Polymicrogyria

Summary

Polymicrogyria (MONDO:0000087) is a disease with 19 cohort genes and 2 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 19
• ClinVar variants: 23
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polymicrogyria
Mondo ID	MONDO:0000087
MeSH	D065706
Orphanet	35981
DOID	DOID:0080918
ICD-11	2081858551
NCIT	C116936
SNOMED CT	4945003
UMLS	C0266464
MedGen	78605
GARD	0018818
Is cancer (heuristic)	no

Data availability: 23 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Related subtypes (216): 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, 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

Subtypes (2): bilateral polymicrogyria, unilateral polymicrogyria

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

23 retrieved; paginated sample, class counts are floors:

6 pathogenic, 6 uncertain significance, 5 likely pathogenic, 5 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2579271	GRCh38/hg38 Xp22.11-21.1(chrX:23730430-32849918)x3	ACOT9	Pathogenic	criteria provided, single submitter
39814	NM_005465.7(AKT3):c.1393C>T (p.Arg465Trp)	AKT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
549759	NM_000702.4(ATP1A2):c.2869G>T (p.Glu957Ter)	ATP1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
549760	NM_000702.4(ATP1A2):c.295_296dup (p.Ile100fs)	ATP1A2	Pathogenic	criteria provided, single submitter
374034	NM_024757.5(EHMT1):c.2712+1G>A	EHMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1804031	NM_002804.5(PSMC3):c.910C>T (p.Arg304Trp)	PSMC3	Pathogenic	criteria provided, single submitter
373960	NM_006922.4(SCN3A):c.2624T>C (p.Ile875Thr)	SCN3A	Pathogenic	reviewed by expert panel
691929	NM_032656.4(DHX37):c.1145A>G (p.Asp382Gly)	DHX37	Likely pathogenic	no assertion criteria provided
373929	NM_001376.5(DYNC1H1):c.1802T>A (p.Ile601Asn)	DYNC1H1	Likely pathogenic	no assertion criteria provided
1077138	NM_003611.3(OFD1):c.2387+1G>C	OFD1	Likely pathogenic	criteria provided, single submitter
812760	NM_001080517.3(SETD5):c.2476+2T>C	SETD5	Likely pathogenic	no assertion criteria provided
4820214	NM_153354.5(TMEM161B):c.745C>T (p.Arg249Ter)	TMEM161B	Likely pathogenic	criteria provided, single submitter
242898	NM_058169.6(BORCS5):c.203-1G>T	BORCS5	Conflicting classifications of pathogenicity	no assertion criteria provided
374088	NM_001776.6(ENTPD1):c.25G>A (p.Val9Met)	ENTPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
92968	NM_000426.4(LAMA2):c.5530C>A (p.Arg1844Ser)	LAMA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
438605	NM_005560.6(LAMA5):c.10726G>A (p.Glu3576Lys)	LAMA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
438606	NM_005560.6(LAMA5):c.7114G>A (p.Asp2372Asn)	LAMA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
268038	46;XY;t(6;16)(p21.1;q21)dn		Uncertain significance	criteria provided, single submitter
355276	NM_000426.4(LAMA2):c.5179G>C (p.Glu1727Gln)	LAMA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
438603	NM_001004432.4(LINGO4):c.1262G>A (p.Arg421Gln)	LINGO4	Uncertain significance	criteria provided, single submitter
438604	NM_001004432.4(LINGO4):c.851C>T (p.Ser284Phe)	LINGO4	Uncertain significance	criteria provided, single submitter
977301	NM_000466.3(PEX1):c.2744T>C (p.Ile915Thr)	PEX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
437119	NM_006009.4(TUBA1A):c.1298AGG[1] (p.Glu434del)	TUBA1A	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 35 · 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
ENO1	Limited	Autosomal dominant	polymicrogyria

