CRELD1

Summary

CRELD1 (CRELD disulfide isomerase 1, HGNC:14630) is a protein-coding gene on chromosome 3p25.3, encoding Protein disulfide isomerase CRELD1 (Q96HD1). Protein disulfide isomerase.

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.

Source: NCBI Gene 78987 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 256 total — 11 pathogenic, 6 likely-pathogenic
• GTEx eGene: eQTL in 43 tissues, sQTL in 43 (q < 0.05)
• Phenotypes (HPO): 117
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.89 (unconstrained)
• MANE Select transcript: NM_001077415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14630
Approved symbol	CRELD1
Name	CRELD disulfide isomerase 1
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	CIRRIN
Ensembl gene	ENSG00000163703
Ensembl biotype	protein_coding
OMIM	607170
Entrez	78987

Gene structure

Transcript identifiers

Ensembl transcripts: 136 — 67 nonsense_mediated_decay, 48 protein_coding, 16 retained_intron, 5 protein_coding_CDS_not_defined

MANE Select: ENST00000452070

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 4, TSL 3: 1, TSL 5: 4

ENST00000452070, ENST00000326434, ENST00000383811, ENST00000397170, ENST00000414117, ENST00000435417, ENST00000465716, ENST00000467713, ENST00000482691, ENST00000489674, ENST00000491527, ENST00000602411, ENST00000673635, ENST00000673677, ENST00000673737, ENST00000673935, ENST00000674057, ENST00000674067, ENST00000682120, ENST00000682200, ENST00000682318, ENST00000682355, ENST00000682372, ENST00000682397, ENST00000682403, ENST00000682570, ENST00000682642, ENST00000682771, ENST00000682783, ENST00000682790, ENST00000682798, ENST00000682866, ENST00000682884, ENST00000682906, ENST00000682907, ENST00000682929, ENST00000682967, ENST00000683083, ENST00000683122, ENST00000683127, ENST00000683189, ENST00000683232, ENST00000683239, ENST00000683279, ENST00000683301, ENST00000683316, ENST00000683388, ENST00000683467, ENST00000683507, ENST00000683547, ENST00000683601, ENST00000683603, ENST00000683736, ENST00000683835, ENST00000683849, ENST00000683888, ENST00000683891, ENST00000683921, ENST00000683970, ENST00000683982, ENST00000684181, ENST00000684212, ENST00000684243, ENST00000684291, ENST00000684318, ENST00000684419, ENST00000684493, ENST00000684526, ENST00000684532, ENST00000684601, ENST00000684613, ENST00000684629, ENST00000684648, ENST00000684659, ENST00000891727, ENST00000891731, ENST00000891734, ENST00000891736, ENST00000934769, ENST00000934770, ENST00000952392, ENST00000952393, ENST00000952394, ENST00000952395, ENST00000952396, ENST00000952397, ENST00000988014, ENST00000988015, ENST00000988017, ENST00000988018, ENST00000988019, ENST00000988020, ENST00000988021, ENST00000988022, ENST00000988023, ENST00000988024, ENST00000988025, ENST00001056440, ENST00001056442, ENST00001056443, ENST00001056444, ENST00001056445, ENST00001056446, ENST00001056447, ENST00001056448, ENST00001056450, ENST00001056451, ENST00001056452, ENST00001056453, ENST00001056454, ENST00001056455, ENST00001056457, ENST00001056458, ENST00001056462, ENST00001056463, ENST00001056464, ENST00001080071, ENST00001080072, ENST00001080073, ENST00001080074, ENST00001080075, ENST00001080076, ENST00001080077, ENST00001080078, ENST00001080079, ENST00001080080, ENST00001080081, ENST00001080082, ENST00001080083, ENST00001101038, ENST00001107442, ENST00001107443, ENST00001114760, ENST00001125471, ENST00001125472, ENST00001141577

RefSeq mRNA: 9 — MANE Select: NM_001077415 NM_001031717, NM_001077415, NM_001374316, NM_001374317, NM_001374318, NM_001374319, NM_001374320, NM_001410713, NM_015513

CCDS: CCDS2593, CCDS33693, CCDS93206, CCDS93207, CCDS93208

Canonical transcript exons

ENST00000452070 — 11 exons

Exon	Start	End
ENSE00001077478	9943077	9943172
ENSE00001077481	9940850	9941026
ENSE00001077483	9938015	9938106
ENSE00001683914	9933834	9933920
ENSE00003493617	9934835	9934917
ENSE00003537693	9941111	9941206
ENSE00003605183	9943381	9943515
ENSE00003633655	9942813	9942896
ENSE00003655275	9937562	9937672
ENSE00003899871	9944365	9945406
ENSE00003918209	9934420	9934612

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.0451 / max 372.8987, expressed in 1813 samples.

