CES5A

Summary

CES5A (carboxylesterase 5A, HGNC:26459) is a protein-coding gene on chromosome 16q12.2, encoding Carboxylesterase 5A (Q6NT32). Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs.

This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They also participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This gene, also called CES5, is predominantly expressed in peripheral tissues, including brain, kidney, lung and testis. It encodes a secreted enzyme. Because of high levels in the urine of male domestic cats, this enzyme is also called cauxin (carboxylesterase-like urinary excreted protein). The enzyme functions in regulating the production of a pheromone precursor and may contribute to lipid and cholesterol transfer processes within male reproductive fluids. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 221223 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_001143685

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26459
Approved symbol	CES5A
Name	carboxylesterase 5A
Location	16q12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31547, CES4C1, CES5, CAUXIN
Ensembl gene	ENSG00000159398
Ensembl biotype	protein_coding
OMIM	618678
Entrez	221223

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000290567, ENST00000319165, ENST00000518005, ENST00000520435, ENST00000521228, ENST00000521992, ENST00000536025, ENST00000541580, ENST00000544479

RefSeq mRNA: 3 — MANE Select: NM_001143685 NM_001143685, NM_001190158, NM_145024

CCDS: CCDS10755, CCDS45490, CCDS54012

Canonical transcript exons

ENST00000290567 — 13 exons

Exon	Start	End
ENSE00001867019	55875149	55875373
ENSE00003469702	55859547	55859687
ENSE00003517905	55852881	55853028
ENSE00003535855	55846768	55846840
ENSE00003540020	55849624	55849773
ENSE00003557759	55846154	55846682
ENSE00003593215	55871625	55871763
ENSE00003608516	55869611	55869744
ENSE00003616873	55861412	55861516
ENSE00003618209	55863348	55863452
ENSE00003667323	55865963	55866116
ENSE00003677521	55873833	55874037
ENSE00003694532	55856377	55856445

Expression profiles

Bgee: expression breadth broad, 59 present calls, max score 91.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0288 / max 37.0480, expressed in 7 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157462	0.0126	5
157460	0.0116	3
157461	0.0046	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.91	gold quality
right lobe of liver	UBERON:0001114	74.28	gold quality
liver	UBERON:0002107	71.45	gold quality
prefrontal cortex	UBERON:0000451	59.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	58.49	gold quality
gall bladder	UBERON:0002110	55.58	gold quality
frontal cortex	UBERON:0001870	55.49	gold quality
superior frontal gyrus	UBERON:0002661	55.11	gold quality
substantia nigra	UBERON:0002038	54.28	gold quality
anterior cingulate cortex	UBERON:0009835	53.39	gold quality
cerebral cortex	UBERON:0000956	53.06	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	51.46	gold quality
skin of leg	UBERON:0001511	51.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	51.18	gold quality
Ammon’s horn	UBERON:0001954	50.93	gold quality
zone of skin	UBERON:0000014	50.35	gold quality
temporal lobe	UBERON:0001871	50.04	gold quality
cortical plate	UBERON:0005343	49.95	gold quality
amygdala	UBERON:0001876	49.89	gold quality
right frontal lobe	UBERON:0002810	49.17	gold quality
skin of abdomen	UBERON:0001416	48.88	gold quality
putamen	UBERON:0001874	47.81	gold quality
primary visual cortex	UBERON:0002436	47.65	gold quality
hypothalamus	UBERON:0001898	47.27	gold quality
brain	UBERON:0000955	47.22	gold quality
caudate nucleus	UBERON:0001873	45.89	gold quality
ganglionic eminence	UBERON:0004023	45.89	gold quality
nucleus accumbens	UBERON:0001882	44.03	gold quality
minor salivary gland	UBERON:0001830	43.92	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting CES5A, 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-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-6871-5P	98.90	66.67	671

