AWAT1

Summary

AWAT1 (acyl-CoA wax alcohol acyltransferase 1, HGNC:23252) is a protein-coding gene on chromosome Xq13.1, encoding Acyl-CoA wax alcohol acyltransferase 1 (Q58HT5). Acyltransferase that catalyzes the formation of ester bonds between fatty alcohols and fatty acyl-CoAs to form wax monoesters.

The protein encoded by this gene belongs to the diacylglycerol acyltransferase family. It esterifies long chain (wax) alcohols with acyl-CoA-derived fatty acids to produce wax esters. Wax esters are enriched in sebum, suggesting that this enzyme plays a central role in lipid metabolism in skin. Consistent with this observation, this protein is predominantly expressed in the sebaceous gland of the skin.

Source: NCBI Gene 158833 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 58 total
• Druggable target: yes
• MANE Select transcript: NM_001013579

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23252
Approved symbol	AWAT1
Name	acyl-CoA wax alcohol acyltransferase 1
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204195
Ensembl biotype	protein_coding
OMIM	300924
Entrez	158833

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374521, ENST00000480702

RefSeq mRNA: 1 — MANE Select: NM_001013579 NM_001013579

CCDS: CCDS35321

Canonical transcript exons

ENST00000374521 — 7 exons

Exon	Start	End
ENSE00001463717	70240136	70240659
ENSE00001463718	70239735	70239934
ENSE00001463720	70238212	70238383
ENSE00001463722	70237044	70237248
ENSE00003519533	70234655	70234771
ENSE00003527351	70235716	70235823
ENSE00003590322	70236069	70236139

Expression profiles

Bgee: expression breadth broad, 43 present calls, max score 93.12.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	93.12	gold quality
mammalian vulva	UBERON:0000997	78.36	gold quality
myocardium	UBERON:0002349	62.14	gold quality
endothelial cell	CL:0000115	61.91	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	54.16	gold quality
biceps brachii	UBERON:0001507	53.75	gold quality
mucosa of sigmoid colon	UBERON:0004993	51.78	gold quality
buccal mucosa cell	CL:0002336	51.04	gold quality
quadriceps femoris	UBERON:0001377	48.82	gold quality
vastus lateralis	UBERON:0001379	48.63	gold quality
colonic mucosa	UBERON:0000317	47.81	gold quality
zone of skