Table 1.
Summary of APOBEC3 variations and their effects.
| Description | Allelic Frequency | Studied Populations and References | Effect | |||
|---|---|---|---|---|---|---|
| African | European | Asian | ||||
| APOBEC3A/B | ||||||
| rs12628403 (surrogate for ~30 kb APOBEC3B deletion) | ~30 kb deletion (Δ) of all APOBEC3B exons and introns except for exon 8; In-frame fusion to APOBEC3A. | n = 3394 Δ = 0.03 |
n = 20,404 Δ = 0.08 |
n = 116 Δ = 0.4 |
Indonesian PMID: 26305823 |
HIV-1 co-infections: Δ > reference |
| Moroccan PMID: 24010642 |
%Δ: HBV patients ~ healthy donors Progression to liver diseases: Δ > reference |
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| Western Indian PMID: 27522954 |
Risk of HIV-1 acquisition: Δ > reference | |||||
| European Americans and African Americans PMID: 19698078 |
HIV-1 acquisition, progression to AIDS, and viral set point: Δ/Δ > reference | |||||
| Japanese and Indian PMID: 20684727 |
%Δ: HIV-1 patients ~ healthy donors | |||||
| Japanese PMID: 19788695 |
%Δ: HBV patients ~ healthy donors Hypermutation context: Δ ~ reference |
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| Japanese PMID: 24667791 |
%Δ: HIV-1 patients ~ healthy donors HIV-1 co-infections: Δ ~ reference HIV-1 progression: Δ ~ reference |
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| APOBEC3C | ||||||
| rs112120857 | Missense (G > C / G > T) S188I |
n = 3574 G = 0.94 C = 0.00 T = 0.06 |
n = 37,290 G = 0.99962 C = 0.00003 T = 0.00035 |
n = 168 G = 1.00 C = 0.00 T = 0.00 |
PMIDs: 27732658, 30558640 | In vitro anti-HIV-1 activity: I > S |
| APOBEC3D | ||||||
| rs201709403 | Missense (A > G) T238A |
n = 2898 A = 1.00 G = 0.00 |
n = 9690 A = 1.00 G = 0.00 |
n = 112 A = 1.00 G = 0.00 |
Northern South African PMID: 30660178 |
%G (238A): HIV-1 patients > 1000 Genomes Africans |
| rs75858538 | Missense (C > T) R97C |
n = 5146 C = 0.98 T = 0.02 |
n = 180,258 C = 0.9999 T = 0.0001 |
n = 6364 C = 0.9998 T = 0.0002 |
Northern South African PMID: 30660178 |
%T (97C): HIV-1 patients > 1000 Genomes Africans |
| PMID: 23755966 | Protein expression: R ~ C Anti-HIV-1 activity: R > C Sensitivity to HIV-1 Vif: R ~ C Anti-Alu activity: R ~ C |
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| rs61748819 | Missense (G > A) R248K |
n = 3574 G = 0.91 A = 0.09 |
n = 32,834 G = 0.9997 A = 0.00034 |
n = 168 G = 1.00 A = 0.000 |
PMID: 23755966 | Protein expression: R > K Anti-HIV-1 activity: R > K Sensitivity to HIV-1 Vif: R ~ K Anti-Alu activity: R > K |
| APOBEC3F | ||||||
| rs2020390 | Missense (G > T) A108S |
n = 3512 G = 0.60 T = 0.40 |
n = 37,024 G = 0.49 T = 0.51 |
n = 168 G = 0.29 T = 0.71 |
Northern South African PMID: 30660178 |
%T (108S): HIV-1 patients > 1000 Genomes African populations |
| rs12157816 | Missense (A > G) Y307C |
n = 3574 A = 0.97 G = 0.03 |
n = 37,264 A = 0.9881 G = 0.0119 |
n = 168 A = 1.0 G = 0.0 |
Northern South African PMID: 30660178 |
%G (307C): HIV-1 patients > 1000 Genomes African populations |
| rs2076101 | Missense (G > A) V231I |
n = 8220 G = 0.73 A = 0.27 |
n = 256,418 G = 0.48 A = 0.52 |
n = 3812 G = 0.3 A = 0.7 |
European American and African American PMID: 26942578 |
Set-point viral load: I > V Progression to AIDS: I > V Pneumocystis pneumonia: I > V |
| PMID: 30448640 | HIV-1 restriction: V > I Protection against HIV-1 Vif: V > I Level of viral encapsidation: V > I |
