Cohen syndrome

Summary

Cohen syndrome (MONDO:0008999) is a disease caused by VPS13B (GenCC Definitive), with 7 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: VPS13B (GenCC Definitive)
• Cohort genes: 7
• ClinVar variants: 6,055
• Phenotypes (HPO): 64
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		200	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000164	Abnormality of the dentition	Very frequent (80-99%)
HP:0000194	Open mouth	Very frequent (80-99%)
HP:0000212	Gingival overgrowth	Very frequent (80-99%)
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000294	Low anterior hairline	Very frequent (80-99%)
HP:0000322	Short philtrum	Very frequent (80-99%)
HP:0000327	Hypoplasia of the maxilla	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000426	Prominent nasal bridge	Very frequent (80-99%)
HP:0000492	Abnormal eyelid morphology	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0000499	Abnormal eyelash morphology	Very frequent (80-99%)
HP:0000527	Long eyelashes	Very frequent (80-99%)
HP:0000545	Myopia	Very frequent (80-99%)
HP:0000574	Thick eyebrow	Very frequent (80-99%)
HP:0001135	Chorioretinal dystrophy	Very frequent (80-99%)
HP:0001166	Arachnodactyly	Very frequent (80-99%)
HP:0001182	Tapered finger	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001852	Sandal gap	Very frequent (80-99%)
HP:0001875	Decreased total neutrophil count	Very frequent (80-99%)
HP:0002167	Abnormality of speech or vocalization	Very frequent (80-99%)
HP:0002705	High, narrow palate	Very frequent (80-99%)
HP:0009804	Tooth agenesis	Very frequent (80-99%)
HP:0010295	Aplasia/Hypoplasia of the tongue	Very frequent (80-99%)
HP:0010669	Hypoplasia of the zygomatic bone	Very frequent (80-99%)
HP:0011308	Slender toe	Very frequent (80-99%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0000823	Delayed puberty	Frequent (30-79%)
HP:0001000	Abnormality of skin pigmentation	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001513	Obesity	Frequent (30-79%)
HP:0001531	Failure to thrive in infancy	Frequent (30-79%)
HP:0001558	Decreased fetal movement	Frequent (30-79%)
HP:0001572	Macrodontia	Frequent (30-79%)
HP:0001612	Weak cry	Frequent (30-79%)
HP:0002857	Genu valgum	Frequent (30-79%)
HP:0002967	Cubitus valgus	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0004283	Narrow palm	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0006101	Finger syndactyly	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0100874	Thick hair	Frequent (30-79%)
HP:0200046	Cat cry	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000384	Preauricular skin tag	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Cohen syndrome
Mondo ID	MONDO:0008999
MeSH	C536438
OMIM	216550
Orphanet	193
DOID	DOID:0111590
ICD-11	1188737383
SNOMED CT	56604005
UMLS	C0265223
MedGen	78539
GARD	0006126
MedDRA	10049066
NORD	986
Is cancer (heuristic)	no

Also known as: Chs1 · COH1 · Cohen syndrome · cutis verticis gyrata, retinitis pigmentosa, and sensorineural deafness

Data availability: 6,055 ClinVar variants · 7 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › Cohen syndrome

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, 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, Bailey-Bloch congenital myopathy, 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

600 retrieved; paginated sample, class counts are floors:

