CRELD1 (CRELD disulfide isomerase 1)

Gene

• Entrez ID: 78987
• Gene name: CRELD disulfide isomerase 1
• Gene symbol: CRELD1
• Synonyms (NCBI Gene): AVSD2, CIRRIN, JELANS
• Chromosome: 3
• Chromosome location: 3p25.3
• 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 th

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28941780	G>A	Pathogenic, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, missense variant, coding sequence variant
rs28942091	C>G,T	Likely-benign, risk-factor	Non coding transcript variant, missense variant, coding sequence variant
rs28942092	C>T	Uncertain-significance, risk-factor	Non coding transcript variant, missense variant, coding sequence variant
rs121912626	C>G	Risk-factor	Non coding transcript variant, missense variant, coding sequence variant
rs121912627	G>A	Risk-factor	Non coding transcript variant, missense variant, coding sequence variant, 3 prime UTR variant
rs759473511	A>-	Likely-pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1553600601	->A	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1575631130	ACAG>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1575650682	TG>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004230	hsa-miR-346	Microarray	16822819
MIRT029353	hsa-miR-26b-5p	Microarray	19088304
MIRT909472	hsa-miR-1200	CLIP-seq
MIRT909473	hsa-miR-1207-3p	CLIP-seq
MIRT909474	hsa-miR-1207-5p	CLIP-seq
MIRT909475	hsa-miR-1273f	CLIP-seq
MIRT909476	hsa-miR-1301	CLIP-seq
MIRT909477	hsa-miR-143	CLIP-seq
MIRT909478	hsa-miR-3074-5p	CLIP-seq
MIRT909479	hsa-miR-4300	CLIP-seq
MIRT909480	hsa-miR-4324	CLIP-seq
MIRT909481	hsa-miR-4419a	CLIP-seq
MIRT909482	hsa-miR-4459	CLIP-seq
MIRT909483	hsa-miR-4510	CLIP-seq
MIRT909484	hsa-miR-4660	CLIP-seq
MIRT909485	hsa-miR-4679	CLIP-seq
MIRT909486	hsa-miR-4708-5p	CLIP-seq
MIRT909487	hsa-miR-4722-5p	CLIP-seq
MIRT909488	hsa-miR-4736	CLIP-seq
MIRT909489	hsa-miR-4763-3p	CLIP-seq
MIRT909490	hsa-miR-4770	CLIP-seq
MIRT909491	hsa-miR-4779	CLIP-seq
MIRT909492	hsa-miR-5047	CLIP-seq
MIRT909493	hsa-miR-544b	CLIP-seq
MIRT909494	hsa-miR-920	CLIP-seq
MIRT909495	hsa-miR-103a	CLIP-seq
MIRT909496	hsa-miR-107	CLIP-seq
MIRT909473	hsa-miR-1207-3p	CLIP-seq
MIRT909474	hsa-miR-1207-5p	CLIP-seq
MIRT909476	hsa-miR-1301	CLIP-seq
MIRT909484	hsa-miR-4660	CLIP-seq
MIRT909488	hsa-miR-4736	CLIP-seq
MIRT909489	hsa-miR-4763-3p	CLIP-seq
MIRT909492	hsa-miR-5047	CLIP-seq
MIRT909497	hsa-miR-885-3p	CLIP-seq
MIRT2205722	hsa-miR-198	CLIP-seq
MIRT2205723	hsa-miR-214	CLIP-seq
MIRT2205724	hsa-miR-338-3p	CLIP-seq
MIRT2205725	hsa-miR-3616-3p	CLIP-seq
MIRT2205726	hsa-miR-3619-5p	CLIP-seq
MIRT2205727	hsa-miR-4436b-3p	CLIP-seq
MIRT909482	hsa-miR-4459	CLIP-seq
MIRT2205728	hsa-miR-4530	CLIP-seq
MIRT2205729	hsa-miR-4690-3p	CLIP-seq
MIRT909487	hsa-miR-4722-5p	CLIP-seq
MIRT909491	hsa-miR-4779	CLIP-seq
MIRT2205730	hsa-miR-761	CLIP-seq
MIRT2508789	hsa-miR-1197	CLIP-seq
MIRT2508790	hsa-miR-18a	CLIP-seq
MIRT2508791	hsa-miR-18b	CLIP-seq
MIRT2508792	hsa-miR-4320	CLIP-seq
MIRT2508793	hsa-miR-4446-5p	CLIP-seq
MIRT2508794	hsa-miR-4735-3p	CLIP-seq
MIRT2508795	hsa-miR-4755-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003197	Process	Endocardial cushion development	TAS	18076106
GO:0003279	Process	Cardiac septum development	TAS	18076106
GO:0003756	Function	Protein disulfide isomerase activity	IEA
GO:0005201	Function	Extracellular matrix structural constituent	RCA	28675934
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	20508391, 32814053
GO:0016020	Component	Membrane	IEA
GO:0016853	Function	Isomerase activity	IEA
GO:0031012	Component	Extracellular matrix	HDA	28675934
GO:0045202	Component	Synapse	IEA
GO:0098978	Component	Glutamatergic synapse	IEA

