rs855791
This is a variant in the TMPRSS6 gene that changes a valine to an alanine.
▶GWAS Catalog Trait Associations (51)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (51)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
erythrocyte volume
Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele G
OR 0.12
p —
N 480,305
Large GWAS
multi-ancestry
Vuckovic D et al. “The Polygenic and Monogenic Basis of Blood Traits and Diseases.” Cell 182(5):1214-1231.e11 (2020)
Allele G
OR 0.06
p 2.0e-149
N 408,112
Large GWAS
European
Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele G
OR 0.05
p 3.0e-156
N 394,642
Large GWAS
European
Thompson A et al. “Assessing the impact of alcohol consumption on the genetic contribution to mean corpuscular volume.” Human Molecular Genetics 30(21):2040-2051 (2021)
Allele G
OR —
β 0.590
p —
N 362,595
Large GWAS
European
Jee YH et al. “Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures.” Nature Communications 16(1):4935 (2025)
Allele G
OR 0.09
p 3.0e-130
N 153,950
Large GWAS
East Asian
Chen MH et al. “Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.” Cell 182(5):1198-1213.e14 (2020)
Allele G
OR 0.09
p 2.0e-115
N 121,047
Large GWAS
East Asian
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele G
OR 0.09
p 2.0e-36
N 114,848
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean
Hu Y et al. “Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program.” American Journal of Human Genetics 108(5):874-893 (2021)
Allele G
OR 0.65
p 3.0e-65
N 48,830
Large GWAS
multi-ancestry
Jacobs BM et al. “Genetic architecture of routinely acquired blood tests in a British South Asian cohort.” Nature Communications 15(1):8929 (2024)
Allele G
OR 0.10
p 1.0e-45
N 38,000
Large GWAS
South Asian
Kamatani Y et al. “Genome-wide association study of hematological and biochemical traits in a Japanese population.” Nature Genetics 42(3):210-5 (2010)
Allele G
OR 0.10
p 1.0e-15
N 14,364
Large GWAS
East Asian
Li J et al. “GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.” Human Molecular Genetics 22(7):1457-64 (2013)
Allele G
OR 0.48
p 2.0e-9
N 14,177
Large GWAS
multi-ancestry
Hodonsky CJ et al. “Genome-wide association study of red blood cell traits in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos.” Plos Genetics 13(4):e1006760 (2017)
Allele G
OR 0.64
p 2.0e-17
N 12,502
Large GWAS
Hispanic or Latin American
Sun P et al. “An Asian-specific MPL genetic variant alters JAK-STAT signaling and influences platelet count in the population.” Human Molecular Genetics 30(9):836-842 (2021)
Allele G
OR —
β 0.010
p 5.0e-11
N 5,257
Large GWAS
East Asian
Read RW et al. “GWAS and PheWAS of red blood cell components in a Northern Nevadan cohort.” Plos One 14(6):e0218078 (2019)
Allele G
OR 0.62
p 5.0e-12
N 4,675
Large GWAS
multi-ancestry
Kullo IJ et al. “A genome-wide association study of red blood cell traits using the electronic medical record.” Plos One 5(9) (2010)
Allele G
OR 0.62
p 5.0e-9
N 3,012
Large GWAS
European
mean corpuscular hemoglobin
Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele G
OR 0.14
p —
N 478,500
Large GWAS
multi-ancestry
Vuckovic D et al. “The Polygenic and Monogenic Basis of Blood Traits and Diseases.” Cell 182(5):1214-1231.e11 (2020)
Allele G
OR 0.15
p —
N 408,112
Large GWAS
European
Jee YH et al. “Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures.” Nature Communications 16(1):4935 (2025)
Allele G
OR 0.03
p 2.0e-60
N 153,950
Large GWAS
East Asian
van der Harst P et al. “Seventy-five genetic loci influencing the human red blood cell.” Nature 492(7429):369-75 (2012)
Allele G
OR 0.01
p 1.0e-69
N 71,861
Large GWAS
multi-ancestry
Hu Y et al. “Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program.” American Journal of Human Genetics 108(5):874-893 (2021)
Allele G
OR 0.31
p 3.0e-89
N 46,241
Large GWAS
multi-ancestry
Li J et al. “GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.” Human Molecular Genetics 22(7):1457-64 (2013)
Allele G
OR 0.23
p 5.0e-14
N 14,177
Large GWAS
multi-ancestry
Hodonsky CJ et al. “Genome-wide association study of red blood cell traits in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos.” Plos Genetics 13(4):e1006760 (2017)
Allele G
OR 0.34
p 1.0e-34
N 12,502
Large GWAS
Hispanic or Latin American
Sun P et al. “An Asian-specific MPL genetic variant alters JAK-STAT signaling and influences platelet count in the population.” Human Molecular Genetics 30(9):836-842 (2021)
Allele G
OR —
β 0.010
p 4.0e-12
N 5,257
Large GWAS
East Asian
Kullo IJ et al. “A genome-wide association study of red blood cell traits using the electronic medical record.” Plos One 5(9) (2010)
Allele G
OR 0.29
p 1.0e-12
N 3,012
Large GWAS
European
Red cell distribution width
Vuckovic D et al. “The Polygenic and Monogenic Basis of Blood Traits and Diseases.” Cell 182(5):1214-1231.e11 (2020)
Allele G
OR 0.11
p —
N 408,112
Large GWAS
European
Pilling LC et al. “Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers.” Plos One 12(9):e0185083 (2017)
Allele G
OR 0.12
p 1.0e-204
N 116,666
Large GWAS
European
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele G
OR 0.09
p 2.0e-40
N 110,610
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean
Jacobs BM et al. “Genetic architecture of routinely acquired blood tests in a British South Asian cohort.” Nature Communications 15(1):8929 (2024)
Allele G
OR 0.10
p 1.0e-48
N 38,000
Large GWAS
South Asian
Hu Y et al. “Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program.” American Journal of Human Genetics 108(5):874-893 (2021)
Allele G
OR 0.14
p 3.0e-29
N 28,982
Large GWAS
multi-ancestry
Chen MH et al. “Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.” Cell 182(5):1198-1213.e14 (2020)
Allele G
OR 0.11
p 2.0e-11
N 8,166
Large GWAS
South Asian
serum iron amount
Bell S et al. “A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.” Communications Biology 4(1):156 (2021)
Allele A
OR 0.17
p 1.0e-300
N 163,511
Meta-analysisLarge GWAS
European
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.15
p 3.0e-245
N 127,440
Major Consortium StudyLarge GWAS
multi-ancestry
Raffield LM et al. “Genome-wide association study of iron traits and relation to diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): potential genomic intersection of iron and glucose regulation?” Human Molecular Genetics 26(10):1966-1978 (2017)
Allele A
OR 0.32
p 5.0e-46
N 12,580
Large GWAS
Hispanic or Latin American
transferrin saturation measurement
Bell S et al. “A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.” Communications Biology 4(1):156 (2021)
Allele A
OR 0.17
p 1.0e-300
N 131,471
Meta-analysisLarge GWAS
European
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.16
p 2.0e-18
N 7,147
Major Consortium StudyLarge GWAS
Hispanic or Latin American
mean corpuscular hemoglobin concentration
Vuckovic D et al. “The Polygenic and Monogenic Basis of Blood Traits and Diseases.” Cell 182(5):1214-1231.e11 (2020)
Allele A
OR 0.09
p 7.0e-278
N 408,112
Large GWAS
European
Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele A
OR 0.07
p 4.0e-260
N 485,950
Large GWAS
multi-ancestry
Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele A
OR 0.07
p 1.0e-191
N 394,642
Large GWAS
European
Jee YH et al. “Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures.” Nature Communications 16(1):4935 (2025)
Allele A
OR 0.06
p 5.0e-49
N 153,950
Large GWAS
East Asian
Chen MH et al. “Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.” Cell 182(5):1198-1213.e14 (2020)
Allele A
OR 0.08
p 7.0e-93
N 126,151
Large GWAS
East Asian
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.17
p 3.0e-180
N 55,783
Major Consortium StudyLarge GWAS
Hispanic or Latin American
Hu Y et al. “Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program.” American Journal of Human Genetics 108(5):874-893 (2021)
Allele A
OR 0.07
p 3.0e-26
N 52,648
Large GWAS
multi-ancestry
Jacobs BM et al. “Genetic architecture of routinely acquired blood tests in a British South Asian cohort.” Nature Communications 15(1):8929 (2024)
Allele A
OR 0.13
p 3.0e-88
N 38,000
Large GWAS
South Asian
Hodonsky CJ et al. “Genome-wide association study of red blood cell traits in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos.” Plos Genetics 13(4):e1006760 (2017)
Allele A
OR 0.14
p 2.0e-16
N 12,502
Large GWAS
Hispanic or Latin American
HbA1c measurement
Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele G
OR 0.06
p 1.0e-212
N 394,642
Large GWAS
European
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele G
OR 0.05
p 1.0e-71
N 338,848
Major Consortium StudyLarge GWAS
European
Kim YJ et al. “The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians.” Nature Communications 13(1):6642 (2022)
Allele G
OR 0.05
p 2.0e-26
N 288,127
Large GWAS
East Asian
Chen J et al. “The trans-ancestral genomic architecture of glycemic traits.” Nature Genetics 53(6):840-860 (2021)
Allele G
OR —
β 0.019
p 1.0e-56
N 146,806
Large GWAS
European
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-51
N 144,060
Large GWAS
multi-ancestry
Soranzo N et al. “Common variants at 10 genomic loci influence hemoglobin A₁(C) levels via glycemic and nonglycemic pathways.” Diabetes 59(12):3229-39 (2010)
Allele G
OR 0.03
p 3.0e-14
N 46,368
Large GWAS
European
Downie CG et al. “Multi-ethnic GWAS and fine-mapping of glycaemic traits identify novel loci in the PAGE Study.” Diabetologia 65(3):477-489 (2022)
Allele G
OR 0.09
p 4.0e-18
N 23,357
Large GWAS
European, African American or Afro-Caribbean, Hispanic or Latin American, Asian unspecified
Moon JY et al. “A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A(1c) With Implications for Glycemic Status in U.S. Hispanics/Latinos.” Diabetes Care 42(9):1784-1791 (2019)
Allele G
OR 0.03
p 9.0e-10
N 9,636
Large GWAS
Hispanic or Latin American
hemoglobin A1 measurement
Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele G
OR 0.05
p 3.0e-146
N 415,403
Large GWAS
multi-ancestry
transferrin receptor protein 1 measurement
Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele G
OR 0.11
p 8.0e-142
N 47,745
Large GWAS
European
Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)
Allele G
OR 0.15
p 1.0e-29
N 10,708
Large GWAS
European
Allele G
OR —
β 0.200
p 2.0e-16
N 3,301
Large GWAS
European
iron biomarker measurement, serum iron amount
Benyamin B et al. “Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis.” Nature Communications 5:4926 (2014)
Allele A
OR 0.18
p 1.0e-139
N 23,986
Large GWAS
European
▶ClinVar annotation
Benign★★★☆
9 submitters2 publicationsIron-refractory iron deficiency anemia (IRIDA); Microcytic anemia; not specified
View on ClinVar →▶Research that mentions this SNP (2)
▶Patatin-like phospholipase domain-containing 3 I148M affects liver steatosis in patients with chronic hepatitis BReviewMauro Viganò et al.(2013)· Hepatology
Patatin-like phospholipase domain-containing 3 I148M affects liver steatosis in patients with chronic hepatitis B
ReviewMauro Viganò et al.(2013)· Hepatology
This comprehensive review examines the genetic background of nonalcoholic fatty liver disease (NAFLD), focusing on variants identified by genome-wide association studies (GWAS) and candidate gene studies. The most significant GWAS-identified variants are PNPLA3 rs738409 (I148M), which strongly associates with increased liver steatosis, fibrosis severity, and HCC risk (12-fold increased risk for homozygous carriers), and TM6SF2 rs58542926 (E167K), which increases NASH progression but reduces cardiovascular risk. The review also discusses numerous candidate genes involved in lipid and glucose metabolism and liver injury mechanisms.
Traits studied:Cardiovascular diseaseChronic kidney diseaseCirrhosisHepatic injuryHepatic steatosisHepatocellular carcinomaInsulin resistanceLipid metabolismLiver fibrosisMetabolic syndromeNecroinflammationNonalcoholic fatty liver disease (NAFLD)Nonalcoholic steatohepatitis (NASH)ObesityType 2 diabetes
▶Dissociation betweenAPOC3variants, hepatic triglyceride content and insulin resistanceReviewJulia Kozlitina et al.(2011)· Hepatology
Dissociation betweenAPOC3variants, hepatic triglyceride content and insulin resistance
ReviewJulia Kozlitina et al.(2011)· Hepatology
Comprehensive review of genetic background in nonalcoholic fatty liver disease (NAFLD). The PNPLA3 I148M variant (rs738409 C>G) is identified as a major genetic player strongly associated with increased liver fat content, NASH development, fibrosis severity, and HCC risk. The TM6SF2 E167K variant (rs58542926) emerges as another key contributor to NAFLD pathogenesis and disease progression. Multiple additional GWAS-identified variants and candidate genes are reviewed for their roles in NAFLD susceptibility and progression.
Traits studied:Alcoholic liver diseaseCardiovascular diseaseChronic kidney diseaseHCCHepatic steatosisHepatic triglyceridesHepatitis B steatosisHepatitis C progressionHepatocellular carcinomaInsulin resistanceLipid metabolismLiver fat contentLiver fibrosisNAFLDNASHNecroinflammationNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisType 2 diabetes
About TMPRSS6
The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
View all TMPRSS6 variants →Gene information from NCBI Gene. Variant classifications from ClinVar.
Community Wiki
No community notes yet for this variant. Sign in to start one.
Comments
Sign in to join the discussion.
Loading comments…