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN3A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SCN3A	Orphanet:98820	Familial focal epilepsy with variable foci
DHX37	Orphanet:242	46,XY complete gonadal dysgenesis
DHX37	Orphanet:251510	46,XY partial gonadal dysgenesis
DHX37	Orphanet:983	Testicular regression syndrome
TUBA1A	Orphanet:171680	Lissencephaly due to TUBA1A mutation
TUBA1A	Orphanet:45358	Congenital fibrosis of extraocular muscles
TUBA1A	Orphanet:467166	Tubulinopathy-associated dysgyria
TUBA1A	Orphanet:994	Fetal akinesia deformation sequence
EHMT1	Orphanet:261652	Kleefstra syndrome due to a point mutation
EHMT1	Orphanet:96147	Kleefstra syndrome due to 9q34 microdeletion
SETD5	Orphanet:435638	3p25.3 microdeletion syndrome
SETD5	Orphanet:528084	Non-specific syndromic intellectual disability
OFD1	Orphanet:244	Primary ciliary dyskinesia
OFD1	Orphanet:2750	Orofaciodigital syndrome type 1
OFD1	Orphanet:2754	Orofaciodigital syndrome type 6
OFD1	Orphanet:475	Isolated Joubert syndrome
OFD1	Orphanet:791	Retinitis pigmentosa
DYNC1H1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
DYNC1H1	Orphanet:209341	DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy
DYNC1H1	Orphanet:284232	Autosomal dominant Charcot-Marie-Tooth disease type 2O
ENTPD1	Orphanet:401810	Autosomal recessive spastic paraplegia type 64
AKT3	Orphanet:83473	Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
AKT3	Orphanet:99802	Hemimegalencephaly
LAMA2	Orphanet:258	Laminin subunit alpha 2-related congenital muscular dystrophy
LAMA2	Orphanet:565837	Laminin subunit alpha 2-related limb-girdle muscular dystrophy R23
LAMA5	Orphanet:521450	LAMA5-related multisystemic syndrome
LAMA5	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
ATP1A2	Orphanet:2131	Alternating hemiplegia of childhood
ATP1A2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
ATP1A2	Orphanet:569	Familial or sporadic hemiplegic migraine
PEX1	Orphanet:3220	Deafness-enamel hypoplasia-nail defects syndrome
PEX1	Orphanet:44	Neonatal adrenoleukodystrophy
PEX1	Orphanet:772	Infantile Refsum disease
PEX1	Orphanet:912	Zellweger syndrome

Cohort genes → proteins

19 cohort genes, 19 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	19

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ENO1	HGNC:3350	ENSG00000074800	P06733	Alpha-enolase	gencc
SCN3A	HGNC:10590	ENSG00000153253	Q9NY46	Sodium channel protein type 3 subunit alpha	clinvar
ACOT9	HGNC:17152	ENSG00000123130	Q9Y305	Acyl-coenzyme A thioesterase 9, mitochondrial	clinvar
DHX37	HGNC:17210	ENSG00000150990	Q8IY37	Probable ATP-dependent RNA helicase DHX37	clinvar
BORCS5	HGNC:17950	ENSG00000165714	Q969J3	BLOC-1-related complex subunit 5	clinvar
TUBA1A	HGNC:20766	ENSG00000167552	Q71U36	Tubulin alpha-1A chain	clinvar
EHMT1	HGNC:24650	ENSG00000181090	Q9H9B1	Histone-lysine N-methyltransferase EHMT1	clinvar
SETD5	HGNC:25566	ENSG00000168137	Q9C0A6	Histone-lysine N-methyltransferase SETD5	clinvar
OFD1	HGNC:2567	ENSG00000046651	O75665	Centriole and centriolar satellite protein OFD1	clinvar
TMEM161B	HGNC:28483	ENSG00000164180	Q8NDZ6	Transmembrane protein 161B	clinvar
DYNC1H1	HGNC:2961	ENSG00000197102	Q14204	Cytoplasmic dynein 1 heavy chain 1	clinvar
LINGO4	HGNC:31814	ENSG00000213171	Q6UY18	Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 4	clinvar
ENTPD1	HGNC:3363	ENSG00000138185	P49961	Ectonucleoside triphosphate diphosphohydrolase 1	clinvar
AKT3	HGNC:393	ENSG00000117020	Q9Y243	RAC-gamma serine/threonine-protein kinase	clinvar
LAMA2	HGNC:6482	ENSG00000196569	P24043	Laminin subunit alpha-2	clinvar
LAMA5	HGNC:6485	ENSG00000130702	O15230	Laminin subunit alpha-5	clinvar
ATP1A2	HGNC:800	ENSG00000018625	P50993	Sodium/potassium-transporting ATPase subunit alpha-2	clinvar
PEX1	HGNC:8850	ENSG00000127980	O43933	Peroxisomal ATPase PEX1	clinvar
PSMC3	HGNC:9549	ENSG00000165916	P17980	26S proteasome regulatory subunit 6A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ENO1	Alpha-enolase	Enolase that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in glycolysis and the reverse reaction in gluconeogenesis.
SCN3A	Sodium channel protein type 3 subunit alpha	Pore-forming subunit of Nav1.3, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
ACOT9	Acyl-coenzyme A thioesterase 9, mitochondrial	Mitochondrial acyl-CoA thioesterase.
DHX37	Probable ATP-dependent RNA helicase DHX37	ATP-binding RNA helicase that plays a role in maturation of the small ribosomal subunit in ribosome biogenesis.
BORCS5	BLOC-1-related complex subunit 5	As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery.
TUBA1A	Tubulin alpha-1A chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
EHMT1	Histone-lysine N-methyltransferase EHMT1	Histone methyltransferase that specifically mono-, di- and trimethylates ‘Lys-9’ of histone H3 (H3K9me1, H3K9me2 and H3K9me3, respectively) in euchromatin.
SETD5	Histone-lysine N-methyltransferase SETD5	Chromatin regulator required for brain development: acts as a regulator of RNA elongation rate, thereby regulating neural stem cell (NSC) proliferation and synaptic transmission.
OFD1	Centriole and centriolar satellite protein OFD1	Component of the centrioles controlling mother and daughter centrioles length.
TMEM161B	Transmembrane protein 161B	Essential for maintaining normal cardiac rhythm in the developing heart and for neonatal survival.
DYNC1H1	Cytoplasmic dynein 1 heavy chain 1	Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules.
ENTPD1	Ectonucleoside triphosphate diphosphohydrolase 1	Catalyzes the hydrolysis of nucleoside triphosphates (NTPs) and diphosphates (NDPs).
AKT3	RAC-gamma serine/threonine-protein kinase	AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
LAMA2	Laminin subunit alpha-2	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
LAMA5	Laminin subunit alpha-5	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
ATP1A2	Sodium/potassium-transporting ATPase subunit alpha-2	This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane.
PEX1	Peroxisomal ATPase PEX1	Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling.
PSMC3	26S proteasome regulatory subunit 6A	Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.

