Short-rib thoracic dysplasia 9 with or without polydactyly

Summary

Short-rib thoracic dysplasia 9 with or without polydactyly (MONDO:0009964) is a disease caused by IFT140 (GenCC Definitive), with 6 cohort genes. The dominant Reactome pathway is Intraflagellar transport (3 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: IFT140 (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 1,989

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		13	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	short-rib thoracic dysplasia 9 with or without polydactyly
Mondo ID	MONDO:0009964
OMIM	266920
Orphanet	140969
DOID	DOID:0110097
SNOMED CT	254092004
UMLS	C1849437
MedGen	341455
GARD	0015227
Is cancer (heuristic)	no

Also known as: Conorenal syndrome · Mainzer Saldino syndrome · Mainzer-Saldino syndrome · renal dysplasia-retinal pigmentary dystrophy-cerebellar ataxia-skeletal dysplasia syndrome · Saldino-Mainzer syndrome · short-rib thoracic dysplasia 9 with or without polydactyly · SRTD9

Data availability: 1,989 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › short-rib thoracic dysplasia 9 with or without polydactyly

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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:

277 uncertain significance, 216 likely benign, 45 conflicting classifications of pathogenicity, 21 pathogenic, 14 benign, 11 pathogenic/likely pathogenic, 9 benign/likely benign, 7 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069327	NM_014714.4(IFT140):c.2677G>T (p.Glu893Ter)	IFT140	Pathogenic	criteria provided, single submitter
1069388	NM_014714.4(IFT140):c.2500C>T (p.Arg834Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071413	NM_014714.4(IFT140):c.1501C>T (p.Arg501Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1073514	NM_014714.4(IFT140):c.54del (p.Ser19fs)	IFT140	Pathogenic	criteria provided, single submitter
1074487	NM_014714.4(IFT140):c.482dup (p.Pro162fs)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184606	NM_014714.4(IFT140):c.1422_1423insAA (p.Arg475fs)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1298391	NM_014714.4(IFT140):c.2214_2217del (p.Asp738fs)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1323104	NM_014714.4(IFT140):c.1359_1359+3delinsAC	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1325702	NM_014714.4(IFT140):c.1039C>T (p.Arg347Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1328235	NM_014714.4(IFT140):c.3109C>T (p.Gln1037Ter)	IFT140	Pathogenic	criteria provided, single submitter
1328335	NM_014714.4(IFT140):c.3214C>T (p.Arg1072Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1358543	NM_014714.4(IFT140):c.3691_3692del (p.Thr1231fs)	IFT140	Pathogenic	criteria provided, single submitter
1373449	NM_014714.4(IFT140):c.2671del (p.Gln890_Val891insTer)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1375858	NM_014714.4(IFT140):c.1992_2005dup (p.Thr669fs)	IFT140	Pathogenic	criteria provided, single submitter
1383614	NM_014714.4(IFT140):c.2934C>A (p.Tyr978Ter)	IFT140	Pathogenic	criteria provided, single submitter
1391821	NM_014714.4(IFT140):c.3727C>T (p.Gln1243Ter)	IFT140	Pathogenic	criteria provided, single submitter
1391918	NM_014714.4(IFT140):c.3672_3673del (p.Leu1225fs)	IFT140	Pathogenic	criteria provided, single submitter
1398675	NM_014714.4(IFT140):c.2443C>T (p.Gln815Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1408932	NM_014714.4(IFT140):c.3489del (p.Asn1163fs)	IFT140	Pathogenic	criteria provided, single submitter
1417771	NM_014714.4(IFT140):c.919C>T (p.Arg307Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1424674	NM_014714.4(IFT140):c.3408_3409del (p.His1136fs)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1428555	NM_014714.4(IFT140):c.2038C>T (p.Gln680Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1449273	NC_000016.9:g.(?1568197)(1570829_?)dup	IFT140	Pathogenic	criteria provided, single submitter
1451353	NM_014714.4(IFT140):c.490G>T (p.Glu164Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1453885	NC_000016.9:g.(?1607916)(1608155_?)del	IFT140	Pathogenic	criteria provided, single submitter
1455247	NM_014714.4(IFT140):c.3640C>T (p.Gln1214Ter)	IFT140	Pathogenic	criteria provided, single submitter
1458035	NC_000016.9:g.(?1621388)(1621555_?)del	IFT140	Pathogenic	criteria provided, single submitter
1458870	NC_000016.9:g.(?1633295)(1637325_?)del	IFT140	Pathogenic	criteria provided, single submitter
1458986	NM_014714.4(IFT140):c.1795dup (p.Ile599fs)	IFT140	Pathogenic	criteria provided, single submitter
1459143	NM_014714.4(IFT140):c.1513C>T (p.Arg505Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 23 · 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
IFT140	Definitive	Autosomal recessive	short-rib thoracic dysplasia 9 with or without polydactyly	11
IFT172	Definitive	Autosomal recessive	short-rib thoracic dysplasia 10 with or without polydactyly	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
IFT172	Orphanet:110	Bardet-Biedl syndrome
IFT172	Orphanet:140969	Saldino-Mainzer syndrome
IFT172	Orphanet:474	Jeune syndrome
IFT172	Orphanet:791	Retinitis pigmentosa
WDR19	Orphanet:1515	Cranioectodermal dysplasia
WDR19	Orphanet:3156	Senior-Loken syndrome
WDR19	Orphanet:474	Jeune syndrome
WDR19	Orphanet:93592	Juvenile nephronophthisis
CLCN7	Orphanet:210110	Intermediate osteopetrosis
CLCN7	Orphanet:53	Albers-Schönberg osteopetrosis
CLCN7	Orphanet:667	Autosomal recessive malignant osteopetrosis
ABCA3	Orphanet:2032	Idiopathic pulmonary fibrosis
ABCA3	Orphanet:217563	Neonatal acute respiratory distress syndrome
ABCA3	Orphanet:440402	Interstitial lung disease due to ABCA3 deficiency
ABCA3	Orphanet:685082	Pediatric acute respiratory distress syndrome

