Jeune syndrome

disease

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Also known as Asphyxiating Thoracic Dystrophyasphyxiating thoracic dystrophy of the newbornATDChondroectodermal dysplasia-like syndromeinfantile thoracic dystrophyJATDJeune asphyxiating thoracic dystrophyJeune's syndromeshort-rib thoracic dysplasiathoracic pelvic phalangeal dystrophy

Summary

Jeune syndrome (MONDO:0018770) is a disease (an umbrella term covering 24 Mondo subtypes) with 35 cohort genes and 3 clinical trials. The dominant Reactome pathway is Intraflagellar transport (16 cohort genes).

At a glance

Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
Umbrella term: 24 Mondo subtypes
Cohort genes: 35
ClinVar variants: 4,738
Phenotypes (HPO): 24
Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1.4	Europe	Validated
Prevalence at birth	1-9 / 1 000 000	0.89	Australia	Not yet validated

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0000772	Abnormal rib morphology	Very frequent (80-99%)
HP:0000774	Narrow chest	Very frequent (80-99%)
HP:0002644	Abnormality of pelvic girdle bone morphology	Very frequent (80-99%)
HP:0002652	Skeletal dysplasia	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0010306	Short thorax	Very frequent (80-99%)
HP:0000766	Abnormal sternum morphology	Frequent (30-79%)
HP:0000889	Abnormality of the clavicle	Frequent (30-79%)
HP:0000944	Abnormal metaphysis morphology	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0001773	Short foot	Frequent (30-79%)
HP:0002093	Respiratory insufficiency	Frequent (30-79%)
HP:0010579	Cone-shaped epiphysis	Frequent (30-79%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000090	Nephronophthisis	Occasional (5-29%)
HP:0000112	Nephropathy	Occasional (5-29%)
HP:0001162	Postaxial hand polydactyly	Occasional (5-29%)
HP:0001392	Abnormality of the liver	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0001830	Postaxial foot polydactyly	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0006703	Aplasia/Hypoplasia of the lungs	Occasional (5-29%)
HP:0007703	Abnormality of retinal pigmentation	Occasional (5-29%)
HP:0008872	Feeding difficulties in infancy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Jeune syndrome
Mondo ID	MONDO:0018770
MeSH	C537571
OMIM	208500
Orphanet	474
DOID	DOID:0050592
ICD-11	554018956
NCIT	C84794
SNOMED CT	75049004
UMLS	C0265275
MedGen	78548
GARD	0003049
MedDRA	10057621
NORD	1074
Is cancer (heuristic)	no

Also known as: Asphyxiating Thoracic Dystrophy · asphyxiating thoracic dystrophy of the newborn · ATD · Chondroectodermal dysplasia-like syndrome · infantile thoracic dystrophy · JATD · Jeune asphyxiating thoracic dystrophy · Jeune syndrome · Jeune’s syndrome · short-rib thoracic dysplasia · thoracic pelvic phalangeal dystrophy

Data availability: 4,738 ClinVar variants · 14 GenCC gene-disease records · 2 cell lines.

Disease family

An umbrella term covering 24 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › Jeune syndrome

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

600 retrieved; paginated sample, class counts are floors:

399 uncertain significance, 78 likely benign, 40 pathogenic, 35 conflicting classifications of pathogenicity, 18 benign, 12 likely pathogenic, 12 pathogenic/likely pathogenic, 6 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069785	NM_001177701.3(IFT27):c.404C>G (p.Ser135Ter)	CACNG2-DT	Pathogenic	criteria provided, single submitter
1031037	NM_001377.3(DYNC2H1):c.5176C>T (p.Arg1726Ter)	DYNC2H1	Pathogenic	criteria provided, multiple submitters, no conflicts
1071685	NM_001377.3(DYNC2H1):c.11915del (p.Pro3972fs)	DYNC2H1	Pathogenic	criteria provided, single submitter
1071871	NM_001377.3(DYNC2H1):c.5808del (p.Glu1935_Tyr1936insTer)	DYNC2H1	Pathogenic	criteria provided, single submitter
1224315	NM_001377.3(DYNC2H1):c.7435C>T (p.Gln2479Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333515	NM_001377.3(DYNC2H1):c.499C>T (p.Arg167Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1350595	NM_001377.3(DYNC2H1):c.4724del (p.Thr1575fs)	DYNC2H1	Pathogenic	criteria provided, single submitter
1373072	NM_001377.3(DYNC2H1):c.2140C>T (p.Gln714Ter)	DYNC2H1	Pathogenic	criteria provided, single submitter
1425264	NM_001377.3(DYNC2H1):c.7380G>A (p.Trp2460Ter)	DYNC2H1	Pathogenic	criteria provided, single submitter
1426527	NM_001377.3(DYNC2H1):c.2818+1G>C	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1429195	NM_001377.3(DYNC2H1):c.3076C>T (p.Gln1026Ter)	DYNC2H1	Pathogenic	criteria provided, single submitter
1451461	NM_001377.3(DYNC2H1):c.2008G>T (p.Glu670Ter)	DYNC2H1	Pathogenic	criteria provided, single submitter
1452722	NM_001377.3(DYNC2H1):c.4328del (p.Gln1443fs)	DYNC2H1	Pathogenic	criteria provided, single submitter
1453557	NM_001377.3(DYNC2H1):c.9823C>T (p.Arg3275Ter)	DYNC2H1	Pathogenic	criteria provided, single submitter
1456954	NC_000011.9:g.(?103325894)(103349981_?)del	DYNC2H1	Pathogenic	criteria provided, single submitter
1460112	NM_001377.3(DYNC2H1):c.8310T>G (p.Tyr2770Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184830	NM_001619.5(GRK2):c.469C>T (p.Leu157Phe)	GRK2	Pathogenic	no assertion criteria provided
1072907	NM_020800.3(IFT80):c.972_973insNNNNNNNNTTTTTTTT (p.Asn325delinsXaaXaaXaaPhePheTer)	IFT80	Pathogenic	criteria provided, single submitter
1075438	NM_020800.3(IFT80):c.639+1del	IFT80	Pathogenic	criteria provided, single submitter
1435198	NM_020800.3(IFT80):c.898_899del (p.Glu300fs)	IFT80	Pathogenic	criteria provided, single submitter
1442026	NM_020800.3(IFT80):c.225_226insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAGAAACAAACC (p.Gln76fs)	IFT80	Pathogenic	criteria provided, single submitter
1451633	NM_020800.3(IFT80):c.1388del (p.Ile463fs)	IFT80	Pathogenic	criteria provided, single submitter
1453983	NM_020800.3(IFT80):c.1066del (p.Tyr356fs)	IFT80	Pathogenic	criteria provided, single submitter
1455268	NC_000011.9:g.(?101323686)(103349981_?)del	MMP10	Pathogenic	criteria provided, single submitter
1054402	NC_000002.11:g.(?165946660)(167168266_?)del	SCN1A	Pathogenic	criteria provided, single submitter
1071537	NM_020800.3(IFT80):c.1882C>T (p.Arg628Ter)	TRIM59-IFT80	Pathogenic	criteria provided, single submitter
1330851	NM_020800.3(IFT80):c.411dup (p.Met138fs)	TRIM59-IFT80	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1365265	NM_020800.3(IFT80):c.629_630del (p.Asp209_Cys210insTer)	TRIM59-IFT80	Pathogenic	criteria provided, single submitter
1453252	NM_020800.3(IFT80):c.551G>A (p.Trp184Ter)	TRIM59-IFT80	Pathogenic	criteria provided, single submitter
