Table 1.
Missense Variants Detected Across Study Participants in TFV- and FTC-Activating Kinases
| Racial and ethnic self-identification | Participant sex at birth | Gene | Protein position | Amino acid substitution (ref.>alt.) | SIFT prediction | PolyPhen prediction | Frequency |
|---|---|---|---|---|---|---|---|
| Asian | Male | DCK | 93 | S > F | Deleterious (0) | Probably_damaging (0.969) | 0.2% (1/498) |
| Black or African | Female | DCK | 151 | E>* | N/A | N/A | 0.6% (3/498) |
| Black or African | Female | DCK | 87 | E > D | Tolerated (0.61) | Benign (0) | 0.2% (1/498) |
| Multiracial | Male | DCK | 24 | I > V | Tolerated (0.65) | Benign (0.002) | 0.2% (1/498) |
| White | Male | DCK | 122 | P > S | Tolerated (0.06) | Probably_damaging (1) | 0.8% (4/498) |
| Other | Male | DCK | 122 | P > S | Tolerated (0.06) | Probably_damaging (1) | 0.2% (1/498) |
| Multiracial | Male | DCK | 122 | P > S | Tolerated (0.06) | Probably_damaging (1) | 0.2% (1/498) |
| Multiracial | Male | CMPK1 | 166 | R > S | Deleterious (0) | Probably_damaging (0.999) | 0.2% (1/498) |
| White | Male | CMPK1 | 80 | Q > H | Deleterious (0) | Benign (0.31) | 0.2% (1/498) |
| Other | Male | CMPK1 | 80 | Q > H | Deleterious (0) | Benign (0.31) | 0.2% (1/498) |
| Black or African | Female | CMPK1 | 80 | Q > H | Deleterious (0) | Benign (0.31) | 0.2% (1/498) |
| White | Male | CMPK1 | 183 | R > I | Deleterious (0) | Probably_damaging (0.998) | 0.2% (1/498) |
| Black or African | Male | CMPK1 | 74 | R > S | Deleterious (0.03) | Benign (0.374) | 0.2% (1/498) |
| Multiracial | Male | CMPK1 | 80 | Q > H | Deleterious (0) | Benign (0.31) | 0.2% (1/498) |
| White | Male | CMPK1 | 80 | Q > H | Deleterious (0) | Benign (0.31) | 0.6% (3/498) |
| White | Male | CMPK1 | 74 | R > S | Deleterious (0.03) | Benign (0.374) | 0.2% (1/498) |
| Other | Male | CMPK1 | 80 | Q > H | Deleterious (0) | Benign (0.31) | 0.4% (2/498) |
| Black or African | Male | CMPK1 | 80 | Q > H | Deleterious (0) | Benign (0.31) | 0.4% (2/498) |
| Multiracial | Male | CMPK1 | 107 | E > K | Deleterious (0.01) | Benign (0.023) | 0.2% (1/498) |
| Multiracial | Male | CMPK1 | 115 | N > S | Tolerated (0.84) | Benign (0.001) | 0.4% (2/498) |
| Black or African | Male | CMPK1 | 115 | N > S | Tolerated (0.84) | Benign (0.001) | 0.2% (1/498) |
| White | Male | CMPK1 | 115 | N > S | Tolerated (0.84) | Benign (0.001) | 0.2% (1/498) |
| White | Male | CMPK1 | 66 | A > S | Deleterious (0) | Possibly_damaging (0.901) | 1.0% (5/498) |
| Black or African | Male | CMPK1 | 66 | A > S | Deleterious (0) | Possibly_damaging (0.901) | 0.6% (3/498) |
| White | Female | CMPK1 | 66 | A > S | Deleterious (0) | Possibly_damaging (0.901) | 0.2% (1/498) |
| Black or African | Female | CMPK1 | 66 | A > S | Deleterious (0) | Possibly_damaging (0.901) | 0.2% (1/498) |
| Black or African | Female | CMPK1 | 74 | R > S | Deleterious (0.03) | Benign (0.374) | 0.4% (2/498) |
| White | Female | CMPK1 | 74 | R > S | Deleterious (0.03) | Benign (0.374) | 0.2% (1/498) |
| White | Male | PGK1 | 145 | A > S | Tolerated (0.16) | Benign (0.023) | 0.2% (1/498) |
| White | Female | PGK1 | 145 | A > S | Tolerated (0.16) | Benign (0.023) | 0.2% (1/498) |
