CCR5 C101X - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

CCR5 C101X

(CCR5 Cys101Stop)


Short summary

The CCR5-C101X allele confers resistance to infection by CCR5-dependent HIV in a recessive manner. Compound heterozygotes with the CCR5-delta32 allele are resistant.

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr3:46414696: 0.1% (10/10750) in EVS
  • Frequency shown in summary reports: 0.1% (10/10750)

Publications
 

Quillent C, Oberlin E, Braun J, Rousset D, Gonzalez-Canali G, M├ętais P, Montagnier L, Virelizier JL, Arenzana-Seisdedos F, Beretta A. HIV-1-resistance phenotype conferred by combination of two separate inherited mutations of CCR5 gene. Lancet. 1998 Jan 3;351(9095):14-8. PubMed PMID: 9433423.

We assessed the susceptibility of PBMC to in-vitro infection by HIV-1 isolates that use the CCR5 as the major coreceptor for viral entry in 18 men who had frequent unprotected sexual intercourse with a seropositive partner. We also did genotypic analysis of CCR5 alleles. One of the 18 exposed but uninfected men (who we refer to as ExU2) showed total resistance to in-vitro infection by CCR5-dependent viruses, and was found to carry a CCR5 delta 32 allele and a single point mutation (T—>A) at position 303 on the other allele. To find out whether the CCR5 mutation was restricted to ExU2’s family or existed in the general population, we did genetic analyses of the CCR5 genotype in ExU2’s father and sister and also in 209 healthy blood donors who were not exposed to HIV-1.

The m303 mutation found in ExU2 introduced a premature stop codon and prevented the expression of a functional coreceptor. The family studies revealed that the m303 mutant allele was inherited as a single mendelian trait. Genotype analysis showed that three of the 209 healthy blood donors were heterozygous for the mutant allele.

Genomes
 

Other external references
 

Other in silico analyses
 

  • NBLOSUM100 score = 10
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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