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CRELD2 CRELD disulfide isomerase 2 [ Homo sapiens (human) ]

Gene ID: 79174, updated on 6-Jul-2026
Official Symbol
CRELD2provided by HGNC
Official Full Name
CRELD disulfide isomerase 2provided by HGNC
Primary source
HGNC:HGNC:28150
See related
Ensembl:ENSG00000184164 MIM:607171; AllianceGenome:HGNC:28150
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
Predicted to enable calcium ion binding activity and protein disulfide isomerase activity. Predicted to be located in Golgi apparatus; endoplasmic reticulum; and extracellular space. [provided by Alliance of Genome Resources, Jul 2025]
Expression
Ubiquitous expression in thyroid (RPKM 19.3), testis (RPKM 9.9) and 25 other tissues See more
Orthologs
all
Try the new Gene page
Try the new Transcripts and proteins table
See CRELD2 in Genome Data Viewer
Location:
22q13.33
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (49918634..49927537)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (50423116..50432198)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (50312282..50321185)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124905147 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50250325-50250985 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50252588-50253125 Neighboring gene zinc finger BED-type containing 4 Neighboring gene ALG12 alpha-1,6-mannosyltransferase Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19282 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50281931-50282432 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50294104-50294824 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50294825-50295544 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50295545-50296264 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13928 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13929 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50316438-50317008 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50317009-50317578 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19284 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19286 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19285 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19287 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13930 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19288 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13931 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13932 Neighboring gene Sharpr-MPRA regulatory region 8073 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50336353-50337079 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50337080-50337805 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50340469-50341056 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50343989-50344576 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50344577-50345162 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50346923-50347508 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13935 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13936 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13937 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13938 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13939 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13940 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13941 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50358856-50359356 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19289 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19290 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13942 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19291 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19292 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13943 Neighboring gene microRNA 6821 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13944 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19293 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19294 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19295 Neighboring gene Pim-3 proto-oncogene, serine/threonine kinase Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50421116-50422037 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50437830-50438788 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50438789-50439748 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50439749-50440706 Neighboring gene interleukin 17 receptor E like Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13945 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13946 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50451079-50451679

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. Molecular characterization of the ER stress-inducible factor CRELD2. Hinaga S, et al. Cell Biochem Biophys, 2024 Jun. PMID 38753249
  2. Characterization of V-ATPase inhibitor-induced secretion of cysteine-rich with EGF-like domains 2. Oh-hashi K, et al. Cell Biol Toxicol, 2014 Jun. PMID 24687431
  3. CRELD2: gene mapping, alternate splicing, and comparative genomic identification of the promoter region. Maslen CL, et al. Gene, 2006 Nov 1. PMID 16919896
  4. CRELD2, endoplasmic reticulum stress, and human diseases. Tang Q, et al. Front Endocrinol (Lausanne), 2023. PMID 36936176, Free PMC Article
  5. Creld2 function during unfolded protein response is essential for liver metabolism homeostasis. Kern P, et al. FASEB J, 2021 Oct. PMID 34549824, Free PMC Article

