Asphyxiating thoracic dystrophy 3

Summary

Asphyxiating thoracic dystrophy 3 (MONDO:0013127) is a disease caused by DYNC2H1 (GenCC Definitive), with 12 cohort genes. The dominant Reactome pathway is Intraflagellar transport (4 cohort genes).

At a glance

• Causal gene: DYNC2H1 (GenCC Definitive)
• Cohort genes: 12
• ClinVar variants: 716

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	asphyxiating thoracic dystrophy 3
Mondo ID	MONDO:0013127
MeSH	C537602
OMIM	613091
Orphanet	93270, 93271
DOID	DOID:0050549, DOID:0110087
NCIT	C163755
SNOMED CT	254051008, 27330009
UMLS	C0036069
MedGen	19860
GARD	0015613
Is cancer (heuristic)	no

Also known as: asphyxiating thoracic dystrophy 3 · asphyxiating thoracic dystrophy type 3 · ATD3 · DYNC2H1-related short rib thoracic dysplasia · polydactyly with neonatal chondrodystrophy type 1 · polydactyly with neonatal chondrodystrophy type III · polydactyly with neonatal chondrodystrophy, type 3 · Saldino-Noonan syndrome · short rib polydactyly syndrome Verma Naumoff type · short rib-polydactyly syndrome Saldino-Noonan type · short rib-polydactyly syndrome type 1 · short rib-polydactyly syndrome type 3 · short rib-polydactyly syndrome type III · short rib-polydactyly syndrome, type 2B · short-rib thoracic dysplasia 3 with or without polydactyly · SRPS type 1 · SRPS type 3 · SRPS1 · SRPS2B · SRPS3 (+3 more)

Data availability: 716 ClinVar variants · 6 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › Jeune syndrome › asphyxiating thoracic dystrophy 3

Related subtypes (23): asphyxiating thoracic dystrophy 1, Ellis-van Creveld syndrome, short-rib thoracic dysplasia 6 with or without polydactyly, short-rib thoracic dysplasia 9 with or without polydactyly, Beemer-Langer syndrome, asphyxiating thoracic dystrophy 2, asphyxiating thoracic dystrophy 4, short-rib thoracic dysplasia 7 with or without polydactyly, asphyxiating thoracic dystrophy 5, short-rib thoracic dysplasia 8 with or without polydactyly, short-rib thoracic dysplasia 10 with or without polydactyly, short-rib thoracic dysplasia 11 with or without polydactyly, short-rib thoracic dysplasia 13 with or without polydactyly, short-rib thoracic dysplasia 14 with polydactyly, short-rib thoracic dysplasia 15 with polydactyly, short-rib thoracic dysplasia 16 with or without polydactyly, short-rib thoracic dysplasia 21 without polydactyly, short-rib thoracic dysplasia 19 with or without polydactyly, short-rib thoracic dysplasia 18 with polydactyly, short-rib thoracic dysplasia 20 with polydactyly, short-rib thoracic dysplasia 17 with or without polydactyly, Jeune syndrome - GRK2-related, short-rib thoracic dysplasia 22 without polydactyly

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:

