MBL2 R52C - GET-Evidence



(MBL2 Arg52Cys)

Short summary

This variant is associated with mannose binding protein deficiency which leads to impaired complement system immune response to mannose-rich pathogens. Patients homozygous for this allele or compound heterozygous are likely to have increased susceptibility to infection, but Hellemann et al. report heterosis for intensive care outcomes in heterozygous subjects. The wild-type version of this gene is known as variant allele A, while this is called variant allele D. See G54D (variant B) and G57E (variant C).

Variant evidence
Computational 2

Other mutations in the gene are associated with mannose binding protein deficiency, NBLOSUM = 5.

Functional -
Case/Control 3

significance = 0.008

See Hibberd ML et al. 1999 (10199352).


No familial data.

Clinical importance
Severity 2

Mixed effect: some reports indicate heterozygotes are more susceptible to infection, but another claims heterozygotes are less likely to have lethal outcomes in intensive care.

See Garred P et al. 1995 (7564730), Hibberd ML et al. 1999 (10199352), Hellemann D et al. 2007 (17872904).


No recommendations for clinical intervention exist

Penetrance 1

Meningococcal infection is very rare



Low clinical importance, Likely pathogenic

(The "low clinical importance, likely" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary


Total cases/controls case+ case– control+ control– p-value odds ratio
Mannose-Binding Lectin Deficiency
18 477 4 501 0.0021 4.726


Allele frequency

  • A @ chr10:54531242: 4.9% (523/10758) in EVS
  • A @ chr10:54201247: 4.0% (5/126) in GET-Evidence
  • Frequency shown in summary reports: 4.9% (523/10758)


Garred P, Madsen HO, Hofmann B, Svejgaard A. Increased frequency of homozygosity of abnormal mannan-binding-protein alleles in patients with suspected immunodeficiency. Lancet. 1995 Oct 7;346(8980):941-3. PubMed PMID: 7564730.

A study of patients with suspected immunodeficiency found a higher number of homozygous and compound heterozygous patients with abnormal mannan-binding protein (MBP) alleles (variants B, C, and D). In the case group of 229 patients, one patient was homozygous for D and five were compound heterozygous for B/D. No patients in the control population of 123 controls were homozygous or compound heterozygous for this allele.

Case+: 6, Case-: 223, Control+: 0, Control-: 123. Our 2-tailed Fisher’s Exact test finds this has a p=0.0953.

Cases/controls case+ case– control+ control– p-value odds ratio
Mannose-Binding Lectin Deficiency
6 223 0 123 0.0953


Hibberd ML, Sumiya M, Summerfield JA, Booy R, Levin M. Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group. Lancet. 1999 Mar 27;353(9158):1049-53. PubMed PMID: 10199352.

A study of the frequency of MBL2 variants was made comparing children meningococcal disease with controls in both a hospital-based study and community-based.

Of 266 patients and 382 controls in the combined data, none were homozygous for R52C. In the patients, 12 were compound heterozygous for R52C and either G54D or G57E. Of 382 controls, 4 were compound heterozygous for R52C and G54D or G57E. (Note: G57E was not checked in the community-based groups.)

Case+: 12, Case-: 254, Control+: 4, Control-: 378. Two-tailed Fisher’s Exact: p=0.0081

Cases/controls case+ case– control+ control– p-value odds ratio
Mannose-Binding Lectin Deficiency
12 254 4 378 0.0081 4.465


Hellemann D, Larsson A, Madsen HO, Bonde J, Jarløv JO, Wiis J, Faber T, Wetterslev J, Garred P. Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients. Hum Mol Genet. 2007 Dec 15;16(24):3071-80. Epub 2007 Sep 14. PubMed PMID: 17872904.



hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het A @ chr10:54531242


hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het A @ chr10:54531242


hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
het A @ chr10:54531242


hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
hom A @ chr10:54531242



huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
het A @ chr10:54531242


huD81F3D - CGI sample GS01173-DNA_D06 from PGP sample 69488604
het A @ chr10:54531242


huE80E3D - CGI sample GS00253-DNA_D01_200_37
het A @ chr10:54531242


GS06985 - var-GS06985-1100-36-ASM
het A @ chr10:54201248


GS10851 - var-GS10851-1100-36-ASM
het A @ chr10:54201248


Other external references

  • rs5030737
  • Score: 0.999 (probably damaging)

Other in silico analyses

  • NBLOSUM100 score = 8
  • GET-Evidence autoscore = 5

Edit history

Gene search

"GENE" or "GENE A123C":

Log in