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    CRELD1 cysteine rich with EGF like domains 1 [ Homo sapiens (human) ]

    Gene ID: 78987, updated on 19-May-2024

    Summary

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    Official Symbol
    CRELD1provided by HGNC
    Official Full Name
    cysteine rich with EGF like domains 1provided by HGNC
    Primary source
    HGNC:HGNC:14630
    See related
    Ensembl:ENSG00000163703 MIM:607170; AllianceGenome:HGNC:14630
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    AVSD2; CIRRIN; JELANS
    Summary
    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]
    Expression
    Ubiquitous expression in thyroid (RPKM 17.8), heart (RPKM 15.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    3p25.3
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (9933834..9945406)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (9925824..9937392)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (9975518..9987090)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:9944736-9945405 Neighboring gene interleukin 17 receptor E Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14047 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14048 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14049 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:9958035-9958574 Neighboring gene RNA, U6 small nuclear 882, pseudogene Neighboring gene interleukin 17 receptor C Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:9970047-9970546 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14050 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14051 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19413 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:9980935-9981732 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:9987356-9988018 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:9988681-9989342 Neighboring gene 3p25 PRRT3 Alu-mediated recombination region Neighboring gene PRRT3 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14052 Neighboring gene proline rich transmembrane protein 3 Neighboring gene ER membrane protein complex subunit 3 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:10018113-10019312 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:10028343-10028990 Neighboring gene EMC3 antisense RNA 1 Neighboring gene FANCD2 pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome. Pinnaro CT, et al. Hum Genet, 2023 Apr. PMID 36929416, Free PMC Article
    2. CRELD1 gene variants and atrioventricular septal defects in Down syndrome. Asim A, et al. Gene, 2018 Jan 30. PMID 29054759
    3. [Potential role of CRELD1 gene in the pathogenesis of atrioventricular septal defect]. Guo Y, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2014 Jun. PMID 24927998
    4. Polymorphic haplotypes of CRELD1 differentially predispose Down syndrome and euploids individuals to atrioventricular septal defect. Ghosh P, et al. Am J Med Genet A, 2012 Nov. PMID 22987595
    5. Specific association of missense mutations in CRELD1 with cardiac atrioventricular septal defects in heterotaxy syndrome. Zhian S, et al. Am J Med Genet A, 2012 Aug. PMID 22740159, Free PMC Article

    See all (43) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections.
      Title: Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections.
    2. CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome.
      Title: CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome.
    3. The CRELD1 gene is likely to have a major role in causation of AVSD phenotype in selected DS patients.
      Title: CRELD1 gene variants and atrioventricular septal defects in Down syndrome.
    4. Germline mutations in the NKX2-5, GATA4, and CRELD1 genes do not appear to be associated with CHD in Mexican DS patients.
      Title: Germline mutations in NKX2-5, GATA4, and CRELD1 are rare in a Mexican sample of Down syndrome patients with endocardial cushion and septal heart defects.
    5. Mutation of the CRELD1 gene increased the risk for atrioventricular septal defect.
      Title: [Potential role of CRELD1 gene in the pathogenesis of atrioventricular septal defect].
    6. we identified two CRELD1 haplotypes associated with AVSD phenotype among DS and euploid individuals.
      Title: Polymorphic haplotypes of CRELD1 differentially predispose Down syndrome and euploids individuals to atrioventricular septal defect.
    7. study indicates that deleterious CRELD1 missense mutations are specifically associated with AVSD and are not correlated with other aspects of the heterotaxy phenotype
      Title: Specific association of missense mutations in CRELD1 with cardiac atrioventricular septal defects in heterotaxy syndrome.
    8. SNP c.985 C>T of CRELD1 is involved in causing congenital heart disease in patients of Mysore, South India.
      Title: A maiden report on CRELD1 single-nucleotide polymorphism association in congenital heart disease patients of Mysore, South India.
    9. CRELD1 is likely to be an AVSD-susceptibility gene and CRELD1 mutations may increase the risk of developing a heart defect rather than being a direct causative mutation
      Title: Novel CRELD1 gene mutations in patients with atrioventricular septal defect.
    10. Observational study of gene-disease association. (HuGE Navigator)
      Title: Novel CRELD1 gene mutations in patients with atrioventricular septal defect.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Atrioventricular septal defect, susceptibility to, 2
    MedGen: C1853508 OMIM: 606217 GeneReviews: Not available
    		Compare labs
    Jeffries-Lakhani neurodevelopmental syndrome
    MedGen: CN377243 OMIM: 620771 GeneReviews: Not available
    		not available