1070283	NM_024753.5(TTC21B):c.1546C>T (p.Gln516Ter)	TTC21B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 93 · Orphanet: 69 · 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
GRK2	Moderate	Autosomal recessive	Jeune syndrome	2
CEP120	Supportive	Autosomal recessive	Jeune syndrome	6
DYNC2H1	Supportive	Autosomal recessive	Jeune syndrome	9
DYNC2I1	Supportive	Autosomal recessive	Jeune syndrome	7
DYNC2I2	Supportive	Autosomal recessive	Jeune syndrome	8
DYNC2LI1	Supportive	Autosomal recessive	Jeune syndrome	5
IFT140	Supportive	Autosomal recessive	Jeune syndrome	11
IFT172	Supportive	Autosomal recessive	Jeune syndrome	12
IFT80	Supportive	Autosomal recessive	Jeune syndrome	7
KIAA0753	Supportive	Autosomal recessive	Jeune syndrome	6
TTC21B	Supportive	Autosomal recessive	Jeune syndrome	8
WDR19	Supportive	Autosomal recessive	Jeune syndrome	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR19	Orphanet:1515	Cranioectodermal dysplasia
WDR19	Orphanet:3156	Senior-Loken syndrome
WDR19	Orphanet:474	Jeune syndrome
WDR19	Orphanet:93592	Juvenile nephronophthisis
DYNC2I1	Orphanet:474	Jeune syndrome
DYNC2I1	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
TTC21B	Orphanet:474	Jeune syndrome
TTC21B	Orphanet:93591	Infantile nephronophthisis
DYNC2I2	Orphanet:474	Jeune syndrome
DYNC2I2	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
IFT140	Orphanet:140969	Saldino-Mainzer syndrome
IFT140	Orphanet:474	Jeune syndrome
IFT140	Orphanet:65	Leber congenital amaurosis
IFT140	Orphanet:730	Autosomal dominant polycystic kidney disease
IFT140	Orphanet:791	Retinitis pigmentosa
KIAA0753	Orphanet:2754	Orofaciodigital syndrome type 6
KIAA0753	Orphanet:474	Jeune syndrome
KIAA0753	Orphanet:475	Isolated Joubert syndrome
IFT80	Orphanet:474	Jeune syndrome
IFT80	Orphanet:93268	Short rib-polydactyly syndrome, Beemer-Langer type
IFT80	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
DYNC2H1	Orphanet:474	Jeune syndrome
DYNC2H1	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type
DYNC2H1	Orphanet:93270	Short rib-polydactyly syndrome, Saldino-Noonan type
DYNC2H1	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
DYNC2LI1	Orphanet:289	Ellis Van Creveld syndrome
DYNC2LI1	Orphanet:474	Jeune syndrome
CEP120	Orphanet:220493	Joubert syndrome with ocular defect
CEP120	Orphanet:474	Jeune syndrome
CEP120	Orphanet:475	Isolated Joubert syndrome
IFT172	Orphanet:110	Bardet-Biedl syndrome
IFT172	Orphanet:140969	Saldino-Mainzer syndrome
IFT172	Orphanet:474	Jeune syndrome
IFT172	Orphanet:791	Retinitis pigmentosa
SCN1A	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SCN1A	Orphanet:2382	Lennox-Gastaut syndrome
SCN1A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN1A	Orphanet:33069	Dravet syndrome
SCN1A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN1A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SCN1A	Orphanet:569	Familial or sporadic hemiplegic migraine
IFT52	Orphanet:1515	Cranioectodermal dysplasia
IFT54	Orphanet:3156	Senior-Loken syndrome
IFT54	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type
EVC2	Orphanet:289	Ellis Van Creveld syndrome
EVC2	Orphanet:952	Acrofacial dysostosis, Weyers type
KIAA0586	Orphanet:397715	Joubert syndrome with Jeune asphyxiating thoracic dystrophy
KIAA0586	Orphanet:475	Isolated Joubert syndrome
IFT88	Orphanet:791	Retinitis pigmentosa
IFT74	Orphanet:110	Bardet-Biedl syndrome

