Renal agenesis

Summary

Renal agenesis (MONDO:0018470) is a disease (an umbrella term covering 6 Mondo subtypes) caused by NPNT (GenCC Strong), with 9 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: NPNT (GenCC Strong)
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 9
• ClinVar variants: 12
• Phenotypes (HPO): 16

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-5 / 10 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000104	Renal agenesis	Obligate (100%)
HP:0000122	Unilateral renal agenesis	Frequent (30-79%)
HP:0012300	Ureteral agenesis	Frequent (30-79%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000093	Proteinuria	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0001562	Oligohydramnios	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0002009	Potter facies	Occasional (5-29%)
HP:0002023	Anal atresia	Occasional (5-29%)
HP:0002089	Pulmonary hypoplasia	Occasional (5-29%)
HP:0008684	Aplasia/hypoplasia of the uterus	Occasional (5-29%)
HP:0010476	Aplasia/Hypoplasia of the bladder	Occasional (5-29%)
HP:0010958	Bilateral renal agenesis	Occasional (5-29%)
HP:0012873	Absent vas deferens	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	renal agenesis
Mondo ID	MONDO:0018470
OMIM	191830
Orphanet	411709
DOID	DOID:14766
ICD-11	683319223
NCIT	C99041
SNOMED CT	204942005
UMLS	C0542519
MedGen	154237
GARD	0009228
Is cancer (heuristic)	no

Also known as: absent/small kidney · absent/underdeveloped kidney · renal agenesis · renal agenesis (disease) · renal agenesis/hypoplasia

Data availability: 12 ClinVar variants · 3 GenCC gene-disease records · 2 HPO phenotypes · 5 cell lines.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › renal agenesis