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| APOBEC3FΔ2 | Isoform lacking exon 2 | PMID: 20624919 | Sensitivity to Vif: main isoform > APOBEC3FΔ2 Viral packaging: main isoform > APOBEC3FΔ2 Antiviral activity: main isoform > APOBEC3FΔ2 Deamination: main isoform > APOBEC3FΔ2 |
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| APOBEC3FΔ2-4 | Isoform lacking exons 2, 3 and 4 | PMID: 20624919 | Sensitivity to Vif: APOBEC3FΔ2–4 > main isoform Viral packaging: main isoform > APOBEC3FΔ2–4 Antiviral activity: Main isoform > APOBEC3FΔ2–4 deamination: main isoform > APOBEC3FΔ2–4 |
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| APOBEC3G | ||||||
| rs5757463 | -571G/C upstream (G > C) |
n = 106 G = 0.29 C = 0.71 |
n = 6564 G = 0.06 C = 0.94 |
n = 4 G = 0.0 C = 1.0 |
African Americans and European Americans PMID: 15452227 |
Susceptibility to HIV-1 infection: G ~ C |
| Brazilian PMID: 20874421 |
CD4 T-cell count: CC > CG and GG | |||||
| West Indian PMID: 29864532 |
%CG: HIV patients > healthy donors %(GC + CC): HIV patients > healthy donors |
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| Zimbabwean PMID: 27245545 |
Susceptibility to HIV-1 infection: G ~ C | |||||
| rs34550797 | -199G/A upstream (G > A) |
n = 2816 G = 0.995 A = 0.005 |
n = 7618 G = 0.9992 A = 0.0008 |
n = 108 G = 1.0 A = 0.0 |
African Americans and European Americans PMID: 15452227 |
Susceptibility to HIV-1 infection: G ~ A |
| rs5750743 | -90C/G upstream/5′UTR (C > G) |
n = 276 C = 1.00 G = 0.00 |
n = 5330 C = 0.54 G = 0.46 |
n = 8 C = 1.0 G = 0.0 |
African Americans and European Americans PMID: 15452227 |
Susceptibility to HIV-1 infection: C ~ G |
| West Indian PMID: 29864532 |
%CG: HIV-1 patients > healthy donors %GG: healthy donors > HIV patients |
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| Zimbabwean PMID: 27245545 |
Susceptibility to HIV-1 infection: C ~ G | |||||
| rs5757465 | Synonymous (T > C) F119F |
n = 11,214 T = 0.90 C = 0.10 |
n = 248,594 T = 0.56 C = 0.44 |
n = 3908 T = 0.76 C = 0.24 |
African Americans and European Americans PMID: 15452227 |
Susceptibility to HIV-1 infection: T ~ C |
| Diverse populations PMID: 23138837 |
HIV-1 disease progression: T > C CNS impairment: T > C |
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| rs3736685 | 197193T/C intron (T > C) |
n = 7982 T = 0.63 C = 0.37 |
n = 223,498 T = 0.97 C = 0.03 |
n = 3870 T = 0.92 C = 0.08 |
African Americans and European Americans PMID: 15452227 |
Susceptibility to HIV-1 infection: T ~ C |
| Zimbabwean PMID: 27245545 |
Susceptibility to HIV-1 infection: T ~ C | |||||
| rs2294367 | 199376G/C intron (C > G) |
n = 2036 C = 0.99 G = 0.01 |
n = 8254 C = 0.57 G = 0.43 |
n = 16 C = 0.75 G = 0.25 |
African Americans and European Americans PMID: 15452227 |
Susceptibility to HIV-1 infection: C ~ G Progression to AIDS: G > C |
| Zimbabwean PMID: 27245545 |
Susceptibility to HIV-1 infection: C ~ G | |||||
| rs8177832 | Missense (A > G) H186R |
n = 11,678 A = 0.66 G = 0.34 |
n = 252,598 A = 0.97 G = 0.03 |
n = 6820 A = 0.92 G = 0.08 |
African Americans and European Americans PMID: 15452227 |
Susceptibility to HIV-1 infection: H ~ R Rate of CD4 T cell loss: R > H Progression to AIDS: R > H |
| PMID: 27064995 | Antiviral activity: H > R Counteraction by Vif: H ~ R |
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| Diverse populations PMID: 23138837 |
HIV-1 disease progression: R > H CNS impairment: R > H |
