CPA6

Summary

CPA6 (carboxypeptidase A6, HGNC:17245) is a protein-coding gene on chromosome 8q13.2, encoding Carboxypeptidase A6 (Q8N4T0). May be involved in the proteolytic inactivation of enkephalins and neurotensin in some brain areas.

The gene encodes a member of the peptidase M14 family of metallocarboxypeptidases. The encoded preproprotein is proteolytically processed to generate the mature enzyme, which catalyzes the release of large hydrophobic C-terminal amino acids. This enzyme has functions ranging from digestion of food to selective biosynthesis of neuroendocrine peptides. Mutations in this gene may be linked to epilepsy and febrile seizures, and a translocation t(6;8)(q26;q13) involving this gene has been associated with Duane retraction syndrome.

Source: NCBI Gene 57094 — RefSeq curated summary.

At a glance

• Gene–disease (curated): benign familial mesial temporal lobe epilepsy (Supportive, GenCC) — +4 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 132 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 36
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_020361

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17245
Approved symbol	CPA6
Name	carboxypeptidase A6
Location	8q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CPAH
Ensembl gene	ENSG00000165078
Ensembl biotype	protein_coding
OMIM	609562
Entrez	57094

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 2 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000297770, ENST00000479862, ENST00000518549, ENST00000638254, ENST00000639116, ENST00000639508, ENST00000956854

RefSeq mRNA: 1 — MANE Select: NM_020361 NM_020361

CCDS: CCDS6200

Canonical transcript exons

ENST00000297770 — 11 exons

Exon	Start	End
ENSE00001090061	67434038	67434240
ENSE00001090069	67428047	67428131
ENSE00002108275	67422038	67422691
ENSE00002109358	67746014	67746360
ENSE00003475129	67517923	67518047
ENSE00003560622	67624176	67624251
ENSE00003570134	67509517	67509618
ENSE00003647249	67484679	67484789
ENSE00003655621	67506787	67506888
ENSE00003667856	67483768	67483858
ENSE00003672802	67511541	67511655

Expression profiles

Bgee: expression breadth ubiquitous, 103 present calls, max score 87.57.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1556 / max 196.5847, expressed in 318 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93454	1.0690	298
93452	0.0666	27
93453	0.0200	8

Top tissues by expression

215 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	87.57	gold quality
mucosa of transverse colon	UBERON:0004991	72.95	gold quality
urethra	UBERON:0000057	72.78	gold quality
rectum	UBERON:0001052	71.76	gold quality
colonic epithelium	UBERON:0000397	69.21	gold quality
prostate gland	UBERON:0002367	68.90	gold quality
vagina	UBERON:0000996	67.03	gold quality
transverse colon	UBERON:0001157	66.23	gold quality
tibia	UBERON:0000979	63.28	silver quality
mucosa of sigmoid colon	UBERON:0004993	62.85	silver quality
colon	UBERON:0001155	62.31	gold quality
large intestine	UBERON:0000059	62.09	gold quality
colonic mucosa	UBERON:0000317	61.99	gold quality
intestine	UBERON:0000160	59.48	gold quality
smooth muscle tissue	UBERON:0001135	59.40	gold quality
muscle layer of sigmoid colon	UBERON:0035805	59.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	57.07	gold quality
lower esophagus	UBERON:0013473	57.04	gold quality
esophagus	UBERON:0001043	56.92	gold quality
esophagus mucosa	UBERON:0002469	56.88	gold quality
vermiform appendix	UBERON:0001154	56.10	gold quality
urinary bladder	UBERON:0001255	55.01	gold quality
lower esophagus mucosa	UBERON:0035834	54.15	gold quality
cauda epididymis	UBERON:0004360	52.84	silver quality
caecum	UBERON:0001153	52.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	52.18	gold quality
small intestine	UBERON:0002108	51.77	gold quality
body of uterus	UBERON:0009853	49.14	gold quality
metanephros cortex	UBERON:0010533	48.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	48.10	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting CPA6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-6886-3P	96.96	66.36	844
HSA-MIR-193A-5P	95.70	65.33	613
HSA-MIR-5186	94.63	66.76	627
HSA-MIR-6853-5P	93.94	61.88	114

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 12)