Cohort genes → proteins

35 cohort genes, 32 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	35

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WDR19	HGNC:18340	ENSG00000157796	Q8NEZ3	WD repeat-containing protein 19	gencc,clinvar
DYNC2I1	HGNC:21862	ENSG00000126870	Q8WVS4	Cytoplasmic dynein 2 intermediate chain 1	gencc,clinvar
TTC21B	HGNC:25660	ENSG00000123607	Q7Z4L5	Tetratricopeptide repeat protein 21B	gencc,clinvar
DYNC2I2	HGNC:28296	ENSG00000119333	Q96EX3	Cytoplasmic dynein 2 intermediate chain 2	gencc,clinvar
GRK2	HGNC:289	ENSG00000173020	P25098	Beta-adrenergic receptor kinase 1	gencc,clinvar
IFT140	HGNC:29077	ENSG00000187535	Q96RY7	Intraflagellar transport protein 140 homolog	gencc,clinvar
KIAA0753	HGNC:29110	ENSG00000198920	Q2KHM9	Protein moonraker	gencc,clinvar
IFT80	HGNC:29262	ENSG00000068885	Q9P2H3	Intraflagellar transport protein 80 homolog	gencc,clinvar
DYNC2H1	HGNC:2962	ENSG00000187240	Q8NCM8	Cytoplasmic dynein 2 heavy chain 1	gencc,clinvar
DYNC2LI1	HGNC:24595	ENSG00000138036	Q8TCX1	Cytoplasmic dynein 2 light intermediate chain 1	gencc
CEP120	HGNC:26690	ENSG00000168944	Q8N960	Centrosomal protein of 120 kDa	gencc
IFT172	HGNC:30391	ENSG00000138002	Q9UG01	Intraflagellar transport protein 172 homolog	gencc
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	clinvar
IFT81	HGNC:14313	ENSG00000122970	Q8WYA0	Intraflagellar transport protein 81 homolog	clinvar
IFT52	HGNC:15901	ENSG00000101052	Q9Y366	Intraflagellar transport protein 52 homolog	clinvar
RAB34	HGNC:16519	ENSG00000109113	P0DI83	Ras-related protein Rab-34, isoform NARR	clinvar
IFT54	HGNC:17861	ENSG00000204104	Q8TDR0	TRAF3-interacting protein 1	clinvar
EVC2	HGNC:19747	ENSG00000173040	Q86UK5	Limbin	clinvar
KIAA0586	HGNC:19960	ENSG00000100578	Q9BVV6	Protein TALPID3	clinvar
IFT88	HGNC:20606	ENSG00000032742	Q13099	Intraflagellar transport protein 88 homolog	clinvar
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	clinvar
IFT74	HGNC:21424	ENSG00000096872	Q96LB3	Intraflagellar transport protein 74 homolog	clinvar
B9D1	HGNC:24123	ENSG00000108641	Q9UPM9	B9 domain-containing protein 1	clinvar
C2CD3	HGNC:24564	ENSG00000168014	Q4AC94	C2 domain-containing protein 3	clinvar
FLVCR1	HGNC:24682	ENSG00000162769	Q9Y5Y0	Choline/ethanolamine transporter FLVCR1	clinvar
FUZ	HGNC:26219	ENSG00000010361	Q9BT04	Protein fuzzy homolog	clinvar
INTU	HGNC:29239	ENSG00000164066	Q9ULD6	Protein inturned	clinvar
WDR35	HGNC:29250	ENSG00000118965	Q9P2L0	WD repeat-containing protein 35	clinvar
IFT43	HGNC:29669	ENSG00000119650	Q96FT9	Intraflagellar transport protein 43 homolog	clinvar
TTC21B-AS1	HGNC:41115	ENSG00000224490		TTC21B antisense RNA 1	clinvar
CACNG2-DT	HGNC:55682	ENSG00000234688		CACNG2 divergent transcript	clinvar
TRIM59-IFT80	HGNC:56756	ENSG00000248710		TRIM59-IFT80 readthrough (NMD candidate)	clinvar
LBR	HGNC:6518	ENSG00000143815	Q14739	Delta(14)-sterol reductase LBR	clinvar
MMP10	HGNC:7156	ENSG00000166670	P09238	Stromelysin-2	clinvar
NEK1	HGNC:7744	ENSG00000137601	Q96PY6	Serine/threonine-protein kinase Nek1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WDR19	WD repeat-containing protein 19	As 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), it is involved in cilia function and/or assembly.
DYNC2I1	Cytoplasmic dynein 2 intermediate chain 1	Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the i…
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).
DYNC2I2	Cytoplasmic dynein 2 intermediate chain 2	Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the i…
GRK2	Beta-adrenergic receptor kinase 1	Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them.
IFT140	Intraflagellar transport protein 140 homolog	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).
KIAA0753	Protein moonraker	Involved in centriole duplication.
IFT80	Intraflagellar transport protein 80 homolog	Component of the intraflagellar transport (IFT) complex B, which is essential for the development and maintenance of motile and sensory cilia.
DYNC2H1	Cytoplasmic dynein 2 heavy chain 1	May function as a motor for intraflagellar retrograde transport.
DYNC2LI1	Cytoplasmic dynein 2 light intermediate chain 1	Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the i…
CEP120	Centrosomal protein of 120 kDa	Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome.
IFT172	Intraflagellar transport protein 172 homolog	Required for the maintenance and formation of cilia.
SCN1A	Sodium channel protein type 1 subunit alpha	Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
IFT81	Intraflagellar transport protein 81 homolog	Component of the intraflagellar transport (IFT) complex B: together with IFT74, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium.
IFT52	Intraflagellar transport protein 52 homolog	Involved in ciliogenesis as part of a complex involved in intraflagellar transport (IFT), the bi-directional movement of particles required for the assembly, maintenance and functioning of primary cilia.
IFT54	TRAF3-interacting protein 1	Plays an inhibitory role on IL13 signaling by binding to IL13RA1.
EVC2	Limbin	Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.
KIAA0586	Protein TALPID3	Required for ciliogenesis and sonic hedgehog/SHH signaling.
IFT88	Intraflagellar transport protein 88 homolog	Positively regulates primary cilium biogenesis.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
IFT74	Intraflagellar transport protein 74 homolog	Component of the intraflagellar transport (IFT) complex B: together with IFT81, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium.
B9D1	B9 domain-containing protein 1	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.
C2CD3	C2 domain-containing protein 3	Component of the centrioles that acts as a positive regulator of centriole elongation.
FLVCR1	Choline/ethanolamine transporter FLVCR1	Uniporter that mediates the transport of extracellular choline and ethanolamine into cells, thereby playing a key role in phospholipid biosynthesis.
FUZ	Protein fuzzy homolog	Probable planar cell polarity effector involved in cilium biogenesis.
INTU	Protein inturned	Plays a key role in ciliogenesis and embryonic development.
WDR35	WD repeat-containing protein 35	As a 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), it is involved in ciliogenesis and ciliary protein trafficking.
IFT43	Intraflagellar transport protein 43 homolog	As a component of IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in ciliogenesis.
LBR	Delta(14)-sterol reductase LBR	Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis.
MMP10	Stromelysin-2	Can degrade fibronectin, gelatins of type I, III, IV, and V; weakly collagens III, IV, and V.
NEK1	Serine/threonine-protein kinase Nek1	Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity.

