Migraine disorder

Summary

Migraine disorder (MONDO:0005277) is a disease with 75 cohort genes (826 GWAS associations across 74 studies) and 1,313 clinical trials. Top therapeutic interventions include sumatriptan, topiramate, and erenumab.

At a glance

• Cohort genes: 75
• GWAS associations: 826
• ClinVar variants: 17
• Clinical trials: 1,313

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	migraine disorder
Mondo ID	MONDO:0005277
MeSH	D008881
DOID	DOID:6364
ICD-10-CM	G43
ICD-11	669367341
NCIT	C89715
UMLS	C0149931
MedGen	57451
Is cancer (heuristic)	no

Also known as: migraine · migraine headache

Data availability: 17 ClinVar variants · 826 GWAS associations (74 studies) · 25 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › migraine disorder

Related subtypes (70): leukoencephalopathy, megalencephalic, encephalopathy, acute, infection-induced, diabetic encephalopathy, complex cortical dysplasia with other brain malformations, hydrocephalus, brain compression, cerebral sarcoidosis, hepatic encephalopathy, visual pathway disorder, central nervous system origin vertigo, cerebellar disorder, cerebritis, olfactory nerve disorder, thalamic disorder, pituitary gland disorder, disorder of optic chiasm, basal ganglia disorder, epilepsy, mental disorder, central nervous system cyst, multiple sclerosis, prion disease, carbon monoxide-induced delayed encephalopathy, cerebral malaria, akinetic mutism, bulbar polio, Reye syndrome, brain edema, encephalomalacia, intracranial hypertension, intracranial hypotension, Wernicke encephalopathy, encephalopathy, recurrent, of childhood, XK aprosencephaly, progressive bulbar palsy, cerebrovascular disorder, glycine encephalopathy, autosomal recessive frontotemporal pachygyria, occipital pachygyria and polymicrogyria, insomnia, narcolepsy-cataplexy syndrome, megalencephaly, meningoencephalocele, cerebral cortical dysplasia, encephaloclastic disorder, bilirubin encephalopathy, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, narcolepsy without cataplexy, hypothalamic hamartomas with gelastic seizures, encephalitis, cerebral lipidosis with dementia, brain neoplasm, colpocephaly, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cerebral degeneration, acute bilirubin encephalopathy, chronic bilirubin encephalopathy, atelencephaly, aprosencephaly, brain injury, traumatic encephalopathy, cluster headache syndrome, cerebral cortex disorder, midbrain disorder, encephalopathy due to mitochondrial and peroxisomal fission defect, brain malformations with or without urinary tract defects, encephalopathy, acute transient

Subtypes (2): migraine with aura, migraine without aura

Genetics & variants

GWAS landscape

826 GWAS associations across 74 studies. Top hits map to 21 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs11172113	1e-90	LRP1	T	1.11
rs57866767	7e-71	PLCE1	?
rs10218452	7e-71	PRDM16	G	1.12
rs11153082	7e-54	FHL5	G	1.09
rs6035355	9e-54	SLC24A3	?
rs10166942	9e-51	MSL3B - TRPM8	T	1.1
rs9349379	1e-47	PHACTR1	A	1.08
rs3001426	4e-42	STAT6	?
rs2078371	6e-42	LINC01765 - NGF-AS1	C	1.11
rs4888408	1e-41	CFDP1	?
rs17171710	3e-41	SUGCT	?
rs2274319	3e-41	MEF2D	T	1.08
rs9486715	7e-39	FHL5	?
rs2983896	2e-37	FHL5	?
rs7968719	9e-37	LRP1, LRP1-AS	?
rs2160875	3e-36	FGF23 - FGF6	C	1.07
rs12134493	6e-36	LINC01765 - NGF-AS1	A	1.11
rs2971603	2e-35	FHL5	?
rs62155750	5e-34	LINC00342	?
rs1332844	3e-33	PHACTR1	?
rs2052692	5e-31	IRAG1	?
rs1925950	3e-30	MEF2D	A	0.94
chr12:57132863	3e-30		A	0.11
rs4814864	1e-28	SLC24A3	C	1.07
chr1:3155918	1e-28		A	0.12
rs1075550	2e-28	FGF23 - FGF6	T	0.94
rs10234636	4e-28	SUGCT	T	1.09
rs1048483	5e-28	SMG6, HIC1	?
rs2075968	9e-28	PRDM16	?	1.1
rs67338227	2e-27	FHL5	T	1.09

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90281112	Islam MR	2023	102,084	771,257	Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin.
GCST90281113	Islam MR	2023	102,084	771,257	Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin.
GCST90281114	Islam MR	2023	102,084	771,257	Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin.
GCST90281115	Islam MR	2023	102,084	771,257	Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin.
GCST90281116	Islam MR	2023	102,084	771,257	Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin.
GCST90281117	Islam MR	2023	102,084	771,257	Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin.
GCST90281118	Islam MR	2023	102,084	771,257	Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin.
GCST90102553	Hautakangas H	2022	102,084	771,257	Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles.
GCST90429186	Choquet H	2021	85,726	803,292	New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis.
GCST90244660	Islam MR	2022	74,124	1,595,263	Genetic Overlap Analysis Identifies a Shared Etiology between Migraine and Headache with Type 2 Diabetes.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	2
Tier 3: regulatory	1
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	48
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	37
intergenic_variant	5
missense_variant	2
unknown	2
regulatory_region_variant	1
3_prime_UTR_variant	1
splice_polypyrimidine_tract_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11172113	12	57133500	T>C,G	0.415	intron_variant	LRP1	1e-90	Tier 4: intronic/intergenic
rs57866767	10	94263320	T>C,G	0.05	intron_variant	PLCE1	7e-71	Tier 4: intronic/intergenic
rs10218452	1	3159033	A>G	0.229	intron_variant	PRDM16	7e-71	Tier 4: intronic/intergenic
rs11153082	6	96611790	A>C,G	0.331	intron_variant	FHL5	7e-54	Tier 4: intronic/intergenic
rs6035355	20	19484445	T>A,C	0.05	intron_variant	SLC24A3	9e-54	Tier 4: intronic/intergenic
rs10166942	2	233916448	T>A,C	0.195	intergenic_variant	MSL3B - TRPM8	9e-51	Tier 4: intronic/intergenic
rs9349379	6	12903725	A>C,G,T	0.41	intron_variant	PHACTR1	1e-47	Tier 4: intronic/intergenic
rs3001426	12	57115272	T>C	0.05	intergenic_variant	STAT6	4e-42	Tier 4: intronic/intergenic
rs2078371	1	115134562	T>A,C,G	0.117	intergenic_variant	LINC01765 - NGF-AS1	6e-42	Tier 4: intronic/intergenic
rs4888408	16	75398926	G>A,C,T	0.05	intron_variant	CFDP1	1e-41	Tier 4: intronic/intergenic
rs17171710	7	40400634	C>T	0.05	intron_variant	SUGCT	3e-41	Tier 4: intronic/intergenic
rs2274319	1	156481081	T>C	0.347	intron_variant	MEF2D	3e-41	Tier 4: intronic/intergenic
rs9486715	6	96611893	A>C,T	0.05	intron_variant	FHL5	7e-39	Tier 4: intronic/intergenic
rs2983896	6	96581995	G>A	0.05	intron_variant	FHL5	2e-37	Tier 4: intronic/intergenic
rs7968719	12	57146968	C>G	0.05	intron_variant	LRP1, LRP1-AS	9e-37	Tier 4: intronic/intergenic
rs2160875	12	4418156	C>T	0.477	intron_variant	FGF23 - FGF6	3e-36	Tier 4: intronic/intergenic
rs12134493	1	115135325	C>A	0.12	regulatory_region_variant	LINC01765 - NGF-AS1	6e-36	Tier 3: regulatory
rs2971603	6	96587542	C>G,T	0.05	intron_variant	FHL5	2e-35	Tier 4: intronic/intergenic
rs62155750	2	95825708	A>G	0.05	intron_variant	LINC00342	5e-34	Tier 4: intronic/intergenic
rs1332844	6	12888772	C>T	0.05	intron_variant	PHACTR1	3e-33	Tier 4: intronic/intergenic
rs2052692	11	10646094	A>C,G	0.05	intron_variant	IRAG1	5e-31	Tier 4: intronic/intergenic
rs1925950	1	156480948	G>A,C	0.35	missense_variant	MEF2D	3e-30	Tier 1: coding
chr12:57132863							3e-30	Tier 4: intronic/intergenic
rs4814864	20	19489173	G>A,C,T	0.254	intron_variant	SLC24A3	1e-28	Tier 4: intronic/intergenic
chr1:3155918							1e-28	Tier 4: intronic/intergenic
rs1075550	12	4417341	C>A,T	0.48	intron_variant	FGF23 - FGF6	2e-28	Tier 4: intronic/intergenic
rs10234636	7	40388018	T>C,G	0.111	intron_variant	SUGCT	4e-28	Tier 4: intronic/intergenic
rs1048483	17	2063163	C>T	0.05	3_prime_UTR_variant	SMG6, HIC1	5e-28	Tier 2: splice/UTR
rs2075968	1	3164677	C>T	0.05	intron_variant	PRDM16	9e-28	Tier 4: intronic/intergenic
rs67338227	6	96594271	A>C,G,T	0.23	intron_variant	FHL5	2e-27	Tier 4: intronic/intergenic