348 likely benign, 181 uncertain significance, 51 pathogenic, 8 likely pathogenic, 7 pathogenic/likely pathogenic, 5 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012252	NM_152564.5(VPS13B):c.1044G>A (p.Trp348Ter)	VPS13B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1033869	NM_152564.5(VPS13B):c.10557del (p.Leu3519fs)	VPS13B	Pathogenic	criteria provided, single submitter
1048631	NM_152564.5(VPS13B):c.3446-23T>G	VPS13B	Pathogenic	criteria provided, single submitter
1048632	NC_000008.10:g.100246250_100460500del	VPS13B	Pathogenic	criteria provided, single submitter
1067322	NM_152564.5(VPS13B):c.11216-1G>C	VPS13B	Pathogenic	criteria provided, single submitter
1068499	NM_152564.5(VPS13B):c.8430del (p.Val2811fs)	VPS13B	Pathogenic	criteria provided, single submitter
1068584	NM_152564.5(VPS13B):c.8230C>T (p.Gln2744Ter)	VPS13B	Pathogenic	criteria provided, multiple submitters, no conflicts
1068728	NC_000008.10:g.(?100654019)(100673739_?)del	VPS13B	Pathogenic	criteria provided, single submitter
1068729	NC_000008.10:g.(?100654029)(100712170_?)del	VPS13B	Pathogenic	criteria provided, single submitter
1069053	NM_152564.5(VPS13B):c.11727_11728del (p.Arg3909fs)	VPS13B	Pathogenic	criteria provided, single submitter
1069136	NM_152564.5(VPS13B):c.6395T>A (p.Leu2132Ter)	VPS13B	Pathogenic	criteria provided, single submitter
1069292	NM_152564.5(VPS13B):c.8494_8495del (p.Ile2832fs)	VPS13B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069655	NM_152564.5(VPS13B):c.10975del (p.Arg3659fs)	VPS13B	Pathogenic	criteria provided, single submitter
1070547	NM_152564.5(VPS13B):c.2387_2388del (p.Leu796fs)	VPS13B	Pathogenic	criteria provided, single submitter
1070680	NM_152564.5(VPS13B):c.6315C>A (p.Cys2105Ter)	VPS13B	Pathogenic	criteria provided, single submitter
1070729	NC_000008.10:g.(?100182257)(100479872_?)del	VPS13B	Pathogenic	criteria provided, single submitter
1070731	NC_000008.10:g.(?100286406)(100874194_?)del	VPS13B	Pathogenic	criteria provided, single submitter
1070732	NC_000008.10:g.(?100396426)(100403942_?)del	VPS13B	Pathogenic	criteria provided, single submitter
1070733	NC_000008.10:g.(?100396426)(100523750_?)del	VPS13B	Pathogenic	criteria provided, single submitter
1070870	NC_000008.10:g.(?100108530)(100287492_?)del	VPS13B	Pathogenic	criteria provided, single submitter
1070881	NM_152564.5(VPS13B):c.1527del (p.Arg510fs)	VPS13B	Pathogenic	criteria provided, single submitter
1070923	NM_152564.5(VPS13B):c.10982del (p.Pro3661fs)	VPS13B	Pathogenic	criteria provided, single submitter
1070957	NM_152564.5(VPS13B):c.1366del (p.Cys456fs)	VPS13B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071088	NM_152564.5(VPS13B):c.8341G>T (p.Glu2781Ter)	VPS13B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071592	NM_152564.5(VPS13B):c.2560C>T (p.Gln854Ter)	VPS13B	Pathogenic	criteria provided, single submitter
1072023	NM_152564.5(VPS13B):c.9333T>G (p.Tyr3111Ter)	VPS13B	Pathogenic	criteria provided, single submitter
1073138	NM_152564.5(VPS13B):c.6625dup (p.Ile2209fs)	VPS13B	Pathogenic	criteria provided, single submitter
1073212	NM_152564.5(VPS13B):c.11252del (p.Asn3751fs)	VPS13B	Pathogenic	criteria provided, single submitter
1073423	NM_152564.5(VPS13B):c.8461_8462del (p.Leu2821fs)	VPS13B	Pathogenic	criteria provided, single submitter
1073463	NM_152564.5(VPS13B):c.8437C>T (p.Gln2813Ter)	VPS13B	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 5 · 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
VPS13B	Definitive	Autosomal recessive	Cohen syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
VPS13B	Orphanet:193	Cohen syndrome
MYO7A	Orphanet:231169	Usher syndrome type 1
MYO7A	Orphanet:231178	Usher syndrome type 2
MYO7A	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MYO7A	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

7 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
VPS13B	HGNC:2183	ENSG00000132549	Q7Z7G8	Intermembrane lipid transfer protein VPS13B	gencc,clinvar
BAALC	HGNC:14333	ENSG00000164929	Q8WXS3	Brain and acute leukemia cytoplasmic protein	clinvar
OSR2	HGNC:15830	ENSG00000164920	Q8N2R0	Protein odd-skipped-related 2	clinvar
ERICH5	HGNC:26823	ENSG00000177459	Q6P6B1	Glutamate-rich protein 5	clinvar
MIR599	HGNC:32855	ENSG00000207804		microRNA 599	clinvar
KCNS2	HGNC:6301	ENSG00000156486	Q9ULS6	Delayed-rectifier potassium channel regulatory subunit KCNS2	clinvar
MYO7A	HGNC:7606	ENSG00000137474	Q13402	Unconventional myosin-VIIa	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VPS13B	Intermembrane lipid transfer protein VPS13B	Mediates the transfer of lipids between membranes at organelle contact sites.
BAALC	Brain and acute leukemia cytoplasmic protein	May play a synaptic role at the postsynaptic lipid rafts possibly through interaction with CAMK2A.
OSR2	Protein odd-skipped-related 2	May be involved in the development of the mandibular molar tooth germ at the bud stage.
KCNS2	Delayed-rectifier potassium channel regulatory subunit KCNS2	Potassium channel regulatory subunit that modulate the delayed rectifier voltage-gated potassium channel activity of KCNB1 and KCNB2 by altering their kinetics, expression levels, and shifting the half-inactivation potential to more polari…
MYO7A	Unconventional myosin-VIIa	Myosins are actin-based motor molecules with ATPase activity.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.14

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
Ion channel	1	15.9×	0.244
Scaffold/PPI	1	2.5×	0.626
Transcription factor	1	1.2×	0.626
Other/Unknown	4	1.0×	0.626

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VPS13B	Other/Unknown	no		VPS13_VAB, VPS13_N, VPS13B
BAALC	Other/Unknown	no		BAALC
OSR2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, C2H2-ZF_Transcription_Reg
ERICH5	Other/Unknown	no		Glu-rich_5
MIR599	Other/Unknown	no
KCNS2	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
MYO7A	Scaffold/PPI	no		IQ_motif_EF-hand-BS, FERM_domain, MyTH4_dom

Expression context

Cohort genes with no expression data: 0.