Protein-family classification

Druggable: 6 · Difficult: 8 · Unknown: 21 · Druggable fraction: 0.17

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	3.0×	0.113
Ion channel	1	3.2×	0.598
Transporter	1	2.2×	0.598
Kinase	2	1.6×	0.598
Other/Unknown	21	1.1×	0.598
Protease	1	1.1×	0.828
Transcription factor	2	0.5×	0.953
Enzyme (other)	1	0.3×	0.953

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WDR19	Transcription factor	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
DYNC2I1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
TTC21B	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B
DYNC2I2	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
GRK2	Kinase	yes	2.7.11.15	GPCR_kinase, Prot_kinase_dom, AGC-kinase_C
IFT140	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
KIAA0753	Other/Unknown	no		MNR
IFT80	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
DYNC2H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DYNC2LI1	Other/Unknown	no		Dynein_light_int_chain, P-loop_NTPase, DYNC2LI1
CEP120	Other/Unknown	no		C2_dom, DUF3668, C2_domain_sf
IFT172	Scaffold/PPI	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
SCN1A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a1su
IFT81	Other/Unknown	no		IFT81, IFT81_CH, IFT81_N_sf
IFT52	Other/Unknown	no		IFT52, Itf52_C, IFT52_GIFT
RAB34	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase
IFT54	Other/Unknown	no		TRAF3IP1, TRAF3IP1_N, TRAF3IP1_C
EVC2	Other/Unknown	no		Limbin, Limbin/EVC
KIAA0586	Other/Unknown	no		TALPID3
IFT88	Other/Unknown	no		Sel1-like, TPR-like_helical_dom_sf, TPR_rpt
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
IFT74	Other/Unknown	no		IFT74
B9D1	Other/Unknown	no		C2_B9-type_dom
C2CD3	Other/Unknown	no		C2_dom, C2_domain_sf, C2_C2CD3
FLVCR1	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
FUZ	Other/Unknown	no		Fuzzy, FUZ/MON1/HPS1_longin_3, FUZ/MON1/HPS1_longin_2
INTU	Scaffold/PPI	no		PDZ, PDZ_sf, INTU
WDR35	Transcription factor	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WDR35
IFT43	Other/Unknown	no		IFT43
TTC21B-AS1	Other/Unknown	no
CACNG2-DT	Other/Unknown	no
TRIM59-IFT80	Other/Unknown	no
LBR	Enzyme (other)	yes	1.3.1.70	ERG24_DHCR-like, Tudor, Sterol_reductase_CS
MMP10	Protease	yes	3.4.24.22	Hemopexin-like_dom, Pept_M10_metallopeptidase, Peptidoglycan-bd-like
NEK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

31 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)	35
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	15
bronchial epithelial cell	12
sural nerve	4
calcaneal tendon	4
mucosa of paranasal sinus	4
left testis	4
ventricular zone	3
male germ line stem cell (sensu Vertebrata) in testis	3
adenohypophysis	2
sperm	2
pancreatic ductal cell	2
cortical plate	2
secondary oocyte	2
epithelial cell of pancreas	2
oocyte	2
primordial germ cell in gonad	2
right testis	2
bronchus	2
cerebellar hemisphere	1
apex of heart	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WDR19	269	ubiquitous	marker	right uterine tube, bronchial epithelial cell, adenohypophysis
DYNC2I1	269	ubiquitous	marker	sural nerve, right uterine tube, sperm
TTC21B	179	ubiquitous	marker	right uterine tube, calcaneal tendon, cerebellar hemisphere
DYNC2I2	238	ubiquitous	marker	right uterine tube, pancreatic ductal cell, apex of heart
GRK2	231	ubiquitous	marker	granulocyte, monocyte, leukocyte
IFT140	214	ubiquitous	marker	right uterine tube, right lobe of thyroid gland, left lobe of thyroid gland
KIAA0753	243	ubiquitous	marker	cortical plate, lower esophagus, lower esophagus muscularis layer
IFT80	256	ubiquitous	marker	colonic epithelium, oviduct epithelium, endothelial cell
DYNC2H1	230	ubiquitous	marker	secondary oocyte, bronchial epithelial cell, right uterine tube
DYNC2LI1	293	ubiquitous	marker	right uterine tube, bronchial epithelial cell, mucosa of paranasal sinus
CEP120	254	ubiquitous	yes	calcaneal tendon, epithelial cell of pancreas, mucosa of paranasal sinus
IFT172	236	ubiquitous	marker	right uterine tube, bronchial epithelial cell, left testis
SCN1A	154	tissue_specific	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex
IFT81	273	ubiquitous	marker	bronchial epithelial cell, ventricular zone, right uterine tube
IFT52	254	ubiquitous	marker	ganglionic eminence, cortical plate, ventricular zone
RAB34	248	ubiquitous	marker	descending thoracic aorta, left ovary, right ovary
IFT54	265	ubiquitous	marker	oocyte, bronchial epithelial cell, sural nerve
EVC2	182	ubiquitous	marker	pancreatic ductal cell, calcaneal tendon, primordial germ cell in gonad
KIAA0586	247	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
IFT88	284	ubiquitous	marker	bronchial epithelial cell, sperm, epithelium of bronchus
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
IFT74	272	ubiquitous	marker	bronchial epithelial cell, caput epididymis, right uterine tube
B9D1	224	ubiquitous	marker	right uterine tube, adenohypophysis, left testis
C2CD3	282	ubiquitous	marker	sural nerve, right uterine tube, bronchial epithelial cell
FLVCR1	240	ubiquitous	marker	jejunal mucosa, ileal mucosa, epithelial cell of pancreas
FUZ	243	ubiquitous	marker	right uterine tube, right testis, left testis
INTU	226	ubiquitous	marker	right uterine tube, bronchial epithelial cell, ventricular zone
WDR35	257	ubiquitous	marker	bronchial epithelial cell, mucosa of paranasal sinus, bronchus
IFT43	252	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus
TTC21B-AS1	119	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell, skeletal muscle tissue

