Gene

The Official Name of the Gene is BCL2, Apoptosis Regulator (1)

The Gene ID provided by Entrez is 596 (2)

The Official Symbol of the Gene is BCL2 (1)

BCL2 exists in 2 Known Isoforms, Alpha and Beta and Has the Following Genomic Sequence Which Was Found Using Entrez Gene

• NCBI RefSeq Databank Genomic Accession Number: NG_009361.1 (3)
• NCBI RefSeq Databank mRNA Accession Number(Alpha): NM_000633.2 (4)
• NCBI RefSeq Databank Protein Accession Number(Alpha): NP_000624.2 (5)
• NCBI RefSeq Databank mRNA Accession Number(Beta): NM_000657.2 (6)
• NCBI RefSeq Databank Protein Accession Number(Beta): NP_000648.2 (7)

It should also be noted that indicated by NCBI there exists two other predicted isoforms which were predicted by automated computational analysis derived from the genomic sequence NC_000018.10 (GRCh38.p12 Primary Assembly) and annotated using gene prediction method: Gnomon, supported by mRNA and EST evidence (2).

• Isoform X1: Protein: XP_011524437.1, Genomic: NC_000018.10, Nucleotide: XM_011526135.3
• Isoform X2: Protein: XP_016881406.1 , Genomic: NC_000018.10, Nucleotide: XM_017025917.2

The Gene is located at 18q21.33 (8)

According to NCBI(2) and Ensembl(8,9), BCL2( NG_009361.1) is 203,035 bp long and has 4 transcript variant possibilities with two isoforms being protein coding, Isoform Alpha and Isoform Beta. The Beta transcript variant is a result of the differentiation in the 3' UTR and coding region compared to the alpha variant alpha resulting in a shorter isoform(2).

Alpha

Transcript Alpha (NM_000633.2) contains a longer transcript consisting of 6492bp containing 3 exons and 2 introns compared to isoform Beta's 2 exons and 1 intron. Each isoform shares a noncoding exon that runs from 5001bp to 5217bp while also containing similar second exons that both start at 5429bp but differ in length with Alpha terminating at 6299bp and Beta terminating at 6427bp. This alpha variant has a third exon which extends from 195622bp to 201035bp, most of which consists of the 3' UTR which starts at 195757bp resulting in an exon only 135bp in length. This differentiation in 3' UTR is what leads to the difference in transcript length between the coding isoforms(4). Within the 3'UTR is contained the validated poly A signal of "TATAAA" confirmed by ensembl(8) and located at 20101bp2 to 201017bp; 18bp downstream from the poly-A site at 201035bp. This results in a coding sequence of 718bp which is translated into a polypeptide 239 amino acids in length(4).

Beta

Transcript Beta (NM_000657.2) is a shorter transcript as a result of it's varied 3' UTR region. The transcript is 1207bp in length containing the same non-coding exon 1 as transcript alpha along with the same intron ranging from 5208bp to 5428bp since both have their second startinng at 5429bp. However, beta's second exon is longer extending to 6427bp resulting in a 998bp longer exon. However, Beta contains a 3' UTR starting at 6333bp housing an ensembl(9) validated poly A signal coded by "AATAAA" ranging from 6406bp to 6412bp located 14bp downstream from its poly A site which NCBI indicates is 1 bp prior to the transcript termination at 6427bp. These variations result in a coding sequence of 620bp in length which is translated to a 205 amino acid long polypeptide(6).

The variations in transcript 3" UTR regions is what results in the differentiation in coding sequences and transcript lengths. Variant Alpha contains a 3' UTR 5278bp in length compared to variant alphas which is only 94bp. This much larger 3' UTR implicates that variant alpha is more strictly regulated from the bind of cis- and trans- regulatory elements which play a role in expression of the gene. The extended 3' UTR is due to the additional exon contained in transcript alpha which ranges from 195622bp to 201035bp(2). While the actual processed mRNA transcripts may differ in length greatly, 6492bp to 1207bp, the actual coding sequences that the polypeptides are derived from are much more comparable at 718bp to 620bp. This results in polypeptides differing by 24 amino acids in length.(8,9)

BCL2 is found to be broadly expressed in both the thyroid and spleen. Out of 4 samples of cells isolated from the human spleen, the average expression was 21.854 RPKM (± 1.733). This is followed by the spleen which carries an expression value of 9.107 RPKM (± .807) from 4 samples isolated from humans. Due to it's actions in blocking cellular apoptosis by coding an integral outer mitochondrial membrane protein that mainly targets lymphocytes, it is expected to have it's highest expression in organs that interact with the lymphatic system. The thyroid has overwhelmingly the highest expression rate which can be linked to its relation to the lymphatic drainage which frequently passes through the prelaryngeal lymph nodes, and the pretracheal and paratracheal lymph nodes. High expression in the spleen is expected, due to its major role played in the lymphatic system, mainly it's composition of white pulp which house lymphoid follicles which are rich in B-lymphocytes. Other noticeable expression levels were found from cells of the ovary, lymph nodes, fat, and endometrium with the lymph node cells being the most accurate from being isolated from a total of 5 samples, compared to only 2 of the ovary, and 3 of fat and endometrium.(2)