{{Rsnum
|rsid=2653349
|Gene=HCRTR2
|Chromosome=6
|position=55277539
|Orientation=plus
|GMAF=0.1286
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=HCRTR2
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 1.8 | 27.7 | 70.5
| HCB | 0.0 | 12.5 | 87.5
| JPT | 0.0 | 7.1 | 92.9
| YRI | 0.7 | 20.1 | 79.2
| ASW | 1.8 | 26.3 | 71.9
| CHB | 0.0 | 12.5 | 87.5
| CHD | 0.9 | 15.6 | 83.5
| GIH | 2.0 | 24.8 | 73.3
| LWK | 0.0 | 22.4 | 77.6
| MEX | 3.4 | 20.7 | 75.9
| MKK | 0.0 | 8.4 | 91.6
| TSI | 2.0 | 27.5 | 70.6
| HapMapRevision=28
}}[[rs2653349]], also known as G1246A, is a SNP in the [[HCRTR2]] hypocretin-orexin gene. It has been linked primarily to [[cluster headaches]]. The more common allele (G) has been linked to increased risk; alternatively, this could be seen as implying that the less common (A) allele reduces cluster headache risk.

In the (first) study, 100+ Italian patients were analyzed to reveal that [[rs2653349]](G;G) genotypes were at 5x increased risk for the disorder, compared with (A;G) and (A;A) genotypes.{{PMID|15477554}} 

A study of 200+ German patients indicated that (G;G) homozygotes were at 2x increased risk (CI: 1.32-2.92, p = 0.0007) for [[cluster headaches]].{{PMID|16554494}}

A meta-analysis of 3 pooled studies concluded that the [[rs2653349]](G;G) genotype showed a higher disease risk compared to the remaining genotypes (odds ratio 1.69, CI:1.11-2.58).{{PMID|17563843|OA=1
}}

Not all studies have found this association; a study of Northern Europeans did not find an association.{{PMID|16801656}}

Also, a study has been performed to find out if treatment success for [[cluster headaches]] is correlated with [[rs2653349]] genotype. Among 184 Caucasian patients, while the [[rs2653349]](G) allele was significantly associated with [[cluster headaches]], treatment outcomes with [[triptans]], oxygen, [[verapamil]] and corticosteroids were not.{{PMID|17376114}}

Independently, a study has been performed to see if [[rs2653349]] might be associated with [[migraine]]; in this study at least, the answer was no.{{PMID|17883525}}

{{omim
|desc=CLUSTER HEADACHE, FAMILIAL
|id=119915
|rsnum=2653349
}}

{{omim
|desc=HYPOCRETIN RECEPTOR 2; HCRTR2
|id=602393
|rsnum=2653349
}}

{{GET Evidence
|gene=HCRTR2
|aa_change=Ile308Val
|aa_change_short=I308V
|impact=not reviewed
|qualified_impact=Insufficiently evaluated not reviewed
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs2653349
|overall_frequency_n=8879
|overall_frequency_d=10758
|overall_frequency=0.825339
|n_genomes=53
|n_genomes_annotated=0
|n_haplomes=97
|n_articles=0
|n_articles_annotated=0
|nblosum100=-4
|autoscore=0
|webscore=N
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}