Related subtypes (189): precocious puberty, complex cortical dysplasia with other brain malformations, imperforate anus, microcephaly, demyelinating disease, hypospadias, bone development disease, primary basilar invagination, familial bicuspid aortic valve, camptodactyly of fingers, isolated congenital digital clubbing, aorta coarctation, gingival fibromatosis-progressive deafness syndrome, Eng-Strom syndrome, Morgagni-Stewart-Morel syndrome, familial partial lipodystrophy, Dunnigan type, megalodactyly, odontomatosis-aortae esophagus stenosis syndrome, otodental syndrome, oculodental syndrome, Rutherfurd type, spina bifida, steatocystoma multiplex-natal teeth syndrome, distal symphalangism, thumb deformity-alopecia-pigmentation anomaly syndrome, double uterus-hemivagina-renal agenesis syndrome, amelogenesis imperfecta type 1G, Bloom syndrome, cardiac valvular defect, developmental, isolated cerebellar hypoplasia/agenesis, cleft palate-stapes fixation-oligodontia syndrome, Jalili syndrome, craniodiaphyseal dysplasia, craniofacial dyssynostosis, deafness-oligodontia syndrome, duodenal atresia, Fowler syndrome, multiple intestinal atresia, natal teeth-intestinal pseudoobstruction-patent ductus syndrome, atresia of small intestine, mulibrey nanism, oculocerebral hypopigmentation syndrome, Cross type, familial osteodysplasia, Anderson type, pancreatic agenesis, postaxial polydactyly-dental and vertebral anomalies syndrome, familial primary pulmonary hypoplasia, renal tubular dysgenesis of genetic origin, Rothmund-Thomson syndrome, familial isolated congenital asplenia, subaortic stenosis, membranous, non-eruption of teeth-maxillary hypoplasia-genu valgum syndrome, corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome, CK syndrome, Ogden syndrome, Nance-Horan syndrome, colonic atresia, Aicardi syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, 46,XY complete gonadal dysgenesis, loose anagen syndrome, lung agenesis-heart defect-thumb anomalies syndrome, Chudley-McCullough syndrome, macrocephaly-autism syndrome, DNA ligase IV deficiency, horizontal gaze palsy with progressive scoliosis, cataract - congenital heart disease - neural tube defect syndrome, autosomal recessive frontotemporal pachygyria, craniofacial dysplasia - osteopenia syndrome, porencephaly-microcephaly-bilateral congenital cataract syndrome, congenital short bowel syndrome, familial median cleft of the upper and lower lips, progeroid features-hepatocellular carcinoma predisposition syndrome, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, aneurysm of sinus of Valsalva, blepharoptosis-cleft palate-ectrodactyly-dental anomalies syndrome, medullary sponge kidney, isolated congenital syngnathia, cleft lip and alveolus, diprosopus, T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency, high anorectal malformation, intermediate anorectal malformation, low anorectal malformation, microcephaly-polymicrogyria-corpus callosum agenesis syndrome, cordiform uterus, septate uterus, bicornuate uterus, uterine hypoplasia, agenesis and aplasia of uterine body, uterine cervical aplasia and agenesis, longitudinal vaginal septum, transverse vaginal septum, axial mesodermal dysplasia spectrum, multicystic dysplastic kidney, diabetic embryopathy, congenital microgastria, isolated cleft lip, cleft lip/palate, hereditary gingival fibromatosis, congenital bronchobiliary fistula, congenital hydrocephalus, maternal hyperthermia induced birth defects, diphallia, epibulbar lipodermoid-preauricular appendage-polythelia syndrome, bronchogenic cyst, duplication of urethra, hypohidrotic ectodermal dysplasia, Lowe-Kohn-Cohen syndrome, biliary atresia with splenic malformation syndrome, congenital pulmonary airway malformation, familial intestinal malrotation-facial anomalies syndrome, megalencephaly, cephalocele, cerebral cortical dysplasia, L1 syndrome, familial omphalocele syndrome with facial dysmorphism, penoscrotal transposition, pericardial and diaphragmatic defect, hypogonadotropic hypogonadism-severe microcephaly-sensorineural hearing loss-dysmorphism syndrome, congenital deformities of limbs, familial isolated clinodactyly of fingers, congenital shoulder dislocation, congenital elbow dislocation, congenital knee dislocation, congenital patella dislocation, macrodactyly of fingers, macrodactyly of toes, upper limb hypertrophy, lower limb hypertrophy, duplication of the pituitary gland, diencephalic-mesencephalic junction dysplasia, steroid dehydrogenase deficiency-dental anomalies syndrome, congenital achiasma, tracheal agenesis, hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome, isolated splenogonadal fusion, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, congenital bilateral absence of vas deferens, congenital portosystemic shunt, lissencephaly spectrum disorders, Berardinelli-Seip congenital lipodystrophy, congenital primary megaureter, craniorachischisis, vaginal atresia, bronchopulmonary dysplasia, dentinogenesis imperfecta-short stature-hearing loss-intellectual disability syndrome, aniridia, atypical Werner syndrome, X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome, anterior segment dysgenesis, congenital esophageal diverticulum, renal hypoplasia, renal dysplasia, overgrowth syndrome, developmental defect during embryogenesis, acalvaria, congenital aortic valve insufficiency, congenital anomaly of superior vena cava, congenital anomaly of hepatic vein, posterior hypospadias, isolated micropenis, isolated partial vaginal agenesis, anorectal malformation, pulmonary agenesis, congenital tricuspid malformation, Noonan syndrome and Noonan-related syndrome, coronary sinus stenosis, coronary sinus atresia, cartilage development disorder, syndactyly, polydactyly, brachydactyly, neurocristopathy, congenital absence of septum pellucidum, branchial arch disease, congenital anomaly of cardiovascular system, atelencephaly, aprosencephaly, aortic valve stenosis, hereditary lethal multiple congenital anomalies/dysmorphic syndrome, congenital agenesis of the scrotum, keratinization disease, lactation disease, COACH syndrome, constitutional delay of growth and puberty, isolated congenital femoral bifurcation, congenital peritoneal encapsulation, isolated short stature, congenital high airway obstruction syndrome

Subtypes (6): renal hypodysplasia/aplasia 2, bilateral renal agenesis, renal agenesis, unilateral, renal hypodysplasia/aplasia 1, renal hypodysplasia/aplasia 3, renal hypodysplasia/aplasia 4

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

12 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 5 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
978641	NM_001384125.1(BLTP1):c.9153del (p.Val3052fs)	BLTP1	Pathogenic	criteria provided, single submitter
1328410	NM_025074.7(FRAS1):c.879C>G (p.Tyr293Ter)	FRAS1	Pathogenic	criteria provided, single submitter
1328421	NM_025074.7(FRAS1):c.1176C>G (p.Tyr392Ter)	FRAS1	Pathogenic	criteria provided, single submitter
1328427	NM_025074.7(FRAS1):c.7747C>T (p.Gln2583Ter)	FRAS1	Pathogenic	criteria provided, single submitter
2579201	GRCh38/hg38 20p13-11.21(chr20:87153-23635465)x3	LOC112694698	Pathogenic	criteria provided, single submitter
1328431	NM_001080512.3(BICC1):c.387+1G>C	BICC1	Likely pathogenic	criteria provided, single submitter
978642	NM_001384125.1(BLTP1):c.14113+11G>C	BLTP1	Uncertain significance	criteria provided, single submitter
1328407	NM_001142966.3(GREB1L):c.2441T>C (p.Leu814Pro)	GREB1L	Uncertain significance	criteria provided, single submitter
1328408	NM_001142966.3(GREB1L):c.1720+5G>A	GREB1L	Uncertain significance	criteria provided, single submitter
1328409	NM_001142966.3(GREB1L):c.3170G>C (p.Arg1057Pro)	GREB1L	Uncertain significance	criteria provided, single submitter
1252040	NM_016126.4(IFT25):c.183dup (p.Leu62fs)	IFT25	Uncertain significance	no assertion criteria provided
813842	GRCh37/hg19 6q14.3(chr6:85220808-85517846)x3	TBX18	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 17 · 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
NPNT	Strong	Autosomal recessive	renal agenesis
WNT9B	Moderate	Autosomal recessive	renal agenesis
RET	Supportive	Autosomal recessive	bilateral renal agenesis	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WNT9B	Orphanet:1848	Renal agenesis, bilateral
RET	Orphanet:146	Differentiated thyroid carcinoma
RET	Orphanet:1848	Renal agenesis, bilateral
RET	Orphanet:247698	Multiple endocrine neoplasia type 2A
RET	Orphanet:247709	Multiple endocrine neoplasia type 2B
RET	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
RET	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
RET	Orphanet:388	Hirschsprung disease
RET	Orphanet:93100	Renal agenesis, unilateral
RET	Orphanet:99361	Isolated familial medullary thyroid carcinoma
RET	Orphanet:99803	Haddad syndrome
FRAS1	Orphanet:2052	Fraser syndrome
FRAS1	Orphanet:93100	Renal agenesis, unilateral
BICC1	Orphanet:730	Autosomal dominant polycystic kidney disease
BLTP1	Orphanet:610569	KIAA1109-related early lethal congenital brain malformations-arthrogryposis syndrome
GREB1L	Orphanet:1848	Renal agenesis, bilateral
GREB1L	Orphanet:93100	Renal agenesis, unilateral

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WNT9B	HGNC:12779	ENSG00000158955	O14905	Protein Wnt-9b	gencc
NPNT	HGNC:27405	ENSG00000168743	Q6UXI9	Nephronectin	gencc
RET	HGNC:9967	ENSG00000165731	P07949	Proto-oncogene tyrosine-protein kinase receptor Ret	gencc
TBX18	HGNC:11595	ENSG00000112837	O95935	T-box transcription factor TBX18	clinvar
FRAS1	HGNC:19185	ENSG00000138759	Q86XX4	Extracellular matrix organizing protein FRAS1	clinvar
BICC1	HGNC:19351	ENSG00000122870	Q9H694	Protein bicaudal C homolog 1	clinvar
IFT25	HGNC:25019	ENSG00000081870	Q9Y547	Intraflagellar transport protein 25 homolog	clinvar
BLTP1	HGNC:26953	ENSG00000138688	Q2LD37	Bridge-like lipid transfer protein family member 1	clinvar
GREB1L	HGNC:31042	ENSG00000141449	Q9C091	GREB1-like protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WNT9B	Protein Wnt-9b	Ligand for members of the frizzled family of seven transmembrane receptors.
NPNT	Nephronectin	Functional ligand of integrin alpha-8/beta-1 in kidney development.
RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…
TBX18	T-box transcription factor TBX18	Acts as a transcriptional repressor involved in developmental processes of a variety of tissues and organs, including the heart and coronary vessels, the ureter and the vertebral column.
FRAS1	Extracellular matrix organizing protein FRAS1	Involved in extracellular matrix organization.
BICC1	Protein bicaudal C homolog 1	Putative RNA-binding protein.
IFT25	Intraflagellar transport protein 25 homolog	Component of the IFT complex B required for sonic hedgehog/SHH signaling.
BLTP1	Bridge-like lipid transfer protein family member 1	Bridge-like lipid transfer protein that functions as molecular bridges between endoplasmic reticulum and the membranes targeted for lipid delivery.
GREB1L	GREB1-like protein	Plays a major role in early metanephros and genital development.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 7 · Druggable fraction: 0.11

