Joubert syndrome 1
diseaseOn this page
Also known as cerebellooculorenal syndrome 1CORS1CPD4INPP5E Joubert syndromeJBTS1Joubert syndrome caused by mutation in INPP5EJoubert syndrome type 1
Summary
Joubert syndrome 1 (MONDO:0008944) is a disease caused by INPP5E (GenCC Definitive), with 16 cohort genes. The dominant Reactome pathway is Anchoring of the basal body to the plasma membrane (7 cohort genes).
At a glance
- Causal gene: INPP5E (GenCC Definitive)
- Cohort genes: 16
- ClinVar variants: 261
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Joubert syndrome 1 |
| Mondo ID | MONDO:0008944 |
| OMIM | 213300 |
| DOID | DOID:0110980 |
| UMLS | C4551568 |
| MedGen | 1644883 |
| GARD | 0024643 |
| Is cancer (heuristic) | no |
Also known as: cerebellooculorenal syndrome 1 · CORS1 · CPD4 · INPP5E Joubert syndrome · JBTS1 · Joubert syndrome 1 · Joubert syndrome caused by mutation in INPP5E · Joubert syndrome type 1
Data availability: 261 ClinVar variants · 5 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 1
Related subtypes (38): Joubert syndrome 10, Joubert syndrome 2, Joubert syndrome 3, Joubert syndrome with renal defect, Joubert syndrome 5, Joubert syndrome 6, Joubert syndrome 7, Joubert syndrome 9, Joubert syndrome 8, Joubert syndrome 13, Joubert syndrome 14, Joubert syndrome 15, Joubert syndrome 16, Joubert syndrome 17, Joubert syndrome 18, Joubert syndrome 20, Joubert syndrome 21, Joubert syndrome 22, Joubert syndrome 23, Joubert syndrome 24, Joubert syndrome 25, Joubert syndrome 26, Joubert syndrome 27, Joubert syndrome 28, Joubert syndrome 38, Joubert syndrome 39, Joubert syndrome 40, Joubert syndrome 37, Joubert syndrome 35, Joubert syndrome 36, Joubert syndrome 30, Joubert syndrome 32, Joubert syndrome 31, Joubert syndrome 33, Joubert syndrome 19, Joubert syndrome 29, Joubert syndrome 11, Joubert syndrome 34
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
261 retrieved; paginated sample, class counts are floors:
112 uncertain significance, 56 conflicting classifications of pathogenicity, 21 benign, 19 likely pathogenic, 17 pathogenic, 17 pathogenic/likely pathogenic, 14 benign/likely benign, 5 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 202167 | NM_001134831.2(AHI1):c.1205del (p.Pro402fs) | AHI1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 638504 | NM_001134831.2(AHI1):c.2623+1G>T | AHI1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 802271 | NM_001134831.2(AHI1):c.2742del (p.Leu915fs) | AHI1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1395827 | NM_001378615.1(CC2D2A):c.3688C>T (p.Arg1230Ter) | CC2D2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 242584 | NC_000004.11:g.15601250_15601251delCT | CC2D2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 411851 | NM_001378615.1(CC2D2A):c.1267C>T (p.Arg423Ter) | CC2D2A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1337 | NM_025114.4(CEP290):c.2991+1655A>G | CEP290 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 217622 | NM_025114.4(CEP290):c.1666del (p.Ile556fs) | CEP290 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 217623 | NM_025114.4(CEP290):c.1666dup (p.Ile556fs) | CEP290 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 281411 | NM_025114.4(CEP290):c.2722C>T (p.Arg908Ter) | CEP290 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 659046 | NM_025114.4(CEP290):c.5777G>C (p.Arg1926Pro) | CEP290 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 802875 | NM_025114.4(CEP290):c.6271-8T>G | CEP290 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 802878 | NM_025114.4(CEP290):c.1522+1G>C | CEP290 | Pathogenic | criteria provided, single submitter |
