CKLF like MARVEL transmembrane domain-containing 4
CKLF like MARVEL transmembrane domain-containing 4 (i.e. CMTM4), formerly termed chemokine-like factor superfamily 4 (i.e. CKLFSF4), has 3 known isoforms, the CMTM4-v1 to CMTM4-v3 proteins. Protein isoforms are variant products that are made by alternative splicing of a single gene. The gene for the CMTM4 isoforms is located in band 22 on the long (i.e. "q") arm of chromosome 16. The "CMTM4" gene and its 3 isoform proteins belong to the CKLF-like MARVEL transmembrane domain-containing family of structurally and functionally related genes and proteins. CMTM4-v1 and  CMTM4-v2 are widely expressed in multiple human tissue while CMTM4-v3 has been detected only in the kidney and placental tissues. The Cancer Genome Atlas indicates that CMTM4 protein is frequently reduced in colorectal cancer and its high expression is associated with increased overall survival rates in individuals with this cancer. CMTM4 protein was also found to be greatly reduced in the tissues of clear cell renal cell carcinoma compared to nearby normal renal (i.e. kidney) tissues and the forced overexpression of this protein in 786-O cells (a renal cancer cell line) inhibited their growth in culture as  well as in a xenograph nude mouse model. Finally, CMTM4 protein levels were lower in several brain cancers, such as glioblastomas, neuroblastomas, and medulloblastomas, compared to their levels in nearby normal, non-tumorous brain tissues. These studies suggest CMTM4 may act to suppress these malignancies. Further studies are needed to confirm these relationships and determine if CMTM4 protein can be used as a marker for the severity of these malignancies and/or serve as a therapeutic target for treating them.