Bailey-Bloch congenital myopathy

Summary

Bailey-Bloch congenital myopathy (MONDO:0009722) is a disease caused by STAC3 (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Causal gene: STAC3 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 243
• Phenotypes (HPO): 34

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

34 HPO clinical features (Orphanet curated; top 34 by frequency):

HPO ID	Term	Frequency
HP:0002058	Myopathic facies	Very frequent (80-99%)
HP:0001324	Muscle weakness	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001488	Bilateral ptosis	Frequent (30-79%)
HP:0001762	Talipes equinovarus	Frequent (30-79%)
HP:0002020	Gastroesophageal reflux	Frequent (30-79%)
HP:0002047	Malignant hyperthermia	Frequent (30-79%)
HP:0002093	Respiratory insufficiency	Frequent (30-79%)
HP:0002803	Congenital contracture	Frequent (30-79%)
HP:0002804	Arthrogryposis multiplex congenita	Frequent (30-79%)
HP:0003202	Skeletal muscle atrophy	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0008458	Progressive congenital scoliosis	Frequent (30-79%)
HP:0010674	Abnormality of the curvature of the vertebral column	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0012084	Abnormality of skeletal muscle fiber size	Frequent (30-79%)
HP:0000193	Bifid uvula	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000405	Conductive hearing impairment	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001315	Reduced tendon reflexes	Occasional (5-29%)
HP:0002714	Downturned corners of mouth	Occasional (5-29%)
HP:0011819	Submucous cleft soft palate	Occasional (5-29%)
HP:0100295	Muscle fiber atrophy	Occasional (5-29%)
HP:0000329	Facial hemangioma	Very rare (<1-4%)
HP:0001256	Intellectual disability, mild	Very rare (<1-4%)
HP:0001382	Joint hypermobility	Very rare (<1-4%)
HP:0002540	Inability to walk	Very rare (<1-4%)
HP:0012385	Camptodactyly	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Bailey-Bloch congenital myopathy
Mondo ID	MONDO:0009722
MeSH	C538343
OMIM	255995
Orphanet	168572
DOID	DOID:0060346
SNOMED CT	723439002
UMLS	C1850625
MedGen	340586
GARD	0008432
Is cancer (heuristic)	no

Also known as: Bailey-Bloch congenital myopathy · congenital myopathy - cleft palate - malignant hyperthermia · congenital myopathy cleft palate and malignant hyperthermia · congenital myopathy-cleft palate-malignant hyperthermia syndrome · myopathy, congenital, baily-bloch · NAM · Native American myopathy · STAC3 disorder

Data availability: 243 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › Bailey-Bloch congenital myopathy

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

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

243 retrieved; paginated sample, class counts are floors:

110 likely benign, 108 uncertain significance, 8 pathogenic, 6 benign, 4 benign/likely benign, 3 pathogenic/likely pathogenic, 2 likely pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073206	NM_145064.3(STAC3):c.694del (p.Ala232fs)	STAC3	Pathogenic	criteria provided, single submitter
2742179	NM_145064.3(STAC3):c.297_301del (p.Pro100fs)	STAC3	Pathogenic	criteria provided, single submitter
2908864	NM_145064.3(STAC3):c.816_817del (p.Lys273fs)	STAC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2959864	NM_145064.3(STAC3):c.468_469del (p.Tyr157fs)	STAC3	Pathogenic	criteria provided, single submitter
3244314	NC_000012.11:g.(?57641889)(57642001_?)del	STAC3	Pathogenic	criteria provided, single submitter
425007	NM_145064.3(STAC3):c.862A>T (p.Lys288Ter)	STAC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
465659	NM_145064.3(STAC3):c.383_399del (p.His128fs)	STAC3	Pathogenic	criteria provided, single submitter
559850	NM_145064.3(STAC3):c.763_766del (p.Leu255fs)	STAC3	Pathogenic	criteria provided, single submitter
577652	NM_145064.3(STAC3):c.739C>T (p.Gln247Ter)	STAC3	Pathogenic	criteria provided, single submitter
691283	NM_145064.3(STAC3):c.997-1G>T	STAC3	Pathogenic	no assertion criteria provided
88744	NM_145064.3(STAC3):c.851G>C (p.Trp284Ser)	STAC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339522	NM_145064.3(STAC3):c.432+1G>A	STAC3	Likely pathogenic	criteria provided, single submitter
2074431	NM_145064.3(STAC3):c.670+2T>A	STAC3	Likely pathogenic	criteria provided, single submitter
14707	NM_000208.4(INSR):c.3034G>A (p.Val1012Met)	INSR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
425008	NM_145064.3(STAC3):c.432+4A>T	STAC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000605	NM_145064.3(STAC3):c.232C>G (p.Pro78Ala)	STAC3	Uncertain significance	criteria provided, single submitter
1004574	NM_145064.3(STAC3):c.544C>A (p.Arg182Ser)	STAC3	Uncertain significance	criteria provided, single submitter
1007513	NM_145064.3(STAC3):c.145A>G (p.Asn49Asp)	STAC3	Uncertain significance	criteria provided, single submitter
1010716	NM_145064.3(STAC3):c.996+1G>A	STAC3	Uncertain significance	criteria provided, single submitter
1026763	NM_145064.3(STAC3):c.662C>A (p.Pro221His)	STAC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1040958	NM_145064.3(STAC3):c.458G>A (p.Ser153Asn)	STAC3	Uncertain significance	criteria provided, single submitter
1045189	NM_145064.3(STAC3):c.181TAC[1] (p.Tyr62del)	STAC3	Uncertain significance	criteria provided, single submitter
1053508	NM_145064.3(STAC3):c.518G>T (p.Arg173Leu)	STAC3	Uncertain significance	criteria provided, single submitter
1059868	NM_145064.3(STAC3):c.670+3del	STAC3	Uncertain significance	criteria provided, single submitter
1352442	NM_145064.3(STAC3):c.904A>T (p.Ile302Phe)	STAC3	Uncertain significance	criteria provided, single submitter
1357602	NM_145064.3(STAC3):c.214GAG[6] (p.Glu76dup)	STAC3	Uncertain significance	criteria provided, single submitter
1365736	NM_145064.3(STAC3):c.73C>T (p.Arg25Trp)	STAC3	Uncertain significance	criteria provided, single submitter
1395273	NM_145064.3(STAC3):c.166G>C (p.Gly56Arg)	STAC3	Uncertain significance	criteria provided, single submitter
1395579	NM_145064.3(STAC3):c.893C>G (p.Pro298Arg)	STAC3	Uncertain significance	criteria provided, single submitter
1396308	NM_145064.3(STAC3):c.964G>T (p.Glu322Ter)	STAC3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 6 · 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
STAC3	Definitive	Autosomal recessive	Bailey-Bloch congenital myopathy	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STAC3	Orphanet:168572	Native American myopathy
INSR	Orphanet:2297	Insulin-resistance syndrome type A
INSR	Orphanet:263458	Hyperinsulinism due to INSR deficiency
INSR	Orphanet:508	Donohue syndrome
INSR	Orphanet:769	Rabson-Mendenhall syndrome
ATP6V0A4	Orphanet:402041	Autosomal recessive distal renal tubular acidosis

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
STAC3	HGNC:28423	ENSG00000185482	Q96MF2	SH3 and cysteine-rich domain-containing protein 3	gencc,clinvar
INSR	HGNC:6091	ENSG00000171105	P06213	Insulin receptor	clinvar
ATP6V0A4	HGNC:866	ENSG00000105929	Q9HBG4	V-type proton ATPase 116 kDa subunit a 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STAC3	SH3 and cysteine-rich domain-containing protein 3	Required for normal excitation-contraction coupling in skeletal muscle and for normal muscle contraction in response to membrane depolarization.
INSR	Insulin receptor	Receptor tyrosine kinase which mediates the pleiotropic actions of insulin.
ATP6V0A4	V-type proton ATPase 116 kDa subunit a 4	Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.

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
Kinase	1	9.2×	0.246
Scaffold/PPI	1	5.8×	0.246
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STAC3	Scaffold/PPI	no		SH3_domain, PKC_DAG/PE, Stac3_SH3_1
INSR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ATP6V0A4	Other/Unknown	no		V-ATPase_116kDa_su, V-type_ATPase_116kDa_su_euka

Expression context

Cohort genes with no expression data: 0.

2 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
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1
buccal mucosa cell	1
palpebral conjunctiva	1
visceral pleura	1
adult mammalian kidney	1
metanephros cortex	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STAC3	177	tissue_specific	yes	gastrocnemius, hindlimb stylopod muscle, muscle of leg
INSR	296	ubiquitous	marker	buccal mucosa cell, palpebral conjunctiva, visceral pleura
ATP6V0A4	150	tissue_specific	marker	metanephros cortex, adult mammalian kidney, renal medulla

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
INSR	4,446
ATP6V0A4	1,221
STAC3	1,128

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INSR	P06213	88
STAC3	Q96MF2	5
ATP6V0A4	Q9HBG4	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Insulin receptor recycling	2	380.7×	9e-05	INSR, ATP6V0A4
IRS activation	1	1142.0×	0.006	INSR
Signal attenuation	1	519.1×	0.008	INSR
Signaling by Insulin receptor	1	439.2×	0.008	INSR
Insulin receptor signalling cascade	1	335.9×	0.008	INSR
Transferrin endocytosis and recycling	1	184.2×	0.012	ATP6V0A4
ROS and RNS production in phagocytes	1	167.9×	0.012	ATP6V0A4
Negative regulation of the PI3K/AKT network	1	139.3×	0.013	INSR
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	48.4×	0.028	INSR
Ion channel transport	1	48.0×	0.028	ATP6V0A4
Intracellular signaling by second messengers	1	45.7×	0.028	INSR
PIP3 activates AKT signaling	1	33.4×	0.035	INSR
Signaling by Receptor Tyrosine Kinases	1	25.8×	0.041	INSR
Signal Transduction	1	5.1×	0.187	INSR