Protein-family classification

Druggable: 6 · Difficult: 2 · Unknown: 11 · Druggable fraction: 0.32

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	5.9×	0.727
Enzyme (other)	3	1.9×	0.727
Antibody/Immunoglobulin	1	1.5×	0.732
Kinase	1	1.5×	0.732
Other/Unknown	11	1.0×	0.732
Scaffold/PPI	1	0.9×	0.791
Transcription factor	1	0.4×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ENO1	Enzyme (other)	yes	4.2.1.11	Enolase, Enolase_CS, Enolase_C
SCN3A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom
ACOT9	Other/Unknown	no		Thioestr_dom, HotDog_dom_sf, HOTDOG_ACOT
DHX37	Other/Unknown	no		Helicase_C-like, Helicase-assoc_dom, DEAD/DEAH_box_helicase_dom
BORCS5	Other/Unknown	no		TBORCS5
TUBA1A	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
EHMT1	Scaffold/PPI	no	2.1.1.367	SET_dom, Ankyrin_rpt, Pre-SET_dom
SETD5	Other/Unknown	no		SET_dom, SETD5_SET, SET_dom_sf
OFD1	Other/Unknown	no		LisH, OFD1
TMEM161B	Other/Unknown	no		Transmembrane_161A/B
DYNC1H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
LINGO4	Antibody/Immunoglobulin	yes		LRRNT, Cys-rich_flank_reg_C, Leu-rich_rpt
ENTPD1	Enzyme (other)	yes	3.6.1.5	GDA1_CD39_NTPase
AKT3	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
LAMA2	Other/Unknown	no		Laminin_IV, EGF, Laminin_G
LAMA5	Other/Unknown	no		Laminin_IV, EGF, TNFR/NGFR_Cys_rich_reg
ATP1A2	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC
PEX1	Enzyme (other)	yes	3.6.4.7	AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
PSMC3	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS

Expression context

Cohort genes with no expression data: 0.