• The CPAH gene was interrupted in a patient with DURS carrying a translocation break point in the DURS1 region on chromosome 8q13. (PMID:12454025)
• CPA6 may have a role in the regulation of neuropeptides in the extracellular environment within the olfactory bulb and other parts of the brain (PMID:18178555)
• Thrombin activation of osteopontin (OPN) (resulting in OPN-R) and its subsequent inactivation by thrombin-activatable carboxypeptidase B (generating OPN-L) occurs locally within inflamed joints in rheumatoid arthritis. (PMID:19790060)
• Substrate specificity of human carboxypeptidase A6 (PMID:20855895)
• CPA6 mutatins are genetically linked to an autosomal recessive familial form of febrile seizures and temporal lobe epilepsy (TLE), and are associated with sporadic TLE cases. (PMID:21922598)
• These results provide further evidence for the involvement of CPA6 mutations in human epilepsy. (PMID:23105115)
• Significantly higher levels of DNA methylation are found in the CPA6 promoter in focal epilepsy and febrile seizure patients. (PMID:24290490)
• these mutations in CPA6 are deleterious and provide further evidence for the involvement of CPA6 mutations in the predisposition for several types of epilepsy. (PMID:25875328)
• Common variants in PRPF31 and CPA6 were associated with worse and better metformin response, respectively. (PMID:29650774)
• CPA6 promotes the proliferation and migration of hepatocellular carcinoma by up-regulating AKT signaling pathway. (PMID:31612389)
• Carboxypeptidase A6 was identified and validated as a novel potential biomarker for predicting the occurrence of active ulcerative colitis. (PMID:32570281)
• Carboxypeptidase A6 suppresses the proliferation and invasion of colorectal cancer cells and is negatively regulated by miR-96-3p. (PMID:37011707)

Cross-species orthologs

24 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpa6	ENSDARG00000012013
mus_musculus	Cpa6	ENSMUSG00000042501
rattus_norvegicus	Cpa6	ENSRNOG00000005655
drosophila_melanogaster	CG3097	FBGN0029804
drosophila_melanogaster	CG3108	FBGN0029807
drosophila_melanogaster	CG18585	FBGN0031929
drosophila_melanogaster	CG7025	FBGN0031930
drosophila_melanogaster	CG4017	FBGN0032143
drosophila_melanogaster	CG17633	FBGN0032144
drosophila_melanogaster	CG2915	FBGN0033241
drosophila_melanogaster	CG12374	FBGN0033774
drosophila_melanogaster	CG14820	FBGN0035718
drosophila_melanogaster	CG8563	FBGN0035777
drosophila_melanogaster	CG8562	FBGN0035779
drosophila_melanogaster	CG18417	FBGN0035780
drosophila_melanogaster	CG8560	FBGN0035781
drosophila_melanogaster	CG8539	FBGN0035791
drosophila_melanogaster	CG4408	FBGN0039073
drosophila_melanogaster	CG32379	FBGN0052379
drosophila_melanogaster	CG42264	FBGN0259149
caenorhabditis_elegans		WBGENE00004747
caenorhabditis_elegans	T06A4.1	WBGENE00020281
caenorhabditis_elegans	Y47G6A.19	WBGENE00021645
caenorhabditis_elegans		WBGENE00021984

Paralogs (8): CPB2 (ENSG00000080618), CPA1 (ENSG00000091704), CPA4 (ENSG00000128510), CPO (ENSG00000144410), CPB1 (ENSG00000153002), CPA2 (ENSG00000158516), CPA5 (ENSG00000158525), CPA3 (ENSG00000163751)

Protein

Protein identifiers

Carboxypeptidase A6 — Q8N4T0 (reviewed: Q8N4T0)

All UniProt accessions (1): Q8N4T0

UniProt curated annotations — full annotation on UniProt →

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. 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.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in the hippocampus, nucleus raphe, and cortex.

Disease relevance. A chromosomal aberration involving CPA6 was found in a patient with Duane retraction syndrome. Translocation t(6;8)(q26;q13). 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Miscellaneous. May be due to intron retention. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the peptidase M14 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N4T0-1	1	yes
Q8N4T0-2	2
Q8N4T0-3	3

RefSeq proteins (1): NP_065094* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000834	Peptidase_M14	Domain
IPR003146	M14A_act_pep	Domain
IPR033843	CPAH	Domain
IPR036990	M14A-like_propep	Homologous_superfamily
IPR057247	CARBOXYPEPT_ZN_2	Binding_site

Pfam: PF00246, PF02244

UniProt features (25 total): binding site 8, sequence variant 5, glycosylation site 3, splice variant 3, signal peptide 1, propeptide 1, disulfide bond 1, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4T0-F1	90.93	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 398 (proton donor/acceptor)

Ligand- & substrate-binding residues (8): 324; 325–326; 376; 196–199; 196; 199; 254; 271–272

Disulfide bonds (1): 265–288

Glycosylation sites (3): 89, 153, 427

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): AP1_01, GOMF_METALLOPEPTIDASE_ACTIVITY, CAGCTG_AP4_Q5, BACH2_01, TGANTCA_AP1_C, MODULE_48, MODULE_95, NFE2_01, chr8q13, GOBP_PROTEOLYSIS, GOMF_CARBOXYPEPTIDASE_ACTIVITY, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_METALLOCARBOXYPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, GOMF_EXOPEPTIDASE_ACTIVITY