Highest expression (Bgee): hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, cerebellum, pituitary gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CRELD1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 43 tissues and its splicing (sQTL) in 43 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 86 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	2.4e-142	+0.97	3:9933702:C:G
Adipose Subcutaneous	eqtl	2.4e-135	+0.80	3:9933702:C:G
Skin Sun Exposed Lower leg	eqtl	3.6e-127	+0.64	3:9933702:C:G
Artery Tibial	eqtl	1.8e-121	+0.68	3:9933702:C:G
Nerve Tibial	eqtl	7.2e-109	+0.57	3:9933702:C:G
Skin Not Sun Exposed Suprapubic	eqtl	7.4e-105	+0.66	3:9933702:C:G
Thyroid	sqtl	2.6e-86	+1.03	3:9940050:G:T
Breast Mammary Tissue	eqtl	2.2e-73	+0.68	3:9933702:C:G
Adipose Visceral Omentum	eqtl	1.2e-72	+0.60	3:9933702:C:G
Nerve Tibial	sqtl	6.1e-63	+1.11	3:9938785:G:A
Esophagus Mucosa	eqtl	2.7e-61	+0.41	3:9933702:C:G
Esophagus Muscularis	eqtl	6.3e-59	+0.56	3:9933702:C:G
Adipose Visceral Omentum	sqtl	3.4e-58	+1.11	3:9940040:G:A
Lung	eqtl	1.3e-57	+0.51	3:9933702:C:G
Cells Cultured fibroblasts	sqtl	6.0e-57	+1.01	3:9933702:C:G
Skin Not Sun Exposed Suprapubic	sqtl	1.8e-56	+1.12	3:9962439:G:A
Artery Aorta	eqtl	4.5e-55	+0.57	3:9933702:C:G
Esophagus Muscularis	sqtl	3.7e-51	+0.99	3:9962439:G:A
Artery Tibial	sqtl	8.5e-51	+1.04	3:9962439:G:A
Skin Sun Exposed Lower leg	sqtl	1.1e-46	+1.01	3:9938785:G:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
35259	23.3074	1807
35262	3.0627	1406
35260	1.1951	523
35261	0.4798	268

