CRELD1 CRELD disulfide isomerase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CRELD1provided by HGNC
Official Full Name: CRELD disulfide isomerase 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: all
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Genomic context

Location:: 3p25.3

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (9933834..9945406)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (9925824..9937392)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (9975518..9987090)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome.
Title: CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome.
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.
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.
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].
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.
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.
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.
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.
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: C5935596 OMIM: 620771 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D3S3594 (e-PCR)
- UniSTS:23607

CRELD1 (e-PCR)
- UniSTS:505149

D3S4201 (e-PCR)
- UniSTS:40790

D3S1263 (e-PCR), detects polymorphism
- UniSTS:39520

D3S3924 (e-PCR)
- UniSTS:44166

WI-11041 (e-PCR)
- UniSTS:44167

D3S1652 (e-PCR)
- UniSTS:154291

SHGC-31307 (e-PCR)
- UniSTS:40421

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
enables protein disulfide isomerase activity	ISS Inferred from Sequence or Structural Similarity 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 extracellular matrix	HDA more info	PubMed
is_active_in extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
is_active_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in non-collagenous component of basement membrane	IDA Inferred from Direct Assay more info	PubMed
located_in non-collagenous component of basement membrane	IEA Inferred from Electronic Annotation more info
is_active_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: protein disulfide isomerase CRELD1

Names: cysteine rich with EGF like domains 1

NP_001026887.2

EC 5.3.4.1

NP_001070883.2

EC 5.3.4.1

NP_001361245.1

EC 5.3.4.1

NP_001361246.1

EC 5.3.4.1

NP_001361247.1

EC 5.3.4.1

NP_001361248.1

EC 5.3.4.1

NP_001361249.1

EC 5.3.4.1

NP_001397642.1

EC 5.3.4.1

NP_056328.3

EC 5.3.4.1

XP_011532410.1

EC 5.3.4.1

XP_047304853.1

EC 5.3.4.1

XP_047304854.1

EC 5.3.4.1

XP_047304856.1

EC 5.3.4.1

XP_054203808.1

EC 5.3.4.1

XP_054203809.1

EC 5.3.4.1

XP_054203810.1

EC 5.3.4.1

XP_054203811.1

EC 5.3.4.1

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

NG_017069.2 RefSeqGene

Range

5002..16574

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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 ...
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

A0ACI8UP50

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 ...
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

A0ACI8UP50

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 ...
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 ...
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 ...
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

ENSP00000561788.1, ENST00000891727.1

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
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

Related

ENSP00000561793.1, ENST00000891734.1

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
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

A0A804HJM5, A0A804HKP7

Related

ENSP00000508209.1, ENST00000682907.1
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

A0ACI8UP50

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

NR_164475.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018809

Related

ENST00000674067.2
NR_164476.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018809

Related

ENST00000682397.1
NR_164477.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018809

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

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

9933834..9945406

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A804HJB9

Related

ENSP00000507437.1, ENST00000683982.1
XM_047448897.1 → XP_047304853.1 protein disulfide isomerase CRELD1 isoform X1

UniProtKB/TrEMBL

A0A804HJM5, A0A804HKP7

Related

ENSP00000507251.1, ENST00000682642.1
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

NC_060927.1 Alternate T2T-CHM13v2.0

Range

9925824..9937392

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A804HJB9
XM_054347835.1 → XP_054203810.1 protein disulfide isomerase CRELD1 isoform X3

UniProtKB/TrEMBL

A0A804HJB9
XM_054347833.1 → XP_054203808.1 protein disulfide isomerase CRELD1 isoform X1

UniProtKB/TrEMBL

A0A804HJM5
XM_054347836.1 → XP_054203811.1 protein disulfide isomerase CRELD1 isoform X4