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| South Africans PMID: 19996938 |
Viral load: R > H CD4 T cell count: H > R |
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| French PMID: 15609224 |
Progression to AIDS: H ~ R | |||||
| Caucasians PMID: 16988524 |
Progression to AIDS: H ~ R | |||||
| Argentinian PMID: 22145963 |
Progression to AIDS: H ~ R Viral G-to-A mutation: H ~ R |
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| Argentinian PMID: 21571098 |
HIV-1 transmission: H ~ R Progression to AIDS: H ~ R Viral G-to-A mutation: H ~ R |
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| Zimbabwean PMID: 27245545 |
Susceptibility to HIV-1 infection: H ~ R | |||||
| Morocco PMID: 24010642 |
Risk of HBV acquisition: H ~ R | |||||
| Burkina Fasoian PMID: 26741797 |
Protection against HIV-1 infection: GGT [rs6001417, rs8177832 (H186R), rs35228531] > Other haplotypes Risk of HIV-1 infection: GGC and CGC > Other haplotypes |
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| Burkina Fasoian PMID: 27449138 |
HIV-1/HBV co-infection rate: other haplotypes > GGT [rs6001417, rs8177832 (H186R), rs35228531] | |||||
| Western Indian PMID: 26853443 |
Risk of HIV-1 acquisition: H ~ R Progression to AIDS: H ~ R |
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| North Indian PMID: 18652534 |
Absence of 186R variant | |||||
| rs17496018 | C40693T Intron (C > T) |
n = 4296 C = 0.94 T = 0.06 |
n = 26,952 C = 0.93 T = 0.07 |
n = 128 C = 0.97 T = 0.03 |
Caucasians PMID: 16988524 |
Risk of HIV-1 infection: T > C |
| Argentinian PMID 22145963 |
Progression to AIDS: H ~ R Viral G > A mutation: H ~ R |
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| Argentinian PMID: 21571098 |
HIV-1 transmission: H ~ R Progression to AIDS: H ~ R Viral G-to-A mutation: H ~ R C > T polymorphism was associated with Vif variation. |
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| rs17496046 | Missense (C > G) Q275E |
n = 4374 C = 0.87 G = 0.13 |
n = 96,948 C = 0.93 G = 0.07 |
n = 3326 C = 0.97 G = 0.03 |
Caucasians PMID: 16988524 |
Risk of HIV-1 infection: C ~ G |
| Northern South African PMID: 30660178 |
% G (275E): HIV-1 patients > 1000 Genomes Africans | |||||
| rs6001417 | Intron (C > G) |
n = 2960 C = 0.63 G = 0.37 |
n = 16,474 C = 0.97 G = 0.03 |
n = 112 C = 0.94 G = 0.06 |
Burkina Fasoian PMID: 26741797 |
Protection against HIV-1 infection: GGT [rs6001417, rs8177832 (H186R), rs35228531] > Other haplotypes Risk of HIV-1 infection: GGC and CGC > Other haplotypes |
| Burkina Fasoian PMID: 27449138 |
HIV-1/HBV co-infection rate: other haplotypes > GGT [rs6001417, rs8177832 (H186R), rs35228531] | |||||
| rs35228531 | Downstream (C > T) |
n = 1564 C = 0.994 T = 0.006 |
n = 9814 C = 1.00 T = 0.00 |
n = 112 C = 1.00 T = 0.00 |
South African PMID: 19996938 |
Viral load: T > C CD4 T-cell count: C > T |
| Burkina Fasoian PMID: 26741797 |
Protection against HIV-1 infection: GGT [rs6001417, rs8177832 (H186R), rs35228531] > Other haplotypes Risk of HIV-1 infection: GGC and CGC > Other haplotypes |
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| Burkina Fasoian PMID: 27449138 |
HIV-1/HBV co-infection rate: C > T HIV-1/HBV co-infection rate: Other haplotypes > GGT [rs6001417, rs8177832 (H186R), rs35228531] |
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| rs5757467 | Intron (C > T) |