Top tissues by expression

showing 100 of 134 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.41	gold quality
cerebellar hemisphere	UBERON:0002245	98.26	gold quality
cerebellar cortex	UBERON:0002129	98.23	gold quality
cerebellum	UBERON:0002037	98.22	gold quality
pituitary gland	UBERON:0000007	97.74	gold quality
right lobe of thyroid gland	UBERON:0001119	97.72	gold quality
adenohypophysis	UBERON:0002196	97.38	gold quality
right uterine tube	UBERON:0001302	97.09	gold quality
apex of heart	UBERON:0002098	97.05	gold quality
right frontal lobe	UBERON:0002810	96.95	gold quality
left lobe of thyroid gland	UBERON:0001120	96.83	gold quality
primary visual cortex	UBERON:0002436	96.74	gold quality
thyroid gland	UBERON:0002046	96.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.97	gold quality
frontal cortex	UBERON:0001870	95.95	gold quality
superior frontal gyrus	UBERON:0002661	95.90	gold quality
right atrium auricular region	UBERON:0006631	95.85	gold quality
brain	UBERON:0000955	95.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.76	gold quality
heart left ventricle	UBERON:0002084	95.69	gold quality
hypothalamus	UBERON:0001898	95.67	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.63	gold quality
anterior cingulate cortex	UBERON:0009835	95.62	gold quality
cerebral cortex	UBERON:0000956	95.59	gold quality
nucleus accumbens	UBERON:0001882	95.56	gold quality
ascending aorta	UBERON:0001496	95.52	gold quality
thoracic aorta	UBERON:0001515	95.47	gold quality
caudate nucleus	UBERON:0001873	95.40	gold quality
putamen	UBERON:0001874	95.33	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.31	gold quality
prefrontal cortex	UBERON:0000451	95.30	gold quality
lower esophagus	UBERON:0013473	95.30	gold quality
fundus of stomach	UBERON:0001160	95.19	gold quality
prostate gland	UBERON:0002367	95.09	gold quality
heart	UBERON:0000948	95.08	gold quality
Ammon’s horn	UBERON:0001954	95.02	gold quality
right lobe of liver	UBERON:0001114	94.95	gold quality
descending thoracic aorta	UBERON:0002345	94.76	gold quality
lower esophagus mucosa	UBERON:0035834	94.75	gold quality
right adrenal gland	UBERON:0001233	94.54	gold quality
substantia nigra	UBERON:0002038	94.45	gold quality
right coronary artery	UBERON:0001625	94.38	gold quality
temporal lobe	UBERON:0001871	94.35	gold quality
amygdala	UBERON:0001876	94.31	gold quality
popliteal artery	UBERON:0002250	94.16	gold quality
tibial artery	UBERON:0007610	94.15	gold quality
right adrenal gland cortex	UBERON:0035827	93.98	gold quality
left adrenal gland cortex	UBERON:0035825	93.83	gold quality
left coronary artery	UBERON:0001626	93.82	gold quality
body of stomach	UBERON:0001161	93.81	gold quality
left adrenal gland	UBERON:0001234	93.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.56	gold quality
myometrium	UBERON:0001296	93.43	gold quality
mucosa of transverse colon	UBERON:0004991	93.28	gold quality
fallopian tube	UBERON:0003889	93.15	gold quality
colon	UBERON:0001155	93.02	gold quality
gastrocnemius	UBERON:0001388	92.97	gold quality
adrenal gland	UBERON:0002369	92.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.85	gold quality
body of uterus	UBERON:0009853	92.77	gold quality
cortex of kidney	UBERON:0001225	92.65	gold quality
omental fat pad	UBERON:0010414	92.64	gold quality
adult mammalian kidney	UBERON:0000082	92.63	gold quality
body of pancreas	UBERON:0001150	92.52	gold quality
left ovary	UBERON:0002119	92.47	gold quality
saliva-secreting gland	UBERON:0001044	92.44	gold quality
minor salivary gland	UBERON:0001830	92.41	gold quality
transverse colon	UBERON:0001157	92.39	gold quality
left uterine tube	UBERON:0001303	92.33	gold quality
muscle of leg	UBERON:0001383	92.33	gold quality
intestine	UBERON:0000160	92.30	gold quality
mucosa of stomach	UBERON:0001199	92.29	gold quality
multicellular organism	UBERON:0000468	92.26	gold quality
right ovary	UBERON:0002118	92.16	gold quality
stomach	UBERON:0000945	92.14	gold quality
spleen	UBERON:0002106	92.11	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.99	gold quality
ovary	UBERON:0000992	91.84	gold quality
pancreas	UBERON:0001264	91.76	gold quality
esophagus	UBERON:0001043	91.73	gold quality
vagina	UBERON:0000996	91.72	gold quality
endocervix	UBERON:0000458	91.69	gold quality
right testis	UBERON:0004534	91.67	gold quality
tibial nerve	UBERON:0001323	91.65	gold quality
small intestine	UBERON:0002108	91.63	gold quality
adipose tissue	UBERON:0001013	91.34	gold quality
islet of Langerhans	UBERON:0000006	91.29	gold quality
smooth muscle tissue	UBERON:0001135	91.27	gold quality
liver	UBERON:0002107	91.25	gold quality
left testis	UBERON:0004533	91.23	gold quality
placenta	UBERON:0001987	91.11	gold quality
upper lobe of left lung	UBERON:0008952	91.08	gold quality
metanephros cortex	UBERON:0010533	91.01	gold quality
urinary bladder	UBERON:0001255	90.86	gold quality
testis	UBERON:0000473	90.84	gold quality
lymph node	UBERON:0000029	90.56	gold quality
thoracic mammary gland	UBERON:0005200	90.36	gold quality
kidney	UBERON:0002113	90.30	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.29	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.77