See all (36) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Molecular characterization of the ER stress-inducible factor CRELD2.
    Title: Molecular characterization of the ER stress-inducible factor CRELD2.
  2. CRELD2, endoplasmic reticulum stress, and human diseases.
    Title: CRELD2, endoplasmic reticulum stress, and human diseases.
  3. Creld2 function during unfolded protein response is essential for liver metabolism homeostasis.
    Title: Creld2 function during unfolded protein response is essential for liver metabolism homeostasis.
  4. ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism.
    Title: ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism.
  5. intravesicular acidification by V-ATPase regulates the secretion of CRELD2 without relying on the balance of intracellular calcium ions and the expression of endoplasmic reticulum chaperones such as GRP78 and protein disulfide isomerase.
    Title: Characterization of V-ATPase inhibitor-induced secretion of cysteine-rich with EGF-like domains 2.
  6. We demonstrate that Armet and Creld2 are genotype-specific ER stress response proteins with substrate specificities, and that aggregation of mutant matrilin-3 is a key disease trigger in MED that could be exploited as a potential therapeutic target
    Title: Armet/Manf and Creld2 are components of a specialized ER stress response provoked by inappropriate formation of disulphide bonds: implications for genetic skeletal diseases.
  7. results strongly suggest that Creld2 may be directly regulated by BMP9 and ER stress response may play an important role in regulating osteogenic differentiation
    Title: Endoplasmic reticulum (ER) stress inducible factor cysteine-rich with EGF-like domains 2 (Creld2) is an important mediator of BMP9-regulated osteogenic differentiation of mesenchymal stem cells.
  8. Mapping of CRELD2 by FISH shows that it maps to 22q13 rather than the GenBank reported locus of 22p13.
    Title: CRELD2: gene mapping, alternate splicing, and comparative genomic identification of the promoter region.
  9. CRELD2 can act as a specific regulator of alpha4beta2 nAChR expression
    Title: The cysteine-rich with EGF-like domains 2 (CRELD2) protein interacts with the large cytoplasmic domain of human neuronal nicotinic acetylcholine receptor alpha4 and beta2 subunits.
Submit: New GeneRIF Correction

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris.
EBI GWAS Catalog

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ44190, FLJ98733, MGC11256, DKFZp667O055

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein disulfide isomerase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein disulfide isomerase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
located_in Golgi apparatus IEA
Inferred from Electronic Annotation
more info
  
located_in endoplasmic reticulum EXP
Inferred from Experiment
more info
 PubMed 
located_in endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
  
is_active_in extracellular matrix IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular region IEA
Inferred from Electronic Annotation
more info
  
Preferred Names
protein disulfide isomerase CRELD2
Names
cysteine rich with EGF like domains 2
cysteine-rich with EGF-like domain protein 2
NP_001128573.1
NP_001271246.1
NP_001271247.1
NP_077300.3
XP_005261794.1
XP_005261795.1
XP_011528674.1
XP_054181883.1
XP_054181884.1
XP_054181885.1

NEW Try the new Transcript table

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.

mRNA and Protein(s)

  1. NM_001135101.3 → NP_001128573.1  protein disulfide isomerase CRELD2 isoform a precursor

    See identical proteins and their annotated locations for NP_001128573.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a, also known as CRELD2-epsilon).
    Source sequence(s)
    BI462292, DQ470679
    Consensus CDS
    CCDS46730.1
    UniProtKB/TrEMBL
    A0ACI8VJX8
    Related
    ENSP00000383938.3, ENST00000404488.7
    Conserved Domains (3) summary
    smart00261
    Location:304 → 344
    FU; Furin-like repeats
    pfam11938
    Location:31 → 120
    DUF3456; TLR4 regulator and MIR-interacting MSAP
    cl00057
    Location:337 → 377
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

  2. NM_001284317.2 → NP_001271246.1  protein disulfide isomerase CRELD2 isoform c precursor

    See identical proteins and their annotated locations for NP_001271246.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) lacks two alternate in-frame exons in the central coding region, compared to variant 1, resulting in an isoform (c, also known as CRELD2-gamma) that is shorter than isoform a.
    Source sequence(s)
    BI462292, BQ003113, DQ470677
    Consensus CDS
    CCDS63516.1
    UniProtKB/TrEMBL
    A0ACI8S0C6
    Related
    ENSP00000384111.3, ENST00000403427.3
    Conserved Domains (3) summary
    pfam03302
    Location:197 → 266
    VSP; Giardia variant-specific surface protein
    pfam11938
    Location:31 → 120
    DUF3456; TLR4 regulator and MIR-interacting MSAP
    cl00057
    Location:260 → 300
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