| 802879 | NM_025114.4(CEP290):c.881C>G (p.Ser294Ter) | CEP290 | Pathogenic | criteria provided, single submitter |
| 4075828 | NM_024899.4(CEP76):c.307C>T (p.Pro103Ser) | CEP76 | Pathogenic | criteria provided, single submitter |
| 4075833 | NM_024899.4(CEP76):c.1122G>A (p.Lys374=) | CEP76 | Pathogenic | criteria provided, single submitter |
| 1077152 | NM_001384732.1(CPLANE1):c.9063C>A (p.Tyr3021Ter) | CPLANE1 | Pathogenic | no assertion criteria provided |
| 217564 | NM_001384732.1(CPLANE1):c.9017+1G>A | CPLANE1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 31219 | NM_001384732.1(CPLANE1):c.4006C>T (p.Arg1336Trp) | CPLANE1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 392297 | NM_001384732.1(CPLANE1):c.1270C>T (p.Arg424Ter) | CPLANE1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 802117 | NM_001384732.1(CPLANE1):c.2898del (p.Pro968fs) | CPLANE1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 802118 | NM_001384732.1(CPLANE1):c.1394del (p.Leu465fs) | CPLANE1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1805447 | NM_019892.6(INPP5E):c.226dup (p.Ala76fs) | INPP5E | Pathogenic | criteria provided, single submitter |
| 375472 | NM_019892.6(INPP5E):c.1303C>T (p.Arg435Trp) | INPP5E | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 396 | NM_019892.6(INPP5E):c.1879C>T (p.Gln627Ter) | INPP5E | Pathogenic | criteria provided, single submitter |
| 397 | NM_019892.6(INPP5E):c.1543C>T (p.Arg515Trp) | INPP5E | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 399 | NM_019892.6(INPP5E):c.1304G>A (p.Arg435Gln) | INPP5E | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 400 | NM_019892.6(INPP5E):c.1132C>T (p.Arg378Cys) | INPP5E | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 426904 | NM_019892.6(INPP5E):c.1861C>T (p.Arg621Trp) | INPP5E | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 530891 | NM_019892.6(INPP5E):c.1565G>C (p.Gly522Ala) | INPP5E | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 32 · Orphanet: 41 · 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 |
|---|---|---|---|---|
| INPP5E | Definitive | Autosomal recessive | Joubert syndrome 1 | 14 |
| PMPCA | Definitive | Autosomal recessive | Joubert syndrome 1 | 18 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PMPCA | Orphanet:1170 | Autosomal recessive cerebelloparenchymal disorder type 3 |
| INPP5E | Orphanet:1454 | Joubert syndrome with hepatic defect |
| INPP5E | Orphanet:220493 | Joubert syndrome with ocular defect |
| INPP5E | Orphanet:475 | Isolated Joubert syndrome |
| INPP5E | Orphanet:75858 | MORM syndrome |
| TMEM237 | Orphanet:220497 | Joubert syndrome with renal defect |
| TMEM237 | Orphanet:2318 | Joubert syndrome with oculorenal defect |
| TMEM237 | Orphanet:475 | Isolated Joubert syndrome |
| TMEM237 | Orphanet:564 | Meckel syndrome |
| AHI1 | Orphanet:220493 | Joubert syndrome with ocular defect |
| AHI1 | Orphanet:475 | Isolated Joubert syndrome |
| AHI1 | Orphanet:791 | Retinitis pigmentosa |
| TMEM216 | Orphanet:2318 | Joubert syndrome with oculorenal defect |
| TMEM216 | Orphanet:2754 | Orofaciodigital syndrome type 6 |
| TMEM216 | Orphanet:564 | Meckel syndrome |
