CRIPTO

Summary

CRIPTO (cripto, EGF-CFC family member, HGNC:11701) is a protein-coding gene on chromosome 3p21.31, encoding Protein Cripto (P13385). GPI-anchored cell membrane protein involved in Nodal signaling. It is a selective cancer dependency (DepMap: 57.5% of cell lines).

This gene encodes an epidermal growth factor-related protein that contains a cripto, FRL-1, and cryptic domain. The encoded protein is an extracellular, membrane-bound signaling protein that plays an essential role in embryonic development and tumor growth. Mutations in this gene are associated with forebrain defects. Pseudogenes of this gene are found on chromosomes 2, 3, 6, 8, 19 and X. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 6997 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 76 total
• GTEx eGene: eQTL in 44 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 115
• Drug target: yes — 1 curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 57.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.33 (unconstrained)
• MANE Select transcript: NM_003212
• Notable: 76 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11701
Approved symbol	CRIPTO
Name	cripto, EGF-CFC family member
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	CR, Cripto-1, CR-1
Ensembl gene	ENSG00000241186
Ensembl biotype	protein_coding
OMIM	187395
Entrez	6997

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 18 protein_coding, 8 nonsense_mediated_decay, 3 retained_intron

MANE Select: ENST00000296145

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

ENST00000296145, ENST00000459867, ENST00000471721, ENST00000493282, ENST00000542931, ENST00000863382, ENST00000938305, ENST00000938306, ENST00000938307, ENST00000938308, ENST00000938309, ENST00000938310, ENST00000938311, ENST00000938312, ENST00000938313, ENST00000938314, ENST00000951684, ENST00001079929, ENST00001079931, ENST00001079932, ENST00001079935, ENST00001079937, ENST00001079938, ENST00001079940, ENST00001079945, ENST00001079950, ENST00001130083, ENST00001130084, ENST00001142846

RefSeq mRNA: 2 — MANE Select: NM_003212 NM_001174136, NM_003212

CCDS: CCDS2742, CCDS54575

Canonical transcript exons

ENST00000296145 — 6 exons

Exon	Start	End
ENSE00001078649	46579739	46579853
ENSE00001078650	46579951	46580060
ENSE00001423089	46581132	46582457
ENSE00001942602	46577788	46578004
ENSE00003517910	46579232	46579366
ENSE00003579118	46579095	46579147

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 87.73.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9725 / max 89.8936, expressed in 102 samples.

Highest expression (Bgee): adrenal tissue, primordial germ cell in gonad, metanephros cortex, spleen, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CRIPTO is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 44 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 44 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	3.3e-178	+1.25	3:46577748:T:A
Nerve Tibial	eqtl	3.0e-139	+1.23	3:46577748:T:A
Adipose Subcutaneous	eqtl	1.4e-119	+1.19	3:46577748:T:A
Esophagus Muscularis	eqtl	9.9e-107	+1.25	3:46577748:T:A
Breast Mammary Tissue	eqtl	7.1e-98	+1.21	3:46577748:T:A
Adipose Visceral Omentum	eqtl	1.9e-97	+1.17	3:46577748:T:A
Skin Not Sun Exposed Suprapubic	eqtl	4.0e-91	+1.07	3:46577748:T:A
Skin Sun Exposed Lower leg	eqtl	4.4e-87	+1.03	3:46577748:T:A
Esophagus Mucosa	eqtl	2.1e-76	+1.07	3:46577748:T:A
Heart Left Ventricle	eqtl	4.8e-76	+1.21	3:46577748:T:A
Colon Sigmoid	eqtl	6.2e-66	+1.11	3:46577748:T:A
Esophagus Gastroesophageal Junction	eqtl	9.0e-66	+1.15	3:46575847:G:A
Adrenal Gland	eqtl	5.2e-55	+1.28	3:46577748:T:A
Spleen	eqtl	4.4e-54	+1.22	3:46577748:T:A
Heart Atrial Appendage	eqtl	1.2e-50	+0.96	3:46575847:G:A
Lung	eqtl	2.2e-44	+0.81	3:46577748:T:A
Testis	eqtl	6.7e-43	+1.10	3:46575847:G:A
Pituitary	eqtl	1.7e-40	+1.07	3:46577748:T:A
Ovary	eqtl	1.9e-38	+1.10	3:46575847:G:A
Prostate	eqtl	2.3e-38	+1.21	3:46577748:T:A