Cross-species orthologs

55 orthologs

Organism	Symbol	Gene ID
danio_rerio	ces2a	ENSDARG00000041569
danio_rerio	ces3	ENSDARG00000041595
danio_rerio	si:ch73-89b15.3	ENSDARG00000053709
danio_rerio	si:dkey-30c15.17	ENSDARG00000058492
danio_rerio	nlgn3b	ENSDARG00000062376
danio_rerio	nlgn2b	ENSDARG00000079251
danio_rerio	si:ch211-71n6.4	ENSDARG00000102234
mus_musculus	Ces5a	ENSMUSG00000058019
rattus_norvegicus	Ces5a	ENSRNOG00000025710
drosophila_melanogaster	Est-6	FBGN0000592
drosophila_melanogaster	Est-P	FBGN0000594
drosophila_melanogaster	Glt	FBGN0001114
drosophila_melanogaster	Gli	FBGN0001987
drosophila_melanogaster	Jhe	FBGN0010052
drosophila_melanogaster	alpha-Est1	FBGN0015568
drosophila_melanogaster	alpha-Est10	FBGN0015569
drosophila_melanogaster	alpha-Est2	FBGN0015570
drosophila_melanogaster	alpha-Est3	FBGN0015571
drosophila_melanogaster	alpha-Est4	FBGN0015572
drosophila_melanogaster	alpha-Est6	FBGN0015574
drosophila_melanogaster	alpha-Est7	FBGN0015575
drosophila_melanogaster	alpha-Est8	FBGN0015576
drosophila_melanogaster	alpha-Est9	FBGN0015577
drosophila_melanogaster	CG4757	FBGN0027584
drosophila_melanogaster	CG9287	FBGN0032057
drosophila_melanogaster	CG9289	FBGN0032058
drosophila_melanogaster	CG3841	FBGN0032131
drosophila_melanogaster	CG4382	FBGN0032132
drosophila_melanogaster	Jhedup	FBGN0034076
drosophila_melanogaster	gas	FBGN0034736
drosophila_melanogaster	Nlg3	FBGN0083963
drosophila_melanogaster	alpha-Est5	FBGN0261393
caenorhabditis_elegans		WBGENE00000037
caenorhabditis_elegans		WBGENE00000038
caenorhabditis_elegans		WBGENE00001578
caenorhabditis_elegans		WBGENE00006412
caenorhabditis_elegans		WBGENE00007691
caenorhabditis_elegans		WBGENE00007692
caenorhabditis_elegans		WBGENE00007693
caenorhabditis_elegans		WBGENE00007695
caenorhabditis_elegans		WBGENE00008451
caenorhabditis_elegans		WBGENE00011362
caenorhabditis_elegans		WBGENE00011364
caenorhabditis_elegans		WBGENE00013873
caenorhabditis_elegans		WBGENE00013874
caenorhabditis_elegans		WBGENE00013875
caenorhabditis_elegans		WBGENE00015067
caenorhabditis_elegans		WBGENE00015071
caenorhabditis_elegans		WBGENE00015279
caenorhabditis_elegans		WBGENE00015284
caenorhabditis_elegans		WBGENE00016595
caenorhabditis_elegans		WBGENE00016862
caenorhabditis_elegans		WBGENE00016863
caenorhabditis_elegans	cest-27	WBGENE00018958
caenorhabditis_elegans		WBGENE00020688

Paralogs (13): TG (ENSG00000042832), ACHE (ENSG00000087085), BCHE (ENSG00000114200), NLGN4X (ENSG00000146938), NLGN4Y (ENSG00000165246), NLGN1 (ENSG00000169760), NLGN2 (ENSG00000169992), CEL (ENSG00000170835), CES4A (ENSG00000172824), CES3 (ENSG00000172828), CES2 (ENSG00000172831), NLGN3 (ENSG00000196338), CES1 (ENSG00000198848)

Protein

Protein identifiers

Carboxylesterase 5A — Q6NT32 (reviewed: Q6NT32)

Alternative names: Carboxylesterase-like urinary excreted protein homolog

All UniProt accessions (6): Q6NT32, A0A0J9YW16, E5RFG9, F5H0J7, I3NI11, V9HWK3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs.

