CRELD1 Gene

Name	cysteine-rich with EGF-like domains 1
Description	This gene encodes a member of a subfamily of epidermal growth factor-related proteins. The encoded protein is characterized by a cysteine-rich with epidermal growth factor-like domain. This protein may function as a cell adhesion molecule. Mutations in this gene are the cause of atrioventricular septal defect. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CRELD1 is a cell adhesion molecule that plays a critical role in heart development by integrating cell adhesion, signal transduction, and stress response mechanisms. Several studies have identified heterozygous missense mutations in CRELD1—often affecting its calcium‐binding EGF‐like domains—in patients with atrioventricular septal defects (AVSD) observed both in isolated cases and in the context of Down syndrome, indicating that such variants increase the risk for cardiac malformations rather than directly causing them."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In addition, CRELD1 functions as an important regulator of calcineurin/NFATc1 signaling during cardiac morphogenesis; by forming a complex with the calcineurin regulatory subunit, it promotes NFATc1 dephosphorylation and subsequent nuclear translocation, a process essential for the vascular endothelial growth factor–dependent proliferation of endocardial cells and proper septum and valve formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, CRELD1 has been shown to interact with the apoptosis‐inducing protein RTN3, modulating its subcellular localization and reducing its pro‐apoptotic activity, which suggests a role in protecting cells against stress‐induced apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Finally, CRELD1 expression can be induced under conditions of endoplasmic reticulum (ER) stress, further supporting its involvement in stress response pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Susan W Robinson, Cynthia D Morris, Elizabeth Goldmuntz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Missense mutations in CRELD1 are associated with cardiac atrioventricular septal defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/374319"}], "href": "https://doi.org/10.1086/374319"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12632326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12632326"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christine Ackerman, Adam E Locke, Eleanor Feingold, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An excess of deleterious variants in VEGF-A pathway genes in Down-syndrome-associated atrioventricular septal defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.08.017"}], "href": "https://doi.org/10.1016/j.ajhg.2012.08.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23040494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23040494"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ying Guo, Jie Shen, Lang Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel CRELD1 gene mutations in patients with atrioventricular septal defect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Pediatr (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12519-010-0235-7"}], "href": "https://doi.org/10.1007/s12519-010-0235-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21080147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21080147"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ambreen Asim, Sarita Agarwal, Inusha Panigrahi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRELD1 gene variants and atrioventricular septal defects in Down syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2017.10.044"}], "href": "https://doi.org/10.1016/j.gene.2017.10.044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29054759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29054759"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Elvira Mass, Dagmar Wachten, Anna C Aschenbrenner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Murine Creld1 controls cardiac development through activation of calcineurin/NFATc1 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2014.02.012"}], "href": "https://doi.org/10.1016/j.devcel.2014.02.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24697899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24697899"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rong Xiang, Shuiping Zhao "}, {"type": "b", "children": [{"type": "t", "text": "RTN3 inducing apoptosis is modulated by an adhesion protein CRELD1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-009-0163-9"}], "href": "https://doi.org/10.1007/s11010-009-0163-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19521671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19521671"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Henning Gram Hansen, Jonas Damgård Schmidt, Cecilie Lützen Søltoft, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hyperactivity of the Ero1α oxidase elicits endoplasmic reticulum stress but no broad antioxidant response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.405050"}], "href": "https://doi.org/10.1074/jbc.M112.405050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23027870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23027870"}]}]}]}
Synonyms	CIRRIN, AVSD2
Proteins	CREL1_HUMAN
NCBI Gene ID	78987
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CRELD1 has 6,265 functional associations with biological entities spanning 8 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) extracted from 116 datasets.

Click the + buttons to view associations for CRELD1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CRELD1 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 CRELD1 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 CRELD1 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 CRELD1 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 CRELD1 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 CRELD1 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 CRELD1 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 CRELD1 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 CRELD1 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 CRELD1 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 CRELD1 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 CRELD1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRELD1 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 CRELD1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CRELD1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CRELD1 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 CRELD1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CRELD1 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 CRELD1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CRELD1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CRELD1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of CRELD1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CRELD1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CRELD1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CRELD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CRELD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CRELD1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CRELD1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CRELD1 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 CRELD1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRELD1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CRELD1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CRELD1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CRELD1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CRELD1 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 CRELD1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CRELD1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CRELD1 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 CRELD1 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 CRELD1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CRELD1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.