147 uncertain significance, 124 likely pathogenic, 106 conflicting classifications of pathogenicity, 93 pathogenic/likely pathogenic, 49 pathogenic, 42 benign/likely benign, 28 benign, 11 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3901843	NM_001377.3(DYNC2H1):c.[4130C>G];[9044A>G]		Pathogenic	criteria provided, single submitter
429027	NM_001080463.1(DYNC2H1):c.[5053G>A];[7784A>G]		Pathogenic	no assertion criteria provided
266102	NM_024685.4(BBS10):c.959_962del (p.Ser320fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1031037	NM_001377.3(DYNC2H1):c.5176C>T (p.Arg1726Ter)	DYNC2H1	Pathogenic	criteria provided, multiple submitters, no conflicts
1224315	NM_001377.3(DYNC2H1):c.7435C>T (p.Gln2479Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1224327	NM_001377.3(DYNC2H1):c.10094A>T (p.Glu3365Val)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1224371	NM_001377.3(DYNC2H1):c.244C>T (p.Arg82Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1252018	NM_001377.3(DYNC2H1):c.3331G>A (p.Glu1111Lys)	DYNC2H1	Pathogenic	no assertion criteria provided
1322793	NM_001377.3(DYNC2H1):c.4093C>T (p.Gln1365Ter)	DYNC2H1	Pathogenic	criteria provided, single submitter
1332719	NM_001377.3(DYNC2H1):c.12238C>T (p.Gln4080Ter)	DYNC2H1	Pathogenic	criteria provided, single submitter
1333515	NM_001377.3(DYNC2H1):c.499C>T (p.Arg167Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1426527	NM_001377.3(DYNC2H1):c.2818+1G>C	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1460112	NM_001377.3(DYNC2H1):c.8310T>G (p.Tyr2770Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1679489	NM_001377.3(DYNC2H1):c.10606-14A>G	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1683449	NM_001377.3(DYNC2H1):c.4429A>T (p.Lys1477Ter)	DYNC2H1	Pathogenic	criteria provided, single submitter
1698390	NM_001377.3(DYNC2H1):c.3446G>A (p.Trp1149Ter)	DYNC2H1	Pathogenic	criteria provided, single submitter
1707477	NM_001377.3(DYNC2H1):c.6464G>A (p.Trp2155Ter)	DYNC2H1	Pathogenic	criteria provided, single submitter
1722990	NM_001377.3(DYNC2H1):c.7858C>T (p.Arg2620Ter)	DYNC2H1	Pathogenic	criteria provided, multiple submitters, no conflicts
1803487	NM_001377.3(DYNC2H1):c.12462G>A (p.Trp4154Ter)	DYNC2H1	Pathogenic	criteria provided, multiple submitters, no conflicts
1916428	NM_001377.3(DYNC2H1):c.10798_10799del (p.Met3600fs)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
198957	NM_001377.3(DYNC2H1):c.12156+1G>A	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
199053	NM_001377.3(DYNC2H1):c.1360+2del	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
220043	NM_001377.3(DYNC2H1):c.2702+1G>A	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225033	NM_001377.3(DYNC2H1):c.10648T>C (p.Ser3550Pro)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225345	NM_001377.3(DYNC2H1):c.2353C>T (p.Arg785Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
238272	NM_001377.3(DYNC2H1):c.5495C>A (p.Ser1832Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2431209	NM_001377.3(DYNC2H1):c.2692C>T (p.Arg898Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2439947	NM_001377.3(DYNC2H1):c.4219C>T (p.Gln1407Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2701004	NM_001377.3(DYNC2H1):c.7053_7054del (p.Cys2351_Glu2352delinsTer)	DYNC2H1	Pathogenic	criteria provided, multiple submitters, no conflicts
2706230	NM_001377.3(DYNC2H1):c.7894G>T (p.Glu2632Ter)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 20 · 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
DYNC2H1	Definitive	Autosomal recessive	asphyxiating thoracic dystrophy 3	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
DYNC2I1	Orphanet:474	Jeune syndrome
DYNC2I1	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
BBS10	Orphanet:110	Bardet-Biedl syndrome
DYNC2I2	Orphanet:474	Jeune syndrome
DYNC2I2	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
DYNC1H1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
DYNC1H1	Orphanet:209341	DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy
DYNC1H1	Orphanet:284232	Autosomal dominant Charcot-Marie-Tooth disease type 2O
EDA	Orphanet:181	X-linked hypohidrotic ectodermal dysplasia
EDA	Orphanet:99798	Oligodontia
EPAS1	Orphanet:247511	Autosomal dominant secondary polycythemia
EPAS1	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
EPAS1	Orphanet:324299	Multiple paragangliomas associated with polycythemia
NEK1	Orphanet:2751	Orofaciodigital syndrome type 2
NEK1	Orphanet:803	Amyotrophic lateral sclerosis
NEK1	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type

