UniProtKB/Swiss-Prot P20813: Variant p.Asp28Gly

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 28 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B The variants are classified into three categories: LP/P, LB/B and US.

• LP/P: likely pathogenic or pathogenic.
• LB/B: likely benign or benign.
• US: uncertain significance

Residue change: From Aspartate (D) to Glycine (G) at position 28 (D28G, p.Asp28Gly). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: Change from medium size and acidic (D) to glycine (G) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

• Lowest score: -4 (low probability of substitution).
• Highest score: 11 (high probability of substitution).

More information can be found on the following page
Polymorphism: Variability among CYP2B6 alleles may account for differential metabolism of endogenous steroids and endocannabinoids among individuals. For 16-alpha hydroxylation of testosterone, Vmax/Km values between alleles decrease in the following order: 2B6*1 > 2B6*6 > 2B6*9 > 2B7*4. For 16-beta hydroxylation of testosterone, 2B6*6 has the highest catalytic efficiency. For anandamide metabolism, 2B6*6 and 2B6*9 alleles show significantly lower rates of epoxidation (PubMed:21289075). Genetic variations in CYP2B6 are responsible for poor metabolism of efavirenz and, therefore, susceptibility to efavirenz toxicity in the central nervous system [MIM:614546]. Efavirenz is a non-nucleoside reverse transcriptase inhibitor frequently prescribed with 2 nucleoside reverse transcriptase inhibitors as initial therapy for human immunodeficiency virus (HIV) infection. Up to half of patients treated with efavirenz, experience side effects in the central nervous system, including dizziness, insomnia, impaired concentration, somnolence, and abnormal dreams. Severe depression, aggressive behavior, and paranoid or manic reactions may also occur, depending on efavirenz concentration in the plasma. Patients homozygous for 2B6*6 have significantly higher plasma efavirenz levels when compared to 2B6*6 heterozygous ones (PubMed:15194512, PubMed:15622315, PubMed:20639527). Additional information on the polymorphism described.
Other resources: Links to websites of interest for the variant.

• Variant rs33980385 [ dbSNP | Ensembl ]

Sequence information

Variant position: 28 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 491 The length of the canonical sequence.
Location on the sequence: FLALLTGLLLLLVQRHPNTH D RLPPGPRPLPLLGNLLQMDR The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Sequence annotation in neighborhood: The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

• Type: the type of sequence feature.
• Positions: endpoints of the sequence feature.
• Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 491	Cytochrome P450 2B6
Alternative sequence	1 – 57	MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRGLLKSFLR -> MRCMLTNSHPWCGCDWQ. In isoform 2.

Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS CYS-22; SER-26; GLY-28; SER-29; HIS-172; ARG-262; LYS-289; SER-306; THR-328 AND CYS-487;