ClinVar germline variants

17 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 pathogenic, 3 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
195935	NM_001127222.2(CACNA1A):c.4174G>A (p.Val1392Met)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17621	NM_000070.3(CAPN3):c.550del (p.Thr184fs)	CAPN3	Pathogenic	reviewed by expert panel
92408	NM_000070.3(CAPN3):c.1746-20C>G	CAPN3	Pathogenic	reviewed by expert panel
17542	NM_000083.3(CLCN1):c.950G>A (p.Arg317Gln)	CLCN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
373443	NM_001292034.3(TAB2):c.1039C>T (p.Arg347Ter)	LOC126859827	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812745	NM_000435.3(NOTCH3):c.634T>C (p.Cys212Arg)	NOTCH3	Pathogenic	no assertion criteria provided
523355	NM_001122764.3(PPOX):c.1353T>G (p.Tyr451Ter)	PPOX	Pathogenic	criteria provided, single submitter
9733	NC_012920.1(MT-ND1):m.3697G>A	MT-ND1	Likely pathogenic	reviewed by expert panel
523370	NM_000435.3(NOTCH3):c.1450T>G (p.Cys484Gly)	NOTCH3	Likely pathogenic	criteria provided, single submitter
44926	NM_004415.4(DSP):c.5218G>A (p.Glu1740Lys)	DSP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14149	NM_002471.4(MYH6):c.3195G>C (p.Gln1065His)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
239175	NM_002471.4(MYH6):c.4594C>T (p.Arg1532Cys)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
983126	NM_138420.4(AHNAK2):c.6406_6408delinsGAC (p.Gln2136Asp)	AHNAK2	Uncertain significance	criteria provided, single submitter
523536	NM_030662.4(MAP2K2):c.514A>G (p.Lys172Glu)	MAP2K2	Uncertain significance	criteria provided, multiple submitters, no conflicts
9387	NM_000335.5(SCN5A):c.892G>A (p.Gly298Ser)	SCN5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
374095	NM_006516.4(SLC2A1):c.1407G>C (p.Gln469His)	SLC2A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
523431	NM_001382567.1(STIM1):c.1627T>A (p.Ser543Thr)	STIM1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 93 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN5A	Orphanet:101016	Romano-Ward syndrome
SCN5A	Orphanet:130	Brugada syndrome
SCN5A	Orphanet:1344	Isolated atrial standstill
SCN5A	Orphanet:154	Familial isolated dilated cardiomyopathy
SCN5A	Orphanet:166282	Hereditary sick sinus syndrome
SCN5A	Orphanet:228140	Idiopathic ventricular fibrillation
SCN5A	Orphanet:334	Hereditary atrial fibrillation
SCN5A	Orphanet:871	Hereditary progressive cardiac conduction defect
SLC2A1	Orphanet:168577	Hereditary cryohydrocytosis with reduced stomatin
SLC2A1	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SLC2A1	Orphanet:2131	Alternating hemiplegia of childhood
SLC2A1	Orphanet:53583	Paroxysmal dystonic choreathetosis with episodic ataxia and spasticity
SLC2A1	Orphanet:71277	Classic glucose transporter type 1 deficiency syndrome
SLC2A1	Orphanet:86911	Epilepsy with myoclonic absences
SLC2A1	Orphanet:98811	Paroxysmal exertion-induced dyskinesia
SPINK2	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
STAT6	Orphanet:2126	Solitary fibrous tumor
STIM1	Orphanet:2593	Tubular aggregate myopathy
STIM1	Orphanet:317430	Combined immunodeficiency due to STIM1 deficiency
STIM1	Orphanet:3204	Stormorken-Sjaastad-Langslet syndrome
TGFBR2	Orphanet:144	Lynch syndrome
TGFBR2	Orphanet:284973	Marfan syndrome type 2
TGFBR2	Orphanet:60030	Loeys-Dietz syndrome
TGFBR2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
TGFBR2	Orphanet:99977	Squamous cell carcinoma of the esophagus
TSC1	Orphanet:210159	Adult hepatocellular carcinoma
TSC1	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC1	Orphanet:538	Lymphangioleiomyomatosis
TSC1	Orphanet:805	Tuberous sclerosis complex
USP9X	Orphanet:480880	X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability
USP9X	Orphanet:777	X-linked non-syndromic intellectual disability
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
PRDM16	Orphanet:154	Familial isolated dilated cardiomyopathy
PRDM16	Orphanet:1606	1p36 deletion syndrome
PRDM16	Orphanet:54260	Left ventricular noncompaction
JPH3	Orphanet:98934	Huntington disease-like 2
NLRP1	Orphanet:352662	Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome
RNF213	Orphanet:2573	Moyamoya disease
CAPN3	Orphanet:267	Calpain-3-related limb-girdle muscular dystrophy R1
CAPN3	Orphanet:565909	Calpain-3-related limb-girdle muscular dystrophy D4
SUGCT	Orphanet:35706	Glutaric acidemia type 3
YAP1	Orphanet:1473	Uveal coloboma-cleft lip and palate-intellectual disability
YAP1	Orphanet:157791	Epithelioid hemangioendothelioma
CTR9	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	66
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN5A	HGNC:10593	ENSG00000183873	Q14524	Sodium channel protein type 5 subunit alpha	clinvar
SLC24A3	HGNC:10977	ENSG00000185052	Q9HC58	Sodium/potassium/calcium exchanger 3	gwas
SLC2A1	HGNC:11005	ENSG00000117394	P11166	Solute carrier family 2, facilitated glucose transporter member 1	clinvar
SPINK2	HGNC:11245	ENSG00000128040	P20155	Serine protease inhibitor Kazal-type 2	gwas
STAT6	HGNC:11368	ENSG00000166888	P42226	Signal transducer and activator of transcription 6	gwas
STIM1	HGNC:11386	ENSG00000167323	Q13586	Stromal interaction molecule 1	clinvar
TGFBR2	HGNC:11773	ENSG00000163513	P37173	TGF-beta receptor type-2	gwas
MPPED2	HGNC:1180	ENSG00000066382	Q15777	Metallophosphoesterase MPPED2	gwas
TSC1	HGNC:12362	ENSG00000165699	Q92574	Hamartin	gwas
USP9X	HGNC:12632	ENSG00000124486	Q93008	Ubiquitin carboxyl-terminal hydrolase 9X	gwas
CACNA1A	HGNC:1388	ENSG00000141837	O00555	Voltage-dependent P/Q-type calcium channel subunit alpha-1A	clinvar
PRDM16	HGNC:14000	ENSG00000142611	Q9HAZ2	Histone-lysine N-methyltransferase PRDM16	gwas
JPH3	HGNC:14203	ENSG00000154118	Q8WXH2	Junctophilin-3	gwas
NLRP1	HGNC:14374	ENSG00000091592	Q9C000	NACHT, LRR and PYD domains-containing protein 1	gwas
CARF	HGNC:14435	ENSG00000138380	Q8N187	Calcium-responsive transcription factor	gwas
RNF213	HGNC:14539	ENSG00000173821	Q63HN8	E3 ubiquitin-protein ligase RNF213	gwas
IMMP2L	HGNC:14598	ENSG00000184903	Q96T52	Mitochondrial inner membrane protease subunit 2	gwas
CAPN3	HGNC:1480	ENSG00000092529	P20807	Calpain-3	clinvar
SUGCT	HGNC:16001	ENSG00000175600	Q9HAC7	Succinyl-CoA:glutarate CoA-transferase	gwas
CCM2L	HGNC:16153	ENSG00000101331	Q9NUG4	Cerebral cavernous malformations 2 protein-like	gwas
YAP1	HGNC:16262	ENSG00000137693	P46937	Transcriptional coactivator YAP1	gwas
MOAP1	HGNC:16658	ENSG00000165943	Q96BY2	Modulator of apoptosis 1	gwas
CTR9	HGNC:16850	ENSG00000198730	Q6PD62	RNA polymerase-associated protein CTR9 homolog	gwas
CPQ	HGNC:16910	ENSG00000104324	Q9Y646	Carboxypeptidase Q	gwas
ASTN2	HGNC:17021	ENSG00000148219	O75129	Astrotactin-2	gwas
PLCE1	HGNC:17175	ENSG00000138193	Q9P212	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	gwas
FHL5	HGNC:17371	ENSG00000112214	Q5TD97	Four and a half LIM domains protein 5	gwas
MSL3B	HGNC:17837	ENSG00000224287	P0C860	MSL complex subunit 3B	gwas
TRPM8	HGNC:17961	ENSG00000144481	Q7Z2W7	Transient receptor potential cation channel subfamily M member 8	gwas
HPSE2	HGNC:18374	ENSG00000172987	Q8WWQ2	Inactive heparanase-2	gwas
NAXE	HGNC:18453	ENSG00000163382	Q8NCW5	NAD(P)H-hydrate epimerase	gwas
CFDP1	HGNC:1873	ENSG00000153774	Q9UEE9	Heterochromatin-stabilizing protein CFDP1	gwas
DOCK4	HGNC:19192	ENSG00000128512	Q8N1I0	Dedicator of cytokinesis protein 4	gwas
ADAMTSL4	HGNC:19706	ENSG00000143382	Q6UY14	ADAMTS-like protein 4	gwas
AHNAK2	HGNC:20125	ENSG00000185567	Q8IVF2	Protein AHNAK2	clinvar
CLCN1	HGNC:2019	ENSG00000188037	P35523	Chloride channel protein 1	clinvar