Other IDs

• MIM: 607170
• HGNC: 14630
• e!Ensembl: ENSG00000163703

Protein

• UniProt ID: Q96HD1
• Protein name: Protein disulfide isomerase CRELD1 (EC 5.3.4.1) (Cysteine-rich with EGF-like domain protein 1)
• Protein function: Protein disulfide isomerase (By similarity). Promotes the localization of acetylcholine receptors (AChRs) to the plasma membrane (By similarity).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF11938	DUF3456	45 → 103	TLR4 regulator and MIR-interacting MSAP	Family
  PF07645	EGF_CA	245 → 285	Calcium-binding EGF domain	Domain
  PF07645	EGF_CA	305 → 346	Calcium-binding EGF domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in fetal lung, liver, kidney, adult heart, brain and skeletal muscle. Weakly expressed in placenta, fetal brain, and adult lung, liver, kidney and pancreas. {ECO:0000269|PubMed:12137942}.
• Sequence:

  MAPWPPKGLVPAMLWGLSLFLNLPGPIWLQPSPPPQSSPPPQPHPCHTCRGLVDSFNKGL
  ERTIRDNFGGGNTAWEEENLSKYKDSETRLVEVLEGVCSKSDFECHRLLELSEELVESWW
  FHKQQEAPDLFQWLCSDSLKLCCPAGTFGPSCLPCPGGTERPCGGYGQCEGEGTRGGSGH
  CDCQAGYGGEACGQCGLGYFEAERNASHLVCSACFGPCARCSGPEESNCLQCKKGWALHH
  LKCVDIDECGTEGANCGADQFCVNTEGSYECRDCAKACLGCMGAGPGRCKKCSPGYQQVG
  SKCLDVDECETEVCPGENKQCENTEGGYRCICAEGYKQMEGICVKEQIPESAGFFSEMTE
  DELVVLQQMFFGIIICALATLAAKGDLVFTAIFIGAVAAMTGYWLSERSDRVLEGFIKGR
  