Protein interactions among cohort

Intra-cohort edges: 114.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT88	3,166
INTU	2,947
LBR	2,789
GRK2	2,613
SLTM	2,598
IFT80	2,582
SCN1A	2,287
IFT81	2,125
IFT74	1,937
CEP120	1,928

Intra-cohort edges

A	B	Sources
C2CD3	CEP120	string_interaction
C2CD3	IFT88	string_interaction
C2CD3	KIAA0586	string_interaction
CEP120	KIAA0586	intact, string_interaction
CEP120	KIAA0753	intact, string_interaction
DYNC2H1	DYNC2I1	string_interaction
DYNC2H1	DYNC2I2	string_interaction
DYNC2H1	DYNC2LI1	biogrid_interaction, intact, string_interaction
DYNC2H1	IFT140	string_interaction
DYNC2H1	IFT172	string_interaction
DYNC2H1	IFT43	string_interaction
DYNC2H1	IFT80	string_interaction
DYNC2H1	IFT88	string_interaction
DYNC2H1	KIAA0586	string_interaction
DYNC2H1	NEK1	string_interaction
DYNC2H1	TTC21B	string_interaction
DYNC2H1	WDR19	string_interaction
DYNC2H1	WDR35	string_interaction
DYNC2I1	DYNC2I2	intact, string_interaction
DYNC2I1	DYNC2LI1	intact, string_interaction
DYNC2I1	EVC2	string_interaction
DYNC2I1	IFT140	string_interaction
DYNC2I1	IFT172	string_interaction
DYNC2I1	IFT43	string_interaction
DYNC2I1	IFT80	string_interaction
DYNC2I1	KIAA0586	string_interaction
DYNC2I1	NEK1	string_interaction
DYNC2I1	TTC21B	string_interaction
DYNC2I1	WDR19	string_interaction
DYNC2I1	WDR35	string_interaction
DYNC2I2	DYNC2LI1	string_interaction
DYNC2I2	IFT140	string_interaction
DYNC2I2	IFT172	string_interaction
DYNC2I2	IFT43	string_interaction
DYNC2I2	IFT80	string_interaction
DYNC2I2	KIAA0586	string_interaction
DYNC2I2	TTC21B	string_interaction
DYNC2I2	WDR19	string_interaction
DYNC2I2	WDR35	string_interaction
DYNC2LI1	EVC2	string_interaction
DYNC2LI1	IFT140	string_interaction
DYNC2LI1	IFT172	string_interaction
DYNC2LI1	IFT52	string_interaction
DYNC2LI1	IFT80	string_interaction
DYNC2LI1	IFT88	string_interaction
DYNC2LI1	WDR19	string_interaction
DYNC2LI1	WDR35	string_interaction
EVC2	IFT80	string_interaction
EVC2	LBR	biogrid_interaction
EVC2	WDR19	string_interaction

