Periventricular nodular heterotopia

Summary

Periventricular nodular heterotopia (MONDO:0020341) is a disease (an umbrella term covering 8 Mondo subtypes) caused by variants in ARF1, FLNA, and MAP1B, with 10 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal genes: ARF1 (GenCC Definitive), FLNA (GenCC Definitive), MAP1B (GenCC Strong)
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 10
• ClinVar variants: 17
• Phenotypes (HPO): 16
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0001892	Abnormal bleeding	Very frequent (80-99%)
HP:0002020	Gastroesophageal reflux	Very frequent (80-99%)
HP:0002021	Pyloric stenosis	Very frequent (80-99%)
HP:0002650	Scoliosis	Very frequent (80-99%)
HP:0100790	Hernia	Very frequent (80-99%)
HP:0000963	Thin skin	Frequent (30-79%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0001643	Patent ductus arteriosus	Frequent (30-79%)
HP:0001654	Abnormal heart valve morphology	Frequent (30-79%)
HP:0001659	Aortic regurgitation	Frequent (30-79%)
HP:0007165	Periventricular heterotopia	Frequent (30-79%)
HP:0007359	Focal-onset seizure	Frequent (30-79%)
HP:0012639	Abnormal nervous system morphology	Frequent (30-79%)
HP:0002999	Patellar dislocation	Occasional (5-29%)
HP:0003834	Shoulder dislocation	Occasional (5-29%)
HP:0004942	Aortic aneurysm	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	periventricular nodular heterotopia
Mondo ID	MONDO:0020341
MeSH	D054091
OMIM	300049
Orphanet	98892
DOID	DOID:0050454
ICD-11	20200096
UMLS	C1868720
MedGen	358387
GARD	0012724
MedDRA	10066854
Is cancer (heuristic)	no

Also known as: periventricular nodular heterotopia

Data availability: 17 ClinVar variants · 11 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › periventricular nodular heterotopia

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, 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, 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 (8): heterotopia, periventricular, X-linked dominant, periventricular heterotopia with microcephaly, autosomal recessive, heterotopia, periventricular, associated with chromosome 5P anomalies, chromosome 5Q14.3 deletion syndrome, distal, periventricular nodular heterotopia 6, periventricular nodular heterotopia 7, periventricular nodular heterotopia 9, periventricular nodular heterotopia 8

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

17 retrieved; paginated sample, class counts are floors:

