MBL2 R52C

(MBL2 Arg52Cys)

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).

Familial		No familial data.
		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).

Treatability		No recommendations for clinical intervention exist
		No recommendations for clinical intervention exist
Penetrance	1	Meningococcal infection is very rare
		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.)

recessive

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)

Publications

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	∞

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

Genomes

Other external references

dbSNP

rs5030737
www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi

GeneTests

GeneTests records for the MBL2 gene
Mannose-Binding Lectin Deficiency
www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MBL2

OMIM

Mannose-binding protein deficiency
www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=154545
Preterm delivery, susceptibility to, included
www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=154545

PolyPhen-2

Score: 0.999 (probably damaging)

Web search results (77 hits -- see all)

Mannose-Binding Lectin Gene Polymorphisms Are Associated with ...
... studied R52C and G54D polymorphisms of MBL2 gene and plasma MBL ... defective MBL protein (G54D or R52C) to gather the maximal number of women with these mutations. ...
jcem.endojournals.org/cgi/content/full/89/10/5081
Mannose-Binding Lectin Gene Polymorphisms Are Associated with ...
GDM during pregnancy, we studied R52C and G54D polymor- phisms of MBL2 gene and plasma MBL levels from 105 ... plasma MBL levels and carrying a MBL2 mutated allele could ...
jcem.endojournals.org/cgi/reprint/89/10/5081.pdf
Mannose-binding lectin gene polymorphisms are associated with ...
Mannose-binding lectin gene polymorphisms are associated with gestational diabetes mellitus. ... studied R52C and G54D polymorphisms of MBL2 gene and plasma MBL levels from 105 ...
www.ncbi.nlm.nih.gov/pubmed/15472209
LARGE-SCALE CANDIDATE GENE STUDY OF LEPROSY SUSCEPTIBILITY IN ...
The MBL2 R52C, MBL2 G54D, TNF + 70, and –857 variants were very rare in Karonga ... The polymorphisms ICAM1 K29M, MBL2 G57E, SLC11A1 exon 2 9-bp deletion, TGTG ...
www.ajtmh.org/cgi/content/full/71/3/330
Early Rise in Serum VEGF and PDGF Levels Predisposes Patients ...
... MBL2 gene and pathologic processes leading to enhanced production of VEGF and ... lectin (MBL2) compared with patients with MBL2 variant (R52C [D], rs5030737; ...
stroke.ahajournals.org/cgi/content/full/38/8/2247
Variants of the Mannose-Binding Lectin Gene in the Benin ...
The p.R52C allele was not found in this population. There was no difference in allele or genotype frequencies ... Indeed, the fact that MBL2 variant alleles confer selective ...
britannica.com/bps/additionalcontent/18/31655776/...
A Mannose-Binding Lectin-Defective Haplotype Is a Risk Factor ...
The R52C MBL2 mutation (allele D) alters the collagen-like domain of ... Otherwise, MBL2 HYPD haplotype may be in linkage disequilibrium with variants of ...
www.clinchem.org/cgi/content/short/52/8/1625?rss=1
A Novel Genotyping Assay for Mannose Binding Lectin (MBL2 ...
The MBL2 protein is encoded by the MBL2 gene localized on chromosome ... changes in exon 1 [R52C, G54D, G57E] result in decreased functionality of MBL2 . They are ...
innogenetics.com/bestanden/MBL2Poster_hepDART_US_2003(1).pdf

Other in silico analyses

NBLOSUM100 score = 8
GET-Evidence autoscore = 5

Edit history

Nov 29 2012 Genome Importing Robot added CGI sample GS01669-DNA_B03 from PGP sample 14427241 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01669-DNA_D02 from PGP sample 27316983 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01175-DNA_D01 from PGP sample 31286272 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01175-DNA_A04 from PGP sample 13272228 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01173-DNA_D06 from PGP sample 69488604 view
Mar 5 2012 Genome Importing Robot added CGI sample GS000005532 view
Jun 22 2011 Genome Importing Robot removed Stephen Quake view
Mar 29 2011 Genome Importing Robot added var-GS06985-1100-36-ASM view
Mar 29 2011 Genome Importing Robot added var-GS10851-1100-36-ASM view
Mar 19 2011 Madeleine Ball edited OR figures for Mannose-Binding Lectin Deficiency from article 10199352 view
Mar 19 2011 Madeleine Ball edited article 10199352 summary view
Mar 19 2011 Madeleine Ball edited article 7564730 summary view
Mar 19 2011 Madeleine Ball edited variant summary view
Mar 19 2011 Madeleine Ball edited variant summary view
Mar 12 2010 Madeleine Ball edited variant summary view
Feb 28 2010 Madeleine Ball edited variant summary view
Feb 28 2010 Madeleine Ball edited article 17872904 summary view
Feb 28 2010 Madeleine Ball edited variant summary view
Feb 28 2010 Madeleine Ball added article 17872904 view
Feb 26 2010 Genome Importing Robot added CGI sample GS00253-DNA_D01_200_37 view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball edited OR figures for Mannose-Binding Lectin Deficiency from article 7564730 view
Feb 23 2010 Madeleine Ball edited article 7564730 summary view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball edited OR figures for Mannose-Binding Lectin Deficiency from article 10199352 view
Feb 23 2010 Madeleine Ball added OR figures for Mannose-Binding Lectin Deficiency from article 10199352 view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball edited article 10199352 summary view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball added article 10199352 view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball edited OR figures for Mannose-Binding Lectin Deficiency from article 7564730 view
Feb 23 2010 Madeleine Ball added OR figures for Mannose-Binding Lectin Deficiency from article 7564730 view
Feb 23 2010 Madeleine Ball edited article 7564730 summary view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball edited article 7564730 summary view
Feb 23 2010 Madeleine Ball edited variant summary view
Feb 23 2010 Madeleine Ball added article 7564730 view
Feb 23 2010 Madeleine Ball removed article 8206524 view
Feb 23 2010 Madeleine Ball added article 8206524 view
Feb 9 2010 Abraham Rosenbaum edited variant summary view
Jan 5 2010 OMIM Importing Robot edited variant summary view
Dec 27 2009 Genome Importing Robot added Stephen Quake view
Dec 27 2009 Genome Importing Robot added CGI sample GS00253-DNA_F01_200_37 view
Dec 27 2009 Genome Importing Robot added variant view

MBL2 R52C - GET-Evidence