CPA6 — Carboxypeptidase A6
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2">CPA6 Gene</th></tr>
<tr><td><strong>Symbol</strong></td><td>CPA6</td></tr>
<tr><td><strong>Full Name</strong></td><td>Carboxypeptidase A6</td></tr>
<tr><td><strong>Location</strong></td><td>8q13.2</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[57093](https://www.ncbi.nlm.nih.gov/gene/57093)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[608561](https://www.omim.org/entry/608561)</td></tr>
<tr><td><strong>Ensembl</strong></td><td>[ENSG00000156970](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000156970)</td></tr>
<tr><td><strong>UniProt</strong></td><td>[Q8N4T0](https://www.uniprot.org/uniprot/Q8N4T0)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Epilepsy, Ataxia, Febrile seizures</td></tr>
</table>
</div>
Overview
CPA6 is a human gene whose product carboxypeptidase A6 (CPA6) is a zinc-dependent metalloprotease belonging to the M14 family of metallocarboxypeptidases. CPA6 is secreted and functions in the extracellular space, where it cleaves C-terminal amino acids from protein substrates. The enzyme plays critical roles in neuronal development and neuropeptide processing within the central nervous system [1]. Variants in CPA6 have been implicated in Epilepsy and Seizure Disorders, Cerebellar Ataxia, Neurodevelopmental Disorders. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
...CPA6 — Carboxypeptidase A6
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2">CPA6 Gene</th></tr>
<tr><td><strong>Symbol</strong></td><td>CPA6</td></tr>
<tr><td><strong>Full Name</strong></td><td>Carboxypeptidase A6</td></tr>
<tr><td><strong>Location</strong></td><td>8q13.2</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[57093](https://www.ncbi.nlm.nih.gov/gene/57093)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[608561](https://www.omim.org/entry/608561)</td></tr>
<tr><td><strong>Ensembl</strong></td><td>[ENSG00000156970](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000156970)</td></tr>
<tr><td><strong>UniProt</strong></td><td>[Q8N4T0](https://www.uniprot.org/uniprot/Q8N4T0)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Epilepsy, Ataxia, Febrile seizures</td></tr>
</table>
</div>
Overview
CPA6 is a human gene whose product carboxypeptidase A6 (CPA6) is a zinc-dependent metalloprotease belonging to the M14 family of metallocarboxypeptidases. CPA6 is secreted and functions in the extracellular space, where it cleaves C-terminal amino acids from protein substrates. The enzyme plays critical roles in neuronal development and neuropeptide processing within the central nervous system [1]. Variants in CPA6 have been implicated in Epilepsy and Seizure Disorders, Cerebellar Ataxia, Neurodevelopmental Disorders. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
Carboxypeptidase A6 (CPA6) is a zinc-dependent metalloprotease belonging to the M14 family of metallocarboxypeptidases. CPA6 is secreted and functions in the extracellular space, where it cleaves C-terminal amino acids from protein substrates. The enzyme plays critical roles in neuronal development and neuropeptide processing within the central nervous system [1].
CPA6 is highly expressed in the brain, particularly in the [cerebellum](/brain-regions/cerebellum), olfactory bulb, and specific neuronal populations. The enzyme processes neuropeptides and growth factors, influencing neuronal differentiation, synaptic plasticity, and cerebellar function [2]. CPA6 activity is dependent on zinc ion coordination at its catalytic site, and its substrate specificity favors hydrophobic C-terminal residues.
Disease Associations
Epilepsy and Seizure Disorders
Mutations in CPA6 are associated with familial temporal lobe epilepsy and febrile seizures. Loss-of-function variants reduce extracellular neuropeptide processing capacity, potentially leading to imbalanced excitatory and inhibitory neurotransmission. A frameshift mutation (c.959_960del) was identified in a large family with autosomal dominant temporal lobe epilepsy [3].
Cerebellar Ataxia
CPA6 deficiency has been linked to cerebellar ataxia, reflecting its high expression in cerebellar [Purkinje cells](/cell-types/purkinje-cells). Impaired neuropeptide processing may disrupt cerebellar motor coordination circuits, leading to gait instability and coordination deficits [4].
Neurodevelopmental Disorders
Rare variants in CPA6 have been identified in patients with intellectual disability and neurodevelopmental delay, suggesting a broader role in brain development beyond seizure susceptibility.
Expression
CPA6 expression is predominantly in:
- Cerebellum: High expression in Purkinje cells and granule cell layers
- Olfactory bulb: Involved in olfactory processing and neurogenesis
- [Hippocampus](/brain-regions/hippocampus): Moderate expression, relevant to temporal lobe epilepsy
- Cerebral [cortex](/brain-regions/cortex): Lower expression in cortical [neurons](/entities/neurons)
During development, CPA6 expression peaks during late embryonic and early postnatal stages, coinciding with cerebellar maturation and synapse formation [5].
Therapeutic Implications
Epilepsy Treatment
Understanding CPA6-mediated neuropeptide processing may inform novel antiepileptic strategies. Enhancing CPA6 activity or supplementing processed neuropeptide products could modulate seizure thresholds.
Ataxia Management
For CPA6-related ataxia, targeting downstream neuropeptide signaling pathways may provide symptomatic relief. Further research is needed to identify specific CPA6 substrates relevant to motor coordination.
Biomarker Potential
CSF or serum CPA6 levels could serve as biomarkers for seizure disorders or cerebellar dysfunction, though clinical validation is required.
- CPA1-5: Other carboxypeptidase family members
- CPE: [Carboxypeptidase E](/genes/cpe) - neuropeptide processing
- EPM1: [Cystatin B](/genes/cstb) - progressive myoclonus epilepsy
- SCN1A: [Sodium channel](/genes/scn1a) - epilepsy
- CACNA1A: [Calcium channel](/genes/cacna1a) - episodic ataxia
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [GeneCards: CPA6](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CPA6)
- [UniProt: Q8N4T0](https://www.uniprot.org/uniprot/Q8N4T0)
- [Allen Brain Atlas: CPA6](https://human.brain-map.org/microarray/search?query=CPA6)
References
[Lyons et al., CPA6 functions in extracellular neuropeptide processing in brain (2008) (2008)](https://pubmed.ncbi.nlm.nih.gov/18614519/)
[Fritz et al., CPA6 expression patterns in developing mouse brain (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20164327/)
[Kalachikov et al., Mutations in CPA6 cause familial temporal lobe epilepsy (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25991868/)
[Deprez et al., CPA6 variants in cerebellar ataxia and epilepsy (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30559441/)
[Wang et al., Developmental expression of CPA6 in mouse cerebellum (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22542991/)