Structural data

PDB: 20 · AlphaFold-only: 12 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GRK2	P25098	20
FLVCR1	Q9Y5Y0	8
WDR19	Q8NEZ3	4
DYNC2I1	Q8WVS4	4
DYNC2I2	Q96EX3	4
IFT140	Q96RY7	4
DYNC2H1	Q8NCM8	4
CEP120	Q8N960	4
INTU	Q9ULD6	4
WDR35	Q9P2L0	4
MMP10	P09238	4
TTC21B	Q7Z4L5	3
DYNC2LI1	Q8TCX1	3
FUZ	Q9BT04	3
IFT43	Q96FT9	3
IFT54	Q8TDR0	2
NEK1	Q96PY6	2
IFT172	Q9UG01	1
SCN1A	P35498	1
LBR	Q14739	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IFT80	Q9P2H3	92.50
IFT52	Q9Y366	84.21
IFT81	Q8WYA0	83.45
B9D1	Q9UPM9	83.05
IFT74	Q96LB3	81.21
IFT88	Q13099	77.20
EVC2	Q86UK5	73.33
KIAA0753	Q2KHM9	59.08
C2CD3	Q4AC94	55.65
SLTM	Q9NWH9	52.38
KIAA0586	Q9BVV6	47.61
RAB34	P0DI83	46.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 76. Enrichment computed across 35 evidence-associated genes (28 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 28 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Intraflagellar transport	16	114.5×	3e-29	WDR19, DYNC2I1, TTC21B, DYNC2I2, IFT140, IFT80, DYNC2H1, IFT81 (+8 more)
Hedgehog ‘off’ state	10	63.7×	7e-15	WDR19, TTC21B, IFT140, DYNC2H1, IFT52, IFT88, FUZ, INTU (+2 more)
Signaling by Hedgehog	3	19.7×	0.011	GRK2, EVC2, INTU
Activation of SMO	2	45.3×	0.016	GRK2, EVC2
Cilium Assembly	3	11.7×	0.032	IFT54, B9D1, C2CD3
Organelle biogenesis and maintenance	3	7.1×	0.107	IFT54, B9D1, C2CD3
Hedgehog ‘on’ state	2	11.3×	0.145	GRK2, EVC2
Cholesterol biosynthesis	1	40.8×	0.192	LBR
Cholesterol biosynthesis via desmosterol (Bloch pathway)	1	40.8×	0.192	LBR
Anchoring of the basal body to the plasma membrane	2	8.1×	0.192	B9D1, C2CD3
Heme biosynthesis	1	27.2×	0.245	FLVCR1
Initiation of Nuclear Envelope (NE) Reformation	1	21.5×	0.245	LBR
Regulation of pyruvate metabolism	1	20.4×	0.245	NEK1
Chaperone Mediated Autophagy	1	17.7×	0.245	IFT88
Pyruvate metabolism	1	14.6×	0.245	NEK1
Calmodulin induced events	1	13.6×	0.245	GRK2
CaM pathway	1	13.6×	0.245	GRK2
Ca-dependent events	1	13.2×	0.245	GRK2
Interaction between L1 and Ankyrins	1	13.2×	0.245	SCN1A
Regulation of MECP2 expression and activity	1	13.2×	0.245	LBR
Phase 0 - rapid depolarisation	1	12.4×	0.245	SCN1A
Iron uptake and transport	1	12.4×	0.245	FLVCR1
G-protein mediated events	1	11.7×	0.245	GRK2
Late endosomal microautophagy	1	11.7×	0.245	IFT88
DAG and IP3 signaling	1	11.3×	0.245	GRK2
Transcriptional Regulation by MECP2	1	11.3×	0.245	LBR
Activation of Matrix Metalloproteinases	1	11.0×	0.245	MMP10
Nuclear Envelope (NE) Reassembly	1	10.5×	0.248	LBR
Opioid Signalling	1	9.5×	0.254	GRK2
PLC beta mediated events	1	9.5×	0.254	GRK2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 32 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	23	52.9×	2e-34	WDR19, DYNC2I1, TTC21B, DYNC2I2, IFT140, KIAA0753, IFT80, DYNC2H1 (+15 more)
intraciliary retrograde transport	9	316.0×	5e-20	WDR19, DYNC2I1, TTC21B, DYNC2I2, IFT140, DYNC2H1, DYNC2LI1, WDR35 (+1 more)
intraciliary transport	9	158.0×	9e-17	DYNC2I2, IFT81, IFT52, IFT54, IFT88, FUZ, INTU, WDR35 (+1 more)
non-motile cilium assembly	10	90.8×	3e-16	IFT140, IFT80, DYNC2H1, IFT52, IFT88, IFT74, C2CD3, FUZ (+2 more)
intraciliary anterograde transport	7	194.0×	9e-14	IFT80, IFT81, IFT52, IFT54, IFT88, IFT74, IFT172
smoothened signaling pathway	8	45.3×	2e-10	TTC21B, IFT80, IFT52, EVC2, KIAA0586, B9D1, INTU, IFT172
regulation of smoothened signaling pathway	6	117.0×	2e-10	TTC21B, IFT140, IFT81, C2CD3, FUZ, INTU
embryonic digit morphogenesis	7	65.8×	2e-10	IFT140, IFT52, IFT54, B9D1, C2CD3, FLVCR1, INTU
negative regulation of keratinocyte proliferation	5	109.7×	2e-08	IFT80, IFT52, IFT74, INTU, IFT172
regulation of cilium assembly	5	94.0×	4e-08	IFT140, IFT88, DYNC2LI1, FUZ, INTU
intraciliary transport involved in cilium assembly	3	225.7×	4e-06	IFT81, IFT74, DYNC2LI1
keratinocyte proliferation	4	72.6×	4e-06	IFT80, IFT52, IFT74, IFT172
positive regulation of smoothened signaling pathway	4	52.7×	1e-05	DYNC2H1, RAB34, INTU, IFT172
protein localization to cilium	4	50.1×	2e-05	TTC21B, IFT140, DYNC2H1, WDR35
embryonic camera-type eye development	3	112.8×	3e-05	WDR19, IFT140, IFT54
determination of left/right symmetry	4	31.9×	9e-05	IFT140, DYNC2H1, IFT74, DYNC2LI1
positive regulation of cilium assembly	3	71.8×	1e-04	IFT88, FUZ, CEP120
neural tube development	3	49.4×	3e-04	C2CD3, FUZ, INTU
cytosolic ciliogenesis	2	210.7×	4e-04	KIAA0753, RAB34
dorsal/ventral pattern formation	3	39.5×	6e-04	DYNC2H1, IFT52, IFT172
limb development	3	38.5×	6e-04	IFT80, INTU, IFT172
embryonic skeletal system morphogenesis	3	36.7×	7e-04	DYNC2I1, FLVCR1, FUZ
heart looping	3	25.1×	0.002	IFT52, C2CD3, IFT172
establishment of planar polarity	2	65.8×	0.004	FUZ, INTU
spinal cord motor neuron differentiation	2	58.5×	0.004	DYNC2H1, IFT172
protein processing	3	16.0×	0.007	DYNC2H1, C2CD3, IFT172
in utero embryonic development	4	9.0×	0.007	WDR19, B9D1, C2CD3, FLVCR1
protein localization to centrosome	2	42.1×	0.008	KIAA0753, C2CD3
embryonic cranial skeleton morphogenesis	2	36.3×	0.010	WDR19, IFT140
kidney development	3	13.2×	0.010	DYNC2H1, IFT54, IFT88

