MBL2 G54D

(MBL2 Gly54Asp)

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 B. See R52C (variant D) and G57E (variant C).

Variant evidence
Computational	2	Other mutations in the gene are associated with disease, NBLOSUM = 3 See Garred P et al. 1995 (7564730), Hibberd ML et al. 1999 (10199352).

Functional	-

Case/Control	5	Combined data has very low p-value See Garred P et al. 1995 (7564730), Hibberd ML et al. 1999 (10199352).

Familial		No familial data. See unpublished research (below).
		No familial data. See unpublished research (below).

Clinical importance
Severity	2	Increased susceptibility to infection.
		Increased susceptibility to infection.
Treatability	2	No standard treatment. Behavioral changes and increased surveillance may address increased susceptibility to disease.

Penetrance	3	Assuming the suspected immunodeficiency studied by Hibberd et al. has an incidence of around 1 in 200 to 1 in 500, their data is consistent with moderate penetrance (only one individual in 123 controls homozygous for the variant). See Hibberd ML et al. 1999 (10199352).

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	39	454	6	500	0.0000	7.159

Allele frequency

T @ chr10:54531235: 10.4% (1118/10758) in EVS
T @ chr10:54201240: 7.0% (9/128) in GET-Evidence
Frequency shown in summary reports: 10.4% (1118/10758)

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 227 patients, 12 patients were homozygous for B and 6 were compound heterozygous for B/C or B/D. One patient in the control population of 123 patients was homozygous or compound heterozygous.

Cases/controls	case+	case–	control+	control–	p-value	odds ratio
Mannose-Binding Lectin Deficiency	18	209	1	123	0.0050	10.593

A study of the frequency of MBL2 variants was made comparing children meningococcal disease with controls. Of 266 patients, 8 were homozygous for G54D and 13 were compound heterozygous for G54D and either R52C or G57E. Of 382 controls, 1 was homozygous and 4 were compound heterozygous for G54D.

Cases/controls	case+	case–	control+	control–	p-value	odds ratio
Mannose-Binding Lectin Deficiency	21	245	5	377	0.0000	6.463

Genomes

Other external references

dbSNP

rs1800450
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
Gestational diabetes mellitus, susceptibility to, included
www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=154545

PolyPhen-2

Score: 0.994 (probably damaging)

Web search results (77 hits -- see all)

Mannose-Binding Lectin Gene Polymorphisms Are Associated with ...
GDM patients who carried the G54D mutation required insulin therapy more ... G54D is by far the most frequent mutation for MBL2 in the European population, ...
jcem.endojournals.org/cgi/content/full/89/10/5081
Mannose-Binding Lectin Gene Polymorphisms Are Associated with ...
3T) and G54D (G3A), the two most frequently found. MBL2 polymorphisms in the European ... with the G54D mutant allele for MBL2 have a higher risk for ...
jcem.endojournals.org/cgi/reprint/89/10/5081.pdf
Mannose-binding lectin gene polymorphisms are associated with ...
... studied R52C and G54D polymorphisms of MBL2 gene and plasma MBL ... In conclusion, pregnant women bearing the G54D MBL allele have a greater risk for developing GDM and having ...
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
Coding single-nucleotide polymorphisms associated with ...
Coding single-nucleotide polymorphisms associated with complex vs. Mendelian ... Another example is the MBL2 G54D variant associated with systemic lupus ...
www.ncbi.nlm.nih.gov/pmc/articles/PMC523449/?tool=pubmed
Early Rise in Serum VEGF and PDGF Levels Predisposes Patients ...
... mannose-binding lectin (MBL2) than in with patients with MBL2 variant genotypes. ... MBL2 gene and pathologic processes leading to enhanced production of VEGF and ...
stroke.ahajournals.org/cgi/content/full/38/8/2247
Variants of the Mannose-Binding Lectin Gene in the Benin ...
Explore the updated online encyclopedia from Encyclopaedia Britannica with hundreds of thousands of articles, biographies, videos, images, and web sites.
britannica.com/bps/additionalcontent/18/31655776/...
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 = 4
GET-Evidence autoscore = 4

Edit history

Nov 29 2012 Genome Importing Robot added CGI sample GS01175-DNA_B04 from PGP sample 88590671 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01173-DNA_H06 from PGP sample 91708424 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01173-DNA_B07 from PGP sample 61499538 view
Jun 23 2011 Genome Importing Robot removed [NA07022] view
Jun 22 2011 Genome Importing Robot removed Desmond Tutu view
Jun 22 2011 Genome Importing Robot removed [snp-2] view
Apr 18 2011 Madeleine Ball edited article 17872904 summary view
Apr 18 2011 Madeleine Ball edited variant summary view
Apr 18 2011 Madeleine Ball added article 17872904 view
Mar 29 2011 Genome Importing Robot added var-GS19703-1100-36-ASM view
Mar 29 2011 Genome Importing Robot added var-GS19670-1100-36-ASM view
Mar 29 2011 Genome Importing Robot added var-GS19648-1100-36-ASM view
Mar 13 2010 Madeleine Ball edited variant summary view
Mar 13 2010 Madeleine Ball edited variant summary view
Mar 13 2010 Madeleine Ball edited variant summary view
Mar 13 2010 Madeleine Ball edited variant summary view
Feb 28 2010 Madeleine Ball edited variant summary view
Feb 28 2010 Madeleine Ball edited variant summary view
Feb 28 2010 Madeleine Ball edited variant summary view
Feb 28 2010 Madeleine Ball edited variant summary view
Feb 27 2010 Genome Importing Robot added Desmond Tutu 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 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 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 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 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 [NA07022] view
Dec 27 2009 Genome Importing Robot added [snp-2] view
Dec 27 2009 Genome Importing Robot added CGI sample GS00253-DNA_A02_200_37 view
Dec 27 2009 Genome Importing Robot added variant view

MBL2 G54D - GET-Evidence