6 likely pathogenic, 4 pathogenic/likely pathogenic, 3 pathogenic, 2 pathogenic; risk factor, 1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1761872	NM_007294.4(BRCA1):c.806T>A (p.Leu269Ter)	BRCA1	Pathogenic	criteria provided, multiple submitters, no conflicts
280519	NM_001110556.2(FLNA):c.5930_5942del (p.Glu1977fs)	FLNA	Pathogenic	criteria provided, multiple submitters, no conflicts
432416	NM_001110556.2(FLNA):c.3775C>T (p.Gln1259Ter)	FLNA	Pathogenic	criteria provided, multiple submitters, no conflicts
447341	NM_001110556.2(FLNA):c.1027_1028del (p.Ser343fs)	FLNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
548632	NM_005909.5(MAP1B):c.907C>T (p.Arg303Ter)	MAP1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
548633	NM_005909.5(MAP1B):c.1594C>T (p.Gln532Ter)	MAP1B	Pathogenic/Likely pathogenic	no assertion criteria provided
800720	NM_005909.5(MAP1B):c.2134del (p.Glu712fs)	MAP1B	Pathogenic; risk factor	no assertion criteria provided
800721	NM_005909.5(MAP1B):c.3094G>T (p.Glu1032Ter)	MAP1B	Pathogenic; risk factor	no assertion criteria provided
800722	NM_005909.5(MAP1B):c.4990C>T (p.Arg1664Ter)	MAP1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1334402	NM_001366521.1(ATP2B1):c.3060+2T>G	ATP2B1	Likely pathogenic	criteria provided, single submitter
1334403	NM_001366521.1(ATP2B1):c.2938G>T (p.Val980Leu)	ATP2B1	Likely pathogenic	criteria provided, single submitter
1077130	NM_001110556.2(FLNA):c.373G>A (p.Asp125Asn)	FLNA	Likely pathogenic	criteria provided, single submitter
3339746	NM_001110556.2(FLNA):c.5997_6022+1dup	FLNA	Likely pathogenic	criteria provided, single submitter
3376601	NM_001110556.2(FLNA):c.622G>T (p.Gly208Cys)	FLNA	Likely pathogenic	criteria provided, single submitter
548635	NM_005909.5(MAP1B):c.819del (p.Leu274fs)	MAP1B	Likely pathogenic	no assertion criteria provided
548634	NM_005909.5(MAP1B):c.3316C>T (p.Arg1106Ter)	MAP1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
632584	NM_001387994.1(BAG6):c.3415C>T (p.Arg1139Ter)	BAG6	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 61 · Orphanet: 30 · 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
ARF1	Definitive	Autosomal dominant	periventricular nodular heterotopia	6
FLNA	Definitive	X-linked	heterotopia, periventricular, X-linked dominant	30
NEDD4L	Definitive	Autosomal dominant	periventricular nodular heterotopia 7	6
ARFGEF2	Strong	Autosomal recessive	periventricular heterotopia with microcephaly, autosomal recessive	4
MAP1B	Strong	Autosomal dominant	periventricular nodular heterotopia 9	5
ERMARD	Supportive	Autosomal dominant	periventricular nodular heterotopia	6
TMTC3	Supportive	Autosomal dominant	periventricular nodular heterotopia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FLNA	Orphanet:1826	Frontometaphyseal dysplasia
FLNA	Orphanet:2301	Congenital short bowel syndrome
FLNA	Orphanet:2484	Melnick-Needles syndrome
FLNA	Orphanet:482606	X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome
FLNA	Orphanet:555877	FLNA-related X-linked myxomatous valvular dysplasia
FLNA	Orphanet:75497	X-linked Ehlers-Danlos syndrome
FLNA	Orphanet:88630	Terminal osseous dysplasia-pigmentary defects syndrome
FLNA	Orphanet:90650	Otopalatodigital syndrome type 1
FLNA	Orphanet:90652	Otopalatodigital syndrome type 2
FLNA	Orphanet:98892	Periventricular nodular heterotopia
FLNA	Orphanet:99811	Neuronal intestinal pseudoobstruction
MAP1B	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MAP1B	Orphanet:98892	Periventricular nodular heterotopia
ARFGEF2	Orphanet:98892	Periventricular nodular heterotopia
ERMARD	Orphanet:75857	6q terminal deletion syndrome
ERMARD	Orphanet:98892	Periventricular nodular heterotopia
TMTC3	Orphanet:352682	Cobblestone lissencephaly without muscular or ocular involvement
TMTC3	Orphanet:98892	Periventricular nodular heterotopia
ARF1	Orphanet:98892	Periventricular nodular heterotopia
NEDD4L	Orphanet:98892	Periventricular nodular heterotopia
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
ATP2B1	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	gencc,clinvar
MAP1B	HGNC:6836	ENSG00000131711	P46821	Microtubule-associated protein 1B	gencc,clinvar
ARFGEF2	HGNC:15853	ENSG00000124198	Q9Y6D5	Brefeldin A-inhibited guanine nucleotide-exchange protein 2	gencc
ERMARD	HGNC:21056	ENSG00000130023	Q5T6L9	Endoplasmic reticulum membrane-associated RNA degradation protein	gencc
TMTC3	HGNC:26899	ENSG00000139324	Q6ZXV5	Protein O-mannosyl-transferase TMTC3	gencc
ARF1	HGNC:652	ENSG00000143761	P84077	ADP-ribosylation factor 1	gencc
NEDD4L	HGNC:7728	ENSG00000049759	Q96PU5	E3 ubiquitin-protein ligase NEDD4-like	gencc
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
BAG6	HGNC:13919	ENSG00000204463	P46379	Large proline-rich protein BAG6	clinvar
ATP2B1	HGNC:814	ENSG00000070961	P20020	Plasma membrane calcium-transporting ATPase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.
MAP1B	Microtubule-associated protein 1B	Facilitates tyrosination of alpha-tubulin in neuronal microtubules.
ARFGEF2	Brefeldin A-inhibited guanine nucleotide-exchange protein 2	Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6.
ERMARD	Endoplasmic reticulum membrane-associated RNA degradation protein	May play a role in neuronal migration during embryonic development.
TMTC3	Protein O-mannosyl-transferase TMTC3	Transfers mannosyl residues to the hydroxyl group of serine or threonine residues.
ARF1	ADP-ribosylation factor 1	Small GTPase involved in protein trafficking between different compartments.
NEDD4L	E3 ubiquitin-protein ligase NEDD4-like	E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repai…
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
BAG6	Large proline-rich protein BAG6	ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins.
ATP2B1	Plasma membrane calcium-transporting ATPase 1	Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis.