| TMEM216 | Orphanet:791 | Retinitis pigmentosa |
| ARL13B | Orphanet:475 | Isolated Joubert syndrome |
| TTC21B | Orphanet:474 | Jeune syndrome |
| TTC21B | Orphanet:93591 | Infantile nephronophthisis |
| CPLANE1 | Orphanet:2754 | Orofaciodigital syndrome type 6 |
| CPLANE1 | Orphanet:475 | Isolated Joubert syndrome |
| CPLANE1 | Orphanet:65684 | Monomelic amyotrophy |
| TMEM67 | Orphanet:140976 | RHYNS syndrome |
| TMEM67 | Orphanet:1454 | Joubert syndrome with hepatic defect |
| TMEM67 | Orphanet:475 | Isolated Joubert syndrome |
| TMEM67 | Orphanet:564 | Meckel syndrome |
| TMEM67 | Orphanet:84081 | Senior-Boichis syndrome |
| CEP290 | Orphanet:110 | Bardet-Biedl syndrome |
| CEP290 | Orphanet:2318 | Joubert syndrome with oculorenal defect |
| CEP290 | Orphanet:3156 | Senior-Loken syndrome |
| CEP290 | Orphanet:564 | Meckel syndrome |
| CEP290 | Orphanet:65 | Leber congenital amaurosis |
| KATNIP | Orphanet:475 | Isolated Joubert syndrome |
| CC2D2A | Orphanet:1454 | Joubert syndrome with hepatic defect |
| CC2D2A | Orphanet:2318 | Joubert syndrome with oculorenal defect |
| CC2D2A | Orphanet:564 | Meckel syndrome |
| CC2D2A | Orphanet:791 | Retinitis pigmentosa |
| NPHP1 | Orphanet:110 | Bardet-Biedl syndrome |
| NPHP1 | Orphanet:220497 | Joubert syndrome with renal defect |
| NPHP1 | Orphanet:3156 | Senior-Loken syndrome |
| NPHP1 | Orphanet:93592 | Juvenile nephronophthisis |
Cohort genes → proteins
16 cohort genes, 16 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 16 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| PMPCA | HGNC:18667 | ENSG00000165688 | Q10713 | Mitochondrial-processing peptidase subunit alpha | gencc,clinvar |
| INPP5E | HGNC:21474 | ENSG00000148384 | Q9NRR6 | Phosphatidylinositol polyphosphate 5-phosphatase type IV | gencc,clinvar |
| TMEM237 | HGNC:14432 | ENSG00000155755 | Q96Q45 | Transmembrane protein 237 | clinvar |
| SLC30A7 | HGNC:19306 | ENSG00000162695 | Q8NEW0 | Zinc transporter 7 | clinvar |
| AHI1 | HGNC:21575 | ENSG00000135541 | Q8N157 | Jouberin | clinvar |
| TMEM216 | HGNC:25018 | ENSG00000187049 | Q9P0N5 | Transmembrane protein 216 | clinvar |
| ARL13B | HGNC:25419 | ENSG00000169379 | Q3SXY8 | ADP-ribosylation factor-like protein 13B | clinvar |
| TTC21B | HGNC:25660 | ENSG00000123607 | Q7Z4L5 | Tetratricopeptide repeat protein 21B | clinvar |
| CEP76 | HGNC:25727 | ENSG00000101624 | Q8TAP6 | Centrosomal protein of 76 kDa | clinvar |
| CPLANE1 | HGNC:25801 | ENSG00000197603 | Q9H799 | Ciliogenesis and planar polarity effector 1 | clinvar |
| TMEM67 | HGNC:28396 | ENSG00000164953 | Q5HYA8 | Meckelin | clinvar |
| CEP290 | HGNC:29021 | ENSG00000198707 | O15078 | Centrosomal protein of 290 kDa | clinvar |
| KATNIP | HGNC:29068 | ENSG00000047578 | O60303 | Katanin-interacting protein | clinvar |
| CC2D2A | HGNC:29253 | ENSG00000048342 | Q9P2K1 | Coiled-coil and C2 domain-containing protein 2A | clinvar |
| MICALL2 | HGNC:29672 | ENSG00000164877 | Q8IY33 | MICAL-like protein 2 | clinvar |
| NPHP1 | HGNC:7905 | ENSG00000144061 | O15259 | Nephrocystin-1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PMPCA | Mitochondrial-processing peptidase subunit alpha | Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins. |
| INPP5E | Phosphatidylinositol polyphosphate 5-phosphatase type IV | Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,5-bispho… |