Cohort genes → proteins

12 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DYNC2H1	HGNC:2962	ENSG00000187240	Q8NCM8	Cytoplasmic dynein 2 heavy chain 1	gencc,clinvar
KIF24	HGNC:19916	ENSG00000186638	Q5T7B8	Kinesin-like protein KIF24	clinvar
DYNC2I1	HGNC:21862	ENSG00000126870	Q8WVS4	Cytoplasmic dynein 2 intermediate chain 1	clinvar
BBS10	HGNC:26291	ENSG00000179941	Q8TAM1	BBSome complex assembly protein BBS10	clinvar
FAM98C	HGNC:27119	ENSG00000130244	Q17RN3	Protein FAM98C	clinvar
DYNC2I2	HGNC:28296	ENSG00000119333	Q96EX3	Cytoplasmic dynein 2 intermediate chain 2	clinvar
DYNLT2B	HGNC:28482	ENSG00000213123	Q8WW35	Dynein light chain Tctex-type protein 2B	clinvar
DYNC1H1	HGNC:2961	ENSG00000197102	Q14204	Cytoplasmic dynein 1 heavy chain 1	clinvar
EDA	HGNC:3157	ENSG00000158813	Q92838	Ectodysplasin-A	clinvar
EPAS1	HGNC:3374	ENSG00000116016	Q99814	Endothelial PAS domain-containing protein 1	clinvar
TMEM256-PLSCR3	HGNC:49186	ENSG00000262481		TMEM256-PLSCR3 readthrough (NMD candidate)	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)
DYNC2H1	Cytoplasmic dynein 2 heavy chain 1	May function as a motor for intraflagellar retrograde transport.
KIF24	Kinesin-like protein KIF24	Microtubule-dependent motor protein that acts as a negative regulator of ciliogenesis by mediating recruitment of CCP110 to mother centriole in cycling cells, leading to restrict nucleation of cilia at centrioles.
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…
BBS10	BBSome complex assembly protein BBS10	Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis.
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…
DYNLT2B	Dynein light chain Tctex-type protein 2B	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…
DYNC1H1	Cytoplasmic dynein 1 heavy chain 1	Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules.
EDA	Ectodysplasin-A	Cytokine which is involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs.
EPAS1	Endothelial PAS domain-containing protein 1	Transcription factor involved in the induction of oxygen regulated genes.
NEK1	Serine/threonine-protein kinase Nek1	Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity.

Protein-family classification

Druggable: 1 · Difficult: 3 · Unknown: 8 · Druggable fraction: 0.08

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	2	2.9×	0.475
Kinase	1	2.3×	0.475
Other/Unknown	8	1.2×	0.475
Transcription factor	1	0.7×	0.788

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DYNC2H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
KIF24	Other/Unknown	no		SAM, Kinesin_motor_dom, SAM/pointed_sf
DYNC2I1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
BBS10	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_sf
FAM98C	Other/Unknown	no		FAM98
DYNC2I2	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
DYNLT2B	Other/Unknown	no		Tctex-1-like, Tctex-1-like_sf
DYNC1H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
EDA	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_Ligand_Superfamily
EPAS1	Transcription factor	no		PAS, Nuc_translocat, PAC
TMEM256-PLSCR3	Other/Unknown	no
NEK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

10 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)	12
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	4
ventricular zone	3
secondary oocyte	2
male germ line stem cell (sensu Vertebrata) in testis	2
primordial germ cell in gonad	2
cortical plate	2
oocyte	2
bronchial epithelial cell	1
sperm	1
sural nerve	1
calcaneal tendon	1
endothelial cell	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
apex of heart	1
pancreatic ductal cell	1
olfactory segment of nasal mucosa	1
ganglionic eminence	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DYNC2H1	230	ubiquitous	marker	secondary oocyte, bronchial epithelial cell, right uterine tube
KIF24	129	ubiquitous	marker	primordial germ cell in gonad, ventricular zone, male germ line stem cell (sensu Vertebrata) in testis
DYNC2I1	269	ubiquitous	marker	sural nerve, right uterine tube, sperm
BBS10	253	ubiquitous	yes	calcaneal tendon, endothelial cell, ventricular zone
FAM98C	239	ubiquitous	marker	right hemisphere of cerebellum, cerebellar cortex, cerebellar hemisphere
DYNC2I2	238	ubiquitous	marker	right uterine tube, pancreatic ductal cell, apex of heart
DYNLT2B	135	ubiquitous	marker	right uterine tube, cortical plate, olfactory segment of nasal mucosa
DYNC1H1	290	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
EDA	175	broad	marker	tongue squamous epithelium, male germ line stem cell (sensu Vertebrata) in testis, oocyte
EPAS1	298	ubiquitous	marker	right lung, lower lobe of lung, adult organism
TMEM256-PLSCR3	128	ubiquitous	yes	tibial nerve, stromal cell of endometrium, primordial germ cell in gonad
NEK1	288	ubiquitous	marker	secondary oocyte, trigeminal ganglion, oocyte

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPAS1	4,652
DYNC1H1	4,215
BBS10	3,224
DYNC2H1	1,885
NEK1	1,512
KIF24	1,413
DYNC2I2	1,099
DYNC2I1	955
DYNLT2B	830
EDA	792