Subcellular location. Secreted.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the type-B carboxylesterase/lipase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6NT32-1	1	yes
Q6NT32-2	2
Q6NT32-3	3
Q6NT32-4	4

RefSeq proteins (3): NP_001137157, NP_001177087, NP_659461 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002018	CarbesteraseB	Domain
IPR019819	Carboxylesterase_B_CS	Conserved_site
IPR019826	Carboxylesterase_B_AS	Active_site
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR050309	Type-B_Carboxylest/Lipase	Family

Pfam: PF00135

Catalyzed reactions (Rhea), 1 shown:

• a carboxylic ester + H2O = an alcohol + a carboxylate + H(+) (RHEA:21164)

UniProt features (19 total): sequence variant 5, glycosylation site 4, splice variant 3, active site 3, signal peptide 1, chain 1, sequence conflict 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NT32-F1	90.48	0.84

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 (3): 226 (acyl-ester intermediate); 345 (charge relay system); 454 (charge relay system)

Disulfide bonds (1): 94–121

Glycosylation sites (4): 281, 363, 513, 524

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, HNF1_Q6, HNF1_C, HNF1_01, YNGTTNNNATT_UNKNOWN, KEGG_DRUG_METABOLISM_OTHER_ENZYMES, YATGNWAAT_OCT_C, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_CARBOXYLIC_ESTER_HYDROLASE_ACTIVITY, GSE13887_HEALTHY_VS_LUPUS_RESTING_CD4_TCELL_UP, TGATTTRY_GFI1_01, MIKKELSEN_ES_HCP_WITH_H3_UNMETHYLATED, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED, OCT_Q6

GO Biological Process (0):

GO Molecular Function (3): carboxylesterase activity (GO:0106435), hydrolase activity (GO:0016787), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carboxylic ester hydrolase activity	1
catalytic activity	1
hydrolase activity, acting on ester bonds	1
cellular anatomical structure	1

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CES5A	ESD	P10768	923
CES5A	HAGH	Q16775	771
CES5A	ADH5	P11766	754
CES5A	SIAE	Q9HAT2	507
CES5A	LTF	P02788	468
CES5A	AADAC	P22760	462
CES5A	SPINT4	Q6UDR6	449
CES5A	MDH2	P40926	430
CES5A	DEFB127	Q9H1M4	411
CES5A	TGM4	P49221	410
CES5A	QSOX1	O00391	404
CES5A	CRISP2	P16562	401
CES5A	ABHD2	P08910	400
CES5A	PATE1	Q8WXA2	396
CES5A	GJA8	P48165	380

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A8B0RBM2, G3V7J5, O00748, O42275, O46421, O70631, P04058, P07140, P07692, P07882, P0C6R3, P10959, P12337, P14943, P16303, P23141, P23953, P30122, P32749, P56161, Q03311, Q04791, Q27677, Q29550, Q5GRG2, Q5RCL7, Q5XG92, Q63010, Q63108, Q63880, Q64176, Q64285, Q64419, Q64573, Q6AW46, Q6AW47, Q6NT32, Q6UWW8, Q8BK48, Q8I034

Diamond homologs: A0A060S684, A0A0E4AET8, A0A443HK52, D4ASH1, D4AZ78, D4B1N9, I1RDA9, I6Y9F7, O08710, O16168, O16169, O16170, O16171, O16172, O46421, O62760, O62761, P01266, P01267, P04058, P06882, P07692, P08171, P10959, P12337, P12992, P16303, P16854, P17573, P18142, P20261, P21836, P21837, P21927, P22394, P23795, P25725, P25726, P30122, P32749

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1934 predictions. Top by Δscore:

Variant	Effect	Δscore
16:55846678:GATTC:G	acceptor_gain	1.0000
16:55846679:ATTC:A	acceptor_gain	1.0000
16:55846680:TTC:T	acceptor_gain	1.0000
16:55846681:TC:T	acceptor_gain	1.0000
16:55846681:TCCT:T	acceptor_loss	1.0000
16:55846682:CC:C	acceptor_gain	1.0000
16:55846683:C:CC	acceptor_gain	1.0000
16:55846683:CTAG:C	acceptor_loss	1.0000
16:55846764:TTAC:T	donor_loss	1.0000
16:55846765:TA:T	donor_loss	1.0000
16:55846766:A:AC	donor_gain	1.0000
16:55846766:A:C	donor_loss	1.0000
16:55846766:AC:A	donor_gain	1.0000
16:55846766:ACC:A	donor_gain	1.0000
16:55846767:C:CT	donor_gain	1.0000
16:55846767:CC:C	donor_gain	1.0000
16:55846767:CCC:C	donor_gain	1.0000
16:55846767:CCCG:C	donor_gain	1.0000
16:55846767:CCCGG:C	donor_gain	1.0000
16:55846841:C:CC	acceptor_gain	1.0000
16:55849618:CCTTA:C	donor_loss	1.0000
16:55849619:CTTAC:C	donor_loss	1.0000
16:55849620:TTA:T	donor_loss	1.0000
16:55849621:TACC:T	donor_loss	1.0000
16:55849622:A:AC	donor_gain	1.0000
16:55849622:A:AG	donor_loss	1.0000
16:55849623:C:A	donor_loss	1.0000
16:55849623:C:CC	donor_gain	1.0000
16:55849623:CCGAA:C	donor_gain	1.0000
16:55849656:C:CT	donor_gain	1.0000

AlphaMissense

3761 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:55866076:C:G	D198H	0.984
16:55873940:G:C	F57L	0.982
16:55873940:G:T	F57L	0.982
16:55873942:A:G	F57L	0.982
16:55873925:A:C	F62L	0.978
16:55873925:A:T	F62L	0.978
16:55873927:A:G	F62L	0.978
16:55846779:A:C	F495L	0.976
16:55846779:A:T	F495L	0.976
16:55846781:A:G	F495L	0.976
16:55866075:T:G	D198A	0.972
16:55866055:A:G	W205R	0.971
16:55866055:A:T	W205R	0.971
16:55871667:G:C	N125K	0.967
16:55871667:G:T	N125K	0.967
16:55846654:A:G	W509R	0.965
16:55846654:A:T	W509R	0.965
16:55863402:A:C	S252R	0.964
16:55863402:A:T	S252R	0.964
16:55863404:T:G	S252R	0.964
16:55865992:A:G	S226P	0.964
16:55869616:G:C	F182L	0.964
16:55869616:G:T	F182L	0.964
16:55869618:A:G	F182L	0.964
16:55871671:A:G	L124P	0.964
16:55873895:A:C	F72L	0.964
16:55873895:A:T	F72L	0.964
16:55873897:A:G	F72L	0.964
16:55849742:A:C	F435L	0.963
16:55849742:A:T	F435L	0.963

dbSNP variants (sampled 300 via entrez): RS1000048739 (16:55942658 A>G), RS1000135348 (16:55915044 G>A), RS1000250268 (16:55923315 T>C), RS1000257028 (16:55945316 C>A), RS1000297799 (16:55923618 C>T), RS1000307821 (16:55945068 C>T), RS1000360393 (16:55880215 C>A), RS1000367527 (16:55950829 C>T), RS1000399022 (16:55907214 A>G), RS1000584615 (16:55921842 A>T), RS1000590748 (16:55884817 C>G), RS1000635505 (16:55922098 C>T), RS1000657552 (16:55885845 C>G,T), RS1000692748 (16:55878546 C>T), RS1000724879 (16:55879190 C>T)

Disease associations

OMIM: gene MIM:618678 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002938_21	Copper levels	3.000000e-06
GCST007576_403	Chronotype	2.000000e-10
GCST011494_71	Daytime nap	6.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
bisphenol A	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	affects methylation, increases methylation	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Formaldehyde	increases expression	1
Methapyrilene	affects methylation, increases methylation	1
Rotenone	increases expression	1
Vincristine	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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