Familial hemiplegic migraine

Summary

Familial hemiplegic migraine (MONDO:0000700) is a disease (an umbrella term covering 5 Mondo subtypes) with 5 cohort genes and 3 clinical trials. The dominant Reactome pathway is Cardiac conduction (3 cohort genes).

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 5
• ClinVar variants: 1,142
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial hemiplegic migraine
Mondo ID	MONDO:0000700
OMIM	141500
DOID	DOID:0060178
ICD-11	1827007904
NCIT	C117009
SNOMED CT	95656000
UMLS	C0338484
MedGen	87374
GARD	0010975
Is cancer (heuristic)	no

Also known as: familial hemiplegic migraine · FHM · hemiplegic migraine, familial · hemiplegic-ophthalmoplegic migraine · hereditary hemiplegic migraine

Data availability: 1,142 ClinVar variants · 1 ClinGen variant curation · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › migraine disorder › migraine with aura › familial or sporadic hemiplegic migraine › familial hemiplegic migraine

Related subtypes (1): sporadic hemiplegic migraine

Subtypes (5): migraine, familial hemiplegic, 2, migraine, familial hemiplegic, 3, migraine, familial hemiplegic, 1, hemiplegic migraine-developmental and epileptic encephalopathy spectrum, migraine, familial hemiplegic, 4

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:

252 likely benign, 228 uncertain significance, 37 conflicting classifications of pathogenicity, 24 pathogenic, 21 benign, 17 benign/likely benign, 13 likely pathogenic, 8 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1013256	NM_000702.4(ATP1A2):c.1810C>T (p.Arg604Ter)	ATP1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1029935	NM_000702.4(ATP1A2):c.1843G>A (p.Gly615Arg)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071760	NM_000702.4(ATP1A2):c.1097G>T (p.Gly366Val)	ATP1A2	Pathogenic	criteria provided, single submitter
1072573	NM_000702.4(ATP1A2):c.2501G>A (p.Arg834Gln)	ATP1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
12917	NM_000702.4(ATP1A2):c.2291T>C (p.Leu764Pro)	ATP1A2	Pathogenic	no assertion criteria provided
12918	NM_000702.4(ATP1A2):c.2659T>C (p.Trp887Arg)	ATP1A2	Pathogenic	no assertion criteria provided
12921	NM_000702.4(ATP1A2):c.1133C>A (p.Thr378Asn)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12922	NM_000702.4(ATP1A2):c.901G>A (p.Gly301Arg)	ATP1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
12925	NM_000702.4(ATP1A2):c.2936C>T (p.Pro979Leu)	ATP1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
12926	NM_000702.4(ATP1A2):c.1643G>A (p.Arg548His)	ATP1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
12930	NM_000702.4(ATP1A2):c.1127C>T (p.Thr376Met)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1356232	NM_000702.4(ATP1A2):c.1453A>T (p.Lys485Ter)	ATP1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1388779	NM_000702.4(ATP1A2):c.855dup (p.Ile286fs)	ATP1A2	Pathogenic	criteria provided, single submitter
1439209	NM_000702.4(ATP1A2):c.2357C>T (p.Pro786Leu)	ATP1A2	Pathogenic	criteria provided, single submitter
1459217	NM_000702.4(ATP1A2):c.720_721del (p.Ile240fs)	ATP1A2	Pathogenic	criteria provided, single submitter
1719913	NM_000702.4(ATP1A2):c.1130G>T (p.Gly377Val)	ATP1A2	Pathogenic	criteria provided, single submitter
1943929	NM_000702.4(ATP1A2):c.869_872del (p.Ile290fs)	ATP1A2	Pathogenic	criteria provided, single submitter
2009052	NM_000702.4(ATP1A2):c.991C>G (p.Pro331Ala)	ATP1A2	Pathogenic	criteria provided, single submitter
2011853	NM_000702.4(ATP1A2):c.524del (p.Lys175fs)	ATP1A2	Pathogenic	criteria provided, single submitter
2042154	NM_000702.4(ATP1A2):c.2708G>A (p.Trp903Ter)	ATP1A2	Pathogenic	criteria provided, single submitter
204886	NM_000702.4(ATP1A2):c.1148G>A (p.Arg383His)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2202868	NM_000702.4(ATP1A2):c.2977CTC[1] (p.Leu994del)	ATP1A2	Pathogenic	criteria provided, single submitter
2507016	NM_000702.4(ATP1A2):c.1234C>T (p.Arg412Ter)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2699167	NM_000702.4(ATP1A2):c.2126_2127del (p.Val709fs)	ATP1A2	Pathogenic	criteria provided, single submitter
2713294	NM_000702.4(ATP1A2):c.1405A>T (p.Arg469Ter)	ATP1A2	Pathogenic	criteria provided, single submitter
2734006	NM_000702.4(ATP1A2):c.605G>A (p.Arg202Gln)	ATP1A2	Pathogenic	criteria provided, single submitter
2752869	NM_000702.4(ATP1A2):c.2432C>G (p.Thr811Arg)	ATP1A2	Pathogenic	criteria provided, single submitter
2775453	NM_000702.4(ATP1A2):c.1477C>T (p.Arg493Ter)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2814730	NM_000702.4(ATP1A2):c.1570G>T (p.Glu524Ter)	ATP1A2	Pathogenic	criteria provided, single submitter
254268	NM_001127222.2(CACNA1A):c.2134G>A (p.Ala712Thr)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 21 · Orphanet: 20 · 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
SCN1A	Strong	Autosomal dominant	migraine, familial hemiplegic, 3	20
ATP1A4	Limited	Autosomal dominant	familial hemiplegic migraine