| TMEM237 | Transmembrane protein 237 | Component of the transition zone in primary cilia. |
| SLC30A7 | Zinc transporter 7 | Zinc ion transporter mediating zinc entry from the cytosol into the lumen of organelles along the secretory pathway. |
| AHI1 | Jouberin | Involved in vesicle trafficking and required for ciliogenesis, formation of primary non-motile cilium, and recruitment of RAB8A to the basal body of primary cilium. |
| TMEM216 | Transmembrane protein 216 | Essential for primary ciliogenesis and embryonic development, facilitating the activation of Hedgehog (Hh) signaling pathway. |
| ARL13B | ADP-ribosylation factor-like protein 13B | Cilium-specific protein required to control the microtubule-based, ciliary axoneme structure. |
| 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). |
| CEP76 | Centrosomal protein of 76 kDa | Centrosomal protein involved in regulation of centriole duplication. |
| CPLANE1 | Ciliogenesis and planar polarity effector 1 | Involved in ciliogenesis. |
| TMEM67 | Meckelin | Required for ciliary structure and function. |
| CEP290 | Centrosomal protein of 290 kDa | Involved in early and late steps in cilia formation. |
| KATNIP | Katanin-interacting protein | May influence the stability of microtubules (MT), possibly through interaction with the MT-severing katanin complex. |
| CC2D2A | Coiled-coil and C2 domain-containing protein 2A | Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. |
| MICALL2 | MICAL-like protein 2 | Effector of small Rab GTPases which is involved in junctional complexes assembly through the regulation of cell adhesion molecules transport to the plasma membrane and actin cytoskeleton reorganization. |
| NPHP1 | Nephrocystin-1 | Together with BCAR1 it may play a role in the control of epithelial cell polarity. |
Protein-family classification
Druggable: 4 · Difficult: 4 · Unknown: 8 · Druggable fraction: 0.25
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 |
|---|---|---|---|
| Protease | 3 | 6.9× | 0.044 |
| Scaffold/PPI | 3 | 3.2× | 0.154 |
| Other/Unknown | 8 | 0.9× | 0.873 |
| Enzyme (other) | 1 | 0.8× | 0.873 |
| Transcription factor | 1 | 0.5× | 0.873 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PMPCA | Protease | yes | 3.4.24.64 | Pept_M16_Zn_BS, Peptidase_M16_C, Metalloenz_LuxS/M16 |
| INPP5E | Enzyme (other) | yes | 3.1.3.36 | IPPc, Endo/exonu/phosph_ase_sf, INPP5E |
| TMEM237 | Other/Unknown | no | TMEM237 | |
| SLC30A7 | Other/Unknown | no | Cation_efflux, Cation_efflux_TMD_sf, Msc2-like | |
| AHI1 | Scaffold/PPI | no | SH3_domain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf | |
| TMEM216 | Other/Unknown | no | Uncharacterised_TM-17 | |
| ARL13B | Other/Unknown | no | Small_GTP-bd, Small_GTPase_ARF/SAR, P-loop_NTPase | |
| TTC21B | Other/Unknown | no | TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B | |
| CEP76 | Protease | yes | CEP76-C2, Papain-like_cys_pep_sf, CEP76 | |
| CPLANE1 | Scaffold/PPI | no | CPLANE1, WD40_repeat_dom_sf | |
| TMEM67 | Other/Unknown | no | Growth_fac_rcpt_cys_sf, Meckelin | |
| CEP290 | Other/Unknown | no | Cep290, Cep209_CC5 | |
| KATNIP | Other/Unknown | no | KATNIP, KATNIP_dom | |
| CC2D2A | Protease | yes | C2_dom, CC2D2AN-C2, C2_domain_sf | |
| MICALL2 | Transcription factor | no | CH_dom, Znf_LIM, bMERB_dom | |
| NPHP1 | Scaffold/PPI | no | SH3_domain, NPHP1_SH3, SH3-like_dom_sf |
Expression context
Cohort genes with no expression data: 0.