16 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)	19
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	4
calcaneal tendon	4
sural nerve	3
metanephros cortex	2
ventricular zone	2
endothelial cell	2
ganglionic eminence	2
adrenal tissue	2
gastrocnemius	2
muscle of leg	2
mucosa of stomach	2
nucleus accumbens	1
middle temporal gyrus	1
heart left ventricle	1
secondary oocyte	1
medial globus pallidus	1
pancreatic ductal cell	1
tendon of biceps brachii	1
prefrontal cortex	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ENO1	311	ubiquitous	marker	metanephros cortex, ventricular zone, nucleus accumbens
SCN3A	221	broad	marker	endothelial cell, cortical plate, middle temporal gyrus
ACOT9	278	ubiquitous	marker	secondary oocyte, heart left ventricle, calcaneal tendon
DHX37	236	ubiquitous	yes	pancreatic ductal cell, tendon of biceps brachii, medial globus pallidus
BORCS5	139	ubiquitous	yes	sural nerve, primordial germ cell in gonad, prefrontal cortex
TUBA1A	288	ubiquitous	marker	endothelial cell, cortical plate, ganglionic eminence
EHMT1	257	ubiquitous	marker	sural nerve, adrenal tissue, left testis
SETD5	284	ubiquitous	marker	adrenal tissue, colonic epithelium, sural nerve
OFD1	288	ubiquitous	marker	sperm, bronchial epithelial cell, cervix squamous epithelium
TMEM161B	257	ubiquitous	marker	epithelial cell of pancreas, ileal mucosa, jejunal mucosa
DYNC1H1	290	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
LINGO4	87		yes	male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius, muscle of leg
ENTPD1	274	broad	marker	saphenous vein, monocyte, mononuclear cell
AKT3	231	ubiquitous	marker	cortical plate, calcaneal tendon, embryo
LAMA2	272	ubiquitous	marker	mucosa of stomach, calcaneal tendon, right ovary
LAMA5	264	ubiquitous	marker	right uterine tube, right hemisphere of cerebellum, metanephros cortex
ATP1A2	262	broad	marker	lateral globus pallidus, trigeminal ganglion, superior vestibular nucleus
PEX1	279	ubiquitous	marker	calcaneal tendon, body of pancreas, mucosa of stomach
PSMC3	289	ubiquitous	marker	apex of heart, gastrocnemius, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ENO1	8,096
PSMC3	4,843
DYNC1H1	4,215
EHMT1	3,590
AKT3	3,392
DHX37	3,123
OFD1	2,878
LAMA2	2,688
ATP1A2	2,679
ENTPD1	2,623