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN1A	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SCN1A	Orphanet:2382	Lennox-Gastaut syndrome
SCN1A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN1A	Orphanet:33069	Dravet syndrome
SCN1A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN1A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SCN1A	Orphanet:569	Familial or sporadic hemiplegic migraine
CACNA1A	Orphanet:2131	Alternating hemiplegia of childhood
CACNA1A	Orphanet:2382	Lennox-Gastaut syndrome
CACNA1A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
CACNA1A	Orphanet:569	Familial or sporadic hemiplegic migraine
CACNA1A	Orphanet:71518	Benign paroxysmal torticollis of infancy
CACNA1A	Orphanet:97	Familial paroxysmal ataxia
CACNA1A	Orphanet:98758	Spinocerebellar ataxia type 6
KCNJ10	Orphanet:199343	EAST syndrome
KCNJ10	Orphanet:705	Pendred syndrome
KCNJ10	Orphanet:98809	Paroxysmal kinesigenic dyskinesia
ATP1A2	Orphanet:2131	Alternating hemiplegia of childhood
ATP1A2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
ATP1A2	Orphanet:569	Familial or sporadic hemiplegic migraine

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	gencc,clinvar
ATP1A4	HGNC:14073	ENSG00000132681	Q13733	Sodium/potassium-transporting ATPase subunit alpha-4	gencc
CACNA1A	HGNC:1388	ENSG00000141837	O00555	Voltage-dependent P/Q-type calcium channel subunit alpha-1A	clinvar
KCNJ10	HGNC:6256	ENSG00000177807	P78508	ATP-sensitive inward rectifier potassium channel 10	clinvar
ATP1A2	HGNC:800	ENSG00000018625	P50993	Sodium/potassium-transporting ATPase subunit alpha-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN1A	Sodium channel protein type 1 subunit alpha	Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
ATP1A4	Sodium/potassium-transporting ATPase subunit alpha-4	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.
CACNA1A	Voltage-dependent P/Q-type calcium channel subunit alpha-1A	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
KCNJ10	ATP-sensitive inward rectifier potassium channel 10	May be responsible for potassium buffering action of glial cells in the brain.
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.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 0 · Druggable fraction: 0.6

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	3	66.9×	1e-05
Transcription factor	2	3.3×	0.114

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN1A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a1su
ATP1A4	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC
CACNA1A	Ion channel	yes		VDCCAlpha1, CACNA1A, Ion_trans_dom
KCNJ10	Ion channel	yes		K_chnl_inward-rec_Kir1.2, K_chnl_inward-rec_Kir_cyto, Ig_E-set
ATP1A2	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
lateral nuclear group of thalamus	1
primary visual cortex	1
left testis	1
right testis	1
testis	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
C1 segment of cervical spinal cord	1
globus pallidus	1
medial globus pallidus	1
lateral globus pallidus	1
superior vestibular nucleus	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN1A	154	tissue_specific	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex
ATP1A4	140	tissue_specific	marker	left testis, right testis, testis
CACNA1A	237	broad	marker	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
KCNJ10	185	tissue_specific	marker	C1 segment of cervical spinal cord, medial globus pallidus, globus pallidus
ATP1A2	262	broad	marker	lateral globus pallidus, trigeminal ganglion, superior vestibular nucleus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP1A2	2,679
SCN1A	2,287
ATP1A4	2,155
KCNJ10	1,862
CACNA1A	346

Intra-cohort edges

A	B	Sources
ATP1A2	SCN1A	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CACNA1A	O00555	4
KCNJ10	P78508	4
SCN1A	P35498	1
ATP1A4	Q13733	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP1A2	P50993	88.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 33. Enrichment computed across 5 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
Cardiac conduction	3	65.3×	2e-04	SCN1A, ATP1A4, ATP1A2
Muscle contraction	3	46.3×	3e-04	SCN1A, ATP1A4, ATP1A2
Ion transport by P-type ATPases	2	83.0×	0.002	ATP1A4, ATP1A2
Ion homeostasis	2	81.6×	0.002	ATP1A4, ATP1A2
Potential therapeutics for SARS	2	45.7×	0.005	ATP1A4, ATP1A2
Ion channel transport	2	38.4×	0.006	ATP1A4, ATP1A2
Potassium transport channels	1	761.3×	0.006	KCNJ10
Transmission across Chemical Synapses	2	30.4×	0.007	CACNA1A, KCNJ10
SARS-CoV Infections	2	22.2×	0.011	ATP1A4, ATP1A2
G protein gated Potassium channels	1	228.4×	0.014	KCNJ10
Presynaptic depolarization and calcium channel opening	1	190.3×	0.014	CACNA1A
Neuronal System	2	17.7×	0.014	CACNA1A, KCNJ10
Inwardly rectifying K+ channels	1	142.8×	0.018	KCNJ10
Activation of GABAB receptors	1	120.2×	0.020	KCNJ10
GABA B receptor activation	1	108.8×	0.020	KCNJ10
Viral Infection Pathways	2	12.3×	0.020	ATP1A4, ATP1A2
Activation of G protein gated Potassium channels	1	78.8×	0.022	KCNJ10
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	1	78.8×	0.022	KCNJ10
Interaction between L1 and Ankyrins	1	73.7×	0.022	SCN1A
Phase 0 - rapid depolarisation	1	69.2×	0.022	SCN1A
Transport of small molecules	2	10.1×	0.022	ATP1A4, ATP1A2
Infectious disease	2	9.9×	0.022	ATP1A4, ATP1A2
GABA receptor activation	1	63.4×	0.022	KCNJ10
Regulation of insulin secretion	1	43.9×	0.031	CACNA1A
Integration of energy metabolism	1	35.1×	0.037	CACNA1A
Potassium Channels	1	26.9×	0.047	KCNJ10
L1CAM interactions	1	24.0×	0.050	SCN1A
Neurotransmitter receptors and postsynaptic signal transmission	1	20.0×	0.057	KCNJ10
Disease	2	5.2×	0.057	ATP1A4, ATP1A2
Axon guidance	1	9.0×	0.117	SCN1A

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
potassium ion import across plasma membrane	3	219.8×	2e-05	ATP1A4, KCNJ10, ATP1A2
sodium ion transport	3	163.1×	2e-05	SCN1A, ATP1A4, ATP1A2
sodium ion transmembrane transport	3	121.8×	3e-05	SCN1A, ATP1A4, ATP1A2
potassium ion transport	3	114.9×	3e-05	ATP1A4, KCNJ10, ATP1A2
potassium ion transmembrane transport	3	81.5×	6e-05	ATP1A4, KCNJ10, ATP1A2
neuronal action potential propagation	2	561.7×	6e-05	SCN1A, ATP1A2
sodium ion export across plasma membrane	2	421.3×	1e-04	ATP1A4, ATP1A2
intracellular potassium ion homeostasis	2	396.5×	1e-04	ATP1A4, ATP1A2
intracellular sodium ion homeostasis	2	306.4×	1e-04	ATP1A4, ATP1A2
adult walking behavior	2	198.3×	3e-04	SCN1A, KCNJ10
proton transmembrane transport	2	124.8×	7e-04	ATP1A4, ATP1A2
olfactory cortex development	1	3370.4×	0.002	ATP1A2
transport across blood-brain barrier	2	71.7×	0.002	ATP1A4, ATP1A2
establishment of localization in cell	2	64.2×	0.002	SCN1A, ATP1A4
glutamate reuptake	1	1685.2×	0.003	KCNJ10
regulation of glutamate uptake involved in transmission of nerve impulse	1	1685.2×	0.003	ATP1A2
negative regulation of calcium ion transmembrane transport	1	1685.2×	0.003	ATP1A2
negative regulation of striated muscle contraction	1	1123.5×	0.004	ATP1A2
negative regulation of heart contraction	1	842.6×	0.005	ATP1A2
obsolete regulation of cellular pH	1	674.1×	0.006	ATP1A4
amygdala development	1	561.7×	0.007	ATP1A2
response to glycoside	1	481.5×	0.008	ATP1A2
regulation of striated muscle contraction	1	421.3×	0.008	ATP1A2
response to potassium ion	1	421.3×	0.008	ATP1A2
positive regulation of heart contraction	1	421.3×	0.008	ATP1A2
regulation of muscle contraction	1	337.0×	0.008	ATP1A2
membrane depolarization during action potential	1	337.0×	0.008	SCN1A
L-ascorbic acid metabolic process	1	306.4×	0.008	ATP1A2
locomotion	1	306.4×	0.008	ATP1A2
neurotransmitter uptake	1	280.9×	0.008	ATP1A2

Therapeutics

Drug target analysis

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

Druggability breadth: 5 of 5 evidence-associated genes (100%) 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
SCN1A	MEXILETINE HYDROCHLORIDE
ATP1A4	OMEPRAZOLE
CACNA1A	NIMODIPINE
ATP1A2	OMEPRAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN1A	94	4
ATP1A4	5	4
ATP1A2	5	4
CACNA1A	2	4
KCNJ10	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MEXILETINE HYDROCHLORIDE	4	SCN1A
BEPRIDIL	4	SCN1A
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A
CINNARIZINE	4	SCN1A
THIORIDAZINE	4	SCN1A
ETIDOCAINE	4	SCN1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCN1A	149	Binding:115, Functional:18, ADMET:14, Toxicity:2
ATP1A2	49	Binding:49
ATP1A4	45	Binding:45
CACNA1A	19	Binding:18, Functional:1
KCNJ10	10	Binding:10

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN1A	149

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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)
MEXILETINE HYDROCHLORIDE	4	SCN1A
BEPRIDIL	4	SCN1A
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A
CINNARIZINE	4	SCN1A
THIORIDAZINE	4	SCN1A
ETIDOCAINE	4	SCN1A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	SCN1A, ATP1A4, CACNA1A, ATP1A2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	KCNJ10
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KCNJ10	10	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00358839	Not specified	COMPLETED	Calcitonin Gene Related Peptide-Induced Headache in Patients With Familial Hemiplegic Migraine Type 1 and 2.
NCT00541736	Not specified	COMPLETED	Glyceryl-Trinitrate-Induced Headache in Patients With Familial Hemiplegic Migraine
NCT00687947	Not specified	COMPLETED	Calcitonin Gene-related Peptide in Familial Hemiplegic Migraine (FHM) and Migraine With Aura (MA)