rs17563

This is a variant in the BMP4 gene that changes a valine to an alanine.

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GWAS Catalog Trait Associations (7)

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

heel bone mineral density

Morris JA et al. “An atlas of genetic influences on osteoporosis in humans and mice.” Nature Genetics 51(2):258-266 (2019)
Allele A
OR 0.03
p 2.0e-42
N 426,824
Large GWAS
European

tooth eruption

Fatemifar G et al. “Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances.” Human Molecular Genetics 22(18):3807-17 (2013)
Allele G
OR 0.24
p 9.0e-17
N 11,118
Large GWAS
European

glomerular filtration rate

Liu H et al. “Epigenomic and transcriptomic analyses define core cell types, genes and targetable mechanisms for kidney disease.” Nature Genetics 54(7):950-962 (2022)
Allele G
OR 7.87
p 4.0e-15
N 1,508,659
Large GWAS
multi-ancestry
Stanzick KJ et al. “Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals.” Nature Communications 12(1):4350 (2021)
Allele G
OR 0.00
p 6.0e-10
N 1,201,930
Large GWAS
multi-ancestry

cortical thickness

Shadrin AA et al. “Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology.” Neuroimage 244:118603 (2021)
Allele A
OR —
p 2.0e-10
N 35,657
Large GWAS
European
van der Meer D et al. “The genetic architecture of human cortical folding.” Science Advances 7(51):eabj9446 (2021)
Allele A
OR 6.22
p 5.0e-10
N 33,748
Large GWAS
European

blood urea nitrogen amount

Stanzick KJ et al. “Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals.” Nature Communications 12(1):4350 (2021)
Allele G
OR 0.00
p 2.0e-9
N 852,680
Large GWAS
European

refractive error

Guggenheim JA et al. “Whole exome sequence analysis in 51 624 participants identifies novel genes and variants associated with refractive error and myopia.” Human Molecular Genetics 31(11):1909-1919 (2022)
Allele A
OR 0.04
p 2.0e-9
N 51,624
Large GWAS
European
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ClinVar annotation

Likely Benign★★★☆
12 submitters7 publications

Cleft Lip +/- Cleft Palate, Autosomal Dominant; Microphthalmia with brain and digit anomalies (MCOPS6); Orofacial cleft 11 (OFC11); not specified

View on ClinVar →
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Research that mentions this SNP (4)

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Understanding the participation of GREM1 polymorphisms in nonsyndromic cleft lip with or without cleft palate in the Brazilian population
AssociationN=1,955Camila Sane Viena et al.(2019)· Birth Defects Research

Multicenter case-control study of 1,955 Brazilian individuals examining the WNT5A rs566926 polymorphism in non-syndromic orofacial cleft (NSOC). The C allele was significantly associated with cleft lip only (NSCLO), increasing risk by 32% (OR: 1.32, 95% CI: 1.04-1.67, p=0.01). Multiple epistatic interactions were detected between rs566926 and variants in BMP4, GREM1, and FGFR1, with strongest effects in individuals of European ancestry.

Traits studied:Non-syndromic cleft lip onlyNon-syndromic cleft lip with or without cleft palateNon-syndromic cleft palate onlyNon-syndromic orofacial cleft
PubMedDOIMetascience Observatory
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Common Variations in BMP4 Confer Genetic Susceptibility to Sporadic Congenital Heart Disease in a Han Chinese Population
AssociationN=1,419Bo Qian et al.(2014)· Pediatric Cardiology

This case-control study of 575 Chinese CHD patients and 844 controls identified that BMP4 rs762642 is associated with increased congenital heart disease susceptibility (ORadd 1.22, 95% CI 1.04-1.43, P = 0.02). Stratified analysis showed the rs762642 polymorphism was significantly associated with atrial septal defect (ORadd 1.33, 95% CI 1.04-1.72, P = 0.03) and also with ventricular septal defect in co-dominant models. This is the first study demonstrating that BMP4 common variants contribute to sporadic CHD risk in a Chinese population.

Traits studied:Atrial septal defectCongenital heart diseaseVentricular septal defect
PubMedDOIMetascience Observatory
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The CRISPLD2 gene is involved in cleft lip and/or cleft palate in a Chinese population
ReviewXi Shen et al.(2011)· Birth Defects Research Part A: Clinical and Molecular Teratology

This narrative review examines the genetics of cleft lip with or without cleft palate (CLP) and cleft palate only (CP), which affect approximately 1 in 700 to 1 in 2,000 births worldwide. The paper discusses over 300 genes implicated in palatal fusion, with recent discoveries including variants in VAX1, GLI2, ARHGAP29, CRISPLD2, COL21A1, TBX22, ROCK1, GRHL3, and HYAL2. Key rsID associations identified include rs3821949 (MSX1), rs12532 (MSX1), rs17563 (BMP4), rs4783099, rs1546124, and rs16974880. The review emphasizes the multifactorial etiology involving both genetic and environmental factors in embryonic facial development.

Traits studied:AnkyloglossiaCleft lip with or without cleft palate (CLP)Cleft palate only (CP)Corpus callosum agenesisHypodontiaMicrophthalmiaNon-syndromic cleft lip and palateSyndromic cleftsTooth agenesisVan der Woude Syndrome
PubMedDOIMetascience Observatory
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A predicted functional single-nucleotide polymorphism of bone morphogenetic protein-4 gene affects mRNA expression and shows a significant association with cutaneous melanoma in Southern Italian population
AssociationN=557Mario Capasso et al.(2009)· Journal of Cancer Research and Clinical Oncology

A case-control study of 215 melanoma patients and 342 controls from Southern Italy found that the BMP4 gene SNP rs17563 (6007 C/T, Val152Ala) was significantly associated with cutaneous melanoma risk (OR: 1.39, 95% CI: 1.09-1.78, P = 0.007). The T-allele was more frequent in cases and was associated with higher BMP4 mRNA expression in lymphoblastoid cell lines. A second SNP, rs4898820 (-3445 T/G), showed no significant association.

Traits studied:Cutaneous melanoma
PubMedDOIMetascience Observatory

About BMP4

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates heart development and adipogenesis. Mutations in this gene are associated with orofacial cleft and microphthalmia in human patients. The encoded protein may also be involved in the pathology of multiple cardiovascular diseases and human cancers. [provided by RefSeq, Jul 2016]

View all BMP4 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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