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • DKFZp566D213

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables extracellular matrix structural constituent RCA
    inferred from Reviewed Computational Analysis
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein disulfide isomerase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in cardiac septum development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in endocardial cushion development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in collagen-containing extracellular matrix HDA PubMed 
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    protein disulfide isomerase CRELD1
    NP_001026887.2
    NP_001070883.2
    NP_001361245.1
    NP_001361246.1
    NP_001361247.1
    NP_001361248.1
    NP_001361249.1
    NP_001397642.1
    NP_056328.3
    XP_011532410.1
    XP_047304853.1
    XP_047304854.1
    XP_047304856.1
    XP_054203808.1
    XP_054203809.1
    XP_054203810.1
    XP_054203811.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_017069.2 RefSeqGene

      Range
      5002..16574
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001031717.4 → NP_001026887.2  protein disulfide isomerase CRELD1 isoform 1 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AC018809
      Consensus CDS
      CCDS33693.1
      UniProtKB/TrEMBL
      A0A804HJB9
      Related
      ENSP00000321856.5, ENST00000326434.9
      Conserved Domains (4) summary
      smart00179
      Location:305 → 336
      EGF_CA; Calcium-binding EGF-like domain
      smart00261
      Location:210 → 245
      FU; Furin-like repeats
      pfam11938
      Location:46 → 100
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl21504
      Location:245 → 272
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    2. NM_001077415.3 → NP_001070883.2  protein disulfide isomerase CRELD1 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an exon in the 3' coding region, which results in a frameshift, compared to variant 1. The resulting protein (isoform 2) is shorter and has a distinct C-terminus, compared to isoform 1. Variants 2, 3, and 4 all encode the same isoform (2).
      Source sequence(s)
      AC018809
      Consensus CDS
      CCDS2593.1
      UniProtKB/Swiss-Prot
      A8MX90, B2RAA9, Q6I9X5, Q8NFT4, Q96HD1, Q9Y409
      UniProtKB/TrEMBL
      A0A804HKD9
      Related
      ENSP00000393643.2, ENST00000452070.6
      Conserved Domains (4) summary
      smart00179
      Location:305 → 336
      EGF_CA; Calcium-binding EGF-like domain
      smart00261
      Location:210 → 245
      FU; Furin-like repeats
      pfam11938
      Location:46 → 100
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl21504
      Location:245 → 272
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    3. NM_001374316.1 → NP_001361245.1  protein disulfide isomerase CRELD1 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4), as well as variants 2 and 3, encodes isoform 2.
      Source sequence(s)
      AC018809
      Consensus CDS
      CCDS2593.1
      UniProtKB/Swiss-Prot
      A8MX90, B2RAA9, Q6I9X5, Q8NFT4, Q96HD1, Q9Y409
      UniProtKB/TrEMBL
      A0A804HKD9
      Related
      ENSP00000507127.1, ENST00000684493.1
      Conserved Domains (4) summary
      smart00179
      Location:305 → 336
      EGF_CA; Calcium-binding EGF-like domain
      smart00261
      Location:210 → 245
      FU; Furin-like repeats
      pfam11938
      Location:46 → 100
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl21504
      Location:245 → 272
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    4. NM_001374317.1 → NP_001361246.1  protein disulfide isomerase CRELD1 isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5), as well as variant 6, encodes isoform 3.
      Source sequence(s)
      AC018809
      Consensus CDS
      CCDS93207.1
      UniProtKB/TrEMBL
      A0A804HJB9, A0A804HJJ0
      Conserved Domains (4) summary
      smart00179
      Location:305 → 336
      EGF_CA; Calcium-binding EGF-like domain
      smart00261
      Location:210 → 245
      FU; Furin-like repeats
      pfam11938
      Location:46 → 100
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl21504
      Location:245 → 272
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    5. NM_001374318.1 → NP_001361247.1  protein disulfide isomerase CRELD1 isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6), as well as variant 5, encodes isoform 3.
      Source sequence(s)
      AC018809
      Consensus CDS
      CCDS93207.1
      UniProtKB/TrEMBL
      A0A804HJB9, A0A804HJJ0
      Related
      ENSP00000507522.1, ENST00000684181.1
      Conserved Domains (4) summary
      smart00179
      Location:305 → 336
      EGF_CA; Calcium-binding EGF-like domain
      smart00261
      Location:210 → 245
      FU; Furin-like repeats
      pfam11938
      Location:46 → 100
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl21504
      Location:245 → 272
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    6. NM_001374319.1 → NP_001361248.1  protein disulfide isomerase CRELD1 isoform 4 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7), as well as variant 8, encodes isoform 4.
      Source sequence(s)
      AC018809
      Consensus CDS
      CCDS93208.1
      UniProtKB/TrEMBL
      A0A669KAV0, A0A804HKD9
      Related
      ENSP00000500961.2, ENST00000673935.2
      Conserved Domains (3) summary
      smart00179
      Location:277 → 308
      EGF_CA; Calcium-binding EGF-like domain
      smart00261
      Location:210 → 246
      FU; Furin-like repeats
      pfam11938
      Location:46 → 100
      DUF3456; TLR4 regulator and MIR-interacting MSAP

