Myofibrillar myopathy 5

Summary

Myofibrillar myopathy 5 (MONDO:0012289) is a disease caused by FLNC (GenCC Definitive), with 4 cohort genes.

At a glance

• Causal gene: FLNC (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 5,181
• Phenotypes (HPO): 22

Clinical features

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0003458	EMG: myopathic abnormalities	Very frequent (80-99%)
HP:0008180	Mildly elevated creatine kinase	Very frequent (80-99%)
HP:0008994	Proximal muscle weakness in lower limbs	Very frequent (80-99%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0002093	Respiratory insufficiency	Frequent (30-79%)
HP:0003418	Back pain	Frequent (30-79%)
HP:0003551	Difficulty climbing stairs	Frequent (30-79%)
HP:0003555	Muscle fiber splitting	Frequent (30-79%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0001712	Left ventricular hypertrophy	Occasional (5-29%)
HP:0003691	Scapular winging	Occasional (5-29%)
HP:0009830	Peripheral neuropathy	Occasional (5-29%)
HP:0011712	Right bundle branch block	Occasional (5-29%)
HP:0012548	Fatty replacement of skeletal muscle	Occasional (5-29%)
HP:0025168	Left ventricular diastolic dysfunction	Occasional (5-29%)
HP:0030177	Abnormality of peripheral nervous system electrophysiology	Occasional (5-29%)
HP:0030319	Weakness of facial musculature	Occasional (5-29%)
HP:0034392	Joint contracture	Occasional (5-29%)
HP:0003326	Myalgia	Very rare (<1-4%)
HP:0003722	Neck flexor weakness	Very rare (<1-4%)
HP:0030235	Extremely elevated creatine kinase	Very rare (<1-4%)
HP:0410011	Abnormality of masticatory muscle	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	myofibrillar myopathy 5
Mondo ID	MONDO:0012289
MeSH	C537932
OMIM	609524
Orphanet	171445
DOID	DOID:0080096
UMLS	C1836050
MedGen	372186
GARD	0017062
Is cancer (heuristic)	no

Also known as: FLNC myofibrillar myopathy (disease) · MFM5 · myofibrillar myopathy (disease) caused by mutation in FLNC · myofibrillar myopathy 5 · myofibrillar myopathy type 5 · myopathy, myofibrillar, 5 · myopathy, myofibrillar, type 5

Data availability: 5,181 ClinVar variants · 3 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › myofibrillar myopathy 5

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, 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:

267 likely benign, 205 uncertain significance, 46 conflicting classifications of pathogenicity, 39 pathogenic, 24 benign, 10 benign/likely benign, 7 likely pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1067540	NM_001458.5(FLNC):c.5199+1G>T	FLNC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068545	NM_001458.5(FLNC):c.6955del (p.Ala2319fs)	FLNC	Pathogenic	criteria provided, single submitter
1068586	NM_001458.5(FLNC):c.4432C>T (p.Gln1478Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1068631	NM_001458.5(FLNC):c.1205del (p.Thr402fs)	FLNC	Pathogenic	criteria provided, single submitter
1068840	NM_001458.5(FLNC):c.1991_1994del (p.Asp664fs)	FLNC	Pathogenic	criteria provided, single submitter
1068841	NM_001458.5(FLNC):c.3702del (p.Val1235fs)	FLNC	Pathogenic	criteria provided, single submitter
1069362	NM_001458.5(FLNC):c.1914C>G (p.Tyr638Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1069877	NM_001458.5(FLNC):c.2604del (p.Ser868fs)	FLNC	Pathogenic	criteria provided, single submitter
1070209	NM_001458.5(FLNC):c.4718T>A (p.Leu1573Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1070523	NM_001458.5(FLNC):c.5520T>A (p.Tyr1840Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1070569	NM_001458.5(FLNC):c.6802G>T (p.Glu2268Ter)	FLNC	Pathogenic	criteria provided, single submitter
1070575	NM_001458.5(FLNC):c.4755del (p.Lys1586fs)	FLNC	Pathogenic	criteria provided, single submitter
1071490	NM_001458.5(FLNC):c.1670del (p.Pro557fs)	FLNC	Pathogenic	criteria provided, single submitter
1071491	NM_001458.5(FLNC):c.5733dup (p.Gly1912fs)	FLNC	Pathogenic	criteria provided, single submitter
1071678	NM_001458.5(FLNC):c.5569_5578del (p.Ile1857fs)	FLNC	Pathogenic	criteria provided, single submitter
1071863	NC_000007.13:g.(?128470682)(128498587_?)del	FLNC	Pathogenic	criteria provided, single submitter
1071864	NC_000007.13:g.(?128469483)(128500328_?)del	FLNC	Pathogenic	criteria provided, single submitter
1071931	NM_001458.5(FLNC):c.261del (p.Pro88fs)	FLNC	Pathogenic	criteria provided, single submitter
1072180	NM_001458.5(FLNC):c.2499C>A (p.Tyr833Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1072269	NM_001458.5(FLNC):c.3070C>T (p.Gln1024Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1072270	NM_001458.5(FLNC):c.6240_6259del (p.Pro2081fs)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1072629	NM_001458.5(FLNC):c.181C>T (p.Gln61Ter)	FLNC	Pathogenic	criteria provided, single submitter
1073366	NM_001458.5(FLNC):c.4946del (p.Gly1649fs)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1073410	NM_001458.5(FLNC):c.156dup (p.Val53fs)	FLNC	Pathogenic	criteria provided, single submitter
1074200	NM_001458.5(FLNC):c.5557del (p.Tyr1853fs)	FLNC	Pathogenic	criteria provided, single submitter
1074377	NM_001458.5(FLNC):c.563del (p.Gly188fs)	FLNC	Pathogenic	criteria provided, single submitter
1074392	NM_001458.5(FLNC):c.2548C>T (p.Gln850Ter)	FLNC	Pathogenic	criteria provided, single submitter
1074694	NM_001458.5(FLNC):c.146_147insT (p.Leu50fs)	FLNC	Pathogenic	criteria provided, single submitter
1074904	NM_001458.5(FLNC):c.1893G>A (p.Trp631Ter)	FLNC	Pathogenic	criteria provided, single submitter
1075295	NM_001458.5(FLNC):c.4275dup (p.Arg1426fs)	FLNC	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · 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
FLNC	Definitive	Autosomal dominant	myofibrillar myopathy 5	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FLNC	Orphanet:171445	Muscle filaminopathy
FLNC	Orphanet:63273	FLNC-related handgrip and calf weakness-distal myopathy
FLNC	Orphanet:75249	Familial isolated restrictive cardiomyopathy
TNPO3	Orphanet:186	Primary biliary cholangitis
TNPO3	Orphanet:55595	TNP03-related limb-girdle muscular dystrophy D2

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FLNC	HGNC:3756	ENSG00000128591	Q14315	Filamin-C	gencc,clinvar
ATP6V1F	HGNC:16832	ENSG00000128524	Q16864	V-type proton ATPase subunit F	clinvar
TNPO3	HGNC:17103	ENSG00000064419	Q9Y5L0	Transportin-3	clinvar
FLNC-AS1	HGNC:53474	ENSG00000242902		FLNC antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FLNC	Filamin-C	Muscle-specific filamin, which plays a central role in sarcomere assembly and organization.
ATP6V1F	V-type proton ATPase subunit F	Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
TNPO3	Transportin-3	Importin, which transports target proteins into the nucleus.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.25

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	7.3×	0.260
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FLNC	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
ATP6V1F	Other/Unknown	no		ATPase_V1-cplx_fsu_euk, ATPase_V1-cplx_f_g_su, ATPase_V1_fsu_sf
TNPO3	Other/Unknown	no		ARM-like, Exportin-1/Importin-b-like, ARM-type_fold
FLNC-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	2
gastrocnemius	1
tibialis anterior	1
left testis	1
prefrontal cortex	1
right testis	1
medial globus pallidus	1
secondary oocyte	1
tendon of biceps brachii	1
apex of heart	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FLNC	255	ubiquitous	marker	gastrocnemius, hindlimb stylopod muscle, tibialis anterior
ATP6V1F	294	ubiquitous	marker	prefrontal cortex, left testis, right testis
TNPO3	299	ubiquitous	marker	secondary oocyte, tendon of biceps brachii, medial globus pallidus
FLNC-AS1	114		yes	hindlimb stylopod muscle, apex of heart, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNC	3,174
TNPO3	2,970
ATP6V1F	2,214
FLNC-AS1	0

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLNC	Q14315	14
ATP6V1F	Q16864	8
TNPO3	Q9Y5L0	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 4 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cell-extracellular matrix interactions	1	335.9×	0.008	FLNC
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	335.9×	0.008	ATP6V1F
Insulin receptor recycling	1	190.3×	0.008	ATP6V1F
Transferrin endocytosis and recycling	1	184.2×	0.008	ATP6V1F
ROS and RNS production in phagocytes	1	167.9×	0.008	ATP6V1F
Amino acids regulate mTORC1	1	100.2×	0.012	ATP6V1F
Ion channel transport	1	48.0×	0.021	ATP6V1F

GO biological processes by enrichment

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

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Golgi lumen acidification	1	561.7×	0.007	ATP6V1F
endosomal lumen acidification	1	401.2×	0.007	ATP6V1F
intracellular pH reduction	1	401.2×	0.007	ATP6V1F
synaptic vesicle lumen acidification	1	312.1×	0.007	ATP6V1F
vacuolar acidification	1	244.2×	0.007	ATP6V1F
lysosomal lumen acidification	1	224.7×	0.007	ATP6V1F
sarcomere organization	1	127.7×	0.010	FLNC
proton transmembrane transport	1	104.0×	0.011	ATP6V1F
protein import into nucleus	1	48.0×	0.021	TNPO3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FLNC	0	0
ATP6V1F	0	0
TNPO3	0	0
FLNC-AS1	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
TNPO3	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	FLNC
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	ATP6V1F, TNPO3, FLNC-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FLNC	0	—
ATP6V1F	0	—
TNPO3	1	—
FLNC-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.