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	3.1×	0.422
Other/Unknown	7	1.4×	0.422
Transcription factor	1	0.9×	0.687

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WNT9B	Other/Unknown	no		Wnt, Wnt_CS, Wnt_C
NPNT	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, MAM_dom
RET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom
TBX18	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
FRAS1	Other/Unknown	no		EGF, VWF_dom, Calx_beta
BICC1	Other/Unknown	no		SAM, KH_dom, KH_dom_type_1
IFT25	Other/Unknown	no		FA58C, Galactose-bd-like_sf, IFT25
BLTP1	Other/Unknown	no		BLTP1, BLTP1_N, BLTP1_M
GREB1L	Other/Unknown	no		GREB1, GREB1_N, GREB1-like_C

Expression context

Cohort genes with no expression data: 0.

8 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
germinal epithelium of ovary	2
parietal pleura	2
renal medulla	2
metanephros cortex	1
primordial germ cell in gonad	1
quadriceps femoris	1
left lobe of thyroid gland	1
right lobe of thyroid gland	1
thyroid gland	1
dorsal root ganglion	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1
popliteal artery	1
right coronary artery	1
tibial artery	1
bronchial epithelial cell	1
epithelium of bronchus	1
oocyte	1
Brodmann (1909) area 23	1
corpus callosum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WNT9B	114	tissue_specific	yes	quadriceps femoris, metanephros cortex, primordial germ cell in gonad
NPNT	239	broad	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
RET	193	broad	marker	substantia nigra pars reticulata, dorsal root ganglion, substantia nigra pars compacta
TBX18	162	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery
FRAS1	212	ubiquitous	marker	germinal epithelium of ovary, parietal pleura, renal medulla
BICC1	236	ubiquitous	marker	germinal epithelium of ovary, renal medulla, parietal pleura
IFT25	293	ubiquitous	marker	oocyte, bronchial epithelial cell, epithelium of bronchus
BLTP1	298	ubiquitous	marker	Brodmann (1909) area 23, corpus callosum, postcentral gyrus
GREB1L	184	broad	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RET	4,203
FRAS1	2,552
IFT25	1,447
BICC1	1,265
TBX18	1,246
WNT9B	1,178
BLTP1	1,049
NPNT	735
GREB1L	637

Intra-cohort edges

A	B	Sources
BICC1	RET	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 6 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RET	P07949	34
BICC1	Q9H694	3
IFT25	Q9Y547	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT9B	O14905	84.50
GREB1L	Q9C091	72.90
NPNT	Q6UXI9	67.42
TBX18	O95935	61.09
FRAS1	Q86XX4
BLTP1	Q2LD37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 9 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the nephric duct	2	317.2×	1e-04	NPNT, RET
Formation of the ureteric bud	2	248.3×	1e-04	NPNT, RET
Nephron development	1	219.6×	0.014	WNT9B
NPAS4 regulates expression of target genes	1	124.1×	0.017	RET
WNT ligand biogenesis and trafficking	1	105.7×	0.017	WNT9B
RET signaling	1	64.9×	0.023	RET
Intraflagellar transport	1	50.1×	0.023	IFT25
Class B/2 (Secretin family receptors)	1	47.6×	0.023	WNT9B
RAF/MAP kinase cascade	1	15.3×	0.064	RET

