The sodium/bicarbonate transporter plays a role in intracellular pH regulation in the body. Genetic studies show that some single nucleotide polymorphisms of human SLC4A7 gene are prevalent in alcohol abusers and control individuals in the European American population. In this study, we examined the physiological genomic effect of two SNPs rs3755652 (non-synonymous mutation) and rs3278 (synonymous mutation) on gene transcription and protein expression. These two sites are located upstream of exon 9 that is predicted to produce an N-terminally deleted transporter missing as much as one third of its amino acids. Analyzed by the transcription start site database and promoter prediction algorithm, multiple promoter sites were identified in intron 7. Deleting the promoter site located 0.25 kb upstream of exon 8 markedly decreased transcription activity, determined by luciferase reporter gene assays. The minor allele at rs3755652 increased luciferase activity by 80% compared to the major allele (p < 0.05; n = 6), while the minor allele at rs3278 increased luciferase activity by 20% (p < 0.05; n =6). In transfected HEK 293 cells, the N-terminally deleted transporter caused by alternative transcription had reduced membrane expression compared to the non-deleted canonical transporter. The deleted transporter had reduced colocalization with the endosomal marker Rab5 determined by double-label immunocytochemistry. In functional studies, the deleted transporter failed to raise intracellular pH from a CO2-induced acidification. The non-synonymous mutation E326K caused by rs3755652 produced negligible effect on the canonical transporter function. Our data suggest that rs3278 and rs3755652 enhance an alternative transcription in intron 7, leading to elevated production of the N-terminally deleted transporter with impaired expression and function.