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 meiotic cell cycle	1	2808.7×	0.006	INSR
regulation of female gonad development	1	2808.7×	0.006	INSR
renal tubular secretion	1	1872.4×	0.006	ATP6V0A4
positive regulation of voltage-gated calcium channel activity	1	1872.4×	0.006	STAC3
positive regulation of protein-containing complex disassembly	1	1404.3×	0.006	INSR
positive regulation of developmental growth	1	1404.3×	0.006	INSR
positive regulation of respiratory burst	1	1123.5×	0.007	INSR
exocrine pancreas development	1	561.7×	0.011	INSR
regulation of pH	1	468.1×	0.011	ATP6V0A4
male sex determination	1	468.1×	0.011	INSR
dendritic spine maintenance	1	432.1×	0.011	INSR
intracellular pH reduction	1	401.2×	0.011	ATP6V0A4
neuron projection maintenance	1	374.5×	0.011	INSR
positive regulation of glycogen biosynthetic process	1	330.4×	0.011	INSR
amyloid-beta clearance	1	312.1×	0.011	INSR
synaptic vesicle lumen acidification	1	312.1×	0.011	ATP6V0A4
vacuolar acidification	1	244.2×	0.012	ATP6V0A4
positive regulation of receptor internalization	1	234.1×	0.012	INSR
adrenal gland development	1	224.7×	0.012	INSR
positive regulation of glycolytic process	1	224.7×	0.012	INSR
neuromuscular synaptic transmission	1	200.6×	0.013	STAC3
positive regulation of mitotic nuclear division	1	181.2×	0.013	INSR
skeletal muscle fiber development	1	181.2×	0.013	STAC3
skeletal muscle contraction	1	170.2×	0.013	STAC3
positive regulation of nitric oxide biosynthetic process	1	151.8×	0.013	INSR
positive regulation of D-glucose import across plasma membrane	1	151.8×	0.013	INSR
symbiont entry into host cell	1	133.8×	0.015	INSR
heart morphogenesis	1	124.8×	0.015	INSR
regulation of embryonic development	1	110.1×	0.016	INSR
receptor internalization	1	108.0×	0.016	INSR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 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
INSR	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
INSR	36	4
STAC3	0	0
ATP6V0A4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	INSR
SORAFENIB	4	INSR
NERATINIB	4	INSR
INFIGRATINIB PHOSPHATE	4	INSR
INFIGRATINIB	4	INSR
ENTRECTINIB	4	INSR
CERITINIB	4	INSR
OSIMERTINIB	4	INSR
BRIGATINIB	4	INSR
NINTEDANIB	4	INSR
SUNITINIB	4	INSR
LAPATINIB	4	INSR
CRIZOTINIB	4	INSR
LINSITINIB	3	INSR
LINIFANIB	3	INSR
DOVITINIB	3	INSR
LESTAURTINIB	3	INSR
FORETINIB	2	INSR
SU-014813	2	INSR
CENISERTIB	2	INSR
ILORASERTIB	2	INSR
OSI-632	2	INSR
R-406	2	INSR
TOZASERTIB	2	INSR
BMS-754807	2	INSR
ELLAGIC ACID	2	INSR
PF-00562271	1	INSR
KW-2449	1	INSR
RG-1530	1	INSR
XL-228	1	INSR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
INSR	954	Binding:900, Functional:49, ADMET:4, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
INSR	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
INSR	954

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

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)
FEDRATINIB	4	INSR
SORAFENIB	4	INSR
NERATINIB	4	INSR
INFIGRATINIB PHOSPHATE	4	INSR
INFIGRATINIB	4	INSR
ENTRECTINIB	4	INSR
CERITINIB	4	INSR
OSIMERTINIB	4	INSR
BRIGATINIB	4	INSR
NINTEDANIB	4	INSR
SUNITINIB	4	INSR
LAPATINIB	4	INSR
CRIZOTINIB	4	INSR
LINSITINIB	3	INSR
LINIFANIB	3	INSR
DOVITINIB	3	INSR
LESTAURTINIB	3	INSR
FORETINIB	2	INSR
SU-014813	2	INSR
CENISERTIB	2	INSR
ILORASERTIB	2	INSR
OSI-632	2	INSR
R-406	2	INSR
TOZASERTIB	2	INSR
BMS-754807	2	INSR
ELLAGIC ACID	2	INSR
PF-00562271	1	INSR
KW-2449	1	INSR
RG-1530	1	INSR
XL-228	1	INSR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	INSR
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	2	STAC3, ATP6V0A4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
STAC3	0	—
ATP6V0A4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.