CPA6

carboxypeptidase A6, the group of M14 carboxypeptidases

Basic information

Region (hg38): 8:67422037-67746378

Links

ENSG00000165078 ∙ NCBI:57094 ∙ OMIM:609562 ∙ HGNC:17245 ∙ Uniprot:Q8N4T0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• benign familial mesial temporal lobe epilepsy (Supportive), mode of inheritance: AD
• familial mesial temporal lobe epilepsy with febrile seizures (Supportive), mode of inheritance: AD
• familial temporal lobe epilepsy 5 (Limited), mode of inheritance: AD
• febrile seizures, familial, 11 (Limited), mode of inheritance: AR
• familial temporal lobe epilepsy 5 (Limited), mode of inheritance: AD
• epilepsy (Refuted Evidence), mode of inheritance: AD
• epilepsy (Disputed Evidence), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Febrile seizures, familial, 11; Epilepsy, familial temporal lobe, 5	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	21922598; 23105115
As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CPA6 gene.

• Febrile seizures, familial, 11 (130 variants)
• Familial temporal lobe epilepsy 5 (56 variants)
• not provided (38 variants)
• Inborn genetic diseases (20 variants)
• Familial temporal lobe epilepsy 5;Febrile seizures, familial, 11 (14 variants)
• not specified (11 variants)
• Familial temporal lobe epilepsy 2 (5 variants)
• Febrile seizures, familial, 11;Familial temporal lobe epilepsy 5 (3 variants)
• Childhood epilepsy with centrotemporal spikes (3 variants)
• Global developmental delay (2 variants)
• 7 conditions (2 variants)
• Intellectual disability (2 variants)
• Epilepsy (1 variants)
• See cases (1 variants)
• Seizure (1 variants)
• CPA6-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPA6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	27	2	32
missense		1	96	1	3	101
nonsense			3			3
start loss						0
frameshift			3	1		4
inframe indel			1			1
splice donor/acceptor (+/-2bp)			2			2
splice region			7	5	1	13
non coding			19	2		21
Total	0	1	127	31	5

Highest pathogenic variant AF is 0.0000132

Variants in CPA6

This is a list of pathogenic ClinVar variants found in the CPA6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-67422176-T-C		Familial temporal lobe epilepsy 5	Likely benign (Jan 13, 2018)
8-67422218-T-C		Familial temporal lobe epilepsy 5	Uncertain significance (Jan 13, 2018)
8-67422244-T-G		Familial temporal lobe epilepsy 5	Uncertain significance (Jan 13, 2018)
8-67422262-A-G		Familial temporal lobe epilepsy 5	Likely benign (Jan 13, 2018)
8-67422372-G-A		Familial temporal lobe epilepsy 5	Uncertain significance (Jan 12, 2018)
8-67422510-A-G		Febrile seizures, familial, 11	Likely benign (May 17, 2018)
8-67422520-A-C		Febrile seizures, familial, 11	Uncertain significance (Feb 27, 2020)
8-67422524-G-T		Familial temporal lobe epilepsy 5	Uncertain significance (Jan 13, 2021)
8-67422530-T-C		Familial temporal lobe epilepsy 5 • Febrile seizures, familial, 11 • not specified	Uncertain significance (Mar 21, 2022)
8-67422546-A-G		Febrile seizures, familial, 11	Likely benign (Sep 18, 2018)
8-67422547-G-A		Febrile seizures, familial, 11 • Familial temporal lobe epilepsy 5 • Familial temporal lobe epilepsy 5;Febrile seizures, familial, 11	Uncertain significance (Dec 06, 2022)
8-67422572-G-A		Familial temporal lobe epilepsy 5	Uncertain significance (Jan 13, 2018)
8-67422578-T-C		not specified	Uncertain significance (Jun 26, 2023)
8-67422581-G-A		not specified • Febrile seizures, familial, 11	Benign/Likely benign (Aug 04, 2023)
8-67422601-C-G		Malignant tumor of prostate	Uncertain significance (-)
8-67422607-T-C		not specified	Uncertain significance (Apr 12, 2023)
8-67422611-C-A		Familial temporal lobe epilepsy 5	Uncertain significance (Mar 26, 2024)
8-67422613-G-T		Familial temporal lobe epilepsy 5	Uncertain significance (-)
8-67422619-C-T		Febrile seizures, familial, 11 • See cases	Uncertain significance (Dec 08, 2021)
8-67422621-T-C		Febrile seizures, familial, 11	Likely benign (Jun 07, 2020)
8-67422626-C-T		Febrile seizures, familial, 11	Uncertain significance (Aug 24, 2021)
8-67422627-G-A		Febrile seizures, familial, 11	Likely benign (Sep 01, 2020)
8-67422636-T-C		Febrile seizures, familial, 11	Likely benign (Jul 30, 2019)
8-67422698-G-A		Febrile seizures, familial, 11	Likely benign (Aug 23, 2022)
8-67422705-C-CA		Familial temporal lobe epilepsy 2	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPA6	protein_coding	protein_coding	ENST00000297770	11	324261

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.40e-17	0.0219	125545	0	203	125748	0.000807

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.487	258	237	1.09	0.0000120	2842
Missense in Polyphen		108	108.3	0.99725		1267
Synonymous	0.0199	82	82.2	0.997	0.00000414	808
Loss of Function	0.526	27	30.1	0.897	0.00000187	335

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00313	0.00313
Ashkenazi Jewish	0.00150	0.00149
East Asian	0.00163	0.00158
Finnish	0.000601	0.000601
European (Non-Finnish)	0.000555	0.000554
Middle Eastern	0.00163	0.00158
South Asian	0.000364	0.000359
Other	0.000980	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in the proteolytic inactivation of enkephalins and neurotensin in some brain areas. May convert inactive angiotensin I into the biologically active angiotensin II (PubMed:18178555). Releases a C-terminal amino acid, with preference for large hydrophobic C-terminal amino acids and shows only very weak activity toward small amino acids and histidine (PubMed:20855895). {ECO:0000269|PubMed:18178555, ECO:0000269|PubMed:20855895}.
• Disease: DISEASE: Epilepsy, familial temporal lobe, 5 (ETL5) [MIM:614417]: A focal form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe. Seizures are usually accompanied by sensory symptoms, most often auditory in nature. {ECO:0000269|PubMed:21922598}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Febrile seizures, familial, 11 (FEB11) [MIM:614418]: Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. {ECO:0000269|PubMed:21922598}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.954
• rvis_EVS: 0.73
• rvis_percentile_EVS: 86.27

Haploinsufficiency Scores

• pHI: 0.236
• hipred: N
• hipred_score: 0.171

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	High	Medium	High

Mouse Genome Informatics

• Gene name: Cpa6

Gene ontology

• Biological process: proteolysis
• Cellular component: extracellular space
• Molecular function: metallocarboxypeptidase activity;zinc ion binding