CES4A

Summary

CES4A (carboxylesterase 4A, HGNC:26741) is a protein-coding gene on chromosome 16q22.1, encoding Carboxylesterase 4A (Q5XG92). Probable carboxylesterase.

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 CES6, encodes a secreted enzyme, and may play a role in the detoxification of drugs and xenobiotics in neural and other tissues of the body and in the cerebrospinal fluid. Multiple transcript variants encoding different isoforms have been reported, but the full-length nature and/or biological validity of some variants have not been determined.

Source: NCBI Gene 283848 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_001364782

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26741
Approved symbol	CES4A
Name	carboxylesterase 4A
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ37464
Ensembl gene	ENSG00000172824
Ensembl biotype	protein_coding
OMIM	621153
Entrez	283848

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000397205, ENST00000535543, ENST00000535696, ENST00000535948, ENST00000538199, ENST00000540579, ENST00000540947, ENST00000543561, ENST00000544478, ENST00000544986, ENST00000567587, ENST00000648724, ENST00000862242, ENST00000862243, ENST00000862244, ENST00000862245, ENST00000862246, ENST00000862247, ENST00000862248, ENST00000862249, ENST00000862250, ENST00000948592

RefSeq mRNA: 5 — MANE Select: NM_001364782 NM_001190201, NM_001190202, NM_001318506, NM_001364782, NM_173815

CCDS: CCDS42174, CCDS54024, CCDS54025, CCDS92173

Canonical transcript exons

ENST00000648724 — 14 exons

Exon	Start	End
ENSE00001532934	66995628	66995829
ENSE00002243639	66988589	66988830
ENSE00002700747	67000638	67000779
ENSE00003462430	67000857	67000990
ENSE00003477525	67003256	67003360
ENSE00003516846	67004793	67004873
ENSE00003569847	67003070	67003174
ENSE00003575874	67004084	67004224
ENSE00003595641	67005240	67005393
ENSE00003601164	67006745	67006817
ENSE00003612844	67006391	67006519
ENSE00003623196	67001308	67001461
ENSE00003658588	67003515	67003553
ENSE00003978145	67008974	67010417

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 99.25.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0481 / max 111.7846, expressed in 869 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154555	1.7337	641
154557	0.9037	300
154556	0.2406	117
154549	0.0712	17
154553	0.0708	28
154551	0.0107	5
154552	0.0100	5
154550	0.0074	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.48	gold quality
cerebellar hemisphere	UBERON:0002245	97.06	gold quality
right frontal lobe	UBERON:0002810	97.02	gold quality
cerebellar cortex	UBERON:0002129	97.01	gold quality
adenohypophysis	UBERON:0002196	96.57	gold quality
cerebellum	UBERON:0002037	96.01	gold quality
pituitary gland	UBERON:0000007	95.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.64	gold quality
upper arm skin	UBERON:0004263	94.37	silver quality
skin of leg	UBERON:0001511	94.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.28	gold quality
anterior cingulate cortex	UBERON:0009835	94.19	gold quality
amygdala	UBERON:0001876	93.05	gold quality
skin of abdomen	UBERON:0001416	93.00	gold quality
nucleus accumbens	UBERON:0001882	92.61	gold quality
putamen	UBERON:0001874	92.43	gold quality
hypothalamus	UBERON:0001898	92.23	gold quality
right lobe of liver	UBERON:0001114	91.83	gold quality
zone of skin	UBERON:0000014	91.64	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.63	gold quality
caudate nucleus	UBERON:0001873	91.31	gold quality
oviduct epithelium	UBERON:0004804	91.28	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.83	gold quality
fallopian tube	UBERON:0003889	90.47	gold quality
right lobe of thyroid gland	UBERON:0001119	90.43	gold quality
brain	UBERON:0000955	90.38	gold quality
spinal cord	UBERON:0002240	90.30	gold quality
primary visual cortex	UBERON:0002436	90.10	gold quality
forebrain	UBERON:0001890	89.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.03

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB

miRNA regulators (miRDB)

44 targeting CES4A, 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-1193	100.00	65.93	529
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4306	99.72	70.50	3630
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-6766-5P	99.68	67.70	2325
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-485-5P	99.10	64.78	1889