n = 2946 C = 0.31 T = 0.69 |
n = 15,414 C = 0.36 T = 0.64 |
n = 112 C = 0.21 T = 0.79 |
West Australian PMID: 16940537 |
HIV-1 hypermutation: C > T |
| APOBEC3H | ||||||
| rs139292 (Previously rs140936762) |
Indel (CAA/Δ) N15Δ |
n = 3506 Δ = 0.32 |
n = 20,264 Δ = 0.34 |
n = 168 Δ = 0.23 |
PMID: 32235597 | Antiviral activity: Reference > Δ |
| Northern South African PMID: 30660178 |
%Δ: HIV-1 patients >1000 Genomes Africans | |||||
| Japanese PMID: 25721876 |
Susceptibility to HIV-1 infection: Δ > reference | |||||
| Indian PMID: 26559750 |
Susceptibility to HIV-1 infection: Δ > reference | |||||
| rs139293 | Missense (G > T) R18L |
n = 3158 G = 0.96 T = 0.04 |
n = 36,146 G = 0.75 T = 0.25 |
n = 166 G = 0.92 T = 0.08 |
Northern South Africa PMID: 30660178 |
%T(18L): HIV-1 patients > 1000 Genomes Africans |
| rs139297 | Missense (G > C) G105R |
n = 1308 G = 0.66 C = 0.34 |
n = 35,022 G = 0.56 C = 0.44 |
n = 148 G = 0.89 C = 0.11 |
PMID: 32235597 | Ubiquitination: G (HapI) > R (HapII) |
| PMID: 20519396 | Antiviral activity: R (HapII) > G (HapI) HIV-1 encapsidation: R (HapII) ~ G (HapI) Protein expression: R (HapII) > G (HapI) Interaction with Gag: R (HapII) with nucleocapsid; G (HapI) with C-terminal of matrix and N-terminal of capsid |
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| Japanese PMID: 25721876 |
Susceptibility to HIV-1 infection: G (HapI) > R (HapII) Progression to AIDS: G (HapI) > R (HapII) |
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| Indian PMID: 26559750 |
%15Δ-105R: HIV-1 patients > healthy donors | |||||
| Diverse populations PMID: 21167246 |
Rate of HIV-1 GA-to-AA mutation: R (HapII) > G (HapI) | |||||
| rs139299 | Missense (G > C) K121D |
n = 3574 G = 0.24 C = 0.76 |
n = 37,158 G = 0.52 C = 0.48 |
n = 168 G = 0.72 C = 0.28 |
Diverse populations PMID: 21167246 |
Rate of HIV-1 GA-to-AA mutation: D (HapII) > K (HapI) |
| rs139298 | Missense (A > G) K121D |
n = 11,188 A = 0.21 G = 0.79 |
n = 252,052 A = 0.53 G = 0.47 |
n = 6744 A = 0.69 G = 0.31 |
Diverse populations PMID: 21167246 |
Rate of HIV-1 GA-to-AA mutation: D (HapII) > K (HapI) |
| rs139302 | Missense (G > C) E178D |
n = 3882 G = 0.26 C = 0.74 |
n = 97,472 G = 0.54 C = 0.46 |
n = 3326 G = 0.67 C = 0.33 |
PMID: 21167246 | Rate of HIV-1 GA-to-AA mutation: D (HapII) > E (HapI) |
| Northern South African PMID: 30660178 |
%C (178D): HIV-1 patients > 1000 Genomes Africans | |||||
| PMID: 27534815 | Cytosine deamination: E (HapV) > D (other haplotypes) Methyl cytosine deamination: D (HapII) >> E (other haplotypes) DNA binding: all haplotypes are the same. |
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| rs149229175 | Indel (CTC/Δ) intron |
n = 3410 Δ = 0.32 |
n = 18,142 Δ = 0.13 |
n = 164 Δ = 0.08 |
Diverse populations PMID: 30297863 |
%SV200: Δ > CTC |
| SV200, SV183, SV182, and SV154 | Splice variants with different C-terminals | Diverse populations PMID: 18945781 |
Viral restriction: SV200 (HapII) > other variants | |||
| Diverse populations PMID: 30297863 |
Antiviral activity: HapII-SV200 > SV182/183 Viral encapsidation: HapII-SV182/183 > SV200 Protease processing: only HapII SV200 L1 fragment in transcript: only HapII SV200 |
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| PMID: 27534815 | Cytosine and methyl cytosine deamination: HapI-SV182/183 > SV200 >> SV154 | |||||
| PMID: 31400856 | HBV restriction: HapII SV183 > other variants | |||||