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebral cortex	tissue	50.1	high
Somatosensory cortex	tissue	50.1
Caudate putamen	tissue	47.4
Pons	tissue	45.5
Frontal cortex	tissue	45.0
Occipital cortex	tissue	44.7
Prefrontal cortex	tissue	44.6
Motor cortex	tissue	44.6
Hypothalamus	tissue	43.8
Retrosplenial and cingulate cortex	tissue	43.0
Thalamus	tissue	41.3
Hippocampal formation	tissue	40.2
Entorhinal cortex	tissue	40.2
Temporal cortex	tissue	39.8
Retrosplenial cortex	tissue	39.3
Superior colliculi	tissue	39.1
Insular cortex	tissue	37.5
Septum	tissue	36.3
Midbrain	tissue	35.3
Substantia nigra	tissue	34.5
Medulla oblongata	tissue	34.3
Periaqueductal gray	tissue	33.2
Basal ganglia	tissue	32.8	medium
Ventral forebrain	tissue	32.7
Heart muscle	tissue	31.9	not detected
Amygdala	tissue	31.0
Putamen	tissue	30.6
Spinal cord	tissue	26.7
Cerebellum	tissue	26.6	high
Olfactory bulb	tissue	22.1
Locus coeruleus	tissue	21.3
Corpus callosum	tissue	18.8
Seminal vesicle	tissue	18.7	medium
Adipose tissue	tissue	16.4	not detected
Pituitary gland	tissue	16.3
Thyroid gland	tissue	15.4	medium
Nucleus accumbens	tissue	13.6
Prostate	tissue	12.9	medium
Parathyroid gland	tissue	12.5	medium
Postcentral gyrus	tissue	12.3
Hippocampus	tissue	12.2	high
Smooth muscle	tissue	11.2	not detected
Choroid plexus	tissue	11.0
Tongue	tissue	9.4
Fallopian tube	tissue	9.3	medium
Liver	tissue	8.2	low
Urinary bladder	tissue	8.1	medium
Lung	tissue	7.8	low
Gallbladder	tissue	7.7	medium
Salivary gland	tissue	7.5	high
Adrenal gland	tissue	7.2	medium
Colon	tissue	7.0	high
Small intestine	tissue	6.5	medium
Stomach 1	tissue	6.4	high
Pancreas	tissue	6.4	medium
Ovary	tissue	6.1	low
Placenta	tissue	5.9	high
Kidney	tissue	5.7	medium
Breast	tissue	5.4	medium
Esophagus	tissue	5.4	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral hippocampus (39.8), Subiculum (38.4), Dorsal hippocampus (38.2), Ventral spinal cord (26.7), Dorsal spinal cord (24.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CRELD1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 39 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-608	98.93	67.83	2013

Functional genomics

gnomAD constraint: pLI 7.64e-10, LOEUF 0.885, missense Z 0.969 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000452070 — one region, missense o/e 0.92.

Literature-anchored findings (GeneRIF, showing 12)

• Missense mutations in this protein are associated with cardiac atrioventricular septal defects. (PMID:12632326)
• Mutations in CRELD1,are infrequently found in patients with congenital cardiac septal defects (PMID:18076106)
• CRELD1 could partly change the localization of RTN3 from the endoplasmic reticulum to the plasma membrane and modulate the apoptotic activity of RTN3 through binding with it. (PMID:19521671)
• 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 (PMID:21080147)
• SNP c.985 C>T of CRELD1 is involved in causing congenital heart disease in patients of Mysore, South India. (PMID:21413875)
• study indicates that deleterious CRELD1 missense mutations are specifically associated with AVSD and are not correlated with other aspects of the heterotaxy phenotype (PMID:22740159)
• we identified two CRELD1 haplotypes associated with AVSD phenotype among DS and euploid individuals. (PMID:22987595)
• Mutation of the CRELD1 gene increased the risk for atrioventricular septal defect. (PMID:24927998)
• Germline mutations in the NKX2-5, GATA4, and CRELD1 genes do not appear to be associated with CHD in Mexican DS patients. (PMID:25524324)
• The CRELD1 gene is likely to have a major role in causation of AVSD phenotype in selected DS patients. (PMID:29054759)
• CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome. (PMID:36929416)
• Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections. (PMID:37947183)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	creld1b	ENSDARG00000006990
danio_rerio	creld1a	ENSDARG00000099989
mus_musculus	Creld1	ENSMUSG00000030284
rattus_norvegicus	Creld1	ENSRNOG00000009414
caenorhabditis_elegans		WBGENE00000168
caenorhabditis_elegans		WBGENE00012018
caenorhabditis_elegans		WBGENE00013480
caenorhabditis_elegans		WBGENE00013486
caenorhabditis_elegans		WBGENE00013487
caenorhabditis_elegans		WBGENE00018906
caenorhabditis_elegans		WBGENE00019901
caenorhabditis_elegans		WBGENE00022858

Paralogs (8): DLL3 (ENSG00000090932), CD93 (ENSG00000125810), FBLN7 (ENSG00000144152), WIF1 (ENSG00000156076), DLK2 (ENSG00000171462), CD248 (ENSG00000174807), CLEC14A (ENSG00000176435), CRELD2 (ENSG00000184164)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2152539) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 20 distinct phenotype terms.