Structural data

PDB: 10 · AlphaFold-only: 9 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PSMC3	P17980	130
DYNC1H1	Q14204	97
EHMT1	Q9H9B1	23
TUBA1A	Q71U36	15
ENO1	P06733	8
SCN3A	Q9NY46	2
AKT3	Q9Y243	2
LAMA2	P24043	2
LAMA5	O15230	2
DHX37	Q8IY37	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ENTPD1	P49961	90.85
ATP1A2	P50993	88.25
LINGO4	Q6UY18	85.70
ACOT9	Q9Y305	85.31
TMEM161B	Q8NDZ6	82.99
BORCS5	Q969J3	80.54
OFD1	O75665	68.41
PEX1	O43933	67.19
SETD5	Q9C0A6	47.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 271. Enrichment computed across 19 evidence-associated genes (15 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 15 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MET promotes cell motility	2	80.1×	0.010	LAMA2, LAMA5
Loss of Nlp from mitotic centrosomes	3	31.7×	0.010	TUBA1A, OFD1, DYNC1H1
Loss of proteins required for interphase microtubule organization from the centrosome	3	31.7×	0.010	TUBA1A, OFD1, DYNC1H1
AURKA Activation by TPX2	3	30.4×	0.010	TUBA1A, OFD1, DYNC1H1
Recruitment of mitotic centrosome proteins and complexes	3	27.2×	0.010	TUBA1A, OFD1, DYNC1H1
Regulation of PLK1 Activity at G2/M Transition	3	25.4×	0.010	TUBA1A, OFD1, DYNC1H1
Recruitment of NuMA to mitotic centrosomes	3	23.3×	0.010	TUBA1A, OFD1, DYNC1H1
Anchoring of the basal body to the plasma membrane	3	22.6×	0.010	TUBA1A, OFD1, DYNC1H1
Attachment of bacteria to epithelial cells	2	66.2×	0.012	LAMA2, LAMA5
Laminin interactions	2	50.8×	0.017	LAMA2, LAMA5
MET activates PTK2 signaling	2	50.8×	0.017	LAMA2, LAMA5
Signaling by MET	2	42.3×	0.022	LAMA2, LAMA5
Formation of the dystrophin-glycoprotein complex (DGC)	2	41.1×	0.022	LAMA2, LAMA5
Aggrephagy	2	33.1×	0.031	TUBA1A, DYNC1H1
Separation of Sister Chromatids	3	12.2×	0.031	TUBA1A, DYNC1H1, PSMC3
Developmental Lineage of Pancreatic Ductal Cells	2	30.4×	0.032	LAMA2, LAMA5
COPI-independent Golgi-to-ER retrograde traffic	2	27.7×	0.037	TUBA1A, DYNC1H1
Manipulation of host energy metabolism	1	380.7×	0.037	ENO1
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	2	25.8×	0.037	TUBA1A, DYNC1H1
Signaling by Receptor Tyrosine Kinases	3	10.3×	0.037	AKT3, LAMA2, LAMA5
Regulation of PTEN stability and activity	2	24.6×	0.038	AKT3, PSMC3
Hedgehog ‘off’ state	2	23.8×	0.038	TUBA1A, OFD1
The role of GTSE1 in G2/M progression after G2 checkpoint	2	21.4×	0.045	TUBA1A, PSMC3
Non-integrin membrane-ECM interactions	2	20.6×	0.047	LAMA2, LAMA5
ECM proteoglycans	2	20.0×	0.047	LAMA2, LAMA5
Nervous system development	3	8.6×	0.048	SCN3A, TUBA1A, LAMA2
AKT-mediated inactivation of FOXO1A	1	190.3×	0.052	AKT3
Cytokine Signaling in Immune system	3	8.2×	0.052	TUBA1A, AKT3, LAMA5
Inhibition of TSC complex formation by AKT (PKB)	1	152.3×	0.059	AKT3
L1CAM interactions	2	16.0×	0.059	SCN3A, TUBA1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of embryonic development	3	52.2×	0.005	EHMT1, LAMA2, LAMA5
organelle transport along microtubule	2	126.7×	0.011	BORCS5, TUBA1A
locomotory exploration behavior	2	104.3×	0.011	TUBA1A, ATP1A2
olfactory cortex development	1	887.0×	0.029	ATP1A2
host-mediated perturbation of viral transcription	1	887.0×	0.029	PSMC3
trunk neural crest cell migration	1	443.5×	0.029	LAMA5
regulation of glutamate uptake involved in transmission of nerve impulse	1	443.5×	0.029	ATP1A2
microtubule-based peroxisome localization	1	443.5×	0.029	PEX1
negative regulation of white fat cell differentiation	1	443.5×	0.029	EHMT1
negative regulation of calcium ion transmembrane transport	1	443.5×	0.029	ATP1A2
positive regulation of anterograde synaptic vesicle transport	1	443.5×	0.029	BORCS5
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation	1	443.5×	0.029	OFD1
homeostasis of number of cells within a tissue	2	46.7×	0.029	TUBA1A, AKT3
visual learning	2	32.2×	0.029	TUBA1A, ATP1A2
adult locomotory behavior	2	31.7×	0.029	TUBA1A, ATP1A2
sodium ion transport	2	28.6×	0.029	SCN3A, ATP1A2
negative regulation of striated muscle contraction	1	295.6×	0.034	ATP1A2
short-chain fatty acid metabolic process	1	295.6×	0.034	ACOT9
beige fat cell differentiation	1	295.6×	0.034	EHMT1
morphogenesis of a polarized epithelium	1	221.7×	0.034	LAMA5
nucleoside diphosphate catabolic process	1	221.7×	0.034	ENTPD1
negative regulation of heart contraction	1	221.7×	0.034	ATP1A2
ADP catabolic process	1	221.7×	0.034	ENTPD1
negative regulation of transcription by RNA polymerase III	1	177.4×	0.034	SETD5
peptidyl-lysine dimethylation	1	177.4×	0.034	EHMT1
pyramidal neuron differentiation	1	177.4×	0.034	TUBA1A
positive regulation of synaptic transmission, cholinergic	1	177.4×	0.034	LAMA2
protein unfolding	1	177.4×	0.034	PEX1
regulation of metaphase plate congression	1	177.4×	0.034	DYNC1H1
positive regulation of artery morphogenesis	1	177.4×	0.034	AKT3

Therapeutics

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 8 · Phased (≥1): 9 · Undrugged: 10