TSPAN2	HGNC:20659	ENSG00000134198	O60636	Tetraspanin-2	gwas
PHACTR1	HGNC:20990	ENSG00000112137	Q9C0D0	Phosphatase and actin regulator 1	gwas
TBC1D7	HGNC:21066	ENSG00000145979	Q9P0N9	TBC1 domain family member 7	gwas
NCOA7	HGNC:21081	ENSG00000111912	Q8NI08	Nuclear receptor coactivator 7	gwas
LINGO2	HGNC:21207	ENSG00000174482	Q7L985	Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2	gwas
UFL1	HGNC:23039	ENSG00000014123	O94874	E3 UFM1-protein ligase 1	gwas
GPR149	HGNC:23627	ENSG00000174948	Q86SP6	Probable G-protein coupled receptor 149	gwas
MED14	HGNC:2370	ENSG00000180182	O60244	Mediator of RNA polymerase II transcription subunit 14	gwas
ZCCHC14	HGNC:24134	ENSG00000140948	Q8WYQ9	Zinc finger CCHC domain-containing protein 14	gwas
CDKN2AIP	HGNC:24325	ENSG00000168564	Q9NXV6	CDKN2A-interacting protein	gwas
HJURP	HGNC:25444	ENSG00000123485	Q8NCD3	Holliday junction recognition protein	gwas
AGBL1	HGNC:26504	ENSG00000273540	Q96MI9	Cytosolic carboxypeptidase 4	gwas
LRRIQ3	HGNC:28318	ENSG00000162620	A6PVS8	Leucine-rich repeat and IQ domain-containing protein 3	gwas
WSCD1	HGNC:29060	ENSG00000179314	Q658N2	Sialate:O-sulfotransferase 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN5A	Sodium channel protein type 5 subunit alpha	Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
SLC24A3	Sodium/potassium/calcium exchanger 3	Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+).
SLC2A1	Solute carrier family 2, facilitated glucose transporter member 1	Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake.
SPINK2	Serine protease inhibitor Kazal-type 2	As a strong inhibitor of acrosin, it is required for normal spermiogenesis.
STAT6	Signal transducer and activator of transcription 6	Carries out a dual function: signal transduction and activation of transcription.
STIM1	Stromal interaction molecule 1	Acts as a Ca(2+) sensor that gates two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels.
TGFBR2	TGF-beta receptor type-2	Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
MPPED2	Metallophosphoesterase MPPED2	Displays low metallophosphoesterase activity (in vitro).
TSC1	Hamartin	Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…
USP9X	Ubiquitin carboxyl-terminal hydrolase 9X	Deubiquitinase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins.
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…
PRDM16	Histone-lysine N-methyltransferase PRDM16	Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context.
JPH3	Junctophilin-3	Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells.
NLRP1	NACHT, LRR and PYD domains-containing protein 1	Acts as the sensor component of the NLRP1 inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis.
CARF	Calcium-responsive transcription factor	Acts as a transcriptional activator that mediates the calcium- and neuron-selective induction of BDNF exon III transcription.
RNF213	E3 ubiquitin-protein ligase RNF213	Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity.
IMMP2L	Mitochondrial inner membrane protease subunit 2	Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space.
CAPN3	Calpain-3	Calcium-regulated non-lysosomal thiol-protease.
SUGCT	Succinyl-CoA:glutarate CoA-transferase	Coenzyme A (CoA) transferase that reversibly catalyzes the transfer of a CoA moiety from a dicarboxyl-CoA to a dicarboxylate in a metabolite recycling process.
YAP1	Transcriptional coactivator YAP1	Transcriptional regulator with dual roles as a coactivator and corepressor.
MOAP1	Modulator of apoptosis 1	Retrotransposon-derived protein that forms virion-like capsids.
CTR9	RNA polymerase-associated protein CTR9 homolog	Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency.
CPQ	Carboxypeptidase Q	Carboxypeptidase that may play an important role in the hydrolysis of circulating peptides.
ASTN2	Astrotactin-2	Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons.
PLCE1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
FHL5	Four and a half LIM domains protein 5	May be involved in the regulation of spermatogenesis.
MSL3B	MSL complex subunit 3B	Probable non-catalytic component of the MSL histone acetyltransferase complex, a multiprotein complex that mediates the majority of histone H4 acetylation at ‘Lys-16’ (H4K16ac), an epigenetic mark that prevents chromatin compaction.
TRPM8	Transient receptor potential cation channel subfamily M member 8	Non-selective ion channel permeable to monovalent and divalent cations, including Na(+), K(+), and Ca(2+), with higher permeability for Ca(2+).
HPSE2	Inactive heparanase-2	Binds heparin and heparan sulfate with high affinity, but lacks heparanase activity.
NAXE	NAD(P)H-hydrate epimerase	Catalyzes the epimerization of the S- and R-forms of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration.
CFDP1	Heterochromatin-stabilizing protein CFDP1	Required for the structural stability of pericentromeric heterochromatin.
DOCK4	Dedicator of cytokinesis protein 4	Functions as a guanine nucleotide exchange factor (GEF) that promotes the exchange of GDP to GTP, converting inactive GDP-bound small GTPases into their active GTP-bound form.
ADAMTSL4	ADAMTS-like protein 4	Positive regulation of apoptosis.
CLCN1	Chloride channel protein 1	Voltage-gated chloride channel involved in skeletal muscle excitability.
TSPAN2	Tetraspanin-2	May play a role in signalling in oligodendrocytes in the early stages of their terminal differentiation into myelin-forming glia and may also function in stabilizing the mature sheath.
PHACTR1	Phosphatase and actin regulator 1	Binds actin monomers (G actin) and plays a role in multiple processes including the regulation of actin cytoskeleton dynamics, actin stress fibers formation, cell motility and survival, formation of tubules by endothelial cells, and regula…
TBC1D7	TBC1 domain family member 7	Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…
NCOA7	Nuclear receptor coactivator 7	Enhances the transcriptional activities of several nuclear receptors.
UFL1	E3 UFM1-protein ligase 1	E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in various processes, such as ribosome recycling, response to DNA dam…
GPR149	Probable G-protein coupled receptor 149	Orphan receptor.
MED14	Mediator of RNA polymerase II transcription subunit 14	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
CDKN2AIP	CDKN2A-interacting protein	Regulates DNA damage response in a dose-dependent manner through a number of signaling pathways involved in cell proliferation, apoptosis and senescence.
HJURP	Holliday junction recognition protein	Centromeric protein that plays a central role in the incorporation and maintenance of histone H3-like variant CENPA at centromeres.
AGBL1	Cytosolic carboxypeptidase 4	Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins.
WSCD1	Sialate:O-sulfotransferase 1	Sialate:O-sulfotransferase which catalyzes 8-O-sulfation at the Sia-glycan level using 3’-phosphoadenosine 5’-phosphosulfate (PAPS) as a donor, forming 8-O-sulfated Sia (Sia8S)-glycans.
MARCHF4	E3 ubiquitin-protein ligase MARCHF4	E3 ubiquitin-protein ligase that may mediate ubiquitination of MHC-I and CD4, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies.
MTDH	Protein LYRIC	Down-regulates SLC1A2/EAAT2 promoter activity when expressed ectopically.
SDR9C7	Short-chain dehydrogenase/reductase family 9C member 7	Plays a crucial role in the formation of the epidermal permeability barrier.
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
AJAP1	Adherens junction-associated protein 1	Plays a role in cell adhesion and cell migration.

Protein-family classification

Druggable: 25 · Difficult: 11 · Unknown: 39 · Druggable fraction: 0.33

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	4	6.0×	0.051
Protease	5	2.4×	0.298
Complement	1	3.6×	0.786
Kinase	4	1.5×	0.786
Antibody/Immunoglobulin	3	1.2×	0.876
Transporter	1	1.0×	0.876
Enzyme (other)	6	1.0×	0.876
Scaffold/PPI	4	0.9×	0.876
Other/Unknown	39	0.9×	0.901
Transcription factor	7	0.8×	0.901
GPCR	1	0.3×	0.960

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN5A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a5su
SLC24A3	Other/Unknown	no		K/Na/Ca-exchanger, NaCa_Exmemb, NCX_ion-bd_dom_sf
SLC2A1	Transporter	yes		Glu_transpt_1, Sugar/inositol_transpt, MFS_sugar_transport-like
SPINK2	Other/Unknown	no		Kazal_dom, Kazal_dom_sf, SPINK2
STAT6	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
STIM1	Other/Unknown	no		SAM, SAM/pointed_sf, SOAR_STIM1/2
TGFBR2	Kinase	yes	2.7.10.2	TGFB_receptor, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
MPPED2	Other/Unknown	no		Calcineurin-like_PHP, Calcineurin-like_Pesterase, Metallo-depent_PP-like
TSC1	Other/Unknown	no		Hamartin
USP9X	Protease	yes		Peptidase_C19_UCH, ARM-type_fold, USP_CS
CACNA1A	Ion channel	yes		VDCCAlpha1, CACNA1A, Ion_trans_dom
PRDM16	Transcription factor	no	2.1.1.367	SET_dom, Znf_C2H2_type, Znf_C2H2_sf
JPH3	Other/Unknown	no		MORN, Junctophilin
NLRP1	Other/Unknown	no		CARD, Leu-rich_rpt, DAPIN
CARF	Other/Unknown	no		CaRF
RNF213	Transcription factor	no		Znf_RING, AAA+_ATPase, Znf_RING/FYVE/PHD
IMMP2L	Protease	yes		Pept_S26A_signal_pept_1, Peptidase_S26, Pept_S26A_signal_pept_1_CS
CAPN3	Protease	yes	3.4.22.54	Pept_cys_AS, Peptidase_C2_calpain_cat, EF_hand_dom
SUGCT	Enzyme (other)	yes	2.8.3.13	CoA-Trfase_fam_III, CoA-Trfase_III_dom_1_sf, CoA-Trfase_III_dom3_sf
CCM2L	Other/Unknown	no		PH-like_dom_sf, Malcavernin, CCM2_C
YAP1	Scaffold/PPI	no		WW_dom, WW_dom_sf, YAP1
MOAP1	Other/Unknown	no		PNMA, PNMA_C, PNMA_N
CTR9	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, Ctr9
CPQ	Protease	yes		Peptidase_M28, CPQ
ASTN2	Complement	yes		MACPF, Astrotactin, FN3_sf
PLCE1	Enzyme (other)	yes	3.1.4.11	C2_dom, RA_dom, PLipase_C_PInositol-sp_X_dom
FHL5	Transcription factor	no		Znf_LIM, FHL5_LIM2, LIM_FHL1/2/3/5_N
MSL3B	Other/Unknown	no		MRG, MRG_dom, MRG_C_sf
TRPM8	Ion channel	yes		Ion_trans_dom, TRPM_SLOG, TRPM
HPSE2	Other/Unknown	no		Glyco_hydro_79, GH_hydrolase_sf
NAXE	Enzyme (other)	yes	5.1.99.6	YjeF_N_dom, YJEFN_prot_NAXE-like, YjeF_N_dom_sf
CFDP1	Other/Unknown	no		BCNT-C, Swc5/CFDP1/2
DOCK4	Scaffold/PPI	no		SH3_domain, DOCK, C2_DOCK-type_domain
ADAMTSL4	Other/Unknown	no		TSP1_rpt, ADAMTS_spacer1, PLAC
AHNAK2	Scaffold/PPI	no		PDZ, PDZ_sf, Myelin_sheath_structural
CLCN1	Other/Unknown	no		ClC, Cl_channel-1, Cl-channel_core
TSPAN2	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
PHACTR1	Other/Unknown	no		RPEL_repeat
TBC1D7	Other/Unknown	no		Rab-GAP-TBC_dom, Rab-GAP_TBC_sf, TBC1D7
NCOA7	Other/Unknown	no		TLDc_dom, LysM, LysM_dom_sf
LINGO2	Antibody/Immunoglobulin	yes		LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
UFL1	Other/Unknown	no		Ufl1, Ufl1_N, Ufl1_dom
GPR149	GPCR	yes		GPCR_Rhodpsn_7TM
MED14	Other/Unknown	no		Mediator_Med14, Med14_RM8, Med14_RM2
ZCCHC14	Transcription factor	no		SAM, Znf_CCHC, SAM/pointed_sf
CDKN2AIP	Other/Unknown	no		dsRBD_dom, XTBD, DSRM_CARF/NKRF
HJURP	Other/Unknown	no		Scm3/HJURP, HJURP_central_dom, HJURP_C
AGBL1	Protease	yes		Peptidase_M14, ARM-like, ARM-type_fold
LRRIQ3	Other/Unknown	no		Leu-rich_rpt, LRR_dom_sf, LRR-IQ_domain_protein
WSCD1	Other/Unknown	no		Sulfotransferase_dom, WSC_carb-bd, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

63 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)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
secondary oocyte	8
cortical plate	6
calcaneal tendon	6
male germ line stem cell (sensu Vertebrata) in testis	6
oocyte	6
hindlimb stylopod muscle	5
primordial germ cell in gonad	5
ganglionic eminence	4
ventricular zone	4
apex of heart	3
lateral nuclear group of thalamus	3
saphenous vein	3
sural nerve	3
corpus epididymis	3
granulocyte	3
lateral globus pallidus	3
popliteal artery	3
upper leg skin	3
hair follicle	3
skin of abdomen	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN5A	161	broad	yes	apex of heart, heart left ventricle, cardiac ventricle
SLC24A3	272	broad	marker	lateral nuclear group of thalamus, tongue squamous epithelium, saphenous vein
SLC2A1	250	ubiquitous	marker	tibial nerve, sural nerve, skin of abdomen
SPINK2	177	broad	marker	corpus epididymis, cauda epididymis, seminal vesicle
STAT6	292	ubiquitous	marker	granulocyte, right ovary, left ovary
STIM1	237	ubiquitous	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle
TGFBR2	289	ubiquitous	marker	pericardium, tibia, parietal pleura
MPPED2	255	broad	marker	ventricular zone, ganglionic eminence, cortical plate
TSC1	297	ubiquitous	marker	substantia nigra pars compacta, gluteal muscle, lateral globus pallidus
USP9X	295	ubiquitous	marker	middle frontal gyrus, endometrium epithelium, secondary oocyte
CACNA1A	237	broad	marker	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
PRDM16	202	broad	marker	sural nerve, pigmented layer of retina, ascending aorta
JPH3	166	broad	yes	right frontal lobe, postcentral gyrus, parietal lobe
NLRP1	203	ubiquitous	marker	granulocyte, monocyte, mononuclear cell
CARF	215	ubiquitous	yes	calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
RNF213	252	ubiquitous	marker	granulocyte, metanephros cortex, pancreatic ductal cell
IMMP2L	223	ubiquitous	marker	tibialis anterior, deltoid, calcaneal tendon
CAPN3	134	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue, C1 segment of cervical spinal cord
SUGCT	191	ubiquitous	marker	right adrenal gland cortex, oocyte, right coronary artery
CCM2L	207	broad	marker	spleen, apex of heart, oocyte
YAP1	279	ubiquitous	marker	saphenous vein, germinal epithelium of ovary, cauda epididymis
MOAP1	142	ubiquitous	marker	superior frontal gyrus, prefrontal cortex, frontal cortex
CTR9	292	ubiquitous	marker	corpus epididymis, epithelium of nasopharynx, palpebral conjunctiva
CPQ	293	ubiquitous	marker	left lobe of thyroid gland, thyroid gland, right lobe of thyroid gland
ASTN2	236	ubiquitous	marker	buccal mucosa cell, trigeminal ganglion, dorsal root ganglion
PLCE1	271	broad	marker	renal glomerulus, metanephric glomerulus, ventricular zone
FHL5	210	tissue_specific	marker	popliteal artery, tibial artery, right coronary artery
MSL3B	130	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, testis
TRPM8	122	tissue_specific	marker	right lobe of liver, liver, prostate gland
HPSE2	153	tissue_specific	marker	calcaneal tendon, lower esophagus muscularis layer, lower esophagus

Protein interactions among cohort

Intra-cohort edges: 26.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
YAP1	6,742
TGFBR2	5,777
SLC2A1	5,711
TSC1	5,445
MED14	5,271
GJA1	4,942
DOCK4	4,803
JAG1	4,405
CTR9	4,367
UFL1	3,840

Intra-cohort edges

A	B	Sources
ADAMTSL4	SPINK2	biogrid_interaction, intact
AHNAK2	CAPN3	string_interaction
AHNAK2	DOCK4	intact
AJAP1	MPPED2	string_interaction
AJAP1	TSPAN2	string_interaction
ASTN2	TRPM8	string_interaction
ASTN2	TSPAN2	string_interaction
CCM2L	ZCCHC14	string_interaction
CPQ	MTDH	string_interaction
DOCK4	IMMP2L	string_interaction
FHL5	HEY2	intact
FHL5	SUGCT	string_interaction
FHL5	UFL1	string_interaction
FSHB	MPPED2	string_interaction
GJA1	SCN5A	string_interaction
GPR149	MPPED2	string_interaction
HEY2	JAG1	string_interaction
IGSF9B	YAP1	intact
KCNK5	SLC24A3	string_interaction
LINGO2	WSCD1	string_interaction
MOAP1	YAP1	string_interaction
PHACTR1	TRPM8	string_interaction
PHACTR1	TSPAN2	string_interaction
SUGCT	TSPAN2	string_interaction
TBC1D7	TSC1	biogrid_interaction, intact, string_interaction
USP9X	YAP1	biogrid_interaction