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
36492	0.4081	83
36490	0.3437	53
36489	0.1911	50
36491	0.0139	6
202745	0.0102	3
36493	0.0056	1

Top tissues by expression

showing 100 of 136 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	87.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.47	gold quality
metanephros cortex	UBERON:0010533	81.95	gold quality
spleen	UBERON:0002106	81.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.63	gold quality
adult mammalian kidney	UBERON:0000082	77.39	gold quality
left ovary	UBERON:0002119	77.28	gold quality
ovary	UBERON:0000992	76.09	gold quality
rectum	UBERON:0001052	74.66	gold quality
mucosa of transverse colon	UBERON:0004991	73.68	gold quality
kidney	UBERON:0002113	71.01	gold quality
right ovary	UBERON:0002118	68.53	gold quality
smooth muscle tissue	UBERON:0001135	66.71	gold quality
endometrium	UBERON:0001295	62.52	gold quality
prefrontal cortex	UBERON:0000451	61.94	gold quality
body of stomach	UBERON:0001161	61.33	gold quality
cortex of kidney	UBERON:0001225	60.79	gold quality
muscle tissue	UBERON:0002385	60.78	gold quality
colonic epithelium	UBERON:0000397	60.18	gold quality
liver	UBERON:0002107	60.15	gold quality
right lobe of liver	UBERON:0001114	59.48	gold quality
gall bladder	UBERON:0002110	59.48	gold quality
stomach	UBERON:0000945	59.47	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	58.92	gold quality
skeletal muscle tissue	UBERON:0001134	58.82	gold quality
duodenum	UBERON:0002114	58.36	gold quality
Ammon’s horn	UBERON:0001954	58.33	gold quality
superior frontal gyrus	UBERON:0002661	58.07	gold quality
substantia nigra	UBERON:0002038	57.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	57.67	gold quality
frontal cortex	UBERON:0001870	57.26	gold quality
primary visual cortex	UBERON:0002436	56.96	gold quality
right lobe of thyroid gland	UBERON:0001119	56.30	gold quality
hypothalamus	UBERON:0001898	56.09	gold quality
caudate nucleus	UBERON:0001873	55.54	gold quality
cerebral cortex	UBERON:0000956	55.12	gold quality
putamen	UBERON:0001874	54.95	gold quality
transverse colon	UBERON:0001157	54.92	gold quality
left adrenal gland cortex	UBERON:0035825	54.53	gold quality
left uterine tube	UBERON:0001303	54.41	gold quality
uterus	UBERON:0000995	54.33	gold quality
thyroid gland	UBERON:0002046	54.28	gold quality
adrenal gland	UBERON:0002369	53.88	gold quality
amygdala	UBERON:0001876	53.79	gold quality
temporal lobe	UBERON:0001871	53.77	gold quality
left lobe of thyroid gland	UBERON:0001120	53.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	53.14	gold quality
right adrenal gland cortex	UBERON:0035827	52.83	gold quality
brain	UBERON:0000955	52.29	gold quality
vermiform appendix	UBERON:0001154	52.04	gold quality
left adrenal gland	UBERON:0001234	52.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	51.88	gold quality
anterior cingulate cortex	UBERON:0009835	51.70	gold quality
heart left ventricle	UBERON:0002084	51.09	gold quality
lymph node	UBERON:0000029	50.96	gold quality
myometrium	UBERON:0001296	50.76	gold quality
tibial nerve	UBERON:0001323	50.74	gold quality
fallopian tube	UBERON:0003889	50.74	gold quality
tonsil	UBERON:0002372	50.68	gold quality
nucleus accumbens	UBERON:0001882	50.40	gold quality
intestine	UBERON:0000160	50.28	gold quality
colon	UBERON:0001155	50.22	gold quality
right frontal lobe	UBERON:0002810	50.21	gold quality
small intestine	UBERON:0002108	49.95	gold quality
mucosa of stomach	UBERON:0001199	49.91	gold quality
small intestine Peyer’s patch	UBERON:0003454	49.50	gold quality
body of uterus	UBERON:0009853	49.43	gold quality
placenta	UBERON:0001987	49.32	gold quality
endocervix	UBERON:0000458	49.03	gold quality
fundus of stomach	UBERON:0001160	48.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	47.82	gold quality
skeletal muscle organ	UBERON:0014892	47.73	gold quality
right adrenal gland	UBERON:0001233	47.69	gold quality
omental fat pad	UBERON:0010414	47.66	gold quality
cerebellum	UBERON:0002037	47.56	gold quality
muscle of leg	UBERON:0001383	47.32	gold quality
cerebellar cortex	UBERON:0002129	47.30	gold quality
cerebellar hemisphere	UBERON:0002245	47.21	gold quality
gastrocnemius	UBERON:0001388	46.99	gold quality
uterine cervix	UBERON:0000002	46.87	gold quality
material anatomical entity	UBERON:0000465	46.71	gold quality
multicellular organism	UBERON:0000468	46.71	gold quality
anatomical system	UBERON:0000467	46.63	gold quality
urinary bladder	UBERON:0001255	46.53	gold quality
heart	UBERON:0000948	46.06	gold quality
ectocervix	UBERON:0012249	45.87	gold quality
adipose tissue	UBERON:0001013	45.01	gold quality
thoracic mammary gland	UBERON:0005200	44.99	gold quality
lower esophagus	UBERON:0013473	44.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	44.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	42.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	42.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	42.65	gold quality
hindlimb stylopod muscle	UBERON:0004252	42.46	gold quality
prostate gland	UBERON:0002367	41.55	gold quality
sural nerve	UBERON:0015488	41.49	gold quality
esophagus	UBERON:0001043	41.09	gold quality
right uterine tube	UBERON:0001302	40.62	silver quality
right coronary artery	UBERON:0001625	40.23	silver quality
right atrium auricular region	UBERON:0006631	40.17	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	820.74
E-MTAB-3929	yes	581.96
E-MTAB-8271	yes	6.94
E-ANND-3	no	2.91