14 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) | 16 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| right uterine tube | 7 |
| calcaneal tendon | 6 |
| bronchial epithelial cell | 4 |
| secondary oocyte | 3 |
| adrenal tissue | 2 |
| oocyte | 2 |
| ventricular zone | 2 |
| buccal mucosa cell | 2 |
| pituitary gland | 2 |
| male germ line stem cell (sensu Vertebrata) in testis | 2 |
| sural nerve | 2 |
| apex of heart | 1 |
| right lobe of liver | 1 |
| oviduct epithelium | 1 |
| pancreatic ductal cell | 1 |
| right hemisphere of cerebellum | 1 |
| adenohypophysis | 1 |
| primordial germ cell in gonad | 1 |
| cerebellar hemisphere | 1 |
| sperm | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PMPCA | 276 | ubiquitous | marker | right lobe of liver, adrenal tissue, apex of heart |
| INPP5E | 279 | ubiquitous | yes | right uterine tube, secondary oocyte, oocyte |
| TMEM237 | 250 | ubiquitous | marker | calcaneal tendon, adrenal tissue, ventricular zone |
| SLC30A7 | 249 | ubiquitous | marker | oviduct epithelium, pancreatic ductal cell, buccal mucosa cell |
| AHI1 | 276 | ubiquitous | marker | pituitary gland, calcaneal tendon, right hemisphere of cerebellum |
| TMEM216 | 239 | ubiquitous | marker | primordial germ cell in gonad, adenohypophysis, pituitary gland |
| ARL13B | 237 | ubiquitous | marker | secondary oocyte, calcaneal tendon, bronchial epithelial cell |
| TTC21B | 179 | ubiquitous | marker | right uterine tube, calcaneal tendon, cerebellar hemisphere |
| CEP76 | 247 | ubiquitous | yes | secondary oocyte, oocyte, sperm |
| CPLANE1 | 195 | ubiquitous | marker | sural nerve, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis |
| TMEM67 | 203 | ubiquitous | marker | buccal mucosa cell, right uterine tube, calcaneal tendon |
| CEP290 | 278 | ubiquitous | marker | right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone |
| KATNIP | 251 | ubiquitous | marker | right uterine tube, bronchial epithelial cell, epithelium of bronchus |
| CC2D2A | 247 | ubiquitous | marker | right uterine tube, bronchial epithelial cell, bronchus |
| MICALL2 | 218 | ubiquitous | marker | tibial nerve, sural nerve, right adrenal gland cortex |
| NPHP1 | 193 | ubiquitous | marker | right uterine tube, bronchial epithelial cell, olfactory segment of nasal mucosa |
Protein interactions among cohort
Intra-cohort edges: 38.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PMPCA | 3,679 |
| CEP290 | 2,778 |
| ARL13B | 2,558 |
| NPHP1 | 2,302 |
| TMEM237 | 2,169 |
| CEP76 | 1,759 |
| AHI1 | 1,681 |
| TTC21B | 1,588 |
| SLC30A7 | 1,374 |
| INPP5E | 1,309 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| AHI1 | ARL13B | string_interaction |
| AHI1 | CC2D2A | biogrid_interaction, intact, string_interaction |
| AHI1 | CEP290 | string_interaction |
| AHI1 | CPLANE1 | string_interaction |
| AHI1 | NPHP1 | intact, string_interaction |
| AHI1 | TMEM216 | string_interaction |
| AHI1 | TMEM67 | string_interaction |
| ARL13B | CC2D2A | string_interaction |
| ARL13B | CEP290 | string_interaction |
| ARL13B | INPP5E | string_interaction |
| ARL13B | KATNIP | string_interaction |
| ARL13B | NPHP1 | string_interaction |
| ARL13B | TMEM216 | string_interaction |
| ARL13B | TMEM67 | string_interaction |
| CC2D2A | CEP290 | string_interaction |
| CC2D2A | CPLANE1 | string_interaction |
| CC2D2A | KATNIP | string_interaction |
| CC2D2A | NPHP1 | string_interaction |
| CC2D2A | TMEM216 | string_interaction |
| CC2D2A | TMEM237 | string_interaction |
| CC2D2A | TMEM67 | string_interaction |
| CEP290 | CEP76 | biogrid_interaction, intact |
| CEP290 | INPP5E | string_interaction |
