Migraine: genes and variants
Explore variant evidence for Migraine across 22 analyzed proteins (NOTCH3, CLCN1, ALDH5A1, CA2, CALCA and 17 more). Linked ClinVar records include 3 pathogenic or likely pathogenic variants, 1 variants of uncertain significance and 0 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Migraine
NOTCH3: Neurogenic locus notch homolog protein 3
Its signaling helps maintain vascular smooth-muscle and mural-cell identity in small arteries. Pathogenic cysteine-altering variants cause CADASIL, with migraine, recurrent ischemic strokes, white-matter disease, and progressive cognitive impairment.
2 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in NOTCH3 have source records linked to Migraine. Association strength is not clinical gene validity.
CLCN1: Chloride channel protein 1
Its chloride conductance stabilizes the resting membrane potential of skeletal muscle and prevents repetitive firing after contraction. Loss-of-function variants cause myotonia congenita, with delayed muscle relaxation and stiffness.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CLCN1 have source records linked to Migraine. Association strength is not clinical gene validity.
ALDH5A1: Succinate-semialdehyde dehydrogenase, mitochondrial
A mitochondrial enzyme that converts succinic semialdehyde to succinate during GABA breakdown. Deficiency causes a neurological disorder with developmental delay and seizures.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in ALDH5A1 have source records linked to Migraine. Association strength is not clinical gene validity.
CA2: Carbonic anhydrase 2
It rapidly interconverts carbon dioxide and bicarbonate, supporting acid-base balance, renal acidification, respiration, bone remodeling, and fluid secretion. Biallelic loss-of-function variants cause carbonic anhydrase II deficiency, with osteopetrosis, renal tubular acidosis, and cerebral calcification.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CA2 have source records linked to Migraine. Association strength is not clinical gene validity.
CALCA: Calcitonin gene-related peptide 1
CGRP1 is a secreted peptide hormone that widens blood vessels through the CALCRL-RAMP1 receptor complex. CGRP1 is also abundant in the nervous system, where it can act as a neurotransmitter or neuromodulator.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CALCA have source records linked to Migraine. Association strength is not clinical gene validity.
CALCB: Calcitonin gene-related peptide 2
CGRP2 is a secreted peptide that activates the CALCRL-RAMP1 receptor complex. Like CGRP1, it promotes blood-vessel dilation and may contribute to signaling in the central nervous system.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CALCB have source records linked to Migraine. Association strength is not clinical gene validity.
CALCRL: Calcitonin gene-related peptide type 1 receptor
A G protein-coupled receptor whose ligand specificity is set by receptor activity-modifying proteins (RAMPs). With RAMP1 it forms the receptor for CGRP peptides, while with RAMP2 or RAMP3 it forms adrenomedullin receptors that activate cAMP signaling.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CALCRL have source records linked to Migraine. Association strength is not clinical gene validity.
GABRA1: Gamma-aminobutyric acid receptor subunit alpha-1
The gene product supplies the alpha-1 subunit of a pentameric GABA-A receptor, a ligand-gated chloride channel in the brain. GABA binding allows chloride influx that dampens neuronal activity, making this receptor important for inhibition and seizure biology.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GABRA1 have source records linked to Migraine. Association strength is not clinical gene validity.
GABRB3: Gamma-aminobutyric acid receptor subunit beta-3
It contributes to inhibitory GABA-A receptor currents in the brain and is particularly important during neurodevelopment. Pathogenic variants can cause developmental and epileptic encephalopathy, while altered dosage within chromosome 15q11-q13 contributes to neurodevelopmental disorders.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GABRB3 have source records linked to Migraine. Association strength is not clinical gene validity.
GABRG2: Gamma-aminobutyric acid receptor subunit gamma-2
The gene product supplies the gamma-2 subunit of synaptic GABA-A receptors, which are pentameric chloride channels activated by the inhibitory neurotransmitter GABA. The subunit helps receptor assembly and localization at neuronal membranes, and GABRG2 variants are associated with several epilepsy syndromes.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GABRG2 have source records linked to Migraine. Association strength is not clinical gene validity.
GRIA1: Glutamate receptor 1
An AMPA-type glutamate receptor subunit that forms a ligand-gated cation channel at excitatory synapses. Glutamate opens the receptor to convert a chemical signal into an electrical response, supporting fast transmission and activity-dependent plasticity in the brain.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GRIA1 have source records linked to Migraine. Association strength is not clinical gene validity.
GRIA2: Glutamate receptor 2
An AMPA-type glutamate receptor subunit that contributes to fast excitatory signaling in the nervous system. Together with other subunits it forms a glutamate-gated cation channel, and its presence helps shape the channel's ion permeability and synaptic behavior.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GRIA2 have source records linked to Migraine. Association strength is not clinical gene validity.
IRAG1: Inositol 1,4,5-triphosphate receptor associated 1
An endoplasmic-reticulum-associated regulator of IP3-dependent calcium release. It recruits protein kinase G and helps translate nitric-oxide signaling into reduced calcium release and inhibition of platelet activation and smooth-muscle contraction.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in IRAG1 have source records linked to Migraine. Association strength is not clinical gene validity.
OPRM1: Mu-type opioid receptor
A G protein-coupled receptor for endogenous opioids and medicines such as morphine and fentanyl. Its activation changes neuronal signaling involved in pain, reward, and respiratory control through inhibitory G protein pathways.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in OPRM1 have source records linked to Migraine. Association strength is not clinical gene validity.
RAMP1: Receptor activity-modifying protein 1
An accessory membrane protein that transports CALCRL to the cell surface and changes the receptor's ligand specificity. Together with CALCRL it forms the CGRP receptor complex, linking RAMP1 to vascular signaling and pain pathways.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in RAMP1 have source records linked to Migraine. Association strength is not clinical gene validity.