Mouse phenotype (MP)	Records
embryonic lethality during organogenesis, complete penetrance	2
absent organized vascular network	1
abnormal heart development	1
abnormal craniofacial morphology	1
decreased body weight	1
decreased body size	1
cardiac fibrosis	1
abnormal forebrain development	1
abnormal midbrain development	1
abnormal trabecula carnea morphology	1
abnormal hindbrain development	1
congestive heart failure	1
increased heart atrium size	1
ventricle myocardium hypoplasia	1
postnatal lethality, complete penetrance	1
neonatal lethality, incomplete penetrance	1
abnormal extracellular matrix morphology	1
increased embryonic tissue cell apoptosis	1
atrioventricular cushion hypoplasia	1
cardiovascular shunt	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RC26	99.8%	Diamond
Macaca fascicularis	Q7YQD7	98.0%	Diamond
Cricetulus griseus	O55058	97.1%	Diamond
Bos taurus	Q5EA62	97.1%	Diamond
Macaca mulatta	Q2Q426	89.0%	Diamond
Xenopus laevis	Q4V7M2	85.6%	Diamond
Sus scrofa	C0HL13	73.8%	Diamond
Canis lupus familiaris	Q2Q421	71.4%	Diamond
Xenopus tropicalis	A0A6I8RMG7	58.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PRRT3-AS1	ncRNA	100874032
PRRT3	protein-coding	285368
EMC3-AS1	ncRNA	442075
EMC3	protein-coding	55831
IL17RC	protein-coding	84818
IL17RE	protein-coding	132014
JAGN1	protein-coding	84522
CIDEC	protein-coding	63924

Protein

Protein identifiers

Protein disulfide isomerase CRELD1 — Q96HD1 (reviewed: Q96HD1)

Alternative names: Cysteine-rich with EGF-like domain protein 1

All UniProt accessions (24): A0A669KAV0, A0A669KAY9, A0A669KB87, A0A669KBB3, A0A804HI35, A0A804HJ85, A0A804HJB9, A0A804HJJ0, Q96HD1, A0A804HJM5, A0A804HK40, A0A804HKD9, A0A804HKL1, A0A804HKP7, A0A804HKP9, A0A804HL07, A0A804HL19, A0A804HL34, A0A804HL57, A0A804HL60, A0A804HLG6, A0A8C8KJP3, F8WBY3, H7C2L3

UniProt curated annotations — full annotation on UniProt →

Function. Protein disulfide isomerase. Promotes the localization of acetylcholine receptors (AChRs) to the plasma membrane.

Subcellular location. Membrane.

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.

Disease relevance. Atrioventricular septal defect 2 (AVSD2) [MIM:606217] A congenital heart malformation characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. The complete form involves underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum; the valve itself is also shared. A less severe form, known as ostium primum atrial septal defect, is characterized by separate atrioventricular valvar orifices despite a common junction. Disease susceptibility is associated with variants affecting the gene represented in this entry. Jeffries-Lakhani neurodevelopmental syndrome (JELANS) [MIM:620771] An autosomal recessive neurodevelopmental disorder characterized by developmental delay, early-onset epilepsy, and hypotonia apparent from infancy. Clinical features include motor delay, speech delay, and impaired intellectual development. About half of patients are non-ambulatory and/or non-verbal. Some patients have cardiac rhythm disturbances, and some experience recurrent infections. Premature death due to cardiac arrhythmia or epilepsy may occur. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by inducers of the unfolded protein response (UPR), including tunicamycin and thapsigargin.

