 | NEK9 |
| FORETINIB | 2 | NEK9 |
| REBASTINIB | 2 | NEK9 |
| DANUSERTIB | 2 | NEK9 |
| R-406 | 2 | NEK9 |
| ENMD-2076 | 2 | NEK9 |
| AT-9283 | 2 | NEK9 |
| MILCICLIB | 2 | NEK9 |
| BMS-754807 | 2 | NEK9 |
| GSK-461364 | 1 | NEK9 |
| KW-2449 | 1 | NEK9 |
| XL-019 | 1 | NEK9 |
| CYC-116 | 1 | NEK9 |
| AST-487 | 1 | NEK9 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| NEK9 | 254 | Binding:254 |
| NEK8 | 37 | Binding:37 |
| ERP44 | 1 | Binding:1 |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| NEK9 | 254 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
21 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) |
|---|---|---|
| MOMELOTINIB | 4 | NEK9 |
| FEDRATINIB | 4 | NEK9 |
| DABRAFENIB | 4 | NEK9 |
| PACRITINIB | 4 | NEK9 |
| FOSTAMATINIB | 4 | NEK9 |
| CRIZOTINIB | 4 | NEK9 |
| DOVITINIB | 3 | NEK9 |
| LESTAURTINIB | 3 | NEK9 |
| FORETINIB | 2 | NEK9 |
| REBASTINIB | 2 | NEK9 |
| DANUSERTIB | 2 | NEK9 |
| R-406 | 2 | NEK9 |
| ENMD-2076 | 2 | NEK9 |
| AT-9283 | 2 | NEK9 |
| MILCICLIB | 2 | NEK9 |
| BMS-754807 | 2 | NEK9 |
| GSK-461364 | 1 | NEK9 |
| KW-2449 | 1 | NEK9 |
| XL-019 | 1 | NEK9 |
| CYC-116 | 1 | NEK9 |
| AST-487 | 1 | NEK9 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | NEK9 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 1 | NEK8 |
| E | Difficult family or no structure, no drug | 7 | INVS, TTC21B, ZNF423, CEP83, ANKS6, NPHP3, ERP44 |
Undrugged target profiles
8 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| ANKS6 | 0 | NEK9 |
| NPHP3 | 0 | NEK9 |
| INVS | 0 | — |
| TTC21B | 0 | — |
| NEK8 | 37 | — |
| ZNF423 | 0 | — |
| CEP83 | 0 | — |
| ERP44 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.