Migraine, with or without aura, susceptibility to, 13

disease

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Also known as KCNK18 migraine disorderMGR13migraine disorder caused by mutation in KCNK18migraine, with or without aura, susceptibility to, type 13

Summary

Migraine, with or without aura, susceptibility to, 13 (MONDO:0013344) is a disease caused by KCNK18 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: KCNK18 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	migraine, with or without aura, susceptibility to, 13
Mondo ID	MONDO:0013344
OMIM	613656
UMLS	C4225479
MedGen	900808
Is cancer (heuristic)	no

Also known as: KCNK18 migraine disorder · MGR13 · migraine disorder caused by mutation in KCNK18 · migraine, with or without aura, susceptibility to, 13 · migraine, with or without aura, susceptibility to, type 13

Data availability: 6 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › migraine with or without aura, susceptibility to › migraine, with or without aura, susceptibility to, 13

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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1802569	NM_181840.1(KCNK18):c.487T>G (p.Tyr163Asp)	KCNK18	Pathogenic	criteria provided, single submitter
18398	NM_181840.1(KCNK18):c.414_415del (p.Phe139fs)	KCNK18	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225399	NM_181840.1(KCNK18):c.361dup (p.Tyr121fs)	KCNK18	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1299240	NM_181840.1(KCNK18):c.711_718del (p.Gln237fs)	KCNK18	Uncertain significance	criteria provided, single submitter
1696556	NM_181840.1(KCNK18):c.721C>A (p.Gln241Lys)	KCNK18	Uncertain significance	criteria provided, multiple submitters, no conflicts
4846829	NM_181840.1(KCNK18):c.319C>T (p.Leu107Phe)	KCNK18	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
KCNK18	Strong	Autosomal dominant	migraine, with or without aura, susceptibility to, 13	4

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCNK18	HGNC:19439	ENSG00000186795	Q7Z418	Potassium channel subfamily K member 18	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNK18	Potassium channel subfamily K member 18	K(+) channel that conducts outward and inward rectifying currents at depolarized and hyperpolarized membrane potentials, respectively.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNK18	Ion channel	yes		2pore_dom_K_chnl, K_chnl_dom

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
caudate nucleus	1
colonic epithelium	1
nucleus accumbens	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNK18	11		yes	nucleus accumbens, caudate nucleus, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNK18	711

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNK18	Q7Z418	70.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TWIK-related spinal cord K+ channel (TRESK)	1	11420.0×	6e-04	KCNK18
Tandem pore domain potassium channels	1	951.7×	0.004	KCNK18
Phase 4 - resting membrane potential	1	601.0×	0.004	KCNK18
Potassium Channels	1	134.3×	0.013	KCNK18
Cardiac conduction	1	108.8×	0.013	KCNK18
Muscle contraction	1	77.2×	0.015	KCNK18
Neuronal System	1	44.3×	0.023	KCNK18

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	1	16852.0×	3e-04	KCNK18
cellular response to pH	1	2106.5×	0.001	KCNK18
potassium ion export across plasma membrane	1	1053.2×	0.002	KCNK18
potassium ion transport	1	191.5×	0.007	KCNK18
potassium ion transmembrane transport	1	135.9×	0.007	KCNK18

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNK18	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KCNK18	9	Binding:7, ADMET:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	KCNK18
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)
KCNK18	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: KCNK18