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 5 · Phased (≥1): 5 · Undrugged: 30

Druggability breadth: 6 of 35 evidence-associated genes (17%) 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
GRK2	CAPIVASERTIB
SCN1A	MEXILETINE HYDROCHLORIDE
SLTM	CABOZANTINIB
NEK1	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN1A	94	4
NEK1	12	4
GRK2	6	4
MMP10	2	3
SLTM	1	4
WDR19	0	0
DYNC2I1	0	0
TTC21B	0	0
DYNC2I2	0	0
IFT140	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CAPIVASERTIB	4	GRK2
PAROXETINE	4	GRK2
PAROXETINE HYDROCHLORIDE	4	GRK2
MEXILETINE HYDROCHLORIDE	4	SCN1A
BEPRIDIL	4	SCN1A
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
NEK1	288	Binding:288
GRK2	206	Binding:206
SCN1A	149	Binding:115, Functional:18, ADMET:14, Toxicity:2
MMP10	52	Binding:48, Functional:3, ADMET:1
SLTM	14	Binding:14
LBR	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GRK2	2.7.11.15	beta-adrenergic-receptor kinase
LBR	1.3.1.70	DELTA14-sterol reductase
MMP10	3.4.24.22	stromelysin 2

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
GRK2	206
SCN1A	149
NEK1	288

Pharmacogenomics

Cohort genes with a PharmGKB record: 32; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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)
CAPIVASERTIB	4	GRK2
PAROXETINE	4	GRK2
PAROXETINE HYDROCHLORIDE	4	GRK2
MEXILETINE HYDROCHLORIDE	4	SCN1A
BEPRIDIL	4	SCN1A
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	GRK2, SCN1A, SLTM, NEK1
B	Phased (≥1) drug, not yet approved	1	MMP10
C	Druggable family + PDB, no drug	2	FLVCR1, LBR
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	28	WDR19, DYNC2I1, TTC21B, DYNC2I2, IFT140, KIAA0753, IFT80, DYNC2H1, DYNC2LI1, CEP120 (+18 more)

Undrugged target profiles

30 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DYNC2H1	0	NEK1
WDR19	0	—
DYNC2I1	0	—
TTC21B	0	—
DYNC2I2	0	—
IFT140	0	—
KIAA0753	0	—
IFT80	0	—
DYNC2LI1	0	—
CEP120	0	—
IFT172	0	—
IFT81	0	—
IFT52	0	—
RAB34	0	—
IFT54	0	—
EVC2	0	—
KIAA0586	0	—
IFT88	0	—
IFT74	0	—
B9D1	0	—
C2CD3	0	—
FLVCR1	0	—
FUZ	0	—
INTU	0	—
WDR35	0	—
IFT43	0	—
TTC21B-AS1	0	—
CACNG2-DT	0	—
TRIM59-IFT80	0	—
LBR	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00948376	Not specified	COMPLETED	Natural History of Asphyxiating Thoracic Dystrophy (DTJ)
NCT04143841	Not specified	TERMINATED	Viveye Ocular Magnetic Neurostimulation System (OMNS) for the Management of Severe Dry Eye Disease
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)

Cohort genes: WDR19, DYNC2I1, TTC21B, DYNC2I2, GRK2, IFT140, KIAA0753, IFT80, DYNC2H1, DYNC2LI1, CEP120, IFT172, SCN1A, IFT81, IFT52, RAB34, IFT54, EVC2, KIAA0586, IFT88, SLTM, IFT74, B9D1, C2CD3, FLVCR1, FUZ, INTU, WDR35, IFT43, TTC21B-AS1, CACNG2-DT, LBR, MMP10, NEK1