Townes-Brocks syndrome

Summary

Townes-Brocks syndrome (MONDO:0007142) is a disease with 3 cohort genes.

At a glance

• Prevalence: 1-9 / 1 000 000 (Spain) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 374
• Phenotypes (HPO): 66

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.42	Spain	Validated
Point prevalence	1-9 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

66 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000377	Abnormal pinna morphology	Very frequent (80-99%)
HP:0000143	Rectovaginal fistula	Very frequent (80-99%)
HP:0000384	Preauricular skin tag	Very frequent (80-99%)
HP:0001177	Preaxial hand polydactyly	Very frequent (80-99%)
HP:0001199	Triphalangeal thumb	Very frequent (80-99%)
HP:0002023	Anal atresia	Very frequent (80-99%)
HP:0004792	Rectoperineal fistula	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000083	Renal insufficiency	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000396	Overfolded helix	Frequent (30-79%)
HP:0001482	Subcutaneous nodule	Frequent (30-79%)
HP:0001545	Anteriorly placed anus	Frequent (30-79%)
HP:0001760	Abnormal foot morphology	Frequent (30-79%)
HP:0001763	Pes planus	Frequent (30-79%)
HP:0001863	Toe clinodactyly	Frequent (30-79%)
HP:0002019	Constipation	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0008551	Microtia	Frequent (30-79%)
HP:0000047	Hypospadias	Occasional (5-29%)
HP:0000048	Bifid scrotum	Occasional (5-29%)
HP:0000076	Vesicoureteral reflux	Occasional (5-29%)
HP:0000086	Ectopic kidney	Occasional (5-29%)
HP:0000089	Renal hypoplasia	Occasional (5-29%)
HP:0000130	Abnormality of the uterus	Occasional (5-29%)
HP:0000142	Abnormality of the vagina	Occasional (5-29%)
HP:0000154	Wide mouth	Occasional (5-29%)
HP:0000324	Facial asymmetry	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000504	Abnormality of vision	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000567	Chorioretinal coloboma	Occasional (5-29%)
HP:0000568	Microphthalmia	Occasional (5-29%)
HP:0000581	Blepharophimosis	Occasional (5-29%)
HP:0000612	Iris coloboma	Occasional (5-29%)
HP:0000772	Abnormal rib morphology	Occasional (5-29%)
HP:0000821	Hypothyroidism	Occasional (5-29%)
HP:0000823	Delayed puberty	Occasional (5-29%)
HP:0001140	Limbal dermoid	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001274	Agenesis of corpus callosum	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001636	Tetralogy of Fallot	Occasional (5-29%)
HP:0001641	Abnormal pulmonary valve morphology	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001671	Abnormal cardiac septum morphology	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0002308	Chiari malformation	Occasional (5-29%)
HP:0002607	Bowel incontinence	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Townes-Brocks syndrome
Mondo ID	MONDO:0007142
MeSH	C536974
OMIM	107480
Orphanet	857
DOID	DOID:0050887
ICD-11	66554749
NCIT	C99085
SNOMED CT	24750000
UMLS	C0265246
MedGen	75555
GARD	0007784
NORD	1780
Is cancer (heuristic)	no

Also known as: anus, imperforate, with hand, foot and ear anomalies · deafness, sensorineural, with imperforate anus and hypoplastic thumbs · imperforate anus with hand, foot and ear anomalies · rear syndrome · renal-ear-anal-radial syndrome · sensorineural deafness with imperforate anus and hypoplastic thumbs · TBS · TBS1 · Townes syndrome · Townes-Brocks syndrome

Data availability: 374 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Townes-Brocks syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (2): Townes-Brocks syndrome 1, Townes-Brocks syndrome 2

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

374 retrieved; paginated sample, class counts are floors:

129 uncertain significance, 104 likely benign, 51 conflicting classifications of pathogenicity, 38 pathogenic, 26 benign/likely benign, 23 benign, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069244	NM_002968.3(SALL1):c.1423_1424del (p.Arg475fs)	SALL1	Pathogenic	criteria provided, single submitter
1069953	NM_002968.3(SALL1):c.1028dup (p.Leu344fs)	SALL1	Pathogenic	criteria provided, single submitter
1070663	NM_002968.3(SALL1):c.881_893dup (p.Leu299fs)	SALL1	Pathogenic	criteria provided, multiple submitters, no conflicts
1071229	NM_002968.3(SALL1):c.1027dup (p.Ile343fs)	SALL1	Pathogenic	criteria provided, single submitter
1075840	NM_002968.3(SALL1):c.870dup (p.Gln291fs)	SALL1	Pathogenic	criteria provided, single submitter
1353868	NM_002968.3(SALL1):c.691del (p.Glu231fs)	SALL1	Pathogenic	criteria provided, single submitter
2005719	NM_002968.3(SALL1):c.1417G>T (p.Gly473Ter)	SALL1	Pathogenic	criteria provided, single submitter
2031602	NM_002968.3(SALL1):c.878_887del (p.Leu293fs)	SALL1	Pathogenic	criteria provided, single submitter
2103715	NM_002968.3(SALL1):c.469_512dup (p.Ile172fs)	SALL1	Pathogenic	criteria provided, single submitter
2137807	NM_002968.3(SALL1):c.874C>T (p.Gln292Ter)	SALL1	Pathogenic	criteria provided, single submitter
219151	NM_002968.3(SALL1):c.3160C>T (p.Arg1054Ter)	SALL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2424574	NC_000016.9:g.(?51185057)(51185152_?)del	SALL1	Pathogenic	criteria provided, single submitter
2575075	NM_002968.3(SALL1):c.1240G>T (p.Glu414Ter)	SALL1	Pathogenic	no assertion criteria provided
2694137	NM_002968.3(SALL1):c.1183C>T (p.Gln395Ter)	SALL1	Pathogenic	criteria provided, single submitter
2703340	NM_002968.3(SALL1):c.1309G>T (p.Glu437Ter)	SALL1	Pathogenic	criteria provided, single submitter
2745434	NM_002968.3(SALL1):c.76+5G>A	SALL1	Pathogenic	criteria provided, single submitter
279887	NM_002968.3(SALL1):c.870_871dup (p.Gln291fs)	SALL1	Pathogenic	criteria provided, multiple submitters, no conflicts
2828754	NM_002968.3(SALL1):c.3128_3129del (p.Asn1043fs)	SALL1	Pathogenic	criteria provided, single submitter
2837510	NM_002968.3(SALL1):c.2325_2331dup (p.Ala778fs)	SALL1	Pathogenic	criteria provided, single submitter
3648236	NM_002968.3(SALL1):c.1199C>A (p.Ser400Ter)	SALL1	Pathogenic	criteria provided, single submitter
3725389	NM_002968.3(SALL1):c.350del (p.Asn117fs)	SALL1	Pathogenic	criteria provided, single submitter
3728154	NM_002968.3(SALL1):c.928del (p.Ile310fs)	SALL1	Pathogenic	criteria provided, single submitter
418466	NM_002968.3(SALL1):c.3414_3415del (p.Cys1139fs)	SALL1	Pathogenic	criteria provided, multiple submitters, no conflicts
459257	NM_002968.3(SALL1):c.1214dup (p.Leu406fs)	SALL1	Pathogenic	criteria provided, single submitter
459258	NM_002968.3(SALL1):c.2256del (p.Tyr753fs)	SALL1	Pathogenic	criteria provided, single submitter
4710263	NM_002968.3(SALL1):c.1374del (p.Phe458fs)	SALL1	Pathogenic	criteria provided, single submitter
4710810	NM_002968.3(SALL1):c.1508dup (p.Tyr503Ter)	SALL1	Pathogenic	criteria provided, single submitter
4714405	NM_002968.3(SALL1):c.924del (p.Ser309fs)	SALL1	Pathogenic	criteria provided, single submitter
4755556	NM_002968.3(SALL1):c.2356C>T (p.Arg786Ter)	SALL1	Pathogenic	criteria provided, multiple submitters, no conflicts
488838	NM_002968.3(SALL1):c.814C>T (p.Gln272Ter)	SALL1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · 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
SALL1	Definitive	Autosomal dominant	Townes-Brocks syndrome 1	5
DACT1	Moderate	Autosomal dominant	Townes-Brocks syndrome 2	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SALL1	Orphanet:857	Townes-Brocks syndrome
DACT1	Orphanet:268823	Occipital encephalocele
DACT1	Orphanet:63260	Craniorachischisis
DACT1	Orphanet:857	Townes-Brocks syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SALL1	HGNC:10524	ENSG00000103449	Q9NSC2	Sal-like protein 1	gencc,clinvar
DACT1	HGNC:17748	ENSG00000165617	Q9NYF0	Dapper homolog 1	gencc,clinvar
ADCY7	HGNC:238	ENSG00000121281	P51828	Adenylate cyclase type 7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SALL1	Sal-like protein 1	Transcriptional repressor involved in organogenesis.
DACT1	Dapper homolog 1	Involved in regulation of intracellular signaling pathways during development.
ADCY7	Adenylate cyclase type 7	Adenylate cyclase that mediates formation of both cyclic AMP (cAMP) and cyclic di-AMP (c-di-AMP).

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Enzyme (other)	1	4.0×	0.482
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SALL1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sal_C2H2-zinc-finger
DACT1	Other/Unknown	no		Dapper
ADCY7	Enzyme (other)	yes	4.6.1.1	A/G_cyclase, Adcy_conserved_dom, A/G_cyclase_CS

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
inferior vagus X ganglion	1
renal medulla	1
ventricular zone	1
cortical plate	1
gall bladder	1
right coronary artery	1
granulocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SALL1	195	broad	marker	ventricular zone, inferior vagus X ganglion, renal medulla
DACT1	200	ubiquitous	marker	cortical plate, right coronary artery, gall bladder
ADCY7	271	ubiquitous	marker	granulocyte, monocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SALL1	2,189
ADCY7	1,213
DACT1	1,107

