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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FEZ1
fasciculation and elongation protein zeta 1
Chromosome 11 · 11q24.2
NCBI Gene: 9638Ensembl: ENSG00000149557.15HGNC: HGNC:3659UniProt: Q99689
58PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of autophagosome assemblyprotein bindingGolgi apparatuscytoplasmactinic keratosisIntellectual disabilitytype 2 diabetes mellitusinfection
✦AI Summary

FEZ1 (fasciculation and elongation protein zeta 1) is a multifunctional kinesin-1 adaptor protein with critical roles in neuronal development and intracellular transport. Primary function: FEZ1 regulates axonal outgrowth and cargo transport along microtubules, particularly for mitochondria and synaptic proteins 1. The protein contains disordered regions and functions as a dimer 2, with phosphorylation at key sites modulating its protein-binding interactions 2. Mechanism: FEZ1 operates through multiple pathways—it mediates nuclear translocation of viral capsids 34, regulates heat shock protein HSPA8 localization and innate immune signaling 5, and controls neuroprogenitor specification during cortical development 6. FEZ1 is highly expressed in developing forebrain neurons and oligodendroglia, with expression patterns varying by brain region and developmental stage 78. Disease relevance: FEZ1 mutations are associated with schizophrenia and Jacobsen syndrome 61. Jacobsen syndrome patients exhibit motor impairments correlating with FEZ1 deletion-induced defects in motor neuron development and synaptic protein transport 1. In schizophrenia, dysregulation of FEZ1 through chr11 modifications and RNA-binding proteins impairs oligodendroglia maturation 8. Clinical significance: FEZ1 emerges as a hub protein integrating neuronal development, viral trafficking, and innate immunity—potential therapeutic target for neurodevelopmental and infectious diseases.

Sources cited
1
FEZ1 is hijacked by HIV-1 capsid as an adaptor protein for viral trafficking to the nucleus
PMID: 33572761
2
FEZ1 phosphorylation at S58 regulates HSPA8 localization and interferon-stimulated gene expression through the DNA-PK innate immune pathway
PMID: 35172151
3
FEZ1 mutations are found in schizophrenia and Jacobsen syndrome patients; FEZ1 deletion disrupts neuroprogenitor specification and cortical layer formation in human cerebral organoids
PMID: 38213789
4
FEZ1 is highly expressed in developing human cerebral cortex (7.5-17 PCW) with highest levels in mature glutamatergic neurons; expression patterns vary by forebrain region
PMID: 37746155
5
FEZ1 is upregulated during oligodendroglia development; schizophrenia risk genes regulate FEZ1 through chromatin modification and the RNA-binding protein QKI
PMID: 29249816
6
FEZ1 has dual independent roles in HIV-1 infection: regulating capsid transport to the nucleus and suppressing interferon-stimulated gene expression
PMID: 37219433
7
FEZ1 is a natively unfolded dimeric protein; PKC-mediated phosphorylation in the C-terminus regulates its protein-binding interactions
PMID: 18615714
8
FEZ1 deletion causes motor neuron development defects and locomotion impairments; FEZ1 is deleted in Jacobsen syndrome and regulates synaptic protein transport during motor neuron development
PMID: 33395696
Disease Associationsⓘ20
actinic keratosisOpen Targets
0.30Weak
Intellectual disabilityOpen Targets
0.26Weak
type 2 diabetes mellitusOpen Targets
0.08Suggestive
infectionOpen Targets
0.08Suggestive
asthmaOpen Targets
0.06Suggestive
Alzheimer diseaseOpen Targets
0.06Suggestive
attention deficit hyperactivity disorderOpen Targets
0.06Suggestive
HIV-1 infectionOpen Targets
0.06Suggestive
autismOpen Targets
0.06Suggestive
amyotrophic lateral sclerosisOpen Targets
0.05Suggestive
behavioral variant of frontotemporal dementiaOpen Targets
0.05Suggestive
Potocki-Lupski syndromeOpen Targets
0.05Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.05Suggestive
intellectual disability, autosomal dominant 50Open Targets
0.05Suggestive
schizophreniaOpen Targets
0.05Suggestive
stomach diseaseOpen Targets
0.05Suggestive
attention deficit-hyperactivity disorder 8Open Targets
0.04Suggestive
estrogen-receptor negative breast cancerOpen Targets
0.04Suggestive
Pick diseaseOpen Targets
0.04Suggestive
vascular diseaseOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SCOCProtein interaction95%DISC1Protein interaction92%SYT1Protein interaction86%KIF5BProtein interaction77%ZNF365Protein interaction75%UNC119Protein interaction71%
Tissue Expression6 tissues
Brain
100%
Heart
22%
Lung
11%
Ovary
9%
Liver
3%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
FEZ1SCOCDISC1SYT1KIF5BZNF365UNC119
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q99689
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.66LoF Tolerant
pLIⓘ
0.28Tolerant
Observed/Expected LoF0.41 [0.27–0.66]
RankingsWhere FEZ1 stands among ~20K protein-coding genes
  • #7,866of 20,598
    Most Researched58
  • #4,810of 17,882
    Most Constrained (LOEUF)0.66
Genes detectedFEZ1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Structure, Function, and Interactions of the HIV-1 Capsid Protein.
PMID: 33572761
Life (Basel) · 2021
1.00
2
FEZ1 phosphorylation regulates HSPA8 localization and interferon-stimulated gene expression.
PMID: 35172151
Cell Rep · 2022
0.90
3
FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migrations.
PMID: 38213789
iScience · 2023
0.80
4
Expression of the schizophrenia associated gene
PMID: 37746155
Front Neurosci · 2023
0.70
5
Novel schizophrenia risk factor pathways regulate FEZ1 to advance oligodendroglia development.
PMID: 29249816
Transl Psychiatry · 2017
0.60