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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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CRIPT
CXXC repeat containing interactor of PDZ3 domain
Chromosome 2 Β· 2p21
NCBI Gene: 9419Ensembl: ENSG00000119878.8HGNC: HGNC:14312UniProt: Q9P021
49PubMed Papers
21Diseases
0Drugs
11Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingPDZ domain bindingscaffold protein bindingcytoplasmic microtubule organizationRothmund-Thomson syndrome type 3neurodegenerative diseaseNon-acquired isolated growth hormone deficiencynephritis
✦AI Summary

CRIPT (CXXC repeat containing interactor of PDZ3 domain) is a multifunctional protein with critical roles in RNA splicing and neuronal development. As a component of the minor spliceosome, CRIPT stabilizes U12 snRNP and is involved in splicing U12-type introns in pre-mRNAs 1. In neuronal contexts, CRIPT serves as a binding partner for SAP97's PDZ3 domain and promotes dendrite growth in mammalian spinal cord neurons, localizing to synapses with GluA1 and SAP97 along the dendritic tree 2. The protein also plays an essential role in mitotic spindle disassembly through redox-dependent mechanisms, directly interacting with tubulin subunits via cysteine residue modifications to induce microtubule depolymerization 3. Biallelic mutations in CRIPT cause Rothmund-Thomson-like syndrome (RTS3), characterized by poikiloderma, short stature, dysmorphic features, neurodevelopmental delay, and seizures 4. CRIPT-deficient cells exhibit increased cellular senescence markers, suggesting this contributes to the premature aging phenotype 4. The diverse clinical manifestations, ranging from primordial dwarfism to complex syndromic features, highlight CRIPT's importance in multiple cellular processes including RNA processing, cytoskeletal organization, and cell cycle regulation 5.

Sources cited
1
CRIPT stabilizes U12 snRNP as a component of the minor spliceosome
PMID: 33509932
2
CRIPT binds SAP97's PDZ3 domain and promotes dendrite growth in neurons
PMID: 29218323
3
CRIPT controls mitotic spindle disassembly through redox-dependent tubulin interactions
PMID: 36148798
4
CRIPT mutations cause Rothmund-Thomson-like syndrome with increased cellular senescence
PMID: 37013901
5
CRIPT mutations are associated with primordial dwarfism and distinctive dysmorphic features
PMID: 27250922
Disease Associationsβ“˜21
Rothmund-Thomson syndrome type 3Open Targets
0.74Strong
neurodegenerative diseaseOpen Targets
0.53Moderate
Non-acquired isolated growth hormone deficiencyOpen Targets
0.42Moderate
nephritisOpen Targets
0.27Weak
NephropathyOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
Blackfan-Diamond anemiaOpen Targets
0.08Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.08Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.08Suggestive
inosine triphosphatase deficiencyOpen Targets
0.07Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.07Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.07Suggestive
delta-beta-thalassemiaOpen Targets
0.06Suggestive
Autosomal dominant methemoglobinemiaOpen Targets
0.06Suggestive
hemoglobin D diseaseOpen Targets
0.06Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.06Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.06Suggestive
alpha thalassemia spectrumOpen Targets
0.05Suggestive
Alpha-thalassemiaOpen Targets
0.05Suggestive
beta thalassemiaOpen Targets
0.05Suggestive
Rothmund-Thomson syndrome 3UniProt
Pathogenic Variants11
NM_014171.6(CRIPT):c.132del (p.Ala45fs)Pathogenic
Rothmund-Thomson syndrome type 3
β˜…β˜…β˜†β˜†2021β†’ Residue 45
NM_014171.6(CRIPT):c.132dup (p.Ala45fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 45
NM_014171.6(CRIPT):c.150T>A (p.Tyr50Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 50
NM_014171.6(CRIPT):c.83-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_014171.6(CRIPT):c.82+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_014171.6(CRIPT):c.7_8del (p.Cys3fs)Pathogenic
Rothmund-Thomson syndrome type 3
β˜…β˜†β˜†β˜†2022β†’ Residue 3
NM_014171.6(CRIPT):c.8G>A (p.Cys3Tyr)Likely pathogenic
Rothmund-Thomson syndrome type 3
β˜…β˜†β˜†β˜†2015β†’ Residue 3
NM_014171.5(CRIPT):c.-422_17-582delPathogenic
Rothmund-Thomson syndrome type 3
β˜…β˜†β˜†β˜†2015
NM_014171.6(CRIPT):c.227G>A (p.Cys76Tyr)Pathogenic
Rothmund-Thomson syndrome type 3
β˜†β˜†β˜†β˜†2024β†’ Residue 76
NM_014171.6(CRIPT):c.141del (p.Phe47fs)Pathogenic
Ateleiotic dwarfism|Rothmund-Thomson syndrome type 3
β˜†β˜†β˜†β˜†2014β†’ Residue 47
NM_014171.6(CRIPT):c.133_134insGG (p.Ala45fs)Pathogenic
Ateleiotic dwarfism|Rothmund-Thomson syndrome type 3
β˜†β˜†β˜†β˜†2014β†’ Residue 45
View on ClinVar β†—
Related Genes
DHX16Protein interaction100%DLG4Protein interaction100%BUD13Protein interaction98%RNF113AProtein interaction97%CWC27Protein interaction97%CWC22Protein interaction97%
Tissue Expression6 tissues
Brain
100%
Heart
74%
Bone Marrow
37%
Ovary
34%
Liver
31%
Lung
23%
Gene Interaction Network
Click a node to explore
CRIPTDHX16DLG4BUD13RNF113ACWC27CWC22
PROTEIN STRUCTURE
Preparing viewer…
PDB7DVQ Β· 2.89 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.85LoF Tolerant
pLIβ“˜
0.19Tolerant
Observed/Expected LoF0.73 [0.22–1.85]
RankingsWhere CRIPT stands among ~20K protein-coding genes
  • #8,932of 20,598
    Most Researched49
  • #2,783of 5,498
    Most Pathogenic Variants11
  • #16,859of 17,882
    Most Constrained (LOEUF)1.85
Genes detectedCRIPT
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Structure of the activated human minor spliceosome.
PMID: 33509932
Science Β· 2021
1.00
2
Cross-species and mammal-to-mammal transmission of clade 2.3.4.4b highly pathogenic avian influenza A/H5N1 with PB2 adaptations.
PMID: 40044729
Nat Commun Β· 2025
0.90
3
CRIPT exonic deletion and a novel missense mutation in a female with short stature, dysmorphic features, microcephaly, and pigmentary abnormalities.
PMID: 27250922
Am J Med Genet A Β· 2016
0.80
4
Biallelic variants in CRIPT cause a Rothmund-Thomson-like syndrome with increased cellular senescence.
PMID: 37013901
Genet Med Β· 2023
0.70
5
Rothmund-Thomson syndrome, a disorder far from solved.
PMID: 38021400
Front Aging Β· 2023
0.60