Intra-cohort edges

A	B	Sources
DYNC2H1	DYNC2I1	string_interaction
DYNC2H1	DYNC2I2	string_interaction
DYNC2H1	DYNLT2B	string_interaction
DYNC2H1	NEK1	string_interaction
DYNC2I1	DYNC2I2	intact, string_interaction
DYNC2I1	DYNLT2B	intact, string_interaction
DYNC2I1	NEK1	string_interaction
DYNC2I2	DYNLT2B	intact, string_interaction

Structural data

PDB: 8 · AlphaFold-only: 3 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYNC1H1	Q14204	97
EPAS1	Q99814	43
DYNC2H1	Q8NCM8	4
DYNC2I1	Q8WVS4	4
DYNC2I2	Q96EX3	4
EDA	Q92838	3
DYNLT2B	Q8WW35	2
NEK1	Q96PY6	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FAM98C	Q17RN3	79.51
BBS10	Q8TAM1	71.26
KIF24	Q5T7B8	52.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. Enrichment computed across 12 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Intraflagellar transport	4	80.1×	4e-06	DYNC2H1, DYNC2I1, DYNC2I2, DYNLT2B
Anchoring of the basal body to the plasma membrane	2	22.6×	0.047	KIF24, DYNC1H1
Cilium Assembly	2	21.8×	0.047	KIF24, BBS10
PTK6 Expression	1	190.3×	0.051	EPAS1
Regulation of gene expression by Hypoxia-inducible Factor	1	95.2×	0.055	EPAS1
Pexophagy	1	95.2×	0.055	EPAS1
Cellular response to hypoxia	1	87.8×	0.055	EPAS1
Organelle biogenesis and maintenance	2	13.2×	0.055	KIF24, BBS10
Regulation of pyruvate metabolism	1	57.1×	0.071	NEK1
Transcriptional regulation of pluripotent stem cells	1	54.4×	0.071	EPAS1
BBSome-mediated cargo-targeting to cilium	1	49.6×	0.071	BBS10
Pyruvate metabolism	1	40.8×	0.075	NEK1
TNFs bind their physiological receptors	1	39.4×	0.075	EDA
Cargo trafficking to the periciliary membrane	1	24.8×	0.103	BBS10
Aggrephagy	1	24.8×	0.103	DYNC1H1
COPI-independent Golgi-to-ER retrograde traffic	1	20.8×	0.109	DYNC1H1
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	1	19.7×	0.109	EPAS1
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	19.4×	0.109	DYNC1H1
Hedgehog ‘off’ state	1	17.8×	0.112	DYNC2H1
Loss of Nlp from mitotic centrosomes	1	15.9×	0.113	DYNC1H1
Loss of proteins required for interphase microtubule organization from the centrosome	1	15.9×	0.113	DYNC1H1
AURKA Activation by TPX2	1	15.2×	0.113	DYNC1H1
Recruitment of mitotic centrosome proteins and complexes	1	13.6×	0.121	DYNC1H1
Regulation of PLK1 Activity at G2/M Transition	1	12.7×	0.123	DYNC1H1
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	11.7×	0.123	DYNC1H1
Recruitment of NuMA to mitotic centrosomes	1	11.7×	0.123	DYNC1H1
COPI-mediated anterograde transport	1	11.0×	0.123	DYNC1H1
Regulation of PD-L1(CD274) transcription	1	10.9×	0.123	EPAS1
EML4 and NUDC in mitotic spindle formation	1	9.3×	0.134	DYNC1H1
MHC class II antigen presentation	1	8.9×	0.134	DYNC1H1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intraciliary retrograde transport	4	449.4×	7e-09	DYNC2H1, DYNC2I1, DYNC2I2, DYNLT2B
cilium assembly	6	44.1×	5e-08	DYNC2H1, KIF24, DYNC2I1, DYNC2I2, DYNLT2B, NEK1
microtubule-based movement	2	59.1×	0.011	KIF24, DYNLT2B
non-motile cilium assembly	2	58.1×	0.011	DYNC2H1, BBS10
trachea gland development	1	842.6×	0.017	EDA
regulation of intraciliary retrograde transport	1	842.6×	0.017	DYNLT2B
retinal cone cell differentiation	1	561.7×	0.019	BBS10
positive regulation of cold-induced thermogenesis	2	32.7×	0.019	DYNC1H1, EPAS1
cone retinal bipolar cell differentiation	1	421.3×	0.020	BBS10
myoblast fate commitment	1	337.0×	0.020	EPAS1
salivary gland cavitation	1	337.0×	0.020	EDA
hair follicle placode formation	1	337.0×	0.020	EDA
regulation of metaphase plate congression	1	337.0×	0.020	DYNC1H1
establishment of spindle localization	1	280.9×	0.022	DYNC1H1
positive regulation of spindle assembly	1	210.7×	0.025	DYNC1H1
retinal rod cell differentiation	1	187.2×	0.025	BBS10
positive regulation of intracellular transport	1	168.5×	0.025	DYNC1H1
epithelial cell maturation	1	153.2×	0.025	EPAS1
retrograde axonal transport	1	153.2×	0.025	DYNC1H1
intracellular oxygen homeostasis	1	153.2×	0.025	EPAS1
norepinephrine metabolic process	1	153.2×	0.025	EPAS1
regulation of non-canonical NF-kappaB signal transduction	1	153.2×	0.025	EDA
visual perception	2	15.9×	0.025	BBS10, EPAS1
microtubule depolymerization	1	105.3×	0.033	KIF24
P-body assembly	1	105.3×	0.033	DYNC1H1
spinal cord motor neuron differentiation	1	93.6×	0.034	DYNC2H1
regulation of protein neddylation	1	93.6×	0.034	EPAS1
response to light stimulus	1	88.7×	0.034	BBS10
regulation of mitotic spindle organization	1	84.3×	0.034	DYNC1H1
surfactant homeostasis	1	80.2×	0.034	EPAS1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 9

Druggability breadth: 4 of 12 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
EPAS1	BELZUTIFAN
NEK1	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NEK1	12	4
EPAS1	7	4
DYNC1H1	1	2
DYNC2H1	0	0
KIF24	0	0
DYNC2I1	0	0
BBS10	0	0
FAM98C	0	0
DYNC2I2	0	0
DYNLT2B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BELZUTIFAN	4	EPAS1
EMETINE	4	EPAS1
DOXORUBICIN	4	EPAS1
TOPOTECAN	4	EPAS1
FEDRATINIB	4	NEK1
DABRAFENIB	4	NEK1
LESTAURTINIB	3	NEK1
MOLIBRESIB	2	DYNC1H1
CYCLOHEXIMIDE	2	EPAS1
ALVESPIMYCIN	2	EPAS1
TG100-115	2	NEK1
R-406	2	NEK1
PELITINIB	2	NEK1
BAKUCHIOL	1	EPAS1
GSK-461364	1	NEK1
KW-2449	1	NEK1
AMG-900	1	NEK1
TAK-593	1	NEK1
CYC-116	1	NEK1
AST-487	1	NEK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NEK1	288	Binding:288
EPAS1	241	Binding:233, Functional:8
DYNC1H1	7	Binding:7
KIF24	2	Binding:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
EPAS1	241
NEK1	288

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

20 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)
BELZUTIFAN	4	EPAS1
EMETINE	4	EPAS1
DOXORUBICIN	4	EPAS1
TOPOTECAN	4	EPAS1
FEDRATINIB	4	NEK1
DABRAFENIB	4	NEK1
LESTAURTINIB	3	NEK1
MOLIBRESIB	2	DYNC1H1
CYCLOHEXIMIDE	2	EPAS1
ALVESPIMYCIN	2	EPAS1
TG100-115	2	NEK1
R-406	2	NEK1
PELITINIB	2	NEK1
BAKUCHIOL	1	EPAS1
GSK-461364	1	NEK1
KW-2449	1	NEK1
AMG-900	1	NEK1
TAK-593	1	NEK1
CYC-116	1	NEK1
AST-487	1	NEK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	EPAS1, NEK1
B	Phased (≥1) drug, not yet approved	1	DYNC1H1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	9	DYNC2H1, KIF24, DYNC2I1, BBS10, FAM98C, DYNC2I2, DYNLT2B, EDA, TMEM256-PLSCR3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DYNC2H1	0	NEK1
KIF24	2	—
DYNC2I1	0	—
BBS10	0	—
FAM98C	0	—
DYNC2I2	0	—
DYNLT2B	0	—
EDA	0	—
TMEM256-PLSCR3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.