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IFT140	HGNC:29077	ENSG00000187535	Q96RY7	Intraflagellar transport protein 140 homolog	gencc,clinvar
IFT172	HGNC:30391	ENSG00000138002	Q9UG01	Intraflagellar transport protein 172 homolog	gencc
TSR3	HGNC:14175	ENSG00000007520	Q9UJK0	18S rRNA aminocarboxypropyltransferase	clinvar
WDR19	HGNC:18340	ENSG00000157796	Q8NEZ3	WD repeat-containing protein 19	clinvar
CLCN7	HGNC:2025	ENSG00000103249	P51798	H(+)/Cl(-) exchange transporter 7	clinvar
ABCA3	HGNC:33	ENSG00000167972	Q99758	Phospholipid-transporting ATPase ABCA3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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).
IFT172	Intraflagellar transport protein 172 homolog	Required for the maintenance and formation of cilia.
TSR3	18S rRNA aminocarboxypropyltransferase	Aminocarboxypropyltransferase that catalyzes the aminocarboxypropyl transfer on pseudouridine at position 1248 (Psi1248) in 18S rRNA.
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.
CLCN7	H(+)/Cl(-) exchange transporter 7	Slowly voltage-gated channel mediating the exchange of chloride ions against protons.
ABCA3	Phospholipid-transporting ATPase ABCA3	Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pul…

Protein-family classification

Druggable: 1 · Difficult: 3 · Unknown: 2 · 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
Transporter	1	13.0×	0.149
Scaffold/PPI	2	5.8×	0.149
Transcription factor	1	1.4×	0.719
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IFT140	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
IFT172	Scaffold/PPI	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
TSR3	Other/Unknown	no		Tsr3_C, RNaseL-inhib-like_metal-bd_dom, Tsr3-like
WDR19	Transcription factor	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
CLCN7	Other/Unknown	no		CBS_dom, ClC, CIC-7
ABCA3	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	3
bronchial epithelial cell	2
left lobe of thyroid gland	1
right lobe of thyroid gland	1
left testis	1
apex of heart	1
cervix squamous epithelium	1
tendon of biceps brachii	1
adenohypophysis	1
left adrenal gland cortex	1
metanephros cortex	1
right adrenal gland cortex	1
lower lobe of lung	1
upper lobe of left lung	1
upper lobe of lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT140	214	ubiquitous	marker	right uterine tube, right lobe of thyroid gland, left lobe of thyroid gland
IFT172	236	ubiquitous	marker	right uterine tube, bronchial epithelial cell, left testis
TSR3	287	ubiquitous	marker	tendon of biceps brachii, apex of heart, cervix squamous epithelium
WDR19	269	ubiquitous	marker	right uterine tube, bronchial epithelial cell, adenohypophysis
CLCN7	296	ubiquitous	marker	metanephros cortex, right adrenal gland cortex, left adrenal gland cortex
ABCA3	222	ubiquitous	marker	lower lobe of lung, upper lobe of lung, upper lobe of left lung