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADCY7	P51828	77.32
DACT1	Q9NYF0	50.95
SALL1	Q9NSC2	49.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 52. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Adenylate cyclase activating pathway	1	380.7×	0.022	ADCY7
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation	1	292.8×	0.022	SALL1
Kidney development	1	271.9×	0.022	SALL1
Adenylate cyclase inhibitory pathway	1	253.8×	0.022	ADCY7
PKA activation in glucagon signalling	1	223.9×	0.022	ADCY7
PKA activation	1	211.5×	0.022	ADCY7
Activation of GABAB receptors	1	200.3×	0.022	ADCY7
PKA-mediated phosphorylation of CREB	1	190.3×	0.022	ADCY7
Transcriptional regulation of pluripotent stem cells	1	181.3×	0.022	SALL1
GABA B receptor activation	1	181.3×	0.022	ADCY7
Formation of the ureteric bud	1	165.5×	0.022	SALL1
Anti-inflammatory response favouring Leishmania parasite infection	1	131.3×	0.022	ADCY7
Leishmania parasite growth and survival	1	131.3×	0.022	ADCY7
Calmodulin induced events	1	126.9×	0.022	ADCY7
CaM pathway	1	126.9×	0.022	ADCY7
Ca-dependent events	1	122.8×	0.022	ADCY7
Aquaporin-mediated transport	1	122.8×	0.022	ADCY7
Glucagon signaling in metabolic regulation	1	115.3×	0.022	ADCY7
G-protein mediated events	1	108.8×	0.022	ADCY7
DAG and IP3 signaling	1	105.7×	0.022	ADCY7
GABA receptor activation	1	105.7×	0.022	ADCY7
Response of endothelial cells to shear stress	1	100.2×	0.022	ADCY7
FCGR3A-mediated IL10 synthesis	1	97.6×	0.022	ADCY7
Opioid Signalling	1	88.5×	0.022	ADCY7
PLC beta mediated events	1	88.5×	0.022	ADCY7
Vasopressin regulates renal water homeostasis via Aquaporins	1	88.5×	0.022	ADCY7
Cellular responses to mechanical stimuli	1	86.5×	0.022	ADCY7
ADORA2B mediated anti-inflammatory cytokines production	1	84.6×	0.022	ADCY7
GPER1 signaling	1	82.8×	0.022	ADCY7
Degradation of DVL	1	79.3×	0.022	DACT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of Wnt signaling pathway	2	255.3×	1e-03	SALL1, DACT1
inductive cell-cell signaling	1	5617.3×	0.003	SALL1
olfactory bulb mitral cell layer development	1	2808.7×	0.003	SALL1
kidney epithelium development	1	2808.7×	0.003	SALL1
ureteric bud invasion	1	2808.7×	0.003	SALL1
olfactory nerve development	1	1872.4×	0.003	SALL1
embryonic hindgut morphogenesis	1	1872.4×	0.003	DACT1
negative regulation of beta-catenin-TCF complex assembly	1	1872.4×	0.003	DACT1
olfactory bulb interneuron differentiation	1	1123.5×	0.004	SALL1
regulation of Wnt signaling pathway, planar cell polarity pathway	1	1123.5×	0.004	DACT1
mesenchymal to epithelial transition involved in metanephros morphogenesis	1	702.2×	0.006	SALL1
regulation of adaptive immune response	1	624.1×	0.006	ADCY7
cAMP biosynthetic process	1	468.1×	0.008	ADCY7
gonad development	1	374.5×	0.009	SALL1
cellular response to lithium ion	1	374.5×	0.009	ADCY7
cellular response to ethanol	1	351.1×	0.009	ADCY7
embryonic digestive tract development	1	330.4×	0.009	SALL1
maternal process involved in female pregnancy	1	312.1×	0.009	ADCY7
cellular response to glucagon stimulus	1	280.9×	0.009	ADCY7
vascular endothelial cell response to laminar fluid shear stress	1	244.2×	0.010	ADCY7
adrenal gland development	1	224.7×	0.010	SALL1
pituitary gland development	1	216.1×	0.010	SALL1
negative regulation of JNK cascade	1	187.2×	0.011	DACT1
regulation of canonical Wnt signaling pathway	1	181.2×	0.011	DACT1
neural tube development	1	175.5×	0.011	DACT1
renal water homeostasis	1	170.2×	0.011	ADCY7
ventricular septum development	1	165.2×	0.011	SALL1
ureteric bud development	1	151.8×	0.011	SALL1
negative regulation of cytokine production involved in inflammatory response	1	140.4×	0.012	ADCY7
limb development	1	137.0×	0.012	SALL1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SALL1	0	0
DACT1	0	0
ADCY7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ADCY7	16	Binding:14, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADCY7	4.6.1.1	adenylate cyclase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	0
D	Druggable family + AlphaFold only, no drug	1	ADCY7
E	Difficult family or no structure, no drug	2	SALL1, DACT1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SALL1	0	—
DACT1	0	—
ADCY7	16	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.