PDCD6 Gene

HGNC Family	EF-hand domain containing
Name	programmed cell death 6
Description	This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. Calcium binding is important for homodimerization and for conformational changes required for binding to other protein partners. This gene product participates in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death. In mice deficient for this gene product, however, apoptosis was not blocked suggesting this gene product is functionally redundant. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is also located on the short arm of chromosome 5. [provided by RefSeq, May 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProgrammed cell death‐6 (PDCD6), also known as apoptosis‐linked gene 2 (ALG‐2), is a calcium‐binding protein of the penta‐EF‐hand family that acts as a Ca²⁺ sensor and adaptor. Binding Ca²⁺ triggers a conformational change that permits PDCD6 to interact with a variety of target proteins, thereby coordinating diverse cellular events. For example, in mechanically active tissues its Ca²⁺‐dependent recruitment of the ESCRT machinery contributes to membrane repair following injury, and its association with components of the COPII coat stabilizes Sec31A at endoplasmic reticulum exit sites to regulate ER‐to‐Golgi vesicle trafficking."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPDCD6 also plays a pivotal role in the regulation of cell death. It was originally identified in screens for pro‐apoptotic factors and has since been shown to directly interact with key apoptotic regulators such as Fas and components of the TNF–α pathway, linking its Ca²⁺‐dependent binding to the activation of caspases. Moreover, PDCD6 responds to genotoxic stress in a p53‐dependent manner, with its nuclear accumulation enhancing the apoptotic cascade following DNA damage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in apoptosis and membrane dynamics, PDCD6 has emerged as a significant modulator in cancer biology. Altered expression of PDCD6 is observed in various tumor types—in some contexts reduced levels correlate with aggressive phenotypes and poor overall survival (for example, in gastric and bladder cancers), while in others overexpression is linked to tumor suppression by delaying cell cycle progression or by modulating angiogenesis. These findings support its utility as a prognostic biomarker and even a potential therapeutic target in malignancies such as gastric, ovarian, and colorectal cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, PDCD6/ALG‐2 exerts its multifunctional roles through Ca²⁺‐dependent interactions with a wide array of proteins involved in traffic, signaling, and RNA processing. Its direct binding to proteins such as annexin XI, ALIX, IST1, Sec31A, and RBM22—as well as its association with regulators of alternative mRNA splicing (via partners like CHERP) and with components of the proteasome and cytoskeletal regulators (e.g. MAP1B)—illustrates its versatility as an adaptor. These dynamic interactions help modulate vesicle budding, cargo receptor retention, mRNA decay, and even contribute to proper mitotic spindle function and T cell homeostasis, underscoring PDCD6’s broad impact on cellular physiology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Akinori Yamasaki, Katsuko Tani, Akitsugu Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e06-05-0444"}], "href": "https://doi.org/10.1091/mbc.e06-05-0444"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16957052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16957052"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hideki Shibata, Hironori Suzuki, Haruna Yoshida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ALG-2 directly binds Sec31A and localizes at endoplasmic reticulum exit sites in a Ca2+-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.12.101"}], "href": "https://doi.org/10.1016/j.bbrc.2006.12.101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17196169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17196169"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jared R Helm, Marvin Bentley, Kevin D Thorsen, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The ALG-2 binding site in Sec31A influences the retention kinetics of Sec31A at the endoplasmic reticulum exit sites as revealed by live-cell time-lapse imaging."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Biotechnol Biochem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1271/bbb.100215"}], "href": "https://doi.org/10.1271/bbb.100215"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20834162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20834162"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Mayumi Okumura, Angela M Katsuyama, Hideki Shibata, et al. 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Synonyms	ALG2, ALG-2, PEF1B
Proteins	PDCD6_HUMAN
NCBI Gene ID	10016
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PDCD6 has 8,024 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 116 datasets.

Click the + buttons to view associations for PDCD6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PDCD6 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PDCD6 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 PDCD6 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 PDCD6 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 RNA-seq	tissue samples with high or low expression of PDCD6 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 PDCD6 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 PDCD6 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 PDCD6 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 PDCD6 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 PDCD6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PDCD6 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 PDCD6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PDCD6 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PDCD6 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 PDCD6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PDCD6 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 PDCD6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PDCD6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PDCD6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PDCD6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing PDCD6 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PDCD6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PDCD6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PDCD6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PDCD6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PDCD6 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 PDCD6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PDCD6 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 PDCD6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PDCD6 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 PDCD6 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 PDCD6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PDCD6 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 PDCD6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of PDCD6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PDCD6 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing PDCD6 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of PDCD6 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of PDCD6 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of PDCD6 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PDCD6 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.