Druggability breadth: 12 of 19 evidence-associated genes (63%) 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
SCN3A	BEPRIDIL
TUBA1A	COLCHICINE
EHMT1	DISULFIRAM
AKT3	CAPIVASERTIB
ATP1A2	OMEPRAZOLE
PSMC3	BORTEZOMIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN3A	93	4
TUBA1A	22	4
AKT3	18	4
EHMT1	5	4
ATP1A2	5	4
ENO1	2	3
PSMC3	2	4
DYNC1H1	1	2
ENTPD1	1	3
ACOT9	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN3A
DIBUCAINE	4	SCN3A
ARTICAINE	4	SCN3A
BUPIVACAINE	4	SCN3A
IMIPRAMINE	4	SCN3A
DROPERIDOL	4	SCN3A
DICYCLOMINE	4	SCN3A
TETRABENAZINE	4	SCN3A
PHENIRAMINE	4	SCN3A
PRILOCAINE	4	SCN3A
PROPOXYCAINE	4	SCN3A
PROPARACAINE	4	SCN3A
HEXYLCAINE	4	SCN3A
PRAMOXINE	4	SCN3A
BENOXINATE	4	SCN3A
QUINIDINE	4	SCN3A
FELODIPINE	4	SCN3A
PHENYTOIN	4	SCN3A
QUININE	4	SCN3A
NISOLDIPINE	4	SCN3A
NIFEDIPINE	4	SCN3A
PRAZOSIN	4	SCN3A
DILTIAZEM	4	SCN3A
PRENYLAMINE	4	SCN3A
COCAINE	4	SCN3A
TRIFLUOPERAZINE	4	SCN3A
CINNARIZINE	4	SCN3A
THIORIDAZINE	4	SCN3A
ETIDOCAINE	4	SCN3A
CHLORPHENIRAMINE	4	SCN3A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
TUBA1A	1,696	Binding:1655, Functional:35, ADMET:6
AKT3	660	Binding:644, Functional:16
EHMT1	181	Binding:180, ADMET:1
SCN3A	102	Binding:79, Functional:18, ADMET:4, Toxicity:1
ATP1A2	49	Binding:49
ENTPD1	32	Binding:27, ADMET:5
PSMC3	27	Binding:27
ENO1	19	Binding:19
DYNC1H1	7	Binding:7
ACOT9	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ENO1	4.2.1.11	phosphopyruvate hydratase
EHMT1	2.1.1.367, 2.1.1.368	[histone H3]-lysine9 N-methyltransferase, [histone H3]-lysine9 N-dimethyltransferase
ENTPD1	3.6.1.5	apyrase
AKT3	2.7.11.1	non-specific serine/threonine protein kinase
PEX1	3.6.4.7	peroxisome-assembly ATPase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN3A	102
TUBA1A	1,696
EHMT1	181
AKT3	660

Pharmacogenomics

Cohort genes with a PharmGKB record: 19; 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)
BEPRIDIL	4	SCN3A
DIBUCAINE	4	SCN3A
ARTICAINE	4	SCN3A
BUPIVACAINE	4	SCN3A
IMIPRAMINE	4	SCN3A
DROPERIDOL	4	SCN3A
DICYCLOMINE	4	SCN3A
TETRABENAZINE	4	SCN3A
PHENIRAMINE	4	SCN3A
PRILOCAINE	4	SCN3A
PROPOXYCAINE	4	SCN3A
PROPARACAINE	4	SCN3A
HEXYLCAINE	4	SCN3A
PRAMOXINE	4	SCN3A
BENOXINATE	4	SCN3A
QUINIDINE	4	SCN3A
FELODIPINE	4	SCN3A
PHENYTOIN	4	SCN3A
QUININE	4	SCN3A
NISOLDIPINE	4	SCN3A
NIFEDIPINE	4	SCN3A
PRAZOSIN	4	SCN3A
DILTIAZEM	4	SCN3A
PRENYLAMINE	4	SCN3A
COCAINE	4	SCN3A
TRIFLUOPERAZINE	4	SCN3A
CINNARIZINE	4	SCN3A
THIORIDAZINE	4	SCN3A
ETIDOCAINE	4	SCN3A
CHLORPHENIRAMINE	4	SCN3A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	SCN3A, TUBA1A, EHMT1, AKT3, ATP1A2, PSMC3
B	Phased (≥1) drug, not yet approved	3	ENO1, DYNC1H1, ENTPD1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	LINGO4, PEX1
E	Difficult family or no structure, no drug	8	ACOT9, DHX37, BORCS5, SETD5, OFD1, TMEM161B, LAMA2, LAMA5

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ACOT9	1	—
DHX37	0	—
BORCS5	0	—
SETD5	0	—
OFD1	0	—
TMEM161B	0	—
LINGO4	0	—
LAMA2	0	—
LAMA5	0	—
PEX1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00552045	Not specified	COMPLETED	Epilepsy Phenome/Genome Project
NCT04344626	Not specified	WITHDRAWN	Use of a Tonometer to Identify Epileptogenic Lesions During Pediatric Epilepsy Surgery