CRIPTO3

Summary

CRIPTO3 (cripto, EGF-CFC family member 3, HGNC:11703) is a protein-coding gene on chromosome Xq23, encoding Protein CRIPTO3 (P51864). Could play a role in the determination of the epiblastic cells that subsequently give rise to the mesoderm.

The TDGF3 locus has characteristics of a retrotransposon, including lack of introns and a poly(A) sequence.

Source: NCBI Gene 6998 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001397362

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11703
Approved symbol	CRIPTO3
Name	cripto, EGF-CFC family member 3
Location	Xq23
Locus type	gene with protein product
Status	Approved
Aliases	TDGF2, CR-3, CRIPTO-3
Ensembl gene	ENSG00000225366
Ensembl biotype	protein_coding
Entrez	6998

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000602699, ENST00000851044

RefSeq mRNA: 1 — MANE Select: NM_001397362 NM_001397362

CCDS: CCDS94651

Canonical transcript exons

ENST00000602699 — 1 exons

Exon	Start	End
ENSE00004283548	110520896	110523021

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 72.83.

Top tissues by expression

114 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.83	gold quality
vastus lateralis	UBERON:0001379	64.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	50.25	silver quality
adrenal tissue	UBERON:0018303	45.32	gold quality
colonic epithelium	UBERON:0000397	41.19	gold quality
adult mammalian kidney	UBERON:0000082	40.18	gold quality
kidney	UBERON:0002113	38.78	gold quality
skeletal muscle tissue	UBERON:0001134	38.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	37.43	silver quality
left ovary	UBERON:0002119	37.30	silver quality
ovary	UBERON:0000992	37.07	silver quality
right lobe of liver	UBERON:0001114	36.57	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
sural nerve	UBERON:0015488	36.24	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
endometrium	UBERON:0001295	35.48	gold quality
muscle tissue	UBERON:0002385	34.99	gold quality
apex of heart	UBERON:0002098	34.88	gold quality
prefrontal cortex	UBERON:0000451	34.26	gold quality
spleen	UBERON:0002106	33.90	gold quality
right coronary artery	UBERON:0001625	33.64	gold quality
monocyte	CL:0000576	33.27	gold quality
mucosa of stomach	UBERON:0001199	33.18	gold quality
adrenal gland	UBERON:0002369	33.06	gold quality
bone marrow	UBERON:0002371	32.91	gold quality
leukocyte	CL:0000738	32.76	gold quality
left adrenal gland cortex	UBERON:0035825	32.67	gold quality
blood	UBERON:0000178	32.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	69.38
E-MTAB-9388	yes	11.65
E-ANND-3	yes	3.76

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• 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)
• These data indicate that CRIPTO3 is an expressed gene, particularly in certain cancers, and suggest a potentially novel mechanism of oncogenesis through activation of a retrogene. (PMID:18835250)
• Pseudogene TDGF1P3 regulates the proliferation and metastasis of colorectal cancer cells via the miR-338-3p-PKM2 axis. (PMID:36436343)

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), CRIPTO (ENSG00000241186), EGFL8 (ENSG00000241404)

Protein

Protein identifiers

Protein CRIPTO3 — P51864 (reviewed: P51864)

Alternative names: Cripto, EGF-CFC family member 3, Cripto-3 growth factor, Epidermal growth factor-like cripto protein CR3, Teratocarcinoma-derived growth factor 1 pseudogene 3, Teratocarcinoma-derived growth factor 3

All UniProt accessions (1): P51864

UniProt curated annotations — full annotation on UniProt →

Function. Could play a role in the determination of the epiblastic cells that subsequently give rise to the mesoderm. Activates the Nodal-dependent signaling pathway.

Subcellular location. Cell membrane.

Tissue specificity. Expressed weakly in lung, colon and breast. Expressed also strongly in primary cancer tissues; lung and colon cancers.

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

RefSeq proteins (1): NP_001384291* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF09443

UniProt features (9 total): disulfide bond 6, chain 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51864-F1	66.63	0.31

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 (6): 82–89, 83–95, 97–106, 115–133, 128–149, 131–140

Glycosylation sites (1): 79

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1181150	Signaling by NODAL
R-HSA-1433617	Regulation of signaling by NODAL
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 27 (showing top): GOCC_CELL_SURFACE, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_SPECIFICATION_OF_SYMMETRY, HOFMANN_MYELODYSPLASTIC_SYNDROM_RISK_DN, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_ACTIVIN_RECEPTOR_SIGNALING_PATHWAY, GOMF_SIGNALING_RECEPTOR_BINDING, BACOLOD_RESISTANCE_TO_ALKYLATING_AGENTS_UP, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOMF_RECEPTOR_SERINE_THREONINE_KINASE_BINDING, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, chrXq23, GOBP_NODAL_SIGNALING_PATHWAY, REACTOME_REGULATION_OF_SIGNALING_BY_NODAL, GOBP_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY

GO Biological Process (6): blood vessel development (GO:0001568), signal transduction (GO:0007165), determination of left/right symmetry (GO:0007368), heart development (GO:0007507), anterior/posterior pattern specification (GO:0009952), nodal signaling pathway (GO:0038092)

GO Molecular Function (3): growth factor activity (GO:0008083), nodal binding (GO:0038100), activin receptor binding (GO:0070697)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Biology	1
Signaling by NODAL	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
vasculature development	1
anatomical structure development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
determination of bilateral symmetry	1
left/right pattern formation	1
animal organ development	1
circulatory system development	1
regionalization	1
activin receptor signaling pathway	1
receptor ligand activity	1
protein binding	1
transmembrane receptor protein serine/threonine kinase binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A8M9PDM1, A0A8M9QN10, A1L3I3, A2AWH2, A2CI97, A2CI98, A4IFM1, A4IHZ3, A7E2V4, A7E305, B1AL88, B6CKP4, E7F211, F8W3R9, O55034, O94901, P35054, P51864, P86275, P98153, P98154, Q0VCT2, Q3UHH1, Q498C7, Q4KM46, Q4TUC0, Q58T08, Q5EB20, Q5HZE8, Q5RD34, Q5VUB5, Q6UW32, Q6V9Y8, Q7TNI2, Q7Z5A8, Q80ZA7, Q86VZ4, Q8CB67, Q8CCS2, Q8N0W7

Diamond homologs: P0CG36, P0CG37, P13385, P51864, P51865, P97766, Q9I8Q3, O88277, Q5F226, A0A2K5V015, Q5R6R1, Q5T1H1, O97507, Q20911

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000625825 (X:110519091 C>T), RS1000921116 (X:110523048 G>A), RS1000928093 (X:110519537 G>A), RS1002047432 (X:110520494 G>A), RS1002163619 (X:110520047 G>A), RS1007035247 (X:110519675 T>C), RS1007472542 (X:110519123 T>C,G), RS1007779612 (X:110522214 T>C), RS1008202807 (X:110519477 T>C), RS1008570735 (X:110520854 C>A,T), RS1008651568 (X:110519004 C>A), RS1008951294 (X:110523042 C>T), RS1009374404 (X:110519972 G>A), RS1010361744 (X:110520394 T>C), RS1010477803 (X:110519802 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001612_10	Sex hormone-binding globulin levels	3.000000e-16
GCST001612_14	Sex hormone-binding globulin levels	4.000000e-14
GCST90002397_161	Mean spheric corpuscular volume	3.000000e-28
GCST90011766_6	Glaucoma (primary open-angle)	4.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004696	sex hormone-binding globulin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression	1
Tretinoin	affects binding, increases reaction	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.