SCN10A: Sodium channel protein type 10 subunit alpha
The protein forms Nav1.8, a tetrodotoxin-resistant voltage-gated sodium channel found in excitable membranes. It helps generate sensory-neuron electrical signals and is especially important in mechanisms of neuropathic pain and inherited episodic pain.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN10A have source records linked to Migraine. Association strength is not clinical gene validity.
SCN1A: Sodium channel protein type 1 subunit alpha
Its sodium current is especially important for reliable firing of inhibitory interneurons and therefore for balancing excitation across neural networks. Loss-of-function variants are the major cause of Dravet syndrome, while other variants cause GEFS+ or familial hemiplegic migraine.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN1A have source records linked to Migraine. Association strength is not clinical gene validity.
SCN2A: Sodium channel protein type 2 subunit alpha
The protein forms Nav1.2, a voltage-gated sodium channel that carries sodium current during neuronal action potentials. By shaping neuronal excitability and signal propagation, it supports brain circuits involved in development, learning, and seizure susceptibility.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN2A have source records linked to Migraine. Association strength is not clinical gene validity.
SCN4A: Sodium channel protein type 4 subunit alpha
Its rapid sodium current initiates and propagates skeletal-muscle action potentials. Gain- and loss-of-function variants cause disorders of muscle excitability including sodium-channel myotonia, paramyotonia congenita, periodic paralysis, and some congenital myopathies.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN4A have source records linked to Migraine. Association strength is not clinical gene validity.
SCN5A: Sodium channel protein type 5 subunit alpha
Its rapid inward sodium current drives the upstroke of the cardiac action potential and enables fast electrical conduction through atrial, ventricular, and conduction-system tissue. Pathogenic variants can cause long-QT syndrome type 3, Brugada syndrome, conduction disease, and overlapping arrhythmia phenotypes.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN5A have source records linked to Migraine. Association strength is not clinical gene validity.
SCN8A: Sodium channel protein type 8 subunit alpha
The protein forms Nav1.6, a voltage-gated sodium channel that sets the threshold and propagation of neuronal action potentials. It is widely important for neuronal excitability, and SCN8A variants are associated with developmental and epileptic encephalopathies.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN8A have source records linked to Migraine. Association strength is not clinical gene validity.
SCN9A: Sodium channel protein type 9 subunit alpha
The protein forms Nav1.7, a voltage-gated sodium channel that amplifies electrical signals in peripheral sensory neurons. Changes in Nav1.7 activity can produce either excessive pain or congenital insensitivity to pain, making SCN9A central to pain biology.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN9A have source records linked to Migraine. Association strength is not clinical gene validity.
Weakly linked (only a few uncertain records): MAP2K2.
ClinVar pathogenic and likely pathogenic variants linked to Migraine
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CLCN1 R317Q | 317 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| NOTCH3 C484G | 484 | EGF-like 12 | Pathogenic / likely pathogenic (★) |
| NOTCH3 C212R | 212 | EGF-like 5 | Pathogenic / likely pathogenic |
Same protein, different disease
- CADASIL also has ClinVar records linked to NOTCH3 variants; they fall mostly in different places as the Migraine variants (89 pathogenic / likely pathogenic).
- Infantile myofibromatosis also has ClinVar records linked to NOTCH3 variants; they fall mostly in different places as the Migraine variants (12 pathogenic / likely pathogenic).
- Lateral meningocele syndrome also has ClinVar records linked to NOTCH3 variants; they fall mostly in different places as the Migraine variants (12 pathogenic / likely pathogenic).
- Congenital myotonia, autosomal dominant form also has ClinVar records linked to CLCN1 variants; they fall mostly in different places as the Migraine variants (92 pathogenic / likely pathogenic).
- Congenital myotonia, autosomal recessive form also has ClinVar records linked to CLCN1 variants; they fall mostly in different places as the Migraine variants (90 pathogenic / likely pathogenic).
- Skeletal muscle channelopathy also has ClinVar records linked to CLCN1 variants; they fall mostly in different places as the Migraine variants (11 pathogenic / likely pathogenic).
Diseases related to Migraine
- Epilepsy, also linked to ALDH5A1, CA2, GABRA1, GABRB3 and 10 more
- Lennox-Gastaut syndrome, also linked to CA2, GABRA1, GABRB3, GABRG2 and 7 more
- Cardiac arrhythmia, also linked to SCN10A, SCN1A, SCN2A, SCN4A and 3 more
- Focal epilepsy, also linked to SCN10A, SCN1A, SCN2A, SCN4A and 3 more
- Amyotrophic lateral sclerosis, also linked to SCN10A, SCN1A, SCN2A, SCN4A and 2 more
- Genetic developmental and epileptic encephalopathy, also linked to GABRG2, SCN1A, SCN2A and SCN8A
- Generalized epilepsy with febrile seizures plus, also linked to GABRG2, SCN1A and SCN9A
- EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2, also linked to GABRA1, GABRB3 and GABRG2
- Early-infantile DEE, also linked to SCN1A and SCN8A
- Seizures, benign familial infantile, 3, also linked to SCN2A and SCN8A
- Hyperkalemic periodic paralysis, also linked to CLCN1 and SCN4A
- Complex neurodevelopmental disorder, also linked to SCN2A and SCN8A
Frequently asked questions
Which genes have records linked to Migraine?
This view contains 22 analyzed proteins: NOTCH3, CLCN1, ALDH5A1, CA2, CALCA and 17 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 3 pathogenic or likely pathogenic variants, 1 variants of uncertain significance and 0 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 6 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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