CCR5 S185Shift - GET-Evidence

Curation:
Currentness:

CCR5 S185Shift

(CCR5 185delSinsShift)


Short summary

Also known as CCR5-delta32, this variant is associated with resistance to many strains of HIV (but not all strains, only strains that use target the CCR5 protein). Heterozygotes are reported to have slower HIV progression, and homozygotes are very resistant to being infected by these strains.

Variant evidence
Computational 3

Highly disruptive effect on gene, gene product is known to be involved in HIV infection for some strains

Functional 1

PBMCs resistant to infection

Case/Control 4

See Samson M et al. 1996 (8751444).

Familial -
 
Clinical importance
Severity 4

Evaluated as the risk/effect of HIV infection

Treatability 4
Penetrance 1

Penetrance is estimated assuming low HIV infection rate (< 1%) — this variant would confer less than 1% decreased attributable risk of HIV infection.

 

Impact

Low clinical importance, protective

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

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Allele frequency

  • - @ chr3:46389950: 4.8% (6/126) in GET-Evidence
  • Frequency shown in summary reports: 4.8% (6/126)

Publications
 

Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996 Aug 22;382(6593):722-5. PubMed PMID: 8751444.

Genotype frequencies: seropositive (cases): /: 645, +/del32: 78, del32/del32: 0. seronegative (controls): /: 582, +/del32: 114, del32/del32: 8.

Pooling by recessive hypothesis, case+: 0, case-: 723, control+: 8, control-: 696. This has p = 0.003 using Fisher’s Exact Test.

Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittinghoff E, Gomperts E, Donfield S, Vlahov D, Kaslow R, Saah A, Rinaldo C, Detels R, O'Brien SJ. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science. 1996 Sep 27;273(5283):1856-62. Erratum in: Science 1996 Nov 15;274(5290):1069. PubMed PMID: 8791590.

 

Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K, Kunstman K, Erickson D, Dragon E, Landau NR, Phair J, Ho DD, Koup RA. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996 Nov;2(11):1240-3. PubMed PMID: 8898752.

 

Genomes
 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het - @ chr3:46414944

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
hom - @ chr3:46414944

 

 

 

 

 

 

 

 

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het - @ chr3:46414944

 

GS06985 - var-GS06985-1100-36-ASM
het - @ chr3:46389951

 

GS10851 - var-GS10851-1100-36-ASM
het - @ chr3:46389951

 

Other external references
 

    dbSNP
  • rs333
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi

Other in silico analyses
 

  • NBLOSUM100 score = 4
  • GET-Evidence autoscore = 2

Edit history
 

Gene search

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