| Multiracial | Male | PGK1 | 61 | M > I | Tolerated (0.1) | Benign (0.062) | 0.2% (1/498) |
| White | Male | AK2 | 157 | N > S | Tolerated (0.15) | Benign (0.001) | 0.2% (1/498) |
| White | Male | AK2 | 17 | R > G | Deleterious (0) | Possibly_damaging (0.514) | 0.2% (1/498) |
| White | Male | AK2 | 209 | A > T | Tolerated (0.5) | Benign (0.056) | 0.4% (2/498) |
| Native Hawaiian or Pacific Islander | Male | AK2 | 129 | S > N | Tolerated (0.49) | Benign (0.001) | 0.2% (1/498) |
| White | Male | AK2 | 129 | S > N | Tolerated (0.49) | Benign (0.001) | 0.2% (1/498) |
| White | Male | CKM | 35 | T > I | Deleterious (0) | Probably_damaging (0.914) | 0.2% (1/498) |
| Multiracial | Male | CKM | 251 | R > P | Tolerated (0.09) | Benign (0.129) | 0.2% (1/498) |
| White | Male | CKM | 83 | E > G | Deleterious (0.01) | Possibly_damaging (0.467) | 0.4% (2/498) |
| Black or African | Male | CKM | 83 | E > G | Deleterious (0.01) | Possibly_damaging (0.467) | 0.2% (1/498) |
| Multiracial | Male | CKM | 43 | R > Q | Tolerated (0.07) | Benign (0.288) | 0.2% (1/498) |
| White | Female | CKM | 4 | G > C | Tolerated (0.1) | Probably_damaging (0.998) | 0.2% (1/498) |
| Black or African | Female | CKM | 52 | T > N | Deleterious (0.04) | Probably_damaging (0.972) | 0.2% (1/498) |
| Multiracial | Male | PKLR | 272 | L > V | Deleterious (0) | Probably_damaging (0.974) | 0.2% (1/498) |
| White | Male | PKLR | 569 | R > Q | Deleterious (0.04) | Benign (0.399) | 0.2% (1/498) |
| Black or African | Male | PKLR | 569 | R > Q | Deleterious (0.04) | Benign (0.399) | 0.2% (1/498) |
| Black or African | Male | PKLR | 272 | L > V | Deleterious (0) | Probably_damaging (0.974) | 0.2% (1/498) |
| White | Male | PKLR | 486 | R > W | Deleterious (0) | Probably_damaging (0.996) | 0.2% (1/498) |
| Black or African | Male | PKLR | 406 | G > W | Deleterious (0) | Probably_damaging (1) | 0.2% (1/498) |
| White | Male | PKLR | 133 | N > K | Deleterious (0.03) | Probably_damaging (0.999) | 0.2% (1/498) |
| White | Male | PKM | 178 | L > I | N/A | N/A | 0.4% (2/498) |
| White | Male | PKM | 5 | S>* | N/A | N/A | 0.6% (3/498) |
| White | Male | PKM | 36 | T > S | N/A | N/A | 0.2% (1/498) |
| White | Male | PKM | 132 | V > A | N/A | N/A | 0.2% (1/498) |
| White | Male | PKM | 36 | T > S | N/A | N/A | 0.2% (1/498) |
| White | Female | PKM | 229 | N > S | N/A | N/A | 0.2% (1/498) |
The demographic information for the participants carrying each genetic variant detected are shown for all of the individual kinase-encoding genes that were investigated. The frequency reflects the number of individuals sharing the same racial/ethnic self-identification and sex assigned at birth who were found to carry the indicated variant. The functional consequence of resulting amino acid exchanges were predicted using SIFT and PolyPhen in silico tools. A SIFT score <0.05 was suggestive of a damaging amino acid substitution and >0.05 a tolerated substitution. A PolyPhen score >0.908 was suggestive of a probably damaging, 0.447–0.908 a possibly damaging, or <0.447 a benign amino acid substitution. N/A indicates that in silico tools were not able to predict a functional impact of the amino acid substitution.