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLCN7	1,991
IFT172	1,922
IFT140	1,602
ABCA3	1,436
TSR3	1,362
WDR19	1,251

Intra-cohort edges

A	B	Sources
IFT140	IFT172	string_interaction
IFT140	WDR19	biogrid_interaction, intact, string_interaction
IFT172	WDR19	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CLCN7	P51798	9
IFT140	Q96RY7	4
WDR19	Q8NEZ3	4
ABCA3	Q99758	2
IFT172	Q9UG01	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSR3	Q9UJK0	75.17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 6 evidence-associated genes (6 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Intraflagellar transport	3	100.2×	3e-05	IFT140, WDR19, IFT172
Hedgehog ‘off’ state	3	89.2×	3e-05	IFT140, WDR19, IFT172
Defective ABCA3 causes SMDP3	1	1903.3×	0.002	ABCA3
Diseases associated with surfactant metabolism	1	475.8×	0.007	ABCA3
ABC transporters in lipid homeostasis	1	100.2×	0.027	ABCA3
ABC transporter disorders	1	73.2×	0.031	ABCA3
Surfactant metabolism	1	61.4×	0.032	ABCA3
rRNA modification in the nucleus and cytosol	1	31.2×	0.056	TSR3
Disorders of transmembrane transporters	1	23.2×	0.063	ABCA3
Stimuli-sensing channels	1	22.7×	0.063	CLCN7
ABC-family protein mediated transport	1	20.2×	0.065	ABCA3
Diseases of metabolism	1	13.4×	0.089	ABCA3
Transport of small molecules	1	4.2×	0.247	ABCA3
Disease	1	2.2×	0.397	ABCA3
Metabolism of proteins	1	2.1×	0.397	ABCA3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
embryonic camera-type eye development	2	401.2×	4e-04	IFT140, WDR19
intraciliary retrograde transport	2	374.5×	4e-04	IFT140, WDR19
embryonic cranial skeleton morphogenesis	2	193.7×	9e-04	IFT140, WDR19
cilium assembly	3	36.8×	9e-04	IFT140, WDR19, IFT172
non-motile cilium assembly	2	96.8×	0.003	IFT140, IFT172
positive regulation of protein homooligomerization	1	2808.7×	0.004	ABCA3
hindgut development	1	2808.7×	0.004	IFT172
regulation of phosphatidylcholine metabolic process	1	1404.3×	0.006	ABCA3
xenobiotic export from cell	1	936.2×	0.007	ABCA3
enzyme-directed rRNA pseudouridine synthesis	1	702.2×	0.007	TSR3
ear morphogenesis	1	702.2×	0.007	WDR19
smoothened signaling pathway involved in dorsal/ventral neural tube patterning	1	702.2×	0.007	WDR19
myotome development	1	702.2×	0.007	WDR19
positive regulation of phospholipid efflux	1	702.2×	0.007	ABCA3
rRNA modification	1	561.7×	0.007	TSR3
digestive system development	1	561.7×	0.007	WDR19
protein localization to ciliary membrane	1	561.7×	0.007	WDR19
response to pH	1	468.1×	0.007	CLCN7
neural tube patterning	1	468.1×	0.007	IFT140
regulation of lipid biosynthetic process	1	468.1×	0.007	ABCA3
organelle assembly	1	468.1×	0.007	ABCA3
positive regulation of phospholipid transport	1	401.2×	0.008	ABCA3
transepithelial chloride transport	1	312.1×	0.010	CLCN7
phosphatidylglycerol metabolic process	1	234.1×	0.013	ABCA3
nervous system process	1	200.6×	0.014	WDR19
left/right axis specification	1	200.6×	0.014	IFT172
gonad development	1	187.2×	0.014	WDR19
embryonic camera-type eye morphogenesis	1	187.2×	0.014	IFT172
photoreceptor cell outer segment organization	1	175.5×	0.014	IFT140
phospholipid homeostasis	1	165.2×	0.015	ABCA3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 6

Druggability breadth: 0 of 6 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IFT140	0	0
IFT172	0	0
TSR3	0	0
WDR19	0	0
CLCN7	0	0
ABCA3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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	ABCA3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	IFT140, IFT172, TSR3, WDR19, CLCN7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
IFT140	0	—
IFT172	0	—
TSR3	0	—
WDR19	0	—
CLCN7	0	—
ABCA3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.