CPA6 - Carboxypeptidase A6

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)

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.

Related Genes and Pathways

• 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