Episodic kinesigenic dyskinesia

Summary

Episodic kinesigenic dyskinesia (MONDO:0044202) is a disease caused by TMEM151A (GenCC Strong), with 11 cohort genes.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TMEM151A (GenCC Strong)
• Cohort genes: 11
• ClinVar variants: 577
• Phenotypes (HPO): 9

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.6	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0001332	Dystonia	Very frequent (80-99%)
HP:0002072	Chorea	Very frequent (80-99%)
HP:0002305	Athetosis	Very frequent (80-99%)
HP:0004305	Involuntary movements	Very frequent (80-99%)
HP:0100660	Dyskinesia	Very frequent (80-99%)
HP:0011157	Focal sensory seizure	Frequent (30-79%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0002076	Migraine	Occasional (5-29%)
HP:0002356	Writer’s cramp	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	episodic kinesigenic dyskinesia
Mondo ID	MONDO:0044202
OMIM	128200
Orphanet	98809
UMLS	C1868682
MedGen	358268
GARD	0008721
Is cancer (heuristic)	no

Also known as: EKD · familial paroxysmal kinesigenic dyskinesia · familial PKD · paroxysmal kinesigenic choreathetosis

Data availability: 577 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: human disease › disease by body system or component › nervous system disorder › movement disorder › extrapyramidal and movement disease › dystonic disorder › inherited dystonia › combined dystonia › paroxysmal dystonia › paroxysmal dyskinesia › episodic kinesigenic dyskinesia

Related subtypes (4): infantile convulsions and choreoathetosis, childhood onset GLUT1 deficiency syndrome 2, ECHS1-related paroxysmal dyskinesia, paroxysmal nonkinesigenic dyskinesia

Subtypes (3): episodic kinesigenic dyskinesia 2, episodic kinesigenic dyskinesia 1, episodic kinesigenic dyskinesia 3

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

577 retrieved; paginated sample, class counts are floors:

256 uncertain significance, 146 likely benign, 94 pathogenic, 50 conflicting classifications of pathogenicity, 12 benign/likely benign, 8 pathogenic/likely pathogenic, 6 likely pathogenic, 5 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1075384	NC_000016.9:g.(?29802081)(30200285_?)del	ALDOA	Pathogenic	criteria provided, single submitter
3243485	NC_000016.9:g.(?29824376)(30081533_?)del	ALDOA	Pathogenic	criteria provided, single submitter
584215	NC_000016.10:g.(?29813055)(29904965_?)del	ASPHD1	Pathogenic	criteria provided, single submitter
1098714	NM_000217.3(KCNA1):c.1187G>T (p.Gly396Val)	KCNA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3243486	NC_000016.9:g.(?29814750)(29825274_?)del	KIF22	Pathogenic	criteria provided, single submitter
1054446	NC_000016.9:g.(?29802081)(30199917_?)del	MAZ	Pathogenic	criteria provided, single submitter
1069946	NM_145239.3(PRRT2):c.916_934del (p.Gly305_Ala306insTer)	MVP-DT	Pathogenic	criteria provided, multiple submitters, no conflicts
1070362	NM_145239.3(PRRT2):c.503del (p.Pro168fs)	MVP-DT	Pathogenic	criteria provided, single submitter
1072869	NM_145239.3(PRRT2):c.880-1G>A	MVP-DT	Pathogenic	criteria provided, single submitter
1074997	NM_145239.3(PRRT2):c.543_544del (p.Asn181fs)	MVP-DT	Pathogenic	criteria provided, single submitter
1076546	NM_145239.3(PRRT2):c.842G>A (p.Trp281Ter)	MVP-DT	Pathogenic	criteria provided, single submitter
1352762	NM_145239.3(PRRT2):c.535C>T (p.Gln179Ter)	MVP-DT	Pathogenic	criteria provided, single submitter
1358607	NM_145239.3(PRRT2):c.658C>T (p.Gln220Ter)	MVP-DT	Pathogenic	criteria provided, single submitter
1387417	NM_145239.3(PRRT2):c.268dup (p.Ser90fs)	MVP-DT	Pathogenic	criteria provided, single submitter
1389218	NM_145239.3(PRRT2):c.834C>A (p.Cys278Ter)	MVP-DT	Pathogenic	criteria provided, single submitter
1389708	NM_145239.3(PRRT2):c.224dup (p.Ala76fs)	MVP-DT	Pathogenic	criteria provided, single submitter
1397766	NM_145239.3(PRRT2):c.639_640insC (p.Ala214fs)	MVP-DT	Pathogenic	criteria provided, single submitter
1400478	NM_145239.3(PRRT2):c.970G>T (p.Gly324Ter)	MVP-DT	Pathogenic	criteria provided, single submitter
1436837	NM_145239.3(PRRT2):c.880-1G>C	MVP-DT	Pathogenic	criteria provided, single submitter
1451433	NM_145239.3(PRRT2):c.742del (p.Ser248fs)	MVP-DT	Pathogenic	criteria provided, single submitter
1453871	NM_145239.3(PRRT2):c.870T>G (p.Tyr290Ter)	MVP-DT	Pathogenic	criteria provided, single submitter
2017723	NM_145239.3(PRRT2):c.121del (p.Val41fs)	MVP-DT	Pathogenic	criteria provided, single submitter
2026075	NM_145239.3(PRRT2):c.520_521del (p.Ser174fs)	MVP-DT	Pathogenic	criteria provided, single submitter
2035595	NM_145239.3(PRRT2):c.885del (p.Asn296fs)	MVP-DT	Pathogenic	criteria provided, single submitter
2055376	NM_145239.3(PRRT2):c.1007del (p.Asn335_Leu336insTer)	MVP-DT	Pathogenic	criteria provided, single submitter
2098937	NM_145239.3(PRRT2):c.456del (p.Lys153fs)	MVP-DT	Pathogenic	criteria provided, single submitter
2101100	NM_145239.3(PRRT2):c.422_432dup (p.Arg145fs)	MVP-DT	Pathogenic	criteria provided, single submitter
2113772	NM_145239.3(PRRT2):c.407_408del (p.Pro136fs)	MVP-DT	Pathogenic	criteria provided, single submitter
2119233	NM_145239.3(PRRT2):c.895C>T (p.Gln299Ter)	MVP-DT	Pathogenic	criteria provided, multiple submitters, no conflicts
2137801	NM_145239.3(PRRT2):c.787C>T (p.Gln263Ter)	MVP-DT	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 16 · 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
TMEM151A	Strong	Autosomal dominant	episodic kinesigenic dyskinesia 3	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRRT2	Orphanet:306	Self-limited infantile epilepsy
PRRT2	Orphanet:36387	Genetic epilepsy with febrile seizure plus
PRRT2	Orphanet:569	Familial or sporadic hemiplegic migraine
PRRT2	Orphanet:98809	Paroxysmal kinesigenic dyskinesia
PRRT2	Orphanet:98810	Paroxysmal non-kinesigenic dyskinesia
PRRT2	Orphanet:98811	Paroxysmal exertion-induced dyskinesia
ALDOA	Orphanet:57	Glycogen storage disease due to aldolase A deficiency
KCNA1	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
KCNA1	Orphanet:199326	Isolated autosomal dominant hypomagnesemia, Glaudemans type
KCNA1	Orphanet:37612	Episodic ataxia type 1
KCNA1	Orphanet:972	Hereditary continuous muscle fiber activity
KCNA1	Orphanet:98809	Paroxysmal kinesigenic dyskinesia
KCNJ10	Orphanet:199343	EAST syndrome
KCNJ10	Orphanet:705	Pendred syndrome
KCNJ10	Orphanet:98809	Paroxysmal kinesigenic dyskinesia
KIF22	Orphanet:93360	Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type

Cohort genes → proteins

11 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	11

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TMEM151A	HGNC:28497	ENSG00000179292	Q8N4L1	Transmembrane protein 151A	gencc
FIMP1	HGNC:26346	ENSG00000167194	Q96LL3	Fertilization-influencing membrane protein	clinvar
ASPHD1	HGNC:27380	ENSG00000174939	Q5U4P2	Aspartate beta-hydroxylase domain-containing protein 1	clinvar
PAGR1	HGNC:28707	ENSG00000280789	Q9BTK6	PAXIP1-associated glutamate-rich protein 1	clinvar
PRRT2	HGNC:30500	ENSG00000167371	Q7Z6L0	Proline-rich transmembrane protein 2	clinvar
ALDOA	HGNC:414	ENSG00000149925	P04075	Fructose-bisphosphate aldolase A	clinvar
MVP-DT	HGNC:56029	ENSG00000238045		MVP divergent transcript	clinvar
KCNA1	HGNC:6218	ENSG00000111262	Q09470	Potassium voltage-gated channel subfamily A member 1	clinvar
KCNJ10	HGNC:6256	ENSG00000177807	P78508	ATP-sensitive inward rectifier potassium channel 10	clinvar
KIF22	HGNC:6391	ENSG00000079616	Q14807	Kinesin-like protein KIF22	clinvar
MAZ	HGNC:6914	ENSG00000103495	P56270	Myc-associated zinc finger protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FIMP1	Fertilization-influencing membrane protein	May play a role in sperm-oocyte fusion during fertilization.
PAGR1	PAXIP1-associated glutamate-rich protein 1	Its association with the histone methyltransferase MLL2/MLL3 complex is suggesting a role in epigenetic transcriptional activation.
PRRT2	Proline-rich transmembrane protein 2	As a component of the outer core of AMPAR complex, may be involved in synaptic transmission in the central nervous system.
ALDOA	Fructose-bisphosphate aldolase A	Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis.
KCNA1	Potassium voltage-gated channel subfamily A member 1	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney.
KCNJ10	ATP-sensitive inward rectifier potassium channel 10	May be responsible for potassium buffering action of glial cells in the brain.
KIF22	Kinesin-like protein KIF22	Kinesin family member that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis.
MAZ	Myc-associated zinc finger protein	Transcriptional regulator, potentially with dual roles in transcription initiation and termination.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 7 · Druggable fraction: 0.27

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	2	20.3×	0.017
Other/Unknown	7	1.1×	0.758
Enzyme (other)	1	1.1×	0.758
Transcription factor	1	0.8×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TMEM151A	Other/Unknown	no		Tmem151
FIMP1	Other/Unknown	no		FIMP
ASPHD1	Other/Unknown	no		Asp/Arg/Pro-Hydrxlase, IPNS-like_sf, Asp/Asn_beta-hydroxylase
PAGR1	Other/Unknown	no		PA1
PRRT2	Other/Unknown	no		CD225/Dispanin_fam, CD225/Dispanin
ALDOA	Enzyme (other)	yes	4.1.2.13	FBA_I, Aldolase_TIM, Aldolase_I_AS
MVP-DT	Other/Unknown	no
KCNA1	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
KCNJ10	Ion channel	yes		K_chnl_inward-rec_Kir1.2, K_chnl_inward-rec_Kir_cyto, Ig_E-set
KIF22	Other/Unknown	no		Kinesin_motor_dom, Hlx-hairpin-Hlx_DNA-bd_motif, RuvA_2-like
MAZ	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf

Expression context

Cohort genes with no expression data: 0.

8 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)	11
unknown	0

Top tissues across cohort

Tissue	Cohort genes
C1 segment of cervical spinal cord	3
cerebellar cortex	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
ganglionic eminence	2
ventricular zone	2
Brodmann (1909) area 9	1
spinal cord	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
right testis	1
putamen	1
right frontal lobe	1
gastrocnemius	1
hindlimb stylopod muscle	1
skeletal muscle tissue	1
mucosa of transverse colon	1
oviduct epithelium	1
tendon of biceps brachii	1
Brodmann (1909) area 23	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TMEM151A	126	broad	yes	C1 segment of cervical spinal cord, spinal cord, Brodmann (1909) area 9
FIMP1	114		yes	right testis, left testis, male germ line stem cell (sensu Vertebrata) in testis
ASPHD1	205	ubiquitous	yes	C1 segment of cervical spinal cord, putamen, right frontal lobe
PAGR1	229	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
PRRT2	202	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
ALDOA	134	ubiquitous	marker	skeletal muscle tissue, gastrocnemius, hindlimb stylopod muscle
MVP-DT	191		marker	oviduct epithelium, mucosa of transverse colon, tendon of biceps brachii
KCNA1	151	broad	marker	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus
KCNJ10	185	tissue_specific	marker	C1 segment of cervical spinal cord, medial globus pallidus, globus pallidus
KIF22	242	ubiquitous	marker	ventricular zone, ganglionic eminence, right lobe of thyroid gland
MAZ	288	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 9.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALDOA	3,591
KCNA1	3,157
KIF22	2,097
KCNJ10	1,862
MAZ	1,839
PRRT2	1,545
TMEM151A	774
PAGR1	748
ASPHD1	603
FIMP1	317

Intra-cohort edges

A	B	Sources
ASPHD1	FIMP1	string_interaction
ASPHD1	KIF22	string_interaction
ASPHD1	PAGR1	string_interaction
FIMP1	KIF22	string_interaction
FIMP1	PAGR1	string_interaction
FIMP1	PRRT2	string_interaction
KIF22	MAZ	string_interaction
KIF22	PAGR1	string_interaction
PRRT2	TMEM151A	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 7 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALDOA	P04075	8
KCNJ10	P78508	4
KIF22	Q14807	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNA1	Q09470	78.74
ASPHD1	Q5U4P2	76.01
TMEM151A	Q8N4L1	73.63
FIMP1	Q96LL3	65.84
PAGR1	Q9BTK6	64.26
MAZ	P56270	60.37
PRRT2	Q7Z6L0	51.86

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 38. Enrichment computed across 11 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Potassium Channels	2	53.7×	0.021	KCNA1, KCNJ10
Potassium transport channels	1	761.3×	0.025	KCNJ10
G protein gated Potassium channels	1	228.4×	0.039	KCNJ10
Glucose metabolism	1	175.7×	0.039	ALDOA
Inwardly rectifying K+ channels	1	142.8×	0.039	KCNJ10
Activation of GABAB receptors	1	120.2×	0.039	KCNJ10
GABA B receptor activation	1	108.8×	0.039	KCNJ10
Neuronal System	2	17.7×	0.039	KCNA1, KCNJ10
Hemostasis	2	14.4×	0.039	ALDOA, KIF22
Gluconeogenesis	1	87.8×	0.040	ALDOA
Activation of G protein gated Potassium channels	1	78.8×	0.040	KCNJ10
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	1	78.8×	0.040	KCNJ10
GABA receptor activation	1	63.4×	0.046	KCNJ10
Glycolysis	1	57.1×	0.047	ALDOA
Formation of WDR5-containing histone-modifying complexes	1	53.1×	0.047	PAGR1
Voltage gated Potassium channels	1	48.6×	0.048	KCNA1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	39.4×	0.056	PAGR1
Kinesins	1	35.7×	0.059	KIF22
Response to elevated platelet cytosolic Ca2+	1	32.6×	0.061	ALDOA
Golgi-to-ER retrograde transport	1	26.6×	0.070	KIF22
Metabolism of carbohydrates and carbohydrate derivatives	1	24.0×	0.073	ALDOA
COPI-dependent Golgi-to-ER retrograde traffic	1	22.2×	0.073	KIF22
Platelet activation, signaling and aggregation	1	21.1×	0.073	ALDOA
Intra-Golgi and retrograde Golgi-to-ER traffic	1	20.9×	0.073	KIF22
Neurotransmitter receptors and postsynaptic signal transmission	1	20.0×	0.073	KCNJ10
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	18.3×	0.073	PAGR1
MHC class II antigen presentation	1	17.8×	0.073	KIF22
Platelet degranulation	1	17.6×	0.073	ALDOA
Immune System	2	5.2×	0.073	ALDOA, KIF22
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	16.6×	0.075	PAGR1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of short-term synaptic potentiation	1	2106.5×	0.018	PRRT2
negative regulation of SNARE complex assembly	1	1053.2×	0.018	PRRT2
glutamate reuptake	1	1053.2×	0.018	KCNJ10
regulation of calcium-dependent activation of synaptic vesicle fusion	1	702.2×	0.018	PRRT2
cell communication by electrical coupling	1	526.6×	0.018	KCNA1
detection of mechanical stimulus involved in sensory perception of touch	1	526.6×	0.018	KCNA1
potassium ion transmembrane transport	2	34.0×	0.018	KCNA1, KCNJ10
neuronal signal transduction	1	300.9×	0.020	KCNA1
cellular response to magnesium ion	1	300.9×	0.020	KCNA1
fructose 1,6-bisphosphate metabolic process	1	263.3×	0.020	ALDOA
magnesium ion homeostasis	1	234.1×	0.020	KCNA1
fructose metabolic process	1	210.7×	0.020	ALDOA
regulation of muscle contraction	1	210.7×	0.020	KCNA1
synaptic vesicle fusion to presynaptic active zone membrane	1	210.7×	0.020	PRRT2
membrane repolarization during action potential	1	210.7×	0.020	KCNA1
termination of RNA polymerase II transcription	1	162.0×	0.020	MAZ
regulation of resting membrane potential	1	162.0×	0.020	KCNJ10
positive regulation of intracellular estrogen receptor signaling pathway	1	150.5×	0.020	PAGR1
startle response	1	140.4×	0.020	KCNA1
detection of mechanical stimulus involved in sensory perception of pain	1	140.4×	0.020	KCNA1
positive regulation of cell cycle G1/S phase transition	1	140.4×	0.020	PAGR1
cellular response to potassium ion	1	131.7×	0.020	KCNJ10
neuromuscular process controlling posture	1	131.7×	0.020	PRRT2
metaphase chromosome alignment	1	131.7×	0.020	KIF22
ATP biosynthetic process	1	123.9×	0.020	ALDOA
central nervous system myelination	1	123.9×	0.020	KCNJ10
regulation of long-term neuronal synaptic plasticity	1	123.9×	0.020	KCNJ10
DNA repair	2	16.0×	0.020	PAGR1, KIF22
striated muscle contraction	1	105.3×	0.022	ALDOA
sister chromatid cohesion	1	95.8×	0.023	KIF22

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 9

Druggability breadth: 4 of 11 evidence-associated genes (36%) 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
KCNA1	NIFEDIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNA1	5	4
ALDOA	1	2
TMEM151A	0	0
FIMP1	0	0
ASPHD1	0	0
PAGR1	0	0
PRRT2	0	0
MVP-DT	0	0
KCNJ10	0	0
KIF22	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIFEDIPINE	4	KCNA1
DALFAMPRIDINE	4	KCNA1
CAPSAICIN	4	KCNA1
CORTISONE	3	KCNA1
MOLIBRESIB	2	ALDOA
TETRYLAMMONIUM	2	KCNA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KCNA1	59	Binding:52, Functional:6, Toxicity:1
KCNJ10	10	Binding:10
ALDOA	9	Binding:9
KIF22	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALDOA	4.1.2.13	fructose-bisphosphate aldolase

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

6 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)
NIFEDIPINE	4	KCNA1
DALFAMPRIDINE	4	KCNA1
CAPSAICIN	4	KCNA1
CORTISONE	3	KCNA1
MOLIBRESIB	2	ALDOA
TETRYLAMMONIUM	2	KCNA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KCNA1
B	Phased (≥1) drug, not yet approved	1	ALDOA
C	Druggable family + PDB, no drug	1	KCNJ10
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	8	TMEM151A, FIMP1, ASPHD1, PAGR1, PRRT2, MVP-DT, KIF22, MAZ

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TMEM151A	0	—
FIMP1	0	—
ASPHD1	0	—
PAGR1	0	—
PRRT2	0	—
MVP-DT	0	—
KCNJ10	10	—
KIF22	4	—
MAZ	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.