5 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	2
palpebral conjunctiva	2
nipple	1
sural nerve	1
putamen	1
right frontal lobe	1
superior vestibular nucleus	1
body of uterus	1
endocervix	1
bronchus	1
adrenal tissue	1
adult mammalian kidney	1
kidney	1
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VPS13B	291	ubiquitous	marker	sural nerve, nipple, bronchial epithelial cell
BAALC	213	ubiquitous	marker	putamen, right frontal lobe, superior vestibular nucleus
OSR2	207	broad	marker	palpebral conjunctiva, body of uterus, endocervix
ERICH5	179	broad	marker	palpebral conjunctiva, bronchial epithelial cell, bronchus
MIR599	61		yes	kidney, adult mammalian kidney, adrenal tissue
KCNS2	128	tissue_specific	yes	endothelial cell, middle temporal gyrus, Brodmann (1909) area 23
MYO7A	186	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VPS13B	1,950
KCNS2	1,781
OSR2	1,151
ERICH5	585
MYO7A	43
BAALC	27
MIR599	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYO7A	Q13402	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNS2	Q9ULS6	81.14
OSR2	Q8N2R0	61.81
BAALC	Q8WXS3	60.47
ERICH5	Q6P6B1	48.96
VPS13B	Q7Z7G8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 7 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
The canonical retinoid cycle in rods (twilight vision)	1	173.0×	0.024	MYO7A
Sensory processing of sound	1	102.9×	0.024	MYO7A
Visual phototransduction	1	86.5×	0.024	MYO7A
Voltage gated Potassium channels	1	81.0×	0.024	KCNS2
Developmental Lineage of Pancreatic Ductal Cells	1	76.1×	0.024	ERICH5
Sensory processing of sound by outer hair cells of the cochlea	1	68.0×	0.024	MYO7A
Sensory processing of sound by inner hair cells of the cochlea	1	54.4×	0.026	MYO7A
Potassium Channels	1	44.8×	0.028	KCNS2
Sensory Perception	1	31.7×	0.035	MYO7A
Neuronal System	1	14.8×	0.066	KCNS2

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pigment granule transport	1	4213.0×	0.012	MYO7A
slow endocytic recycling	1	2106.5×	0.012	VPS13B
embryonic skeletal limb joint morphogenesis	1	1053.2×	0.012	OSR2
phagolysosome assembly	1	842.6×	0.012	MYO7A
mechanoreceptor differentiation	1	842.6×	0.012	MYO7A
embryonic skeletal joint development	1	842.6×	0.012	OSR2
Golgi reassembly	1	842.6×	0.012	VPS13B
pronephros development	1	601.9×	0.012	OSR2
equilibrioception	1	601.9×	0.012	MYO7A
maintenance of lens transparency	1	526.6×	0.012	VPS13B
head morphogenesis	1	526.6×	0.012	VPS13B
sensory perception of light stimulus	1	468.1×	0.012	MYO7A
mesonephros development	1	383.0×	0.013	OSR2
embryonic skeletal joint morphogenesis	1	383.0×	0.013	OSR2
osteoblast proliferation	1	351.1×	0.013	OSR2
head development	1	300.9×	0.015	OSR2
eyelid development in camera-type eye	1	263.3×	0.016	OSR2
urogenital system development	1	247.8×	0.016	OSR2
eye photoreceptor cell development	1	210.7×	0.017	MYO7A
auditory receptor cell stereocilium organization	1	210.7×	0.017	MYO7A
actin filament-based movement	1	200.6×	0.017	MYO7A
embryo development ending in birth or egg hatching	1	183.2×	0.017	OSR2
middle ear morphogenesis	1	175.5×	0.017	OSR2
sensory organ development	1	168.5×	0.017	MYO7A
dentate gyrus development	1	156.0×	0.017	VPS13B
regulation of potassium ion transmembrane transport	1	156.0×	0.017	KCNS2
bone morphogenesis	1	150.5×	0.017	OSR2
embryonic hindlimb morphogenesis	1	145.3×	0.017	OSR2
odontogenesis	1	131.7×	0.018	OSR2
positive regulation of stem cell proliferation	1	131.7×	0.018	OSR2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 7

Druggability breadth: 1 of 7 evidence-associated genes (14%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
VPS13B	0	0
BAALC	0	0
OSR2	0	0
ERICH5	0	0
MIR599	0	0
KCNS2	0	0
MYO7A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KCNS2	21	Binding:20, Toxicity:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; 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	KCNS2
E	Difficult family or no structure, no drug	6	VPS13B, BAALC, OSR2, ERICH5, MIR599, MYO7A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
VPS13B	0	—
BAALC	0	—
OSR2	0	—
ERICH5	0	—
MIR599	0	—
KCNS2	21	—
MYO7A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01907555	Not specified	COMPLETED	Clinical, Molecular and Physiopathological Study of Cohen Syndrome and Cohen-like Syndromes