| CEP290 | NPHP1 | string_interaction |
| CEP290 | TMEM216 | string_interaction |
| CEP290 | TMEM237 | string_interaction |
| CEP290 | TMEM67 | string_interaction |
| CPLANE1 | NPHP1 | string_interaction |
| CPLANE1 | TMEM216 | string_interaction |
| CPLANE1 | TMEM237 | string_interaction |
| CPLANE1 | TMEM67 | string_interaction |
| KATNIP | TMEM67 | string_interaction |
| NPHP1 | TMEM216 | string_interaction |
| NPHP1 | TMEM237 | intact, string_interaction |
| NPHP1 | TMEM67 | string_interaction |
| TMEM216 | TMEM237 | string_interaction |
| TMEM216 | TMEM67 | string_interaction |
| TMEM237 | TMEM67 | string_interaction |
Structural data
PDB: 6 · AlphaFold-only: 10 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SLC30A7 | Q8NEW0 | 7 |
| TTC21B | Q7Z4L5 | 3 |
| NPHP1 | O15259 | 2 |
| INPP5E | Q9NRR6 | 1 |
| AHI1 | Q8N157 | 1 |
| TMEM67 | Q5HYA8 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| TMEM216 | Q9P0N5 | 89.18 |
| PMPCA | Q10713 | 88.46 |
| CEP76 | Q8TAP6 | 87.18 |
| ARL13B | Q3SXY8 | 72.92 |
| CC2D2A | Q9P2K1 | 69.46 |
| TMEM237 | Q96Q45 | 63.79 |
| CEP290 | O15078 | 60.90 |
| KATNIP | O60303 | 58.93 |
| MICALL2 | Q8IY33 | 56.94 |
| CPLANE1 | Q9H799 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 47. Enrichment computed across 16 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Anchoring of the basal body to the plasma membrane | 7 | 72.0× | 3e-11 | AHI1, TMEM216, CEP76, TMEM67, CEP290, CC2D2A, NPHP1 |
| Cilium Assembly | 7 | 69.2× | 3e-11 | INPP5E, AHI1, ARL13B, CEP76, TMEM67, CEP290, CC2D2A |
| Organelle biogenesis and maintenance | 7 | 42.0× | 8e-10 | INPP5E, AHI1, ARL13B, CEP76, TMEM67, CEP290, CC2D2A |
| ARL13B-mediated ciliary trafficking of INPP5E | 2 | 692.1× | 3e-05 | INPP5E, ARL13B |
| Centrosome maturation | 2 | 46.1× | 0.007 | CEP76, CEP290 |
| Cargo trafficking to the periciliary membrane | 2 | 45.1× | 0.007 | INPP5E, ARL13B |
| Loss of Nlp from mitotic centrosomes | 2 | 28.8× | 0.012 | CEP76, CEP290 |
| Loss of proteins required for interphase microtubule organization from the centrosome | 2 | 28.8× | 0.012 | CEP76, CEP290 |
| AURKA Activation by TPX2 | 2 | 27.7× | 0.012 | CEP76, CEP290 |
| Recruitment of mitotic centrosome proteins and complexes | 2 | 24.7× | 0.012 | CEP76, CEP290 |
| Regulation of PLK1 Activity at G2/M Transition | 2 | 23.1× | 0.012 | CEP76, CEP290 |
| Mitotic G2-G2/M phases | 2 | 23.1× | 0.012 | CEP76, CEP290 |
| G2/M Transition | 2 | 23.1× | 0.012 | CEP76, CEP290 |
| Recruitment of NuMA to mitotic centrosomes | 2 | 21.2× | 0.013 | CEP76, CEP290 |
| Mitotic Prometaphase | 2 | 12.6× | 0.033 | CEP76, CEP290 |
| M Phase | 2 | 12.0× | 0.034 | CEP76, CEP290 |
| Synthesis of PIPs at the Golgi membrane | 1 | 57.7× | 0.045 | INPP5E |
| Processing of SMDT1 | 1 | 57.7× | 0.045 | PMPCA |
| Mitochondrial calcium ion transport | 1 | 49.4× | 0.049 | PMPCA |
| Cell Cycle, Mitotic | 2 | 8.8× | 0.049 | CEP76, CEP290 |
| Chaperone Mediated Autophagy | 1 | 45.1× | 0.049 | ARL13B |
| PI Metabolism | 1 | 32.4× | 0.065 | INPP5E |
| Late endosomal microautophagy | 1 | 29.7× | 0.068 | ARL13B |
| Cell Cycle | 2 | 6.5× | 0.070 | CEP76, CEP290 |
| Selective autophagy | 1 | 25.3× | 0.073 | ARL13B |
| Aggrephagy | 1 | 22.6× | 0.079 | ARL13B |
| Phospholipid metabolism | 1 | 18.2× | 0.087 | INPP5E |
| Intraflagellar transport | 1 | 18.2× | 0.087 | TTC21B |
| RHOJ GTPase cycle | 1 | 18.2× | 0.087 | ARL13B |
| Protein localization | 1 | 17.3× | 0.088 | PMPCA |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 16 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| cilium assembly | 10 | 46.0× | 1e-13 | INPP5E, TMEM237, AHI1, TMEM216, ARL13B, TTC21B, CPLANE1, TMEM67 (+2 more) |