Cross-species orthologs

49 orthologs

Organism	Symbol	Gene ID
danio_rerio	ces2a	ENSDARG00000041569
danio_rerio	ces3	ENSDARG00000041595
danio_rerio	nlgn3b	ENSDARG00000062376
danio_rerio	nlgn2b	ENSDARG00000079251
danio_rerio	si:ch211-71n6.4	ENSDARG00000102234
mus_musculus	Ces4a	ENSMUSG00000060560
rattus_norvegicus	Ces4a	ENSRNOG00000014257
drosophila_melanogaster	Est-6	FBGN0000592
drosophila_melanogaster	Est-P	FBGN0000594
drosophila_melanogaster	Glt	FBGN0001114
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	alpha-Est5	FBGN0261393
caenorhabditis_elegans		WBGENE00000037
caenorhabditis_elegans		WBGENE00000038
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), CES5A (ENSG00000159398), NLGN4Y (ENSG00000165246), NLGN1 (ENSG00000169760), NLGN2 (ENSG00000169992), CEL (ENSG00000170835), CES3 (ENSG00000172828), CES2 (ENSG00000172831), NLGN3 (ENSG00000196338), CES1 (ENSG00000198848)

Protein

Protein identifiers

Carboxylesterase 4A — Q5XG92 (reviewed: Q5XG92)

All UniProt accessions (4): Q5XG92, A0A0C4DGH1, F5GZV6, I3L191

UniProt curated annotations — full annotation on UniProt →

Function. Probable carboxylesterase.

Subcellular location. Secreted.

Miscellaneous. Inactive. 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 type-B carboxylesterase/lipase family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q5XG92-1	1	yes
Q5XG92-2	2
Q5XG92-4	3
Q5XG92-5	4
Q5XG92-6	5
Q5XG92-7	6
Q5XG92-8	7

RefSeq proteins (5): NP_001177130, NP_001177131, NP_001305435, NP_001351711, NP_776176 (=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

UniProt features (20 total): splice variant 8, active site 3, glycosylation site 3, sequence conflict 2, disulfide bond 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5XG92-F1	92.64	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 (3): 221 (acyl-ester intermediate); 353 (charge relay system); 467 (charge relay system)

Disulfide bonds (2): 88–116, 273–284

Glycosylation sites (3): 214, 276, 388

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 66 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, chr16q22, MARTINEZ_RB1_TARGETS_UP, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_CARBOXYLIC_ESTER_HYDROLASE_ACTIVITY, SENGUPTA_EBNA1_ANTICORRELATED, DODD_NASOPHARYNGEAL_CARCINOMA_DN, BOSCO_ALLERGEN_INDUCED_TH2_ASSOCIATED_MODULE, PAX7_TARGET_GENES, ZNF768_TARGET_GENES, MIR7106_5P, MIR5584_5P, MIR6756_5P, MIR4723_5P, MIR6870_5P

GO Biological Process (0):

GO Molecular Function (2): carboxylic ester hydrolase activity (GO:0052689), hydrolase activity (GO:0016787)

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

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CES4A	TMEM265	A0A087WTH1	477
CES4A	AADAC	P22760	427
CES4A	NUTM2D	Q5VT03	389
CES4A	IAH1	Q2TAA2	375
CES4A	ZNF26	P17031	348
CES4A	PNMA8B	Q9ULN7	346
CES4A	PLA2G15	Q8NCC3	339
CES4A	A0A087WTJ2	A0A087WTJ2	328
CES4A	ZNF696	Q9H7X3	325
CES4A	NR1I2	O75469	308
CES4A	FLYWCH2	Q96CP2	305
CES4A	CCDC183	Q5T5S1	297
CES4A	EXOC3L1	Q86VI1	295
CES4A	LRIT1	Q9P2V4	295
CES4A	FAM25A	B3EWG3	294

IntAct

0 interactions, top by confidence:

BioGRID (4): CES4A (Affinity Capture-MS), CES4A (Negative Genetic), CES4A (Negative Genetic), CES4A (Affinity Capture-MS)

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, A0A8B0RBM2, B0F2B4, D2D3B6, D6WMZ8, G3V7J5, I1RDA9, O00748, O16168, O16169, O16170, O16171, O16172, O16173, O42275, O46421, O62760, O62761, O70631, P04058, P06276, P07882, P08171, P0C6R3, P10959, P12337, P12992, P14943, P16303, P16854, P18142, P19835, P21837, P21927, P23141, P23953, P25725, P25726, P25727