• Sequence length: 420

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Atrioventricular septal defect, susceptibility to, 2	Pathogenic; Likely pathogenic	rs774018674, rs1575650682, rs1188358849	RCV000543058 RCV000782366 RCV001067508	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Congenital heart defects, multiple types, 4	Pathogenic	rs2470480014, rs746951044	RCV003318479 RCV003318481	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ventricular septal defect 1	Pathogenic	rs2470508449, rs760263168	RCV003318480 RCV003318482	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Atrioventricular septal defect, partial, with heterotaxy syndrome	Conflicting classifications of pathogenicity	ClinVar CTD, Disgenet CTD, Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
COMPLETE ATRIOVENTRICULAR CANAL DEFECT WITH VENTRICULAR HYPOPLASIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMPLETE ATRIOVENTRICULAR SEPTAL DEFECT WITH TETRALOGY OF FALLOT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMPLETE ATRIOVENTRICULAR SEPTAL DEFECT WITH VENTRICULAR HYPOPLASIA	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMPLETE ATRIOVENTRICULAR SEPTAL DEFECT-TETRALOGY OF FALLOT	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMPLEX NEURODEVELOPMENTAL DISORDER	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART DISEASE	—	ClinGen, ClinVar, Disgenet ClinGen, ClinVar, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL SEPTAL DEFECT OF HEART	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRELD1-related disorder	Uncertain significance; Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Jeffries-Lakhani neurodevelopmental syndrome	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SPECIFIC SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARTIAL ATRIOVENTRICULAR CANAL DEFECT WITHOUT VENTRICULAR HYPOPLASIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARTIAL ATRIOVENTRICULAR SEPTAL DEFECT WITHOUT VENTRICULAR HYPOPLASIA	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tetralogy of Fallot	Uncertain significance	ClinVar CTD, Disgenet CTD, Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Aortic coarctation	Aortic Coarctation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Aortic Valve Stenosis	Aortic Valve Sclerosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atrioventricular Septal Defect	Atrioventricular septal defect	BEFREE	21080147, 21413875, 22523272, 22987595, 29054759		★☆☆☆☆ Found in Text Mining only
Atrioventricular Septal Defect	Atrioventricular septal defect	Pubtator	23040494	Associate	★☆☆☆☆ Found in Text Mining only
Atrioventricular Septal Defect, Partial, with Heterotaxy Syndrome	Atrioventricular Septal Defect, Partial, With Heterotaxy Syndrome	CLINVAR_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Atrioventricular Septal Defect, Partial, with Heterotaxy Syndrome	Atrioventricular Septal Defect, Partial, With Heterotaxy Syndrome	GENOMICS_ENGLAND_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Atrioventricular Septal Defect, Partial, with Heterotaxy Syndrome	Atrioventricular Septal Defect, Partial, With Heterotaxy Syndrome	CTD_human_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Autistic Disorder	Autism	Pubtator	37322441	Associate	★☆☆☆☆ Found in Text Mining only
Bicuspid aortic valve	Bicuspid aortic valve	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bicuspid Aortic Valve Disease	Bicuspid aortic valve	Pubtator	36929416	Associate	★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathies	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Complete atrioventricular septal defect with ventricular hypoplasia	Complete Atrioventricular Septal Defect With Ventricular Hypoplasia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Complete atrioventricular septal defect-tetralogy of Fallot	Complete Atrioventricular Septal Defect-Tetralogy Of Fallot	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital atresia of pulmonary artery	Congenital Atresia Of Pulmonary Artery	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	21080147, 22987595, 25524324		★☆☆☆☆ Found in Text Mining only
Congenital heart disease	Congenital Heart Disease	BEFREE	21413875		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary heart disease	Coronary Heart Disease	BEFREE	21413875, 22523272, 25524324, 30221396		★☆☆☆☆ Found in Text Mining only
Dextrocardia	Dextrocardia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Double Outlet Right Ventricle	Double outlet right ventricle	Pubtator	37322441	Associate	★☆☆☆☆ Found in Text Mining only
Double Outlet Right Ventricle	Double Outlet Right Ventricle	HPO_DG			★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	BEFREE	21413875, 22523272, 22987595, 25524324, 29054759		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down syndrome	Pubtator	23040494	Associate	★☆☆☆☆ Found in Text Mining only
Heart Defects Congenital	Congenital heart defect	Pubtator	29952356, 36929416	Associate	★☆☆☆☆ Found in Text Mining only
Heart Septal Defects	Heart Septal Defects	BEFREE	22523272, 29952356		★☆☆☆☆ Found in Text Mining only
Heterotaxy Syndrome	Heterotaxia	BEFREE	12632326		★☆☆☆☆ Found in Text Mining only
Heterotaxy Syndrome	Heterotaxia	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Hypoplastic Left Heart Syndrome	Hypoplastic Left Heart Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Partial atrioventricular canal	Partial atrioventricular canal defect	ORPHANET_DG	12632326, 15096951, 21080147		★☆☆☆☆ Found in Text Mining only
Partial defect of atrioventricular canal	Partial Defect Of Atrioventricular Canal	HPO_DG			★☆☆☆☆ Found in Text Mining only
Patent ductus arteriosus	Patent ductus arteriosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pulmonary Venous Return Anomaly	Pulmonary Venous Return Anomaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Situs ambiguus	Situs ambiguus	BEFREE	12632326		★☆☆☆☆ Found in Text Mining only
Situs ambiguus	Situs ambiguus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Tetralogy of Fallot	Tetralogy of Fallot	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Transient Ischemic Attack	Transient Ischemic Attack	HPO_DG			★☆☆☆☆ Found in Text Mining only
Turner Syndrome	Turner syndrome	Pubtator	36929416	Associate	★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	BEFREE	25524324		★☆☆☆☆ Found in Text Mining only