Structural data

PDB: 43 · AlphaFold-only: 32 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
YAP1	P46937	41
HCK	P08631	40
FECH	P22830	25
TGFBR2	P37173	22
CTR9	Q6PD62	21
GJA1	P17302	19
SCN5A	Q14524	16
NLRP1	Q9C000	12
MED14	O60244	11
CLCN1	P35523	9
UFL1	O94874	9
FUT9	Q9Y231	8
STAT6	P42226	7
JAG1	P78504	7
LRP1	Q07954	7
STIM1	Q13586	6
TRPM8	Q7Z2W7	6
PHACTR1	Q9C0D0	6
TBC1D7	Q9P0N9	6
FGF23	Q9GZV9	6
FSHB	P01225	6
SLC2A1	P11166	5
TSC1	Q92574	5
CAPN3	P20807	5
GFRA2	O00451	5
USP9X	Q93008	4
CACNA1A	O00555	4
RNF213	Q63HN8	4
DSP	P15924	4
ITPK1	Q13572	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MPPED2	Q15777	95.43
CPQ	Q9Y646	93.81
SDR9C7	Q8NEX9	93.41
INPP5A	Q14642	91.81
IMMP2L	Q96T52	87.66
TSPAN2	O60636	87.26
NAXE	Q8NCW5	86.71
LINGO2	Q7L985	85.02
HPSE2	Q8WWQ2	82.90
FGF6	P10767	79.20
AGBL1	Q96MI9	78.53
WSCD1	Q658N2	77.87
DOCK4	Q8N1I0	76.47
INA	Q16352	75.42
SLC24A3	Q9HC58	70.31
LRRIQ3	A6PVS8	70.18
KCNK5	O95279	69.94
ECM1	Q16610	69.05
MSL3B	P0C860	68.69
HEY2	Q9UBP5	65.56
ADAMTSL4	Q6UY14	65.18
CFDP1	Q9UEE9	64.86
CDKN2AIP	Q9NXV6	63.54
IGSF9B	Q9UPX0	62.71
MARCHF4	Q9P2E8	62.42
JPH3	Q8WXH2	61.52
CCM2L	Q9NUG4	59.84
ARMS2	P0C7Q2	58.14
CARF	Q8N187	56.59
GPR149	Q86SP6	54.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 352. Enrichment computed across 92 evidence-associated genes (61 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 61 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective LFNG causes SCDO3	2	74.9×	0.073	NOTCH3, NOTCH4
Pre-NOTCH Processing in the Endoplasmic Reticulum	2	62.4×	0.073	NOTCH3, NOTCH4
NOTCH4 Activation and Transmission of Signal to the Nucleus	2	34.0×	0.090	JAG1, NOTCH4
Frs2-mediated activation	2	31.2×	0.090	MAP2K2, NGF
Signaling by activated point mutants of FGFR1	2	31.2×	0.090	FGF23, FGF6
FGFR2c ligand binding and activation	2	28.8×	0.090	FGF23, FGF6
FGFR4 ligand binding and activation	2	26.7×	0.090	FGF23, FGF6
Heme biosynthesis	2	25.0×	0.090	FECH, PPOX
FGFR1c ligand binding and activation	2	25.0×	0.090	FGF23, FGF6
Phospholipase C-mediated cascade; FGFR4	2	25.0×	0.090	FGF23, FGF6
Degradation of the extracellular matrix	4	7.7×	0.090	CAPN3, MMP16, MMP17, HTRA1
Defective SLC2A1 causes GLUT1 deficiency syndrome 1 (GLUT1DS1)	1	187.2×	0.092	SLC2A1
Activated point mutants of FGFR2	2	22.0×	0.092	FGF23, FGF6
Phospholipase C-mediated cascade: FGFR1	2	22.0×	0.092	FGF23, FGF6
Pre-NOTCH Processing in Golgi	2	20.8×	0.092	NOTCH3, NOTCH4
Phospholipase C-mediated cascade; FGFR2	2	20.8×	0.092	FGF23, FGF6
PI-3K cascade:FGFR4	2	18.7×	0.092	FGF23, FGF6
NOTCH4 Intracellular Domain Regulates Transcription	2	18.7×	0.092	HEY2, NOTCH4
Downstream signaling of activated FGFR1	2	17.8×	0.092	FGF23, FGF6
SHC-mediated cascade:FGFR4	2	17.8×	0.092	FGF23, FGF6
Signal transduction by L1	2	17.0×	0.092	MAP2K2, NRP1
PI-3K cascade:FGFR1	2	17.0×	0.092	FGF23, FGF6
SHC-mediated cascade:FGFR1	2	16.3×	0.092	FGF23, FGF6
PI-3K cascade:FGFR2	2	16.3×	0.092	FGF23, FGF6
FRS-mediated FGFR4 signaling	2	16.3×	0.092	FGF23, FGF6
SHC-mediated cascade:FGFR2	2	15.6×	0.092	FGF23, FGF6
NOTCH3 Activation and Transmission of Signal to the Nucleus	2	15.6×	0.092	JAG1, NOTCH3
FRS-mediated FGFR1 signaling	2	15.0×	0.092	FGF23, FGF6
RUNX2 regulates osteoblast differentiation	2	15.0×	0.092	YAP1, HEY2
FRS-mediated FGFR2 signaling	2	14.4×	0.092	FGF23, FGF6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 86 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mammary gland morphogenesis	2	195.9×	0.023	STAT6, TGFBR2
cardiac conduction system development	3	36.7×	0.030	SCN5A, GJA1, HEY2
aorta morphogenesis	3	30.9×	0.035	TGFBR2, JAG1, LRP1
tricuspid valve morphogenesis	2	78.4×	0.040	TGFBR2, HEY2
negative regulation of endothelial cell differentiation	2	78.4×	0.040	JAG1, NOTCH4
artery morphogenesis	3	23.5×	0.040	TGFBR2, NOTCH3, NRP1
pulmonary artery morphogenesis	2	65.3×	0.042	HEY2, JAG1
vasculogenesis	4	11.9×	0.042	TGFBR2, YAP1, HEY2, NRP1
trachea formation	2	56.0×	0.046	TGFBR2, MAP2K2
branching involved in blood vessel morphogenesis	3	18.4×	0.046	TGFBR2, NOTCH4, NRP1
positive regulation of transcription by RNA polymerase II	15	2.6×	0.046	STAT6, YAP1, CTR9, FHL5, NCOA7, MED14, FSHB, HEY2 (+7 more)
sprouting angiogenesis	3	16.8×	0.055	RNF213, NAXE, NRP1
heme B biosynthetic process	2	39.2×	0.058	FECH, PPOX
atrial cardiac muscle cell action potential	2	39.2×	0.058	SCN5A, GJA1
epithelial cell development	2	35.6×	0.058	ADAMTSL4, ONECUT2
cardiac left ventricle morphogenesis	2	35.6×	0.058	TGFBR2, HEY2
heme A biosynthetic process	2	35.6×	0.058	FECH, PPOX
self proteolysis	2	35.6×	0.058	NLRP1, CAPN3
aortic valve morphogenesis	3	15.1×	0.058	TGFBR2, HEY2, JAG1
cellular response to amyloid-beta	3	13.7×	0.058	CACNA1A, GJA1, LRP1
positive regulation of angiogenesis	5	6.7×	0.058	STIM1, TGFBR2, MTDH, ECM1, NRP1
positive regulation of tolerance induction to self antigen	1	195.9×	0.060	TGFBR2
positive regulation of B cell tolerance induction	1	195.9×	0.060	TGFBR2
innate immune response-activating signaling pathway	1	195.9×	0.060	HCK
regulation of type 2 immune response	1	195.9×	0.060	ECM1
visceral muscle development	1	195.9×	0.060	MYH6
detection of UV	1	195.9×	0.060	FECH
obsolete positive regulation of vitamin D 24-hydroxylase activity	1	195.9×	0.060	FGF23
regulation of polarized epithelial cell differentiation	1	195.9×	0.060	AJAP1
leukocyte degranulation	1	195.9×	0.060	HCK

Therapeutics

Drugs indicated for this disease

27 approved, 29 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acetaminophen	Approved (phase 4)
Aspirin	Approved (phase 4)
Atogepant	Approved (phase 4)
Botulinum Toxin Type A	Approved (phase 4)
Butalbital	Approved (phase 4)
Caffeine	Approved (phase 4)
Celecoxib	Approved (phase 4)
Clonidine	Approved (phase 4)
Diclofenac	Approved (phase 4)
Dihydroergotamine	Approved (phase 4)
Eletriptan	Approved (phase 4)
Eptinezumab	Approved (phase 4)
Erenumab	Approved (phase 4)
Ergotamine	Approved (phase 4)
Fremanezumab	Approved (phase 4)
Frovatriptan	Approved (phase 4)
Galcanezumab	Approved (phase 4)
Ibuprofen	Approved (phase 4)
Lasmiditan	Approved (phase 4)
Lisuride	Approved (phase 4)
Methysergide	Approved (phase 4)
Naratriptan	Approved (phase 4)
Rizatriptan	Approved (phase 4)
Sumatriptan	Approved (phase 4)
Topiramate	Approved (phase 4)
Ubrogepant	Approved (phase 4)
Zolmitriptan	Approved (phase 4)
Amitriptyline	Phase 3 (in late-stage trials)
Bupivacaine	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Diphenhydramine	Phase 3 (in late-stage trials)
Ethinyl Estradiol	Phase 3 (in late-stage trials)
Fentanyl	Phase 3 (in late-stage trials)
Ketoprofen	Phase 3 (in late-stage trials)
Ketorolac	Phase 3 (in late-stage trials)
Lacosamide	Phase 3 (in late-stage trials)
Levonorgestrel	Phase 3 (in late-stage trials)
Lidocaine	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Meloxicam	Phase 3 (in late-stage trials)
Memantine	Phase 3 (in late-stage trials)
Metformin	Phase 3 (in late-stage trials)
Metoclopramide	Phase 3 (in late-stage trials)
Naproxen	Phase 3 (in late-stage trials)
Onabotulinumtoxina	Phase 3 (in late-stage trials)
Palmidrol	Phase 3 (in late-stage trials)
Pregabalin	Phase 3 (in late-stage trials)
Prochlorperazine	Phase 3 (in late-stage trials)
Propranolol	Phase 3 (in late-stage trials)
Rimegepant	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Telcagepant	Phase 3 (in late-stage trials)
Valproic Acid	Phase 3 (in late-stage trials)
Vitamin E	Phase 3 (in late-stage trials)
Zavegepant	Phase 3 (in late-stage trials)
Zonisamide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Almotriptan, Atorvastatin, Candesartan, Cannabidiol, Carbon Dioxide, Carisbamate, Corticotropin, Ergocalciferol, Eslicarbazepine Acetate, Estradiol, Fospropofol, Gabapentin Enacarbil, Lactose, Anhydrous, Lornoxicam, Loxapine, Methylprednisolone, Naltrexone, Niacin, Oxygen, Perampanel, Prabotulinumtoxin A, Propofol, Quinidine, Simvastatin, Timolol, Tricaprilin.

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 12 · Phased (≥1): 14 · Undrugged: 61

Druggability breadth: 43 of 92 evidence-associated genes (47%) 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
SCN5A	BEPRIDIL
SLC2A1	EMETINE
STAT6	THIORIDAZINE HYDROCHLORIDE
STIM1	TERIFLUNOMIDE
TGFBR2	PONATINIB
CACNA1A	NIMODIPINE
NLRP1	PERHEXILINE MALEATE
TRPM8	CLOTRIMAZOLE
FECH	VEMURAFENIB
GJA1	KANAMYCIN
HCK	PONATINIB
MAP2K2	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN5A	108	4
HCK	61	4
MAP2K2	52	4
FECH	34	4
TGFBR2	22	4
TRPM8	15	4
STAT6	11	4
SLC2A1	7	4
STIM1	2	4
CACNA1A	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	SCN5A
IMIPRAMINE	4	SCN5A
DROPERIDOL	4	SCN5A
PONATINIB	4	HCK, SCN5A, TGFBR2
DULOXETINE	4	SCN5A
PALONOSETRON	4	SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	SCN5A
FEDRATINIB	4	HCK, MAP2K2, SCN5A, TGFBR2
QUINIDINE	4	SCN5A
DARUNAVIR	4	SCN5A
DARIFENACIN	4	SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	SCN5A
RANOLAZINE	4	SCN5A
PIMOZIDE	4	SCN5A
NIMODIPINE	4	CACNA1A, SCN5A
FELODIPINE	4	SCN5A
NICARDIPINE	4	SCN5A
AMLODIPINE	4	SCN5A
PHENYTOIN	4	SCN5A
PALIPERIDONE	4	SCN5A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 12.

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

Symbol	Assays	Type breakdown
MAP2K2	615	Binding:581, Functional:33, ADMET:1
SCN5A	594	Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1
HCK	431	Binding:429, Functional:1, ADMET:1
TGFBR2	188	Binding:188
TRPM8	160	Binding:148, Functional:12
SLC2A1	158	Binding:130, ADMET:24, Functional:4
YAP1	135	Binding:135
STAT6	81	Binding:77, Functional:4
USP9X	41	Binding:41
STIM1	35	Binding:33, Functional:1, ADMET:1
CACNA1A	19	Binding:18, Functional:1
FECH	9	Binding:9
CTR9	8	Binding:8
INPP5A	6	Binding:6
ITPK1	6	Binding:6
GJA1	4	Binding:4
KCNK5	4	Binding:4
PRDM16	2	Binding:2
NLRP1	2	Functional:1, Binding:1
GPR149	2	Binding:2
MTDH	2	Binding:2
DSP	2	Binding:2
FGF23	2	Binding:2
GFRA2	2	Binding:2
RNF213	1	Binding:1
UFL1	1	Binding:1
FUT9	1	Binding:1
INA	1	Binding:1
JAG1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TGFBR2	2.7.10.2	non-specific protein-tyrosine kinase
PRDM16	2.1.1.367, 2.1.1.370	[histone H3]-lysine9 N-methyltransferase, [histone H3]-lysine4 N-dimethyltransferase
CAPN3	3.4.22.54, 3.4.22.56	calpain-3, caspase-3
SUGCT	2.8.3.13	succinate-hydroxymethylglutarate CoA-transferase
PLCE1	3.1.4.11	phosphoinositide phospholipase C
NAXE	5.1.99.6	NAD(P)H-hydrate epimerase
FECH	4.99.1.1	protoporphyrin ferrochelatase
FUT9	2.4.1.152	4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase
HCK	2.7.10.2	non-specific protein-tyrosine kinase
INPP5A	3.1.3.56	inositol-polyphosphate 5-phosphatase
ITPK1	2.7.1.134, 2.7.1.159	inositol-tetrakisphosphate 1-kinase, inositol-1,3,4-trisphosphate 5/6-kinase
MAP2K2	2.7.12.2	mitogen-activated protein kinase kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN5A	594
SLC2A1	158
TGFBR2	188
YAP1	135
TRPM8	160
HCK	431
MAP2K2	615

