rs6235

This is a variant in the PCSK1 gene that changes a serine to an threonine.

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GWAS Catalog Trait Associations (5)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

blood glucose amount

Willems SM et al. “Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization.” Wellcome Open Research 8:483 (2023)
Allele G
OR 0.02
p 9.0e-24
N 129,665
Large GWAS
multi-ancestry
Hayes MG et al. “Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.” Diabetes 62(9):3282-91 (2013)
Allele G
OR —
β 0.006
p 5.0e-15
N 4,437
Large GWAS
multi-ancestry

body mass index

Pulit SL et al. “Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.” Human Molecular Genetics 28(1):166-174 (2019)
Allele C
OR 0.02
p 4.0e-20
N 374,756
Meta-analysisLarge GWAS
European
Hawkes G et al. “Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion, after accounting for BMI in adulthood.” Diabetologia 66(8):1472-1480 (2023)
Allele C
OR 0.02
p 5.0e-14
N 441,761
Large GWAS
European
Harris BHL et al. “New role of fat-free mass in cancer risk linked with genetic predisposition.” Scientific Reports 14(1):7270 (2024)
Allele C
OR 0.01
p 4.0e-8
N 342,566
Large GWAS
European

smoking initiation

Saunders GRB et al. “Genetic diversity fuels gene discovery for tobacco and alcohol use.” Nature 612(7941):720-724 (2022)
Allele G
OR 0.01
p 7.0e-17
N 2,669,029
Large GWAS
European

fat pad mass

Harris BHL et al. “New role of fat-free mass in cancer risk linked with genetic predisposition.” Scientific Reports 14(1):7270 (2024)
Allele G
OR 0.02
p 1.0e-10
N 337,196
Large GWAS
European
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ClinVar annotation

Likely Benign★★★☆
8 submitters3 publications

Monogenic Non-Syndromic Obesity; Obesity due to prohormone convertase I deficiency; not specified

View on ClinVar →
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Research that mentions this SNP (3)

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Genetic variation of FTO: rs1421085 T&gt;C, rs8057044 G&gt;A, rs9939609 T&gt;A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight
ReviewLizbeth González‐Herrera et al.(2019)· American Journal of Human Biology

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

Traits studied:AdiposityBlood pressureBody mass index (BMI)Cardiovascular risk factorsDyslipidemiaInsulin resistanceMetabolic syndromeObesityOverweightType 2 diabetes
PubMedDOIMetascience Observatory
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Variability in Ethanol Biodisposition in Whites Is Modulated by Polymorphisms in the Adh1b and Adh1c Genes
ReviewCarmen Martínez et al.(2010)· Hepatology

A comprehensive review of nutrigenetics and nutrigenomics examining how genetic variants influence individual responses to nutrients and dietary interventions. The paper discusses associations between numerous SNPs (rs9939609 in FTO, rs2287019 in GIPR, rs7903146 in TCF7L2, rs5219 in KCNJ11, and many others) and metabolic traits including obesity, type 2 diabetes, and other chronic diseases, along with epigenetic mechanisms by which phytochemicals (curcumin, resveratrol, lycopene) modulate gene expression. The review synthesizes current evidence for precision nutrition approaches tailored to individual genetic profiles.

Traits studied:Bone density/osteoporosisCaffeine sensitivityCardiovascular diseaseCeliac diseaseCerebrovascular diseaseCoronary heart diseaseDetoxification capacityEating behaviorGlucose homeostasisHistamine intoleranceInflammatory diseasesInsulin resistanceLactose intoleranceLeptin resistanceMetabolic syndromeNickel intoleranceObesityOsteoarthritisOverweightType 2 diabetes
PubMedDOIMetascience Observatory
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Is the thrifty genotype hypothesis supported by evidence based on confirmed type 2 diabetes- and obesity-susceptibility variants?
AssociationSoutham L et al.(2009)· Diabetologia

This study tests the thrifty genotype hypothesis by examining 17 confirmed type 2 diabetes susceptibility loci and 13 obesity-susceptibility loci for signatures of positive selection. Using ancestral/derived allele analysis, integrated haplotype scores (iHS), and population differentiation (FST), the authors found limited evidence supporting the thrifty genotype hypothesis. Only rs7901695 at TCF7L2 showed notably elevated FST values (0.579 between JPT+CHB and YRI populations), and FTO showed the strongest selection signal among obesity loci (iHS=1.991).

Traits studied:Body mass index (BMI)ObesityType 2 diabetes
PubMedDOIMetascience Observatory

About PCSK1

This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. The protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Mutations in this gene have been associated with susceptibility to obesity and proprotein convertase 1/3 deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene [provided by RefSeq, Jan 2014]

View all PCSK1 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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