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (7): metallocarboxypeptidase activity (GO:0004181), zinc ion binding (GO:0008270), carboxypeptidase activity (GO:0004180), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

573 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPA6	CELA1	Q9UNI1	435
CPA6	PRPF31	Q8WWY3	410
CPA6	CLVS1	Q8IUQ0	370
CPA6	ASPA	P45381	365
CPA6	TIGD2	Q4W5G0	357
CPA6	LANCL3	Q6ZV70	348
CPA6	SCNM1	Q9BWG6	348
CPA6	CPE	P16870	345
CPA6	PRCP	P42785	337
CPA6	FARSA	Q9Y285	337
CPA6	CTRB2	Q6GPI1	336
CPA6	CTRB1	P17538	333
CPA6	THOP1	P52888	333
CPA6	C8orf34	Q49A92	321
CPA6	TCEAL2	Q9H3H9	315

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CPA6	PPM1G	psi-mi:“MI:0914”(association)	0.530
FBXO15	CPA6	psi-mi:“MI:0914”(association)	0.530
FBXO15	HSPD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): CPA6 (Affinity Capture-MS), CPA6 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), AMER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), UBB (Affinity Capture-MS), PPM1G (Affinity Capture-MS), FNTB (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), TARBP2 (Affinity Capture-MS), FUT11 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), CPA6 (Proximity Label-MS), FNTB (Affinity Capture-MS), FUT11 (Affinity Capture-MS)

ESM2 similar proteins: A5A6K7, O02350, O17754, O54858, O75976, O89001, P04836, P09958, P14384, P15087, P15169, P16870, P23188, P23377, P37892, P38836, P42787, P48052, Q00493, Q0II73, Q16769, Q28120, Q28193, Q2KIG3, Q2KJ83, Q4R4M3, Q4R7R2, Q5RFD6, Q5U901, Q66K79, Q80V42, Q8IVL8, Q8N436, Q8N4T0, Q8QGP3, Q8R4H4, Q8R4V4, Q8WXQ8, Q90240, Q96SM3

Diamond homologs: A0A1S4F020, A6XGK3, B6H233, B6Q972, B6V865, B8JLQ9, B8XGR3, C5FH26, C5FVN6, D4AS12, D4DL57, O02350, P00730, P00731, P00732, P04069, P09954, P09955, P15085, P15086, P18143, P19222, P19223, P29068, P38836, P42788, P48052, P55261, Q0C9B4, Q0II73, Q29NC4, Q3T905, Q504N0, Q5U901, Q7TPZ8, Q8IVL8, Q8N4T0, Q9VL86, A1CSU3, A1DGH9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

132 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	94
Likely benign	20
Benign	2

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3897586	NC_000008.11:g.67518048del	Pathogenic
191226	NM_020361.5(CPA6):c.544C>T (p.Arg182Ter)	Likely pathogenic
3764549	NM_020361.5(CPA6):c.383del (p.Arg128fs)	Likely pathogenic
4813838	NM_020361.5(CPA6):c.230C>G (p.Ser77Ter)	Likely pathogenic

SpliceAI

2722 predictions. Top by Δscore:

Variant	Effect	Δscore
8:67428045:A:AC	donor_gain	1.0000
8:67428046:C:CC	donor_gain	1.0000
8:67428046:CA:C	donor_gain	1.0000
8:67428046:CACAA:C	donor_gain	1.0000
8:67434174:T:TA	donor_gain	1.0000
8:67483783:T:A	donor_gain	1.0000
8:67509538:T:TA	donor_gain	1.0000
8:67509539:C:A	donor_gain	1.0000
8:67511536:CATA:C	donor_gain	1.0000
8:67511539:A:AC	donor_gain	1.0000
8:67511540:C:CT	donor_gain	1.0000
8:67511540:CTT:C	donor_gain	1.0000
8:67511542:T:TA	donor_gain	1.0000
8:67511563:T:TA	donor_gain	1.0000
8:67511662:T:C	acceptor_gain	1.0000
8:67607974:T:A	donor_gain	1.0000
8:67624250:CA:C	acceptor_gain	1.0000
8:67624252:C:CC	acceptor_gain	1.0000
8:67422688:ACATC:A	acceptor_loss	0.9900
8:67422689:CAT:C	acceptor_gain	0.9900
8:67422691:TCTAA:T	acceptor_loss	0.9900
8:67422692:C:CC	acceptor_gain	0.9900
8:67422692:C:T	acceptor_loss	0.9900
8:67422693:T:A	acceptor_loss	0.9900
8:67428038:GAAAC:G	donor_loss	0.9900
8:67428039:AAAC:A	donor_loss	0.9900
8:67428040:AACT:A	donor_loss	0.9900
8:67428041:AC:A	donor_loss	0.9900
8:67428042:CT:C	donor_loss	0.9900
8:67428043:T:TA	donor_loss	0.9900