Protein-family classification

Druggable: 1 · Difficult: 3 · Unknown: 6 · Druggable fraction: 0.1

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
Antibody/Immunoglobulin	1	2.9×	0.526
Scaffold/PPI	1	1.7×	0.526
Transcription factor	2	1.6×	0.526
Other/Unknown	6	1.1×	0.526

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
MAP1B	Other/Unknown	no		MAP1B_neuraxin, MAP1, MAP1B/S_N
ARFGEF2	Other/Unknown	no		Sec7_dom, ARM-like, Mon2/Sec7/BIG1-like_HDS
ERMARD	Other/Unknown	no		EMARD_N, ERMARD
TMTC3	Other/Unknown	no		TPR-like_helical_dom_sf, TMTC_DUF1736, TPR_rpt
ARF1	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, Small_GTPase_ARF
NEDD4L	Scaffold/PPI	no	2.3.2.26	C2_dom, HECT_dom, WW_dom
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
BAG6	Other/Unknown	no		Ubiquitin-like_dom, Ubiquitin_CS, BAG6
ATP2B1	Transcription factor	no	7.2.2.10	P_typ_ATPase, ATPase_P-typ_cation-transptr_N, ATPase_P-typ_cation-transptr_C

Expression context

Cohort genes with no expression data: 0.

10 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lateral nuclear group of thalamus	2
left testis	2
right testis	2
Brodmann (1909) area 23	2
ventricular zone	2
popliteal artery	1
right coronary artery	1
tibial artery	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1
cartilage tissue	1
jejunal mucosa	1
parotid gland	1
right uterine tube	1
endothelial cell	1
gingival epithelium	1
adult organism	1
ileal mucosa	1
stromal cell of endometrium	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery
MAP1B	299	ubiquitous	marker	lateral nuclear group of thalamus, substantia nigra pars compacta, substantia nigra pars reticulata
ARFGEF2	289	ubiquitous	marker	cartilage tissue, jejunal mucosa, parotid gland
ERMARD	134	ubiquitous	marker	right uterine tube, right testis, left testis
TMTC3	256	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, gingival epithelium
ARF1	295	ubiquitous	marker	adult organism, ileal mucosa, stromal cell of endometrium
NEDD4L	281	ubiquitous	marker	ventricular zone, ganglionic eminence, olfactory segment of nasal mucosa
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BAG6	144	ubiquitous	marker	right testis, left testis, testis
ATP2B1	296	ubiquitous	marker	frontal pole, Brodmann (1909) area 23, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA1	9,064
FLNA	5,321
MAP1B	3,724
NEDD4L	3,458
ATP2B1	3,055
BAG6	2,326
ERMARD	2,316
TMTC3	2,090
ARFGEF2	2,022
ARF1	485

Intra-cohort edges

A	B	Sources
ARFGEF2	ERMARD	string_interaction
ARFGEF2	FLNA	string_interaction
ARFGEF2	TMTC3	string_interaction
ERMARD	FLNA	string_interaction
ERMARD	TMTC3	string_interaction

Structural data

PDB: 7 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ARF1	P84077	40
BRCA1	P38398	33
FLNA	P21333	26
NEDD4L	Q96PU5	20
BAG6	P46379	10
ARFGEF2	Q9Y6D5	2
ATP2B1	P20020	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ERMARD	Q5T6L9	90.79
TMTC3	Q6ZXV5	87.83
MAP1B	P46821	46.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 132. Enrichment computed across 10 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective DNA double strand break response due to BRCA1 loss of function	1	713.8×	0.050	BRCA1
Defective DNA double strand break response due to BARD1 loss of function	1	713.8×	0.050	BRCA1
HIV Infection	2	29.7×	0.050	ARF1, NEDD4L
Viral Infection Pathways	3	11.5×	0.050	MAP1B, ARF1, NEDD4L
Disease	4	6.5×	0.050	MAP1B, BRCA1, ARF1, NEDD4L
Ion channel transport	2	24.0×	0.052	NEDD4L, ATP2B1
Transport of small molecules	3	9.4×	0.052	ARF1, NEDD4L, ATP2B1
Infectious disease	3	9.3×	0.052	MAP1B, ARF1, NEDD4L
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	203.9×	0.064	BRCA1
Glycosphingolipid transport	1	178.4×	0.064	ARF1
Nef Mediated CD4 Down-regulation	1	158.6×	0.064	ARF1
OAS antiviral response	1	158.6×	0.064	FLNA
Reduction of cytosolic Ca++ levels	1	119.0×	0.064	ATP2B1
GP1b-IX-V activation signalling	1	119.0×	0.064	FLNA
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	119.0×	0.064	BRCA1
Diseases of DNA Double-Strand Break Repair	1	102.0×	0.064	BRCA1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	102.0×	0.064	BRCA1
Platelet calcium homeostasis	1	89.2×	0.064	ATP2B1
Cell-extracellular matrix interactions	1	84.0×	0.064	FLNA
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1	79.3×	0.064	ARF1
The role of Nef in HIV-1 replication and disease pathogenesis	1	79.3×	0.064	ARF1
Synthesis of PIPs at the Golgi membrane	1	79.3×	0.064	ARF1
Resolution of D-Loop Structures	1	79.3×	0.064	BRCA1
Diseases of DNA repair	1	71.4×	0.064	BRCA1
RHO GTPases activate PAKs	1	68.0×	0.064	FLNA
Interleukin-12 family signaling	1	59.5×	0.064	ARF1
DNA Double Strand Break Response	1	59.5×	0.064	BRCA1
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	1	59.5×	0.064	BAG6
Impaired BRCA2 binding to PALB2	1	57.1×	0.064	BRCA1
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	52.9×	0.064	BRCA1

GO biological processes by enrichment

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

GO term	Cohort genes	Fold	FDR	Sample cohort genes
developmental maturation	1	1872.4×	0.019	MAP1B
induction of synaptic plasticity by chemical substance	1	1872.4×	0.019	MAP1B
regulation of membrane repolarization during atrial cardiac muscle cell action potential	1	1872.4×	0.019	FLNA
regulation of membrane repolarization during cardiac muscle cell action potential	1	1872.4×	0.019	FLNA
mitotic cleavage furrow ingression	1	1872.4×	0.019	ARF1
endomembrane system organization	1	936.2×	0.019	ARFGEF2
establishment of monopolar cell polarity	1	936.2×	0.019	MAP1B
endoplasmic reticulum stress-induced pre-emptive quality control	1	936.2×	0.019	BAG6
negative regulation of sodium ion import across plasma membrane	1	936.2×	0.019	NEDD4L
immune response-activating cell surface receptor signaling pathway	1	624.1×	0.019	BAG6
negative regulation of intracellular transport	1	624.1×	0.019	MAP1B
tubulin deacetylation	1	624.1×	0.019	FLNA
formation of radial glial scaffolds	1	468.1×	0.019	FLNA
regulation of microtubule depolymerization	1	468.1×	0.019	MAP1B
obsolete maintenance of unfolded protein	1	468.1×	0.019	BAG6
dendritic spine organization	1	468.1×	0.019	ARF1
positive regulation of caveolin-mediated endocytosis	1	468.1×	0.019	NEDD4L
regulation of vascular associated smooth muscle contraction	1	374.5×	0.019	ATP2B1
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	374.5×	0.019	FLNA
internal peptidyl-lysine acetylation	1	374.5×	0.019	BAG6
cellular response to indole-3-methanol	1	374.5×	0.019	BRCA1
establishment of Sertoli cell barrier	1	374.5×	0.019	FLNA
response to insecticide	1	312.1×	0.019	MAP1B
chordate embryonic development	1	312.1×	0.019	BRCA1
NK T cell activation	1	312.1×	0.019	BAG6
negative regulation of sodium ion transmembrane transport	1	312.1×	0.019	NEDD4L
protein localization to bicellular tight junction	1	312.1×	0.019	FLNA
calcium ion export across plasma membrane	1	312.1×	0.019	ATP2B1
monoatomic ion transmembrane transport	2	46.2×	0.019	NEDD4L, ATP2B1
regulation of protein stability	2	27.9×	0.019	BAG6, NEDD4L

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 8

Druggability breadth: 7 of 10 evidence-associated genes (70%) 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
BRCA1	RIBOFLAVIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRCA1	12	4
FLNA	1	2
MAP1B	0	0
ARFGEF2	0	0
ERMARD	0	0
TMTC3	0	0
ARF1	0	0
NEDD4L	0	0
BAG6	0	0
ATP2B1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
MOLIBRESIB	2	FLNA
SODIUM TANSHINONE IIA SULFONATE	2	BRCA1
HOMIDIUM BROMIDE	2	BRCA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
BRCA1	13	Binding:9, Functional:4
MAP1B	10	Binding:6, Functional:4
FLNA	7	Binding:7
ARF1	4	Binding:4
ARFGEF2	1	Binding:1
TMTC3	1	Binding:1
BAG6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NEDD4L	2.3.2.26, 2.3.2.B8	HECT-type E3 ubiquitin transferase,
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
ATP2B1	7.2.2.10	P-type Ca2+ transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

13 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)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
MOLIBRESIB	2	FLNA
SODIUM TANSHINONE IIA SULFONATE	2	BRCA1
HOMIDIUM BROMIDE	2	BRCA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BRCA1
B	Phased (≥1) drug, not yet approved	1	FLNA
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	8	MAP1B, ARFGEF2, ERMARD, TMTC3, ARF1, NEDD4L, BAG6, ATP2B1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ARFGEF2	1	FLNA
MAP1B	10	—
ERMARD	0	—
TMTC3	1	—
ARF1	4	—
NEDD4L	0	—
BAG6	1	—
ATP2B1	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
NCT05696912	Not specified	UNKNOWN	Functional Tests to Resolve Unsolved Rare Diseases. Rares.