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Compound	Max phase	Cohort target (bioactivity)
BEPRIDIL	4	SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	SCN5A
IMIPRAMINE	4	SCN5A
DROPERIDOL	4	SCN5A
PONATINIB	4	HCK, SCN5A, TGFBR2
DULOXETINE	4	SCN5A
PALONOSETRON	4	SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	SCN5A
FEDRATINIB	4	HCK, MAP2K2, SCN5A, TGFBR2
QUINIDINE	4	SCN5A
DARUNAVIR	4	SCN5A
DARIFENACIN	4	SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	SCN5A
RANOLAZINE	4	SCN5A
PIMOZIDE	4	SCN5A
NIMODIPINE	4	CACNA1A, SCN5A
FELODIPINE	4	SCN5A
NICARDIPINE	4	SCN5A
AMLODIPINE	4	SCN5A
PHENYTOIN	4	SCN5A
PALIPERIDONE	4	SCN5A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	12	SCN5A, SLC2A1, STAT6, STIM1, TGFBR2, CACNA1A, NLRP1, TRPM8, FECH, GJA1 (+2 more)
B	Phased (≥1) drug, not yet approved	2	USP9X, CTR9
C	Druggable family + PDB, no drug	7	CAPN3, SUGCT, ASTN2, PLCE1, FUT9, IGLL1, ITPK1
D	Druggable family + AlphaFold only, no drug	9	IMMP2L, CPQ, NAXE, LINGO2, GPR149, AGBL1, IGSF9B, INPP5A, KCNK5
E	Difficult family or no structure, no drug	45	SLC24A3, SPINK2, MPPED2, TSC1, PRDM16, JPH3, CARF, RNF213, CCM2L, YAP1 (+35 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
YAP1	135	—
SLC24A3	0	—
SPINK2	0	—
MPPED2	0	—
TSC1	0	—
PRDM16	2	—
JPH3	0	—
CARF	0	—
RNF213	1	—
IMMP2L	0	—
CAPN3	0	—
SUGCT	0	—
CCM2L	0	—
MOAP1	0	—
CPQ	0	—
ASTN2	0	—
PLCE1	0	—
FHL5	0	—
MSL3B	0	—
HPSE2	0	—
NAXE	0	—
CFDP1	0	—
DOCK4	0	—
ADAMTSL4	0	—
AHNAK2	0	—
CLCN1	0	—
TSPAN2	0	—
PHACTR1	0	—
TBC1D7	0	—
NCOA7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,313.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	522
PHASE3	203
PHASE4	148
PHASE2	112
PHASE1	82
PHASE2/PHASE3	18
PHASE1/PHASE2	8
EARLY_PHASE1	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT04748601	PHASE4	RECRUITING	Qudexy XR for the Prevention of Migraine in Children 6 to 11 Years Old
NCT04925414	PHASE4	RECRUITING	Migraine and High Flow Oxygenotherapy at the Emergency Department (MiOx)
NCT06173661	PHASE4	ACTIVE_NOT_RECRUITING	Fremanezumab Treatment of Migraine in Women With Menstrual Migraine Ages 18-45
NCT06401642	PHASE4	RECRUITING	Effectiveness and Tolerability of Zavegepant for Acute Migraine Treatment Among Those Using CGRP Targeting Preventive Medications
NCT06432127	PHASE4	NOT_YET_RECRUITING	Role of Ultrasound Guide Greater Occipital Nerve Block at Second Cervical Vertebra in Migraine Headache Prophylaxis
NCT06473597	PHASE4	RECRUITING	A Comparison of Nurtec ODT to Maxalt MLT-ODT in Adult ED Patients With Migraine Headache
NCT06485726	PHASE4	RECRUITING	Valproate Versus Propranolol in Migraine
NCT06499116	PHASE4	NOT_YET_RECRUITING	Comparison of the Effectiveness of First-line Preventive Treatment of Migraine in Primary Care
NCT06509503	PHASE4	RECRUITING	Impact of Combined Oral Contraceptive Pills on Migraine
NCT06701526	PHASE4	ACTIVE_NOT_RECRUITING	A Trial of Eptinezumab in Participants With Migraine and Insufficient Response to Anti-CGRP Medications
NCT06786650	PHASE4	ACTIVE_NOT_RECRUITING	Comparision of the Analgesic Effects of Intravenous Ibuprofen and Tenoxicam in Acute Migraine Attack
NCT06972056	PHASE4	RECRUITING	Comparative Effectiveness of Migraine Preventive Medications: The APT Comparison Study
NCT07022496	PHASE4	RECRUITING	Assessment of Oral Caffeine Intake in Changing the Severity of Acute Migraine Attack Using VAS Score Among Patients Attending Headache and Neurology Outpatients Clinic of Ainshams University Hospitals
NCT07093138	PHASE4	RECRUITING	Evaluation of Efficacy and Safety of Topical Cannabidiol (Canvert-M Produced by Alasht Pharmed co. Iran) in the Treatment of Migraine Attacks
NCT07100496	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of MIG-SPRAY Treatment on Migraine
NCT07301008	PHASE4	RECRUITING	Rimegepant as Preemptive Treatment for Predictable Trigger-Induced Migraine in Adult Patients in the US
NCT07336056	PHASE4	ACTIVE_NOT_RECRUITING	Nerivio Efficacy Under High-Frequency Use
NCT00174395	PHASE4	COMPLETED	A Trial to Study of the Effects of Eletriptan 40mg on Mild vs Moderate to Severe Pain Intensity of Migraine
NCT00208065	PHASE4	COMPLETED	Evaluation of Histamine, CGRP and VIP as Markers for Activation of Trigeminal and Parasympathetic Nerve Fibers
NCT00210496	PHASE4	COMPLETED	Potential Impact (Benefit) of Preventative Treatment With Topamax on the Effectiveness of Axert in the Acute Treatment of Migraine
NCT00210509	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Almotriptan Versus Placebo in the Treatment of Migraine Headache
NCT00212810	PHASE4	COMPLETED	Evaluation of the Effectiveness of Topiramate in Preventing the Transformation From Episodic Migraine to Chronic Daily Headache.
NCT00212823	PHASE4	COMPLETED	The Effectiveness of Almotriptan Malate (AXERT®) 12.5 Milligrams When Taken at the Onset of Migraine Pain
NCT00216736	PHASE4	COMPLETED	Oral Dexamethasone for Treatment of Migraine
NCT00259636	PHASE4	WITHDRAWN	Zonisamide for Fibromyalgia & Migraine
NCT00259649	PHASE4	COMPLETED	Prospective Survey of Menstrual Migraine & Prevention With Eletriptan
NCT00297375	PHASE4	COMPLETED	A Study Comparing the Effectiveness and Safety of ULTRACET® (Tramadol HCl/Acetaminophen) Versus Placebo for the Treatment of Acute Pain From a Migraine Headache
NCT00335777	PHASE4	COMPLETED	A Research Study Examining Migranal and Skin Sensitivity in Subjects With Migraine
NCT00363506	PHASE4	UNKNOWN	American Migraine Prevention Study
NCT00364806	PHASE4	COMPLETED	Prochlorperazine vs Metoclopramide
NCT00391755	PHASE4	TERMINATED	A Double-Blind Placebo-Controlled Trial of Rozerem in Migraine Headaches
NCT00397254	PHASE4	COMPLETED	Two Rizatriptan Prescribing Portions for Treatment of Migraine
NCT00443352	PHASE4	COMPLETED	A Research Study Examining The Use Of Duloxetine In The Prevention Of Migraine Headache
NCT00449787	PHASE4	COMPLETED	Comparing Naproxen to Sumatriptan for Emergency Headache Patients
NCT00632385	PHASE4	COMPLETED	Efficacy and Safety of Eletriptan for the Treatment of Migraine in Patients Not Satisfied With Rizatriptan Therapy
NCT00634985	PHASE4	COMPLETED	Safety and Efficacy of Eletriptan for the Treatment of Migraine in Subjects Unsuccessfully Treated With Nonsteroidal Anti-inflammatory Drugs
NCT00637286	PHASE4	COMPLETED	ZAP, US. Zomig for Appropriate for Primary Care
NCT00753311	PHASE4	COMPLETED	Rizatriptan in Acute Treatment of Migraine in Patients With Unilateral Trigeminal-autonomic Symptoms.
NCT00792636	PHASE4	COMPLETED	A Study to Determine the Effect of Sumatriptan and Naproxen Sodium Combination Tablet, Sumatriptan Tablet, and Naproxen Sodium Tablet on Blood Pressure When Treating Migraine Headaches That Occur During a 6-month Period

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SUMATRIPTAN	4	129
TOPIRAMATE	4	43
ERENUMAB	4	34
RIZATRIPTAN	4	31
PROPRANOLOL	4	25
AMITRIPTYLINE	4	24
FREMANEZUMAB	4	20
GALCANEZUMAB	4	20
RIMEGEPANT	4	20
EPTINEZUMAB	4	19
LASMIDITAN	4	16
ELETRIPTAN	4	15
NAPROXEN	4	15
PROCHLORPERAZINE	4	15
DIHYDROERGOTAMINE	4	14
METOCLOPRAMIDE	4	13
KETOROLAC	4	12
ATOGEPANT	4	11
VALPROIC ACID	4	11
FROVATRIPTAN	4	10
UBROGEPANT	4	10
NARATRIPTAN	4	8
ONABOTULINUMTOXINA	4	8
ZAVEGEPANT	4	8
ZOLMITRIPTAN	4	8
KETOPROFEN	4	6
BOTULINUM TOXIN TYPE A	4	5
CAFFEINE	4	5
ZONISAMIDE	4	5
ACETAMINOPHEN	4	4