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Official Full Name
hyaluronan and proteoglycan link protein 3
This gene belongs to the hyaluronan and proteoglycan binding link protein gene family. The protein encoded by this gene may function in hyaluronic acid binding and cell adhesion.
HAPLN3; hyaluronan and proteoglycan link protein 3; EXLD1, extracellular link domain containing, 1; HsT19883; EXLD1; Extracellular link domain containing, 1; zgc:85609

Recent Research Progress

HAPLN3, a link protein, belonging to the hyaluronan and proteoglycan link protein family, functions in the aggregation of proteoglycan with hyaluronic acid and cell adhesion. In the HAPLN family, HAPLN3 is the most abundant and widely expressed in most tissue, including that of the mammary gland, ovary, lymph node, spleen, thymus, heart and lung, and is believed to play an important role in the construction and stabilization of hyaluronan-dependent extracellular matrix. There was a study has revealed that Lp3/Hapln3 and aggrecan genes were paired on chromosome 1q31. And immunohistochemical analysis showed the prominent expression of Lp3/Hapln3 in the smooth muscle tissues of the vascular wall and gastrointestinal tract. Further comparative studies revealed that Lp3/Hapln3 was well co-localized with versican around the smooth muscle cells of blood vessels but not around endothelial cells. These data were supported by in vivo studies of a mechanical vascular injury model in mice. Vitro experiments demonstrated the coordinated up regulation of Lp3/Hapln3 and versican by platelet-derived growth factor (PDGF). Altogether, accumulating results suggested that Lp3/Hapln3 is involved, together with versican and hyaluronan, in the formation of the pericellular matrix of vascular smooth muscle cells.

HAPLN3 also has a subtle relationship with the immune system. HAPLN3 was identified in a previous research were validated as IFN-b response genes in primary B cells. In that study new IFN-b response genes, HAPLN3, were identified in B cells, with possible implications to B cell-specific functions. The study’s results emphasize the applicability of lymphoblast cell lines (LCLs) for studies of human B cell drug response.

More and more evidences showed that HAPLN3 plays an important role in the occurrence and development of cancer. It has been reported that proteoglycan promotes cancer cell mobility and migration through signal transduction by binding to cell membrane, which relies on the migratory pathway created by migrating cells themselves and cells of their surrounding tissues, and the connection of proteoglycan and hyaluronan by HAPLN. This suggests that over-expression of HAPLN3 may be related to breast cancer development and metastasis. In other words, over-expression of HAPLN3 may be related to breast cancer development and metastasis. Coincidentally, a previous research revealed that the gene up-expression of HAPLN3 was suggested to be involved in the development of breast cancer and to be a biomarker and target treatment for breast cancer. Moreover, Christa Haldrup et al. found that hypermethylation of hapln3 in cfDNA extracted from serum was highly specific for patients with PC compared to patients with BPH. Thus, Biomarker potential of hapln3 hypermethylation In prostate cancer tissue and liquid biopsies was showed.


  1. Katherine E. Varley, et al. Recurrent read-through fusion transcripts in breast cancer. Breast Cancer Res Treat . 2014, 146:287–297.
  2. Mia Møller, et al. Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostatetissue from cancer patients. Scientific Reports. 2017, 7:40636.
  3. Christa Haldrup, et al. Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in prostate cancer tissue and liquid biopsies. Molecular Oncology, 2018, 12(4):545.
  4. Daniel A. Enquobahrie, et al. Early Pregnancy Maternal Blood DNA Methylation in Repeat Pregnancies and Change in Gestational Diabetes Mellitus Status—A Pilot Study. Reproductive Sciences, 2015, 22(7):904-910.