Similarity. Belongs to the CRELD family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96HD1-1	1	yes
Q96HD1-2	2

RefSeq proteins (9): NP_001026887, NP_001070883, NP_001361245, NP_001361246, NP_001361247, NP_001361248, NP_001361249, NP_001397642, NP_056328 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002049	LE_dom	Domain
IPR006212	Furin_repeat	Repeat
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR021852	DUF3456	Domain
IPR049883	NOTCH1_EGF-like	Domain
IPR050751	ECM_structural_protein	Family

Pfam: PF07645, PF11938

UniProt features (42 total): sequence variant 12, disulfide bond 8, sequence conflict 6, topological domain 3, domain 2, short sequence motif 2, glycosylation site 2, transmembrane region 2, repeat 2, signal peptide 1, chain 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96HD1-F1	81.68	0.57

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Isomerase, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of the circulatory system

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoli

Antibody reliability (HPA): IH uncertain · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (8)

Type	Positions
Redox-active	46–49, 278–281
Disulfide bond	155–169, 163–181, 183–192, 309–321, 314–330, 332–343

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	79, 205

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 394 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_ENDOCARDIAL_CUSHION_DEVELOPMENT, GCANCTGNY_MYOD_Q6, AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, AREB6_01, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, BRUNEAU_SEPTATION_VENTRICULAR, CREB_Q4, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, MYOD_Q6

GO Biological Process (2): endocardial cushion development (GO:0003197), cardiac septum development (GO:0003279)

GO Molecular Function (5): protein disulfide isomerase activity (GO:0003756), calcium ion binding (GO:0005509), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (4): membrane (GO:0016020), extracellular matrix (GO:0031012), glutamatergic synapse (GO:0098978), synapse (GO:0045202)

GO top-level categories

15 GO namespaces:

Category	Terms
heart development	1
mesenchyme development	1
cardiac chamber development	1
animal gross anatomical part developmental process	1
intramolecular oxidoreductase activity, transposing S-S bonds	1
catalytic activity, acting on a protein	1
metal ion binding	1
structural molecule activity	1
extracellular matrix	1
binding	1
catalytic activity	1
cellular anatomical structure	1
external encapsulating structure	1
synapse	1
cell junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular matrix	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 744 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRELD1	VPS26C	O14972	660
CRELD1	PSMG1	O95456	606
CRELD1	CFC1	P0CG37	563
CRELD1	MX1	P20591	553
CRELD1	ZIC3	O60481	540
CRELD1	RCAN1	P53805	537
CRELD1	GJA1	P17302	522
CRELD1	A0A087WVV2	A0A087WVV2	510
CRELD1	STMN2	Q93045	510
CRELD1	SPARC	P09486	490
CRELD1	COL6A2	P12110	478
CRELD1	TADA3	O75528	463
CRELD1	BRPF1	P55201	461
CRELD1	NKX2-5	P52952	455
CRELD1	TBX5	Q99593	445

IntAct

Human interaction partners of CRELD1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

19 partners by confidence:

Partner	Interaction type	MIscore	Records
ADRA1A	physical association	0.370	3
DRD2	physical association	0.370	1
HOXA1	physical association	0.370	1
HTR2C	physical association	0.370	1
NUFIP2	physical association	0.370	1
SHANK3	physical association	0.370	1
TMEM223	association	0.350	1
ATP5MF	physical association	0.000	1
COPS6	physical association	0.000	1
EEF1G	physical association	0.000	1
GDF9	physical association	0.000	1
ITGB3BP	physical association	0.000	1
KAT5	physical association	0.000	1
MTNR1B	physical association	0.000	1
POLA2	physical association	0.000	1
PTN	physical association	0.000	1
SETDB1	physical association	0.000	1
SUMO2	physical association	0.000	1
UBA1	ubiquitination reaction	0.000	1

BioGRID (174 interactions; top human partners by supporting records): P2RY12 (Affinity Capture-MS; 3 records), CD27 (Affinity Capture-MS; 2 records), SLC35F6 (Affinity Capture-MS; 2 records), AAAS (Affinity Capture-MS), ABCC3 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCD1 (Affinity Capture-MS), ABCD3 (Affinity Capture-MS), ALG10 (Affinity Capture-MS), ALG10B (Affinity Capture-MS), ALG12 (Affinity Capture-MS), ALG3 (Affinity Capture-MS), ALG6 (Affinity Capture-MS), ALG8 (Affinity Capture-MS), ANKRD9 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for CRELD1: 256 ClinVar records (17 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

256 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	6
Uncertain significance	122
Likely benign	53
Benign	18