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 68 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Spleen	tissue	19.7
Thymus	tissue	14.0
Cerebellum	tissue	11.2
Ovary	tissue	8.9
Pons	tissue	8.7
Kidney	tissue	8.0
Medulla oblongata	tissue	5.0
Rectum	tissue	4.3
Spinal cord	tissue	4.2
Putamen	tissue	4.0
Retrosplenial cortex	tissue	4.0
Hippocampus	tissue	3.9
Choroid plexus	tissue	3.7
Nucleus accumbens	tissue	3.6
Locus coeruleus	tissue	3.6
Substantia nigra	tissue	3.1
Postcentral gyrus	tissue	2.9
Stomach 1	tissue	2.6
Colon	tissue	2.4
Adrenal gland	tissue	2.1
Midbrain	tissue	2.0
Epididymis	tissue	1.9
Thalamus	tissue	1.8
Skeletal muscle	tissue	1.4
Tongue	tissue	1.4
Liver	tissue	1.2
Cerebral cortex	tissue	1.1
Smooth muscle	tissue	1.1
Hypothalamus	tissue	1.1
Somatosensory cortex	tissue	1.1
Endometrium 1	tissue	1.0
Basal ganglia	tissue	1.0
Ventral forebrain	tissue	1.0
Caudate putamen	tissue	1.0
Occipital cortex	tissue	1.0
Salivary gland	tissue	0.9
Frontal cortex	tissue	0.9
Amygdala	tissue	0.9
Corpus callosum	tissue	0.9
Septum	tissue	0.9
Hippocampal formation	tissue	0.8
Thyroid gland	tissue	0.7
Duodenum	tissue	0.7
Entorhinal cortex	tissue	0.7
Cervix	tissue	0.6
Gallbladder	tissue	0.6
Retrosplenial and cingulate cortex	tissue	0.6
Olfactory bulb	tissue	0.6
Testis	tissue	0.5
Small intestine	tissue	0.5
Appendix	tissue	0.5
Pancreas	tissue	0.4
Lung	tissue	0.4
Prostate	tissue	0.4
Skin 1	tissue	0.3
Lymph node	tissue	0.3
Retina	tissue	0.3
Seminal vesicle	tissue	0.3
Adipose tissue	tissue	0.3
Bone marrow	tissue	0.3

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — Posterior thalamic nucleus (6.9), Lateral amygdala (5.4), Lateral lemniscal nuclei (5.2), Anterior cochlear nucleus, ventral (5.0), Nucleus ambiguus (5.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

showing 30 of 70 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
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-5696	99.98	72.36	4487
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-1244	99.33	68.38	832

Functional genomics

gnomAD constraint: pLI 4.19e-07, LOEUF 1.33, missense Z 0.699 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000296145 — one region, missense o/e 0.91. ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 57.5% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): PANC-1 (-1.806), SNU-840 (-1.506), Du4475 (-1.464), KP-N-YN (-1.387), VMRC-RCW (-1.377), JVM-3 (-1.32), KP-2 (-1.308), COLO-678 (-1.262), NCI-H1650 (-1.194), RT4 (-1.194), Panc 05.04 (-1.179), RMUG-S (-1.176), EFE-184 (-1.162), SU.86.86 (-1.138), INA6 (-1.136).

Literature-anchored findings (GeneRIF, showing 40)

• Cripto has dual roles as a coreceptor as well as a coligand for Nodal and that this signaling interaction with Nodal is regulated by an unusual form of glycosylation. (PMID:12052855)
• A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects. (PMID:12073012)
• complexation with activin and type II activin receptors and role in blocking activin signaling (PMID:12682303)
• CRIPTO signaling promotes cardiomyogenesis and redirects the neural fate of embryonic stem cells. (PMID:14581455)
• Results suggest that cripto-1 overexpression might be associated with the progression towards a more aggressive phenotype in breast carcinoma, through the activation of both Akt and Smad-2 signalling pathways. (PMID:14584041)
• The regulation of Netrin-1 expression is important in regulating Cripto-1-dependent invasion and migration of mammary epithelial cells. (PMID:16176936)
• The plasma CR-1 might represent a novel biomarker for the detection of breast and colon carcinomas. A statistically significant increase in the levels of plasma CR-1 was found in patients with colon carcinoma and in patients with breast carcinoma. (PMID:16951234)
• CRIPTO-3, a processed pseudogene of CRIPTO-1 on the X chromosome, is expressed in undifferentiated NT2 cells and is regulated by germ cell nuclear factor in parallel to CRIPTO-1 (PMID:16954206)
• Cripto inhibits the tumor suppressor function of TGF-beta by a novel mechanism. (PMID:17030617)
• Transcriptional regulation of CR-1 expression by WNT signaling through an intronic-exonic enhancer element, containing three tandem TCF/LEF binding sites within the CR-1 gene. (PMID:17291450)
• Growth factor induction of Cripto-1 shedding by glycosylphosphatidylinositol-phospholipase D and enhancement of endothelial cell migration are reported. (PMID:17720976)
• GPI attachment of CR-1 is required for the paracrine activity as a Nodal co-receptor. (PMID:17925387)
• Tese results suggest a differential modulation of CR-1 gene expression in embryonal and colon cancer cells by two different members of the TGF-beta family. (PMID:17941089)
• Cripto facilitates Nodal signaling and inhibits activin signaling by forming receptor complexes with these ligands that are structurally and functionally similar. (PMID:18089557)
• Combined analysis of Cripto-1 and E-cadherin has significant value in evaluating the metastatic potential of gastric cancer and predicting patient prognosis. (PMID:18312357)
• Study indicate that the synthetic h-CFC interacts with the ALK4 receptor with a K(D) in micro M range, that the h-CFC overall topology is determined by the presence of three disulfide bridges. (PMID:19035567)
• Cripto-1 overexpression is involved in the tumorigenesis of gastric- and pancreatobiliary-type intraductal papillary mucinous neoplasms (PMID:19082438)
• Activin A, activin receptor type II, nodal, and cripto mRNA are expressed by eutopic and ectopic endometrium in women with ovarian endometriosis. (PMID:19386982)
• Results show that targeted disruption of the cell surface Cripto/GRP78 complex precludes Cripto activation of MAPK/PI3K and Smad2/3 pathways. (PMID:19421146)
• Cripto-1 overexpression is connected with the tumorigenesis and progression of nasopharyngeal carcinoma. (PMID:19732464)
• work firstly provides human genetic evidence of TDGF1 involved in the pathogenesis of ventricular septal defects (PMID:19853938)
• Nodal and Cripto immunoreactivity increased dramatically in the transition from histologic Grade 1 to histologic Grades 2 and 3 endometrial carcinomas. (PMID:19874624)
• TDGF1 has a role in metachronous metastasis of colorectal cancer (PMID:20126975)
• Data suggest that the up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis (PMID:20128024)
• TDGF-1, which is significantly upregulated in APA and mediates aldosterone hypersecretion and deregulated growth in adrenocortical cells in vitro, may represent a key player in the development and pathophysiology of primary aldosteronism. (PMID:20385969)
• Results demonstrate that CR-1 expression is enriched in an undifferentiated, tumorigenic subpopulation and is regulated by key regulators of pluripotent stem cells. (PMID:20549704)
• molecular model of activin receptor-like kinase 4/Cripto/Nodal complex built by homology modeling as well as docking tests aimed at identifying potential binding epitopes (PMID:20629020)
• expression of CR-1 may alter the physiochemical properties of the plasma membrane resulting in an enhancement of intercellular transfer of cellular signaling components which may account for the paracrine activity of CR-1. (PMID:21055389)
• Disturbed expression of endometrial activin A, cripto , and follistatin suggests a dysfunction of the activin pathway in endometriosis/endometrioma. (PMID:21496809)
• Cripto-1 plays a role in the malignant transformation of oral mucosa and is involved in the tumorigenesis and progression of oral squamous cell carcinoma by promoting the growth and migration of malignant cells. (PMID:21824804)
• High CRIPTO-1 is associated with cutaneous melanoma. (PMID:21863025)
• Cripto/GRP78 modulates the TGF-beta pathway in development and oncogenesis [review] (PMID:22306319)
• Cripto-1 may play a role during developmental EMT, and it may also be involved in the reprogramming of differentiated tumor cells into cancer stem cells through the induction of an EMT program. (PMID:22542493)
• Cross-talk between Cripto-1 and the Wnt/beta-catenin signaling pathway might play a role in mammary transformation leading to a more aggressive behavior of mammary cancer cells. (PMID:23022962)
• human testicular tumors showed upregulation of NODAL and CRIPTO that was proportional to invasiveness and to the number of malignant cells. (PMID:23034635)
• Offer some insight into the transcriptional regulation of CR-1 gene expression and its critical role in the pathogenesis of human cancer. (PMID:23129342)
• The significance of cell surface CR-1 expression in human melanoma cells, was examined. (PMID:23574716)
• Cripto is overexpressed in colonic neoplasms and is related to cancer cell migration/invasion. (PMID:24379580)
• These findings clearly suggest that the downregulation of miR-15a-16 with Cripto amplification may be involved in the development of nonsmall cell lung cancer. (PMID:24500260)
• CR-1 expression in glioblastoma multiforme(GBM)tissue and blood; CR-1 plasma levels from GBM patients were elevated compared with normal; CR-1 concentrations higher than normal correlated with shorter overall survival; identified CR-1 in different areas of GBM tissue including perivascular tumor cells and endothelial cells (PMID:24521322)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cripto	ENSMUSG00000032494
rattus_norvegicus	Cripto	ENSRNOG00000037171

Paralogs (5): CFC1 (ENSG00000136698), CFC1B (ENSG00000152093), EGFL7 (ENSG00000172889), CRIPTO3 (ENSG00000225366), EGFL8 (ENSG00000241404)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98658) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 49 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal mesoderm development	3
abnormal heart development	2
abnormal gastrulation	2
abnormal embryonic neuroepithelium morphology	2
abnormal rostral-caudal axis patterning	2
absent somites	2
absent notochord	1
abnormal germ layer development	1
absent mesoderm	1
abnormal endoderm development	1
failure of primitive streak formation	1
absent vitelline blood vessels	1
failure of embryo implantation	1
embryonic growth arrest	1
reduced female fertility	1
female infertility	1
decreased litter size	1
premature death	1
abnormal developmental patterning	1
abnormal embryonic tissue morphology	1
abnormal extraembryonic tissue morphology	1
abnormal primitive streak formation	1
abnormal chorion morphology	1
abnormal decidualization	1
abnormal uterine environment	1

+24 more (showing top 25).

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
Gallus gallus	Q9I8Q3	59.1%	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
ALS2CL	protein-coding	259173
TMIE	protein-coding	259236
LRRC2	protein-coding	79442
LRRC2-AS1	ncRNA	83598
FAM240A	protein-coding	100132146
RTP3	protein-coding	83597
LTF	protein-coding	4057
PRSS50	protein-coding	29122
LINC02009	ncRNA	105377068

Protein

Protein identifiers

Protein Cripto — P13385 (reviewed: P13385)

Alternative names: Cripto, EGF-CFC family member, Cripto-1 growth factor, Epidermal growth factor-like cripto protein CR1, Teratocarcinoma-derived growth factor 1

All UniProt accessions (2): F5H1T8, P13385

UniProt curated annotations — full annotation on UniProt →

Function. GPI-anchored cell membrane protein involved in Nodal signaling. Cell-associated CRIPTO acts as a Nodal coreceptor in cis. Shedding of CRIPTO by TMEM8A modulates Nodal signaling by allowing soluble CRIPTO to act as a Nodal coreceptor on other cells. Could play a role in the determination of the epiblastic cells that subsequently give rise to the mesoderm.

Subunit / interactions. Interacts with the activin type-1 receptor ACVR1B.

Subcellular location. Cell membrane. Secreted.

Tissue specificity. Preferentially expressed in gastric and colorectal carcinomas than in their normal counterparts. Expressed in breast and lung.

Post-translational modifications. The GPI-anchor is attached to the protein in the endoplasmic reticulum and serves to target the protein to the cell surface. There, it is processed by GPI processing phospholipase A2 (TMEM8A), removing an acyl-chain at the sn-2 position of GPI and releasing CRIPTO as a lysophosphatidylinositol-bearing form, which is further cleaved by phospholipase D (GPLD1) into a soluble form.

Similarity. Belongs to the EGF-CFC (Cripto-1/FRL1/Cryptic) family.

RefSeq proteins (2): NP_001167607, NP_003203* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR017047	Cripto	Family
IPR019011	Cryptic/Cripto_CFC-dom	Domain

Pfam: PF09443

UniProt features (16 total): disulfide bond 6, sequence variant 3, signal peptide 1, chain 1, mutagenesis site 1, propeptide 1, domain 1, lipid moiety-binding region 1, glycosylation site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13385-F1	67.47	0.31

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): 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.

Post-translational modifications (1)

Type	Positions
Gpi-anchor amidated aspartate	150

Disulfide bonds (6)

Type	Positions
Disulfide bond	128–149, 131–140, 82–89, 83–95, 97–106, 115–133

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	79

Mutagenesis-validated functional residues (1)

Position	Phenotype
188	alters the localization and decreases the biological activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-2892247	POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation	curated
R-HSA-1266738	Developmental Biology	—
R-HSA-1433617	Regulation of signaling by NODAL	electronic
R-HSA-1181150	Signaling by NODAL	electronic
R-HSA-452723	Transcriptional regulation of pluripotent stem cells	—

MSigDB gene sets: 428 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_AXIS_SPECIFICATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_EMBRYONIC_AXIS_SPECIFICATION, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_RESPONSE_TO_EPIDERMAL_GROWTH_FACTOR, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY

GO Biological Process (25): blood vessel development (GO:0001568), morphogenesis of a branching structure (GO:0001763), cell migration involved in sprouting angiogenesis (GO:0002042), determination of left/right symmetry (GO:0007368), heart development (GO:0007507), positive regulation of cell population proliferation (GO:0008284), anterior/posterior axis specification, embryo (GO:0008595), embryo development ending in birth or egg hatching (GO:0009792), anterior/posterior pattern specification (GO:0009952), regulation of signal transduction (GO:0009966), positive regulation of endothelial cell migration (GO:0010595), cell differentiation (GO:0030154), positive regulation of cell migration (GO:0030335), mammary gland development (GO:0030879), cellular response to hepatocyte growth factor stimulus (GO:0035729), nodal signaling pathway (GO:0038092), negative regulation of apoptotic process (GO:0043066), positive regulation of MAP kinase activity (GO:0043406), positive regulation of MAPK cascade (GO:0043410), cellular response to fibroblast growth factor stimulus (GO:0044344), cellular response to type II interferon (GO:0071346), cellular response to interleukin-6 (GO:0071354), cellular response to tumor necrosis factor (GO:0071356), cellular response to epidermal growth factor stimulus (GO:0071364), signal transduction (GO:0007165)

GO Molecular Function (5): signaling receptor binding (GO:0005102), growth factor activity (GO:0008083), nodal binding (GO:0038100), activin receptor binding (GO:0070697), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), plasma membrane (GO:0005886), cell surface (GO:0009986), apical plasma membrane (GO:0016324), membrane raft (GO:0045121), side of membrane (GO:0098552)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Developmental Biology	2
Signaling by NODAL	1
Transcriptional regulation of pluripotent stem cells	1

GO top-level categories

55 GO namespaces:

Category	Terms
cellular anatomical structure	3
animal gross anatomical part developmental process	2
cellular response to growth factor stimulus	2
protein binding	2
membrane	2
vasculature development	1
anatomical structure morphogenesis	1
multicellular organismal process	1
sprouting angiogenesis	1
blood vessel endothelial cell migration	1
determination of bilateral symmetry	1
left/right pattern formation	1
animal organ development	1
circulatory system development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
embryonic axis specification	1
tripartite regional subdivision	1
anterior/posterior axis specification	1
embryo development	1
regionalization	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
cellular developmental process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
gland development	1
response to hepatocyte growth factor	1
activin receptor signaling pathway	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
MAP kinase activity	1
regulation of MAP kinase activity	1
positive regulation of MAPK cascade	1
positive regulation of protein serine/threonine kinase activity	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
response to fibroblast growth factor	1
receptor ligand activity	1
transmembrane receptor protein serine/threonine kinase binding	1
binding	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
membrane microdomain	1
leaflet of membrane bilayer	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 20 of 37 annotations. The rest are phylogenetic / computational / electronic (IEA).

20 experimentally-supported GO terms:

GO term	NS	Evidence
cell migration involved in sprouting angiogenesis	BP	mutant phenotype
cellular response to epidermal growth factor stimulus	BP	direct assay
cellular response to fibroblast growth factor stimulus	BP	direct assay
cellular response to hepatocyte growth factor stimulus	BP	direct assay
cellular response to interleukin-6	BP	direct assay
cellular response to tumor necrosis factor	BP	direct assay
cellular response to type II interferon	BP	direct assay
heart development	BP	direct assay
negative regulation of apoptotic process	BP	direct assay
positive regulation of MAP kinase activity	BP	direct assay
positive regulation of MAPK cascade	BP	direct assay
positive regulation of cell migration	BP	direct assay
positive regulation of cell population proliferation	BP	direct assay
positive regulation of endothelial cell migration	BP	direct assay
regulation of signal transduction	BP	direct assay
apical plasma membrane	CC	direct assay
cell surface	CC	direct assay
membrane raft	CC	direct assay
growth factor activity	MF	direct assay
signaling receptor binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 926 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRIPTO	FMNL1	O95466	938
CRIPTO	GDF3	Q9NR23	919
CRIPTO	ACVR1C	Q8NER5	915
CRIPTO	NODAL	Q96S42	911
CRIPTO	LEFTY2	O00292	823
CRIPTO	ZIC3	O60481	819
CRIPTO	SMAD2	Q15796	763
CRIPTO	ACVR1B	P36896	733
CRIPTO	GDF1	P27539	690
CRIPTO	NANOG	Q9H9S0	686
CRIPTO	POU5F1	P31359	635
CRIPTO	LEFTY1	O75610	621
CRIPTO	UTF1	Q5T230	594
CRIPTO	FOXH1	O75593	592
CRIPTO	SOX2	P48431	577

IntAct

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

10 partners by confidence:

Partner	Interaction type	MIscore	Records
AIP	association	0.640	4
GPC1	physical association	0.400	1
AP2S1	physical association	0.370	1
FARSA	physical association	0.370	1
FBLN1	physical association	0.370	1
ANG	physical association	0.000	1
BAG6	physical association	0.000	1
COPS6	physical association	0.000	1
GDF9	physical association	0.000	1
RIF1	physical association	0.000	1

SIGNOR signaling

10 signaling interactions:

A	Effect	B	Mechanism
TDGF1	down-regulates	ACVR2A	binding
TDGF1	“down-regulates activity”	TGFB1	binding
TDGF1	down-regulates	MSTN
TDGF1	up-regulates	Skeletal_muscle_differentiation
TDGF1	“up-regulates activity”	NODAL	binding
TDGF1	“up-regulates activity”	ACVR1B	binding
NODAL	“up-regulates quantity by expression”	TDGF1	“transcriptional regulation”
POU5F1	“up-regulates quantity by expression”	TDGF1	“transcriptional regulation”
SOX2/POU5F1	“up-regulates quantity by expression”	TDGF1	“transcriptional regulation”
SOX17/POU5F1	“up-regulates quantity by expression”	TDGF1	“transcriptional regulation”

Ligand–receptor pairs (CellPhoneDB) (4)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

4 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ACVR1C;ACVR2B;TDGF1		Signaling by NODAL
ACVR1B;ACVR2A;TDGF1		Signaling by NODAL
ACVR1B;ACVR2B;TDGF1		Signaling by NODAL
TDGF1		Signaling by Left-right determination factor

Disease & clinical

Genetic variants

Variant evidence for CRIPTO: 76 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	29
Benign	15

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 439):

Position(s)	Effect	Δscore	Sites
3:46578005–46578006	donor_loss	0.9900	4
3:46578005	donor_loss	0.9800
3:46579738	acceptor_loss	0.9400	2
3:46579737–46579738	acceptor_loss	0.9300	4
3:46579417	donor_gain	0.9100
3:46577836	donor_gain	0.8900
3:46579944	acceptor_loss	0.8900
3:46579948–46579950	acceptor_loss	0.8900	7
3:46579837	donor_gain	0.8600
3:46579093–46579094	acceptor_loss	0.8000	5

AlphaMissense

205 missense substitutions predicted likely pathogenic (of 1,231 scored), across 49 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
F94	8	0.877	0.985
C106	7	0.927	0.962
C89	7	0.896	0.921
C97	7	0.889	0.923
C95	7	0.888	0.927
F101	7	0.871	0.979
C83	7	0.866	0.925
C82	7	0.847	0.884
C133	7	0.823	0.902
C115	7	0.801	0.865
C131	7	0.801	0.858
C140	7	0.796	0.870
N85	6	0.844	0.942
G92	6	0.806	0.857
C149	6	0.725	0.769
G86	6	0.717	0.866
C128	6	0.714	0.786
F145	5	0.862	0.933
G103	5	0.854	0.927
K132	5	0.851	0.932

HPA cancer prognostics

RNA cancer specificity: Group enriched (Colon Adenocarcinoma, Rectum Adenocarcinoma, Testicular Germ Cell Tumor)

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.000377
Liver Hepatocellular Carcinoma (validation)	favorable	0.000791

Disease associations

OMIM: gene MIM:187395 | disease phenotypes:

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital heart disease	Limited	Autosomal dominant
congenital nervous system disorder	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (2): congenital heart disease (MONDO:0005453), congenital nervous system disorder (MONDO:0002320)

HPO phenotypes

showing 60 of 115 phenotypes (HPO-id order):

HPO	Term
HP:0000062	Ambiguous genitalia
HP:0000104	Renal agenesis
HP:0000119	Abnormality of the genitourinary system
HP:0000161	Median cleft upper lip
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000322	Short philtrum
HP:0000407	Sensorineural hearing impairment
HP:0000446	Narrow nasal bridge
HP:0000453	Choanal atresia
HP:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares
HP:0000478	Abnormality of the eye
HP:0000486	Strabismus
HP:0000601	Hypotelorism
HP:0000612	Iris coloboma
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000736	Short attention span
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000772	Abnormal rib morphology
HP:0000818	Abnormality of the endocrine system
HP:0000821	Hypothyroidism
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000826	Precocious puberty
HP:0000830	Anterior hypopituitarism
HP:0000863	Central diabetes insipidus
HP:0000871	Panhypopituitarism
HP:0000873	Diabetes insipidus
HP:0000924	Abnormality of the skeletal system
HP:0001028	Hemangioma
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001254	Lethargy
HP:0001257	Spasticity
HP:0001273	Abnormal corpus callosum morphology
HP:0001274	Agenesis of corpus callosum
HP:0001290	Generalized hypotonia
HP:0001328	Specific learning disability
HP:0001344	Absent speech
HP:0001355	Megalencephaly
HP:0001360	Holoprosencephaly
HP:0001371	Flexion contracture
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001545	Anteriorly placed anus
HP:0001622	Premature birth
HP:0001627	Abnormal heart morphology
HP:0001636	Tetralogy of Fallot
HP:0001680	Coarctation of aorta
HP:0002013	Vomiting
HP:0002015	Dysphagia

GWAS associations

2 associations:

Study	Trait	p-value
GCST010002_422	Refractive error	4e-14
GCST009391_388	Metabolite levels	3e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0010435	triacylglycerol 56:8 measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3713025 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CRIPTO protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
BIIB-015	Unknown	1

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	2
trichostatin A	increases expression	1
sodium arsenite	decreases expression, decreases reaction	1
butylbenzyl phthalate	increases expression	1
monoisoamyl-2,3-dimercaptosuccinate	decreases expression, decreases reaction	1
entinostat	increases expression	1
belinostat	increases expression	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Leflunomide	increases expression	1
Panobinostat	increases expression	1
Acetaminophen	decreases expression	1
Ethanol	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Fluorouracil	decreases expression	1
Folic Acid	increases expression	1
Tretinoin	increases reaction, decreases expression, affects binding	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

showing 60 of 300 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
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
NCT01698567	Phase 1	TERMINATED	Antithrombin III in Infants With Cardiopulmonary Bypass (CPB)
NCT02549625	Phase 1	COMPLETED	Phase I Safety and Feasibility Study of Intracoronary Delivery of Autologous Bone Marrow Derived Mononuclear Cells
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