  3. NM_001284318.2 → NP_001271247.1  protein disulfide isomerase CRELD2 isoform d precursor

    See identical proteins and their annotated locations for NP_001271247.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (d, also known as CRELD2-alpha) that is shorter than isoform a.
    Source sequence(s)
    BC002894, BI462292, BQ003113
    Consensus CDS
    CCDS63515.1
    UniProtKB/TrEMBL
    A0ACI8VLY1
    Related
    ENSP00000386034.3, ENST00000407217.7
    Conserved Domains (3) summary
    smart00261
    Location:194 → 230
    FU; Furin-like repeats
    pfam11938
    Location:31 → 120
    DUF3456; TLR4 regulator and MIR-interacting MSAP
    cl00057
    Location:256 → 296
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

  4. NM_024324.5 → NP_077300.3  protein disulfide isomerase CRELD2 isoform b precursor

    See identical proteins and their annotated locations for NP_077300.3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (b, also known as CRELD2-delta) that is shorter than isoform a.
    Source sequence(s)
    AY358355, BI462292
    Consensus CDS
    CCDS14082.1
    UniProtKB/Swiss-Prot
    A5GZA2, A5GZA3, A5GZA4, A5GZA5, A5GZA6, Q4W0V0, Q6UXH1, Q86UC0, Q9BU47
    UniProtKB/TrEMBL
    A0ACI8S8K3
    Related
    ENSP00000332223.4, ENST00000328268.9
    Conserved Domains (3) summary
    smart00261
    Location:194 → 230
    FU; Furin-like repeats
    pfam11938
    Location:31 → 120
    DUF3456; TLR4 regulator and MIR-interacting MSAP
    cl00057
    Location:288 → 328
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

RNA

  1. NR_104295.2 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (5) lacks an exon and uses an alternate splice site in the central region, compared to variant 1. This variant is represented as non-coding because use of the expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AK308692, AL671710, BI462292, BQ003113

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    49918634..49927537
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005261737.4 → XP_005261794.1  protein disulfide isomerase CRELD2 isoform X1

    UniProtKB/TrEMBL
    A0ACI8RWT5, A0ACI8S1T8
    Related
    ENSP00000575880.1, ENST00000905821.1
    Conserved Domains (3) summary
    smart00261
    Location:305 → 345
    FU; Furin-like repeats
    pfam11938
    Location:31 → 120
    DUF3456; TLR4 regulator and MIR-interacting MSAP
    cl00057
    Location:338 → 378
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

  2. XM_005261738.6 → XP_005261795.1  protein disulfide isomerase CRELD2 isoform X2

    See identical proteins and their annotated locations for XP_005261795.1

    UniProtKB/TrEMBL
    A0ACI8S8K3
    Related
    ENST00000483652.5
    Conserved Domains (3) summary
    smart00261
    Location:194 → 230
    FU; Furin-like repeats
    pfam11938
    Location:31 → 120
    DUF3456; TLR4 regulator and MIR-interacting MSAP
    cl00057
    Location:288 → 328
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

  3. XM_011530372.4 → XP_011528674.1  protein disulfide isomerase CRELD2 isoform X3

    UniProtKB/TrEMBL
    A6PWM2
    Related
    ENSP00000387769.1, ENST00000450207.5
    Conserved Domains (1) summary
    pfam11938
    Location:31 → 120
    DUF3456; TLR4 regulator and MIR-interacting MSAP

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    50423116..50432198
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054325908.1 → XP_054181883.1  protein disulfide isomerase CRELD2 isoform X1

    UniProtKB/TrEMBL
    A0ACI8RWT5, A0ACI8S1T8

  2. XM_054325909.1 → XP_054181884.1  protein disulfide isomerase CRELD2 isoform X2

    UniProtKB/TrEMBL
    A0ACI8S8K3

  3. XM_054325910.1 → XP_054181885.1  protein disulfide isomerase CRELD2 isoform X3

    UniProtKB/TrEMBL
    A6PWM2
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6UXH1.1 GenPept UniProtKB/Swiss-Prot:Q6UXH1

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