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 17 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3361931	NM_001077415.3(CRELD1):c.460+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
465835	NM_001077415.3(CRELD1):c.523C>T (p.Arg175Ter)	Pathogenic	criteria provided, single submitter	1
817355	NM_001077415.3(CRELD1):c.254_257del (p.Asp85fs)	Pathogenic	criteria provided, single submitter	1
861074	NM_001077415.3(CRELD1):c.1048+417_1048+418del	Pathogenic	criteria provided, single submitter	1
3360571	NM_001077415.3(CRELD1):c.196dup (p.Asp66fs)	Pathogenic	criteria provided, single submitter	1
3603018	NM_001077415.3(CRELD1):c.399G>A (p.Trp133Ter)	Pathogenic	criteria provided, single submitter	1
3720341	NM_001077415.3(CRELD1):c.671_672insAAAC (p.Glu225fs)	Pathogenic	criteria provided, single submitter	1
4853633	NM_001077415.3(CRELD1):c.189del (p.Ile64fs)	Pathogenic	criteria provided, single submitter	1
546927	NM_001077415.3(CRELD1):c.959dup (p.Cys321fs)	Likely pathogenic	criteria provided, single submitter	1
633463	NM_001077415.3(CRELD1):c.822_823del (p.Ala275fs)	Likely pathogenic	criteria provided, single submitter	1
3666935	NM_001077415.3(CRELD1):c.913+1G>A	Likely pathogenic	criteria provided, single submitter	1
3897204	NM_001077415.3(CRELD1):c.314G>A (p.Cys105Tyr)	Likely pathogenic	criteria provided, single submitter	1
809601	GRCh37/hg19 3p25.3(chr3:9969850-9979790)x1	Likely pathogenic	criteria provided, single submitter	1
2574123	NM_001077415.3(CRELD1):c.223T>C (p.Trp75Arg)	Pathogenic	no assertion criteria provided	1
2574124	NM_001077415.3(CRELD1):c.587G>T (p.Gly196Val)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CRELD1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 826):

Position(s)	Effect	Δscore	Sites
3:9934834	acceptor_gain	1.0000
3:9934918–9934919	donor_loss	1.0000	4
3:9943379	acceptor_gain	1.0000
3:9943380	acceptor_loss	1.0000
3:9943516	donor_loss	1.0000	3
3:9934833–9934834	acceptor_loss	0.9900	2
3:9934918	donor_loss	0.9900
3:9940848–9940849	acceptor_loss	0.9900	6
3:9942811	acceptor_loss	0.9900	3
3:9942897–9942898	donor_loss	0.9900	5

AlphaMissense

1,095 missense substitutions predicted likely pathogenic (of 2,743 scored), across 253 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M369	9	0.875	0.995
D245	8	0.987	0.997
N323	8	0.985	0.994
N264	8	0.981	0.997
D305	8	0.976	0.992
D386	8	0.966	0.994
F393	8	0.946	0.983
S86	8	0.934	0.993
F56	8	0.895	0.993
F371	8	0.859	0.952
F355	8	0.799	0.966
C262	7	0.996	0.999
C281	7	0.995	0.998
C243	7	0.994	0.999
C249	7	0.994	0.999
C289	7	0.994	0.999
C135	7	0.993	0.997
C232	7	0.993	0.999
C278	7	0.993	0.997
C303	7	0.993	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	1.26e-05
Skin Cutaneous Melanoma (TCGA)	favorable	0.00016
Colon Adenocarcinoma (validation)	unfavorable	0.000183
Glioblastoma Multiforme (TCGA)	unfavorable	0.000526

Disease associations

OMIM: gene MIM:607170 | disease phenotypes: MIM:615779, MIM:614429, MIM:606217, MIM:620771

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
complex neurodevelopmental disorder	Strong	Autosomal recessive
Jeffries-Lakhani neurodevelopmental syndrome	Moderate	Autosomal recessive
congenital heart disease	Limited	Autosomal dominant
atrioventricular septal defect, susceptibility to, 2	Limited	Autosomal dominant	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Familial non syndromic congenital heart disease	amber
Fetal anomalies	amber
Laterality disorders and isomerism	amber

Mondo (6): congenital heart defects, multiple types, 4 (MONDO:0014344), ventricular septal defect 1 (MONDO:0013746), atrioventricular septal defect, susceptibility to, 2 (MONDO:0011650), Jeffries-Lakhani neurodevelopmental syndrome (MONDO:0958329), complex neurodevelopmental disorder (MONDO:0100038), congenital heart disease (MONDO:0005453)

HPO phenotypes

showing 60 of 117 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000122	Unilateral renal agenesis
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000272	Malar flattening
HP:0000280	Coarse facial features
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000322	Short philtrum
HP:0000336	Prominent supraorbital ridges
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000445	Wide nose
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000565	Esotropia
HP:0000577	Exotropia
HP:0000637	Long palpebral fissure
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0000821	Hypothyroidism
HP:0001028	Hemangioma
HP:0001182	Tapered finger
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001269	Hemiparesis
HP:0001288	Gait disturbance
HP:0001336	Myoclonus
HP:0001385	Hip dysplasia
HP:0001488	Bilateral ptosis
HP:0001531	Failure to thrive in infancy
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001562	Oligohydramnios
HP:0001596	Alopecia
HP:0001651	Dextrocardia
HP:0001662	Bradycardia
HP:0001695	Cardiac arrest
HP:0001733	Pancreatitis
HP:0001773	Short foot
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0002045	Hypothermia

GWAS associations

1 associations:

Study	Trait	p-value
GCST006585_2773	Blood protein levels	0.000000e+00

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
C565249	Atrioventricular Septal Defect, Partial, with Heterotaxy Syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	3
Tobacco Smoke Pollution	increases expression, affects expression	2
Tunicamycin	increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	increases expression	1
bisphenol S	increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases expression, increases abundance	1
Cisplatin	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Lead	affects splicing	1
Selenium	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SJ75	HAP1 CRELD1 (-) 1	Cancer cell line	Male
CVCL_SJ76	HAP1 CRELD1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 367 trials:

NCT	Phase	Status	Title
NCT00668824	Phase 4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	Phase 4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	Phase 4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	Phase 4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	Phase 4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	Phase 4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	Phase 4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	Phase 4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	Phase 4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	Phase 4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	Phase 4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	Phase 4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT02513940	Phase 4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	Phase 4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	Phase 4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	Phase 4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00000470	Phase 3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	Phase 3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	Phase 3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	Phase 3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	Phase 3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	Phase 3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	Phase 3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	Phase 3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	Phase 3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	Phase 3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	Phase 3	UNKNOWN	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	Phase 3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	Phase 3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	Phase 3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	Phase 3	RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	Phase 2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	Phase 2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	Phase 2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	Phase 2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	Phase 2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	Phase 2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	Phase 2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	Phase 2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	Phase 2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	Phase 2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	Phase 2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	Phase 2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	Phase 2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE
NCT01841177	Phase 2	COMPLETED	Evaluating Precision of Therapy - Milrinone
NCT02046135	Phase 2	TERMINATED	Sodium Bicarbonate to Prevent Acute Kidney Injury in Children Undergoing Cardiac Surgery
NCT02133573	Phase 2	COMPLETED	Randomized Trial of Maternal Progesterone Therapy
NCT02232399	Phase 2	COMPLETED	Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease?
NCT02492269	Phase 2	COMPLETED	Stress Response and Neurodevelopmental Outcome After Cardiac Surgery Utilizing CPB in Children: A Prospective, Double Blinded and Randomized Study
NCT02564796	Phase 2	TERMINATED	Erythropoietin to Prevent Unnecessary Transfusions In Patients With Cyanotic CHD - A Prospective Control Trial
NCT02618824	Phase 2	UNKNOWN	Role of Terminal Warm Blood Cardioplegia as Myocardial Protection in the Use of Histidine-Tryptophan-Ketoglutarate Cardioplegia in Complex Congenital Heart Surgery
NCT02769624	Phase 2	TERMINATED	Acute Effects of Inhaled Treprostinil in Fontan Patients
NCT02877238	Phase 2	COMPLETED	Remote Preconditioning and Myocardial Protection
NCT03082716	Phase 2	COMPLETED	Custodiol Versus Blood Cardioplegaia in Paediatric Cardiac Surgery
NCT03425734	Phase 2	UNKNOWN	The Effect of Dexmedetomidine on Kidney Perfusion in Paediatric Patients
NCT04434001	Phase 2	TERMINATED	ZEPLAST- PED: ZEro_PLASma Trial in Small Infants Undergoing Cardiac Surgery
NCT04807621	Phase 2	UNKNOWN	Platelets or Fibrinogen as First-line Treatment for Bleeding During Pedatric Heart Surgery
NCT05717049	Phase 2	COMPLETED	Theophylline Effects in the Fontan Circulation
NCT06080074	Phase 2	RECRUITING	Multicenter Trial of ECMO in Children With Severe Cardiac Failure Using the Cardiohelp System
NCT07498803	Phase 2	NOT_YET_RECRUITING	Sota-ES - Sotatercept in Patients With Congenital Heart Disease and Eisenmenger´s Syndrome