AlphaMissense

2858 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:67483787:G:C	N273K	0.998
8:67483787:G:T	N273K	0.998
8:67484688:A:C	S246R	0.998
8:67484688:A:T	S246R	0.998
8:67484690:T:G	S246R	0.998
8:67422597:A:C	F407L	0.997
8:67422597:A:T	F407L	0.997
8:67422599:A:G	F407L	0.997
8:67483790:T:A	R272S	0.997
8:67483790:T:G	R272S	0.997
8:67483791:C:A	R272I	0.997
8:67483791:C:G	R272T	0.997
8:67483842:T:A	K255I	0.997
8:67484709:G:C	N239K	0.997
8:67484709:G:T	N239K	0.997
8:67483786:A:G	W274R	0.996
8:67483786:A:T	W274R	0.996
8:67506805:A:C	C206W	0.996
8:67422668:C:G	D384H	0.995
8:67434198:C:T	G294D	0.995
8:67483772:C:A	W278C	0.995
8:67483772:C:G	W278C	0.995
8:67483784:C:A	W274C	0.995
8:67483784:C:G	W274C	0.995
8:67506807:A:G	C206R	0.995
8:67506827:T:A	E199V	0.995
8:67506844:A:C	C193W	0.995
8:67422564:A:C	C418W	0.994
8:67483793:A:C	N271K	0.994
8:67483793:A:T	N271K	0.994

dbSNP variants (sampled 300 via entrez): RS1000000743 (8:67514037 C>A), RS1000003210 (8:67506941 C>G,T), RS1000004890 (8:67651042 A>G), RS1000015700 (8:67610305 G>T), RS1000042291 (8:67437887 T>C), RS1000061240 (8:67529778 T>C), RS1000062821 (8:67547638 G>A), RS1000069593 (8:67679139 T>C), RS1000070241 (8:67652085 A>G), RS1000078622 (8:67740714 T>C), RS1000083354 (8:67658358 G>C), RS1000089931 (8:67713922 G>A,T), RS1000092199 (8:67462499 A>G,T), RS1000105821 (8:67587902 G>C), RS1000113670 (8:67487103 G>A,C)

Disease associations

OMIM: gene MIM:609562 | disease phenotypes: MIM:614418, MIM:614417, MIM:117100

GenCC curated gene-disease

Disease	Classification	Inheritance
benign familial mesial temporal lobe epilepsy	Supportive	Autosomal dominant
familial mesial temporal lobe epilepsy with febrile seizures	Supportive	Autosomal dominant
familial temporal lobe epilepsy 5	Limited	Autosomal dominant
febrile seizures, familial, 11	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
epilepsy	Refuted	AD
epilepsy	Disputed	AR

Mondo (7): febrile seizures, familial, 11 (MONDO:0024566), familial temporal lobe epilepsy 5 (MONDO:0013741), intellectual disability (MONDO:0001071), epilepsy (MONDO:0005027), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), (MONDO:0015586), (MONDO:0013742)

Orphanet (2): Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001337	Tremor
HP:0001763	Pes planus
HP:0002067	Bradykinesia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002123	Generalized myoclonic seizure
HP:0002133	Status epilepticus
HP:0002197	Generalized-onset seizure
HP:0002311	Incoordination
HP:0002349	Focal aware seizure
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002376	Developmental regression
HP:0002384	Focal impaired awareness seizure
HP:0002539	Cortical dysplasia
HP:0003066	Limited knee extension
HP:0003621	Juvenile onset
HP:0004684	Talipes valgus
HP:0007010	Poor fine motor coordination
HP:0007058	Generalized cerebral atrophy/hypoplasia
HP:0007359	Focal-onset seizure
HP:0008770	Obsessive-compulsive trait
HP:0010819	Atonic seizure
HP:0010850	EEG with spike-wave complexes

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002543_4	Hearing function	3.000000e-07
GCST002560_5	Type 2 diabetes	9.000000e-06
GCST003663_2	Cholesterol, total	4.000000e-06
GCST011742_19	Triglyceride levels in HIV infection	5.000000e-07
GCST011742_5	Triglyceride levels in HIV infection	5.000000e-07
GCST012481_6	Cerebral amyloid angiopathy in Alzheimer’s disease	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2162145	Efficacy	3	metformin	Diabetes Mellitus;Type 2

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2162145	CPA6	3	0.00	1	metformin

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M14: Carboxypeptidase A

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	increases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
aflatoxin B2	decreases methylation	1
phenethyl isothiocyanate	increases expression	1
abrine	decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Oxyquinoline	decreases expression	1
Aflatoxin B1	decreases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation