CD320 Gene

HGNC Family	CD molecules (CD)
Name	CD320 molecule
Description	This gene encodes the transcobalamin receptor that is expressed at the cell surface. It mediates the cellular uptake of transcobalamin bound cobalamin (vitamin B12), and is involved in B-cell proliferation and immunoglobulin secretion. Mutations in this gene are associated with methylmalonic aciduria. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CD320, also known as the transcobalamin receptor (TCblR), is a cell‐surface protein belonging to the low‐density lipoprotein receptor family that mediates the uptake of vitamin B12 (cobalamin) by specifically binding transcobalamin (TC) saturated with B12. The receptor’s extracellular domain is solely responsible for the high‐affinity interaction with holo‐TC, while its cytoplasmic tail plays a critical role in initiating endocytosis of the ligand–receptor complex, ensuring efficient B12 internalization into cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural elucidation of the TC–CD320 complex has revealed the molecular basis for its specificity and the pH‐dependent release of TC during the endocytic process, a mechanism that is essential for proper cellular vitamin B12 delivery."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Ubiquitously expressed in various tissues, CD320 is central to systemic B12 homeostasis. Genetic studies in knockout models indicate that, although alternative uptake mechanisms may partially compensate in some peripheral tissues, CD320 is indispensable in the central nervous system and for reproductive function, thereby influencing embryonic development and neurological health."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, naturally occurring mutations in CD320—such as the p.E88del deletion—compromise ligand binding and cellular uptake of cobalamin, leading to biochemical alterations (elevated methylmalonic acid and homocysteine levels) that have been associated with neural tube defects and reproductive complications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, a soluble form of CD320 (sCD320) has been identified in serum and urine, with levels that fluctuate under physiological conditions such as pregnancy. This finding suggests that sCD320 might modulate systemic B12 transport dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, expression analysis in lymphoid tissues indicates that CD320 is not only expressed by classical B12‐uptake cells but also by germinal center B cells, hinting at potential roles in immune cell proliferation and differentiation that warrant further study."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CD320 is a critical mediator of vitamin B12 internalization, and its proper function is essential for maintaining metabolic balance and supporting diverse physiological processes ranging from neural development to immune regulation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Edward V Quadros, Yasumi Nakayama, Jeffrey M Sequeira "}, {"type": "b", "children": [{"type": "t", "text": "The protein and the gene encoding the receptor for the cellular uptake of transcobalamin-bound cobalamin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-05-158949"}], "href": "https://doi.org/10.1182/blood-2008-05-158949"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18779389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18779389"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wenxia Jiang, Yasumi Nakayama, Jeffrey M Sequeira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mapping the functional domains of TCblR/CD320, the receptor for cellular uptake of transcobalamin-bound cobalamin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.13-230185"}], "href": "https://doi.org/10.1096/fj.13-230185"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23603833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23603833"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Amer Alam, Jae-Sung Woo, Jennifer Schmitz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis of transcobalamin recognition by human CD320 receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms12100"}], "href": "https://doi.org/10.1038/ncomms12100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27411955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27411955"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shao-Chiang Lai, Yasumi Nakayama, Jeffrey M Sequeira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The transcobalamin receptor knockout mouse: a model for vitamin B12 deficiency in the central nervous system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.12-219055"}], "href": "https://doi.org/10.1096/fj.12-219055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23430977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23430977"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "David J Bernard, Faith J Pangilinan, Jun Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mice lacking the transcobalamin-vitamin B12 receptor, CD320, suffer from anemia and reproductive deficits when fed vitamin B12-deficient diet."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddy267"}], "href": "https://doi.org/10.1093/hmg/ddy267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30124850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30124850"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Edward V Quadros, Shao-Chiang Lai, Yasumi Nakayama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21297"}], "href": "https://doi.org/10.1002/humu.21297"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20524213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20524213"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Faith Pangilinan, David Watkins, David Bernard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Probing the functional consequence and clinical relevance of CD320 p.E88del, a variant in the transcobalamin receptor gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.62627"}], "href": "https://doi.org/10.1002/ajmg.a.62627"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35107211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35107211"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Han Sung Park, Jung Oh Kim, Hui Jeong An, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic polymorphisms of the cobalamin transport system are associated with idiopathic recurrent implantation failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-019-01455-4"}], "href": "https://doi.org/10.1007/s10815-019-01455-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31123954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31123954"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Omar Abuyaman, Birgitte H Andreasen, Camilla Kronborg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The soluble receptor for vitamin B12 uptake (sCD320) increases during pregnancy and occurs in higher concentration in urine than in serum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0073110"}], "href": "https://doi.org/10.1371/journal.pone.0073110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24015289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24015289"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Whajung Cho, Jinsuk Choi, Chan-Hum Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of CD320 in human B cells in addition to follicular dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMB Rep (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5483/bmbrep.2008.41.12.863"}], "href": "https://doi.org/10.5483/bmbrep.2008.41.12.863"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19123977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19123977"}]}]}]}
Synonyms	8D6, 8D6A, TCBLR
Proteins	CD320_HUMAN
NCBI Gene ID	51293
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CD320 has 9,405 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 123 datasets.

Click the + buttons to view associations for CD320 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CD320 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CD320 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CD320 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CD320 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CD320 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CD320 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CD320 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CD320 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CD320 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CD320 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CD320 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CD320 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CD320 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CD320 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CD320 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CD320 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CD320 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CD320 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CD320 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CD320 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of CD320 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CD320 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CD320 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CD320 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CD320 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CD320 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CD320 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with CD320 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CD320 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CD320 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CD320 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CD320 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CD320 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CD320 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CD320 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CD320 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CD320 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CD320 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CD320 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CD320 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CD320 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.