| non-motile cilium assembly | 4 | 72.6× | 1e-05 | TMEM216, ARL13B, CEP290, CC2D2A |
| smoothened signaling pathway | 3 | 34.0× | 0.003 | ARL13B, TTC21B, CC2D2A |
| motile cilium assembly | 2 | 72.6× | 0.007 | AHI1, CC2D2A |
| interneuron migration from the subpallium to the cortex | 1 | 1053.2× | 0.014 | ARL13B |
| camera-type eye development | 2 | 44.8× | 0.014 | CEP290, CC2D2A |
| obsolete ciliary basal body-plasma membrane docking | 1 | 526.6× | 0.018 | CEP290 |
| regulation of intraciliary retrograde transport | 1 | 526.6× | 0.018 | TTC21B |
| protein localization involved in establishment of planar polarity | 1 | 351.1× | 0.018 | NPHP1 |
| endosome membrane tubulation | 1 | 351.1× | 0.018 | MICALL2 |
| negative regulation of protein localization to cilium | 1 | 351.1× | 0.018 | INPP5E |
| zinc ion import into Golgi lumen | 1 | 351.1× | 0.018 | SLC30A7 |
| ciliary transition zone assembly | 1 | 351.1× | 0.018 | CEP290 |
| negative regulation of motile cilium assembly | 1 | 351.1× | 0.018 | KATNIP |
| formation of radial glial scaffolds | 1 | 263.3× | 0.020 | ARL13B |
| protein localization to non-motile cilium | 1 | 263.3× | 0.020 | TTC21B |
| response to inositol | 1 | 263.3× | 0.020 | INPP5E |
| negative regulation of centrosome duplication | 1 | 210.7× | 0.021 | TMEM67 |
| receptor localization to non-motile cilium | 1 | 210.7× | 0.021 | ARL13B |
| visual behavior | 1 | 175.5× | 0.021 | NPHP1 |
| photoreceptor cell morphogenesis | 1 | 175.5× | 0.021 | TMEM216 |
| neural tube patterning | 1 | 175.5× | 0.021 | ARL13B |
| negative regulation of eating behavior | 1 | 175.5× | 0.021 | TTC21B |
| kidney development | 2 | 17.6× | 0.021 | CEP290, CC2D2A |
| pronephros development | 1 | 150.5× | 0.022 | CEP290 |
| regulation of establishment of protein localization | 1 | 150.5× | 0.022 | CEP290 |
| protein localization to ciliary transition zone | 1 | 150.5× | 0.022 | CC2D2A |
| obsolete protein processing involved in protein targeting to mitochondrion | 1 | 131.7× | 0.022 | PMPCA |
| forebrain dorsal/ventral pattern formation | 1 | 131.7× | 0.022 | TTC21B |
| otic vesicle formation | 1 | 131.7× | 0.022 | CEP290 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 16
Druggability breadth: 2 of 16 evidence-associated genes (12%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| PMPCA | 0 | 0 |
| INPP5E | 0 | 0 |
| TMEM237 | 0 | 0 |
| SLC30A7 | 0 | 0 |
| AHI1 | 0 | 0 |
| TMEM216 | 0 | 0 |
| ARL13B | 0 | 0 |
| TTC21B | 0 | 0 |
| CEP76 | 0 | 0 |
| CPLANE1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PMPCA | 1 | Binding:1 |
| SLC30A7 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PMPCA | 3.4.24.64 | mitochondrial processing peptidase |
| INPP5E | 3.1.3.36 | phosphoinositide 5-phosphatase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 16; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 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.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | INPP5E |
| D | Druggable family + AlphaFold only, no drug | 3 | PMPCA, CEP76, CC2D2A |
| E | Difficult family or no structure, no drug | 12 | TMEM237, SLC30A7, AHI1, TMEM216, ARL13B, TTC21B, CPLANE1, TMEM67, CEP290, KATNIP (+2 more) |
Undrugged target profiles
16 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| PMPCA | 1 | — |
| INPP5E | 0 | — |
| TMEM237 | 0 | — |
| SLC30A7 | 1 | — |
| AHI1 | 0 | — |
| TMEM216 | 0 | — |
| ARL13B | 0 | — |
| TTC21B | 0 | — |
| CEP76 | 0 | — |
| CPLANE1 | 0 | — |
| TMEM67 | 0 | — |
| CEP290 | 0 | — |
| KATNIP | 0 | — |
| CC2D2A | 0 | — |
| MICALL2 | 0 | — |
| NPHP1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.