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GC

From SNPedia
is agene
is mentioned by
Full namegroup-specific component (vitamin D binding protein)
EntrezGene2638
PheGenI2638
VariationViewer2638
ClinVarGC
GeneCardsGC
dbSNP2638
DiseasesGC
SADR2638
HugeNav2638
wikipediaGC
googleGC
gopubmedGC
EVSGC
HEFalMpGC
MyGene2GC
23andMeGC
UniProtP02774
EnsemblENSG00000145321
OMIM139200
# SNPs23
 Max MagnitudeChromosome positionSummary
rs1048885471,758,418
rs115556371,777,771
rs149171071,743,377
rs1684701571,773,107
rs1684702471,784,962
rs1746782571,739,800
rs22201671,769,258
rs222020071,770,555
rs22202971,779,245
rs22203571,755,957
rs22204071,751,215
rs22826791.571,742,666Less likely to suffer from vitamin D insufficiency
rs229884971,783,134
rs229885071,748,550
rs3733359071,784,057
rs375596771,743,681
rs4588071,752,606Affects vitamin D levels
rs4752071,756,849
rs70411.571,752,617
rs70511771,742,398
rs70512071,748,423
rs84299971,745,973
rs84301071,790,705

The GC gene located on chromosome 4 encodes human group-specific component, which is the major vitamin D-binding protein (VDBP) in plasma.

The presence of absence of two common variants in the GC gene, rs7041 and rs4588, lead to proteins with slightly different characteristics and possibly an effect on circulating vitamin D levels. The protein forms and the variant combination that leads to each are:


Note that some publications use rs2282679 as a proxy for rs4588; rs2282679(A) is typically co-inherited with rs4588(C) and vica-versa.

Since a person normally has two copies of the GC gene, this leads to six possible VDBP phenotypes (or haplotypes), each identifiable from the SNP genotypes as shown:


Does a person's GC (VDBP) haplotype influence the amount of vitamin D circulating in their blood, i.e. serum 25(OH)D levels? Yes, at least to some extent. One large study (11,000 people;[PMID 25993554OA-icon.png]) reported the following averages/haplotype, in nmol/L:

  • Highest vitamin D levels: haplotypes 1s/1s, 1s/1f and 1f/1f: 55.4 +/- 16.8, 53.3 +/- 17.2, 52.2 +/- 16.8, respectively
  • Intermediate vitamin D levels: haplotypes 1f/2 and 1s/2: 50.5 +/- 16.3 and 50.3 +/- 15.6, respectively
  • Lowest vitamin D levels: haplotype 2/2: 46.9 +/- 15.1


However, a more medically relevant question is: Does a person's VDBP haplotype influence their risk for any diseases, most particularly those that have previously been associated in at least some studies with vitamin D levels? A 2013 review of the literature concludes that while VDBP variants may influence immune modulation, disease associations reported to date are "difficult to interpret", and furthermore, "many of the association studies were insufficiently powered and failed to account for multiple comparisons".[PMID 23427793OA-icon.png]