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2625 predictions. Top by Δscore:

Variant	Effect	Δscore
16:66995623:CCCA:C	acceptor_loss	1.0000
16:66995624:CCA:C	acceptor_loss	1.0000
16:66995625:CAGG:C	acceptor_loss	1.0000
16:66995626:A:C	acceptor_loss	1.0000
16:66995828:GG:G	donor_gain	1.0000
16:66995829:GG:G	donor_gain	1.0000
16:67001410:A:T	donor_gain	1.0000
16:67003065:TGCA:T	acceptor_loss	1.0000
16:67003066:GCAG:G	acceptor_loss	1.0000
16:67003067:CA:C	acceptor_loss	1.0000
16:67003068:A:AC	acceptor_loss	1.0000
16:67003068:A:AG	acceptor_gain	1.0000
16:67003068:AGAT:A	acceptor_gain	1.0000
16:67003069:G:A	acceptor_loss	1.0000
16:67003069:G:GA	acceptor_gain	1.0000
16:67003069:GAT:G	acceptor_gain	1.0000
16:67003069:GATG:G	acceptor_gain	1.0000
16:67003175:GTG:G	donor_loss	1.0000
16:67003176:T:A	donor_loss	1.0000
16:67003250:CTATA:C	acceptor_loss	1.0000
16:67003251:TATA:T	acceptor_loss	1.0000
16:67003252:ATAG:A	acceptor_loss	1.0000
16:67003253:TA:T	acceptor_loss	1.0000
16:67003254:A:AG	acceptor_gain	1.0000
16:67003254:A:AT	acceptor_loss	1.0000
16:67003254:AGAAG:A	acceptor_gain	1.0000
16:67003255:G:A	acceptor_loss	1.0000
16:67003255:G:GG	acceptor_gain	1.0000
16:67003255:GA:G	acceptor_gain	1.0000
16:67003255:GAA:G	acceptor_gain	1.0000

AlphaMissense

3686 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67000966:G:T	R171M	0.995
16:66995720:T:C	F51L	0.992
16:66995722:T:A	F51L	0.992
16:66995722:T:G	F51L	0.992
16:67001432:T:C	S221P	0.992
16:66995735:T:C	F56L	0.988
16:66995737:C:A	F56L	0.988
16:66995737:C:G	F56L	0.988
16:67001335:C:A	N188K	0.988
16:67001335:C:G	N188K	0.988
16:67006804:T:C	F502L	0.988
16:67006806:T:A	F502L	0.988
16:67006806:T:G	F502L	0.988
16:67000983:T:C	F177L	0.987
16:67000985:C:A	F177L	0.987
16:67000985:C:G	F177L	0.987
16:67001393:T:C	F208L	0.985
16:67001395:C:A	F208L	0.985
16:67001395:C:G	F208L	0.985
16:67000966:G:C	R171T	0.984
16:67001369:T:A	W200R	0.984
16:67001369:T:C	W200R	0.984
16:66995763:G:T	R65M	0.983
16:67000967:G:C	R171S	0.983
16:67000967:G:T	R171S	0.983
16:67001371:G:C	W200C	0.982
16:67001371:G:T	W200C	0.982
16:67001433:C:T	S221L	0.982
16:67003118:A:C	S247R	0.982
16:67003120:T:A	S247R	0.982

dbSNP variants (sampled 300 via entrez): RS1000845454 (16:66990061 T>C), RS1000947993 (16:66994093 T>A,C), RS1001019954 (16:66993970 G>A,T), RS1001111840 (16:67000214 C>T), RS1001120067 (16:67003513 A>G), RS1001164445 (16:66994460 C>T), RS1001197746 (16:66990371 G>A,T), RS1001276977 (16:67000568 C>T), RS1001403964 (16:67007334 G>T), RS1001486650 (16:67006985 A>C), RS1001630746 (16:66991757 T>C), RS1001749529 (16:67000323 G>C), RS1002068090 (16:66996032 T>C), RS1002366138 (16:66989989 G>A,T), RS1002392963 (16:67010030 G>C)

Disease associations

OMIM: gene MIM:621153 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010083_112	Hemoglobin levels	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, decreases expression, increases abundance	2
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
lead acetate	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
Benzo(a)pyrene	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Nickel	decreases expression	1
Phthalic Acids	increases methylation	1
Progesterone	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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