    7. NM_001374320.1 → NP_001361249.1  protein disulfide isomerase CRELD1 isoform 4 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8), as well as variant 7, encodes isoform 4.
      Source sequence(s)
      AC018809
      Consensus CDS
      CCDS93208.1
      UniProtKB/TrEMBL
      A0A669KAV0, A0A804HKD9
      Conserved Domains (3) summary
      smart00179
      Location:277 → 308
      EGF_CA; Calcium-binding EGF-like domain
      smart00261
      Location:210 → 246
      FU; Furin-like repeats
      pfam11938
      Location:46 → 100
      DUF3456; TLR4 regulator and MIR-interacting MSAP

    8. NM_001410713.1 → NP_001397642.1  protein disulfide isomerase CRELD1 isoform 5 precursor

      Status: REVIEWED

      Source sequence(s)
      AC018809
      Consensus CDS
      CCDS93206.1
      UniProtKB/TrEMBL
      A0A804HKP7
      Related
      ENSP00000508209.1, ENST00000682907.1

    9. NM_015513.6 → NP_056328.3  protein disulfide isomerase CRELD1 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and lacks an exon in the 3' coding region, which results in a frameshift, compared to variant 1. The resulting protein (isoform 2) is shorter and has a distinct C-terminus, compared to isoform 1. Variants 2, 3, and 4 all encode the same isoform (2).
      Source sequence(s)
      AC018809
      Consensus CDS
      CCDS2593.1
      UniProtKB/Swiss-Prot
      A8MX90, B2RAA9, Q6I9X5, Q8NFT4, Q96HD1, Q9Y409
      UniProtKB/TrEMBL
      A0A804HKD9
      Related
      ENSP00000373322.3, ENST00000383811.8
      Conserved Domains (4) summary
      smart00179
      Location:305 → 336
      EGF_CA; Calcium-binding EGF-like domain
      smart00261
      Location:210 → 245
      FU; Furin-like repeats
      pfam11938
      Location:46 → 100
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl21504
      Location:245 → 272
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    RNA

    1. NR_164475.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC018809
      Related
      ENST00000674067.2

    2. NR_164476.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC018809
      Related
      ENST00000682397.1

    3. NR_164477.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC018809

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      9933834..9945406
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011534108.2 → XP_011532410.1  protein disulfide isomerase CRELD1 isoform X2

      UniProtKB/TrEMBL
      A0A804HJB9, A0A804HJJ0
      Conserved Domains (4) summary
      smart00179
      Location:305 → 336
      EGF_CA; Calcium-binding EGF-like domain
      smart00261
      Location:210 → 245
      FU; Furin-like repeats
      pfam11938
      Location:46 → 100
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl21504
      Location:245 → 272
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    2. XM_047448898.1 → XP_047304854.1  protein disulfide isomerase CRELD1 isoform X3

      Related
      ENSP00000507437.1, ENST00000683982.1

    3. XM_047448897.1 → XP_047304853.1  protein disulfide isomerase CRELD1 isoform X1

      UniProtKB/TrEMBL
      A0A804HKP7
      Related
      ENSP00000507251.1, ENST00000682642.1

    4. XM_047448900.1 → XP_047304856.1  protein disulfide isomerase CRELD1 isoform X4

      UniProtKB/TrEMBL
      A0A669KAV2, A0A669KBB3
      Related
      ENSP00000507258.1, ENST00000683547.1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      9925824..9937392
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054347834.1 → XP_054203809.1  protein disulfide isomerase CRELD1 isoform X2

    2. XM_054347835.1 → XP_054203810.1  protein disulfide isomerase CRELD1 isoform X3

    3. XM_054347833.1 → XP_054203808.1  protein disulfide isomerase CRELD1 isoform X1

    4. XM_054347836.1 → XP_054203811.1  protein disulfide isomerase CRELD1 isoform X4

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96HD1.3 GenPept UniProtKB/Swiss-Prot:Q96HD1

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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