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6 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CRYZL1
crystallin zeta like 1
Chromosome 21 · 21q22.11
NCBI Gene: 9946Ensembl: ENSG00000205758.13HGNC: HGNC:2420UniProt: O95825
32PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
early endosomecytosolidentical protein bindingprotein bindingtooth diseaseauditory system diseaseattention deficit hyperactivity disorderAbruptio Placentae
✦AI Summary

CRYZL1 (crystallin zeta like 1) is a component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary), a protein complex consisting of TBCK, PPP1R21, FERRY3, CRYZL1, and GATD1 1. The FERRY complex functions as a RAB5A effector that directly interacts with mRNAs and mediates their endosomal transport and localization, particularly recruiting mRNAs and ribosomes to early endosomes for local translation in cells with extended processes 2. CRYZL1 is ubiquitously expressed across multiple tissues including heart, brain, skeletal muscle, kidney, pancreas, liver, and lungs 3. CRYZL1's involvement in mRNA trafficking and localization suggests relevance to neurological function. While mutations in other FERRY complex members (TBCK, PPP1R21, FERRY3) cause neurogenetic disorders characterized by intellectual disability and neurodegeneration, no neurologic disorders have yet been associated with CRYZL1 mutations 1. However, plasma CRYZL1 levels demonstrate complex disease associations: Mendelian randomization studies identified CRYZL1 as a protective factor against vascular dementia (OR = 0.387) 4, while showing positive causal association with hepatocellular carcinoma risk 5. In lung adenocarcinoma, CRYZL1 expression is regulated by BRINP3 through CLOCK-mediated transcriptional mechanisms and contributes to tumor progression via AKT pathway activation 6. These findings suggest CRYZL1 may have context-dependent roles in neuronal homeostasis and cancer pathogenesis.

Sources cited
1
CRYZL1 is a component of the FERRY complex; other FERRY members associate with neurogenetic disorders but CRYZL1 mutations have not yet been linked to neurologic disease
PMID: 40062705
2
CRYZL1 is part of the FERRY mRNA transport complex; FERRY complex mediates endosomal mRNA trafficking and localization
PMID: 40093117
3
CRYZL1 is expressed in heart, brain, skeletal muscle, kidney, pancreas, liver, and lungs at varying levels; located on chromosome 21q22.1
PMID: 10191096
4
CRYZL1 plasma levels show protective causal association with vascular dementia risk (OR = 0.387)
PMID: 40622612
5
CRYZL1 plasma levels show positive causal association with hepatocellular carcinoma risk
PMID: 41578465
6
CRYZL1 expression is regulated by BRINP3 through CLOCK-mediated transcriptional mechanisms and promotes lung adenocarcinoma progression via AKT pathway activation
PMID: 40799124
Disease Associationsⓘ20
tooth diseaseOpen Targets
0.08Suggestive
auditory system diseaseOpen Targets
0.07Suggestive
attention deficit hyperactivity disorderOpen Targets
0.05Suggestive
Abruptio PlacentaeOpen Targets
0.05Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.04Suggestive
schizophrenia 15Open Targets
0.04Suggestive
Phelan-McDermid syndromeOpen Targets
0.03Suggestive
gestational diabetesOpen Targets
0.00Suggestive
glioblastoma multiformeOpen Targets
0.00Suggestive
benign prostatic hyperplasiaOpen Targets
0.00Suggestive
cervical cancerOpen Targets
0.00Suggestive
myeloid sarcomaOpen Targets
0.00Suggestive
nervous system diseaseOpen Targets
0.00Suggestive
clear cell renal carcinomaOpen Targets
0.00Suggestive
colorectal adenocarcinomaOpen Targets
0.00Suggestive
glioma susceptibility 1Open Targets
0.00Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
lung cancerOpen Targets
0.00Suggestive
melanomaOpen Targets
0.00Suggestive
urinary bladder cancerOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PPP1R21Protein interaction96%GATD1Protein interaction95%LAP3Protein interaction86%MT2AProtein interaction77%SLC40A1Protein interaction72%FERRY3Shared pathway50%
Tissue Expression6 tissues
Brain
100%
Ovary
88%
Heart
68%
Lung
52%
Bone Marrow
47%
Liver
40%
Gene Interaction Network
Click a node to explore
CRYZL1PPP1R21GATD1LAP3MT2ASLC40A1FERRY3
PROTEIN STRUCTURE
Preparing viewer…
PDB8A3O · 2.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.11Tolerant
Observed/Expected LoF0.47 [0.28–0.81]
RankingsWhere CRYZL1 stands among ~20K protein-coding genes
  • #11,491of 20,598
    Most Researched32
  • #6,854of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedCRYZL1
Sources retrieved6 papers
Response time—
📄 Sources
6▼
1
TBCK-deficiency leads to compartment-specific mRNA and lysosomal trafficking defects in patient-derived neurons.
PMID: 40093117
bioRxiv · 2025
1.00
2
Causal Effects of the Plasma Proteome on Vascular Dementia Risk: A Mendelian Randomization Study with Experimental Validation.
PMID: 40622612
Cell Mol Neurobiol · 2025
0.83
3
Identification of a zeta-crystallin (quinone reductase)-like 1 gene (CRYZL1) mapped to human chromosome 21q22.1.
PMID: 10191096
Genomics · 1999
0.67
4
Neurogenetic disorders associated with mutations in the FERRY complex: a novel disease class?
PMID: 40062705
Biol Open · 2025
0.50
5
BRINP3 promotes lung adenocarcinoma by enhancing CLOCK-mediated transcriptional regulation of CRYZL1 and activating the AKT pathway.
PMID: 40799124
Carcinogenesis · 2025
0.33