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
branching involved in ureteric bud morphogenesis	3	122.1×	2e-04	WNT9B, NPNT, GREB1L
male genitalia development	2	197.1×	0.001	WNT9B, GREB1L
smooth muscle cell differentiation	2	197.1×	0.001	TBX18, NPNT
kidney development	3	46.8×	0.001	BICC1, IFT25, GREB1L
ureteric bud development	2	101.2×	0.004	NPNT, RET
morphogenesis of an epithelium	2	76.4×	0.006	FRAS1, GREB1L
regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	1	1872.4×	0.006	WNT9B
regulation of tube size	1	1872.4×	0.006	WNT9B
sinoatrial node cell fate commitment	1	1872.4×	0.006	TBX18
kidney rudiment formation	1	1872.4×	0.006	WNT9B
roof of mouth development	2	55.1×	0.006	WNT9B, FRAS1
cellular response to retinoic acid	2	52.0×	0.006	WNT9B, RET
embryonic epithelial tube formation	1	936.2×	0.007	RET
posterior midgut development	1	936.2×	0.007	RET
mesenchymal stem cell maintenance involved in nephron morphogenesis	1	936.2×	0.007	WNT9B
establishment of planar polarity involved in nephron morphogenesis	1	936.2×	0.007	WNT9B
metanephric tubule formation	1	936.2×	0.007	WNT9B
mesonephric duct formation	1	936.2×	0.007	WNT9B
neural plate anterior/posterior regionalization	1	624.1×	0.009	TBX18
positive regulation of metanephric glomerulus development	1	624.1×	0.009	RET
pilomotor reflex	1	624.1×	0.009	NPNT
metanephros morphogenesis	1	468.1×	0.009	FRAS1
regulation of asymmetric cell division	1	468.1×	0.009	WNT9B
ureter maturation	1	468.1×	0.009	RET
Peyer’s patch morphogenesis	1	468.1×	0.009	RET
paramesonephric duct development	1	468.1×	0.009	GREB1L
collecting duct development	1	468.1×	0.009	WNT9B
GDF15-GFRAL signaling pathway	1	468.1×	0.009	RET
negative regulation of canonical Wnt signaling pathway	2	26.2×	0.010	TBX18, BICC1
mesonephric duct development	1	374.5×	0.011	GREB1L

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 8

Druggability breadth: 1 of 9 evidence-associated genes (11%) 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
RET	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RET	135	4
WNT9B	0	0
NPNT	0	0
TBX18	0	0
FRAS1	0	0
BICC1	0	0
IFT25	0	0
BLTP1	0	0
GREB1L	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	RET
AFATINIB	4	RET
VEMURAFENIB	4	RET
FEDRATINIB	4	RET
TIVOZANIB	4	RET
LENVATINIB	4	RET
AXITINIB	4	RET
SORAFENIB	4	RET
DASATINIB ANHYDROUS	4	RET
ALECTINIB	4	RET
RUXOLITINIB	4	RET
INFIGRATINIB PHOSPHATE	4	RET
INFIGRATINIB	4	RET
IBRUTINIB	4	RET
PALBOCICLIB	4	RET
REGORAFENIB	4	RET
ENTRECTINIB	4	RET
TOFACITINIB CITRATE	4	RET
FOSTAMATINIB	4	RET
CABOZANTINIB	4	RET
BARICITINIB	4	RET
TOFACITINIB	4	RET
CAPIVASERTIB	4	RET
CERITINIB	4	RET
VANDETANIB	4	RET
NILOTINIB	4	RET
BOSUTINIB	4	RET
GILTERITINIB	4	RET
BRIGATINIB	4	RET
UPADACITINIB	4	RET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
RET	1,586	Binding:1573, Functional:10, ADMET:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RET	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
RET	1,586

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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)
PONATINIB	4	RET
AFATINIB	4	RET
VEMURAFENIB	4	RET
FEDRATINIB	4	RET
TIVOZANIB	4	RET
LENVATINIB	4	RET
AXITINIB	4	RET
SORAFENIB	4	RET
DASATINIB ANHYDROUS	4	RET
ALECTINIB	4	RET
RUXOLITINIB	4	RET
INFIGRATINIB PHOSPHATE	4	RET
INFIGRATINIB	4	RET
IBRUTINIB	4	RET
PALBOCICLIB	4	RET
REGORAFENIB	4	RET
ENTRECTINIB	4	RET
TOFACITINIB CITRATE	4	RET
FOSTAMATINIB	4	RET
CABOZANTINIB	4	RET
BARICITINIB	4	RET
TOFACITINIB	4	RET
CAPIVASERTIB	4	RET
CERITINIB	4	RET
VANDETANIB	4	RET
NILOTINIB	4	RET
BOSUTINIB	4	RET
GILTERITINIB	4	RET
BRIGATINIB	4	RET
UPADACITINIB	4	RET

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RET
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	8	WNT9B, NPNT, TBX18, FRAS1, BICC1, IFT25, BLTP1, GREB1L

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WNT9B	0	—
NPNT	0	—
TBX18	0	—
FRAS1	0	—
BICC1	0	—
IFT25	0	—
BLTP1	0	—
GREB1L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.