CRIPTO

Chr 3

cripto, EGF-CFC family member

Also known as: CR, CR-1, CRGF, TDGF1

The encoded protein is a GPI-anchored membrane protein that acts as a coreceptor for Nodal signaling during embryonic development, particularly in mesoderm formation. Mutations cause forebrain defects with inheritance pattern not definitively established in the literature. The gene shows extremely low constraint against loss-of-function variants (pLI near 0), suggesting tolerance to such mutations.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOEUF 1.92
Clinical SummaryCRIPTO
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Gene-Disease Validity (ClinGen)
congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 31 VUS of 77 total submissions
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Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — CRIPTO
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.92LOEUF
pLI 0.000
Z-score -1.28
OE 1.46 (0.931.92)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.06Z-score
OE missense 1.02 (0.871.19)
109 obs / 107.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.46 (0.931.92)
00.351.4
Missense OE1.02 (0.871.19)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 13 / 8.9Missense obs/exp: 109 / 107.1Syn Z: -0.51

ClinVar Variant Classifications

77 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS31
Likely Benign21
Benign16
7
Pathogenic
1
Likely Pathogenic
31
VUS
21
Likely Benign
16
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
30
1
0
31
Likely Benign
0
4
14
3
21
Benign
0
3
10
3
16
Total03733676

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CRIPTO · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Hypophosphatasia

United States Hypophosphatasia Molecular Research Center

ACTIVE NOT RECRUITING
NCT05062629Children's Mercy Hospital Kansas CityStarted 2021-08-24
Whole Genome Sequencing
Whole Exome SequencingRare Diseases

PREcision Diagnostics in Rare genetIC Diseases and Tumors - Long Read Sequencing

RECRUITING
NCT06796751IRCCS Azienda Ospedaliero-Universitaria di BolognaStarted 2024-10-01
DNA/RNA sequencing and bioinformatic data analysis
Multiple Myeloma in RelapseRefractory Multiple MyelomaPlasmacytoid; Lymphoma

BCMA-CD19 cCAR in Multiple Myeloma and Plasmacytoid Lymphoma

RECRUITING
NCT04162353Phase PHASE1iCell Gene TherapeuticsStarted 2019-07-01
BCMA-CD19 cCAR T cells
AdrenoleukodystrophyAdrenomyeloneuropathyMetachromatic Leukodystrophy

Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia

RECRUITING
NCT04925349Assistance Publique - Hôpitaux de ParisStarted 2021-08-30
Blood sample collection
Acute Lymphoid LeukemiaAcute Lymphoblastic Leukemia

UCD19 CAR T Therapy in Adults With B-ALL and MRD Positivity in CR1

RECRUITING
NCT05535855Phase PHASE1University of Colorado, DenverStarted 2024-01-24
CD19 Directed CAR T Cell
Neuromuscular DiseasesEye DiseasesGenetic Disease

Precision Diagnosis and Therapy for Rare Diseases by Interpreting Non-coding Genomes

RECRUITING
NCT06775561IRCCS Azienda Ospedaliero-Universitaria di BolognaStarted 2023-05-20
PARADIGM study aims to streamline the process from genomic characterization of RGD patients with ED/NMD to identification of the suitable personalized therapy.
CNS TumorSolid Tumor

INFORM2 Study Uses Nivolumab and Entinostat in Children and Adolescents With High-risk Refractory Malignancies

RECRUITING
NCT03838042Phase PHASE1, PHASE2University Hospital HeidelbergStarted 2020-05-26
Nivolumab and Entinostat
Philadelphia Chromosome Negative ALLAcute Lymphoblastic Leukemia, Adult

Efficacy and Safety of Chemotherapy Combined With CAR-T Cells in Newly Diagnosed Adult Patients With Ph- B-ALL

RECRUITING
NCT06481241Phase NAInstitute of Hematology & Blood Diseases Hospital, ChinaStarted 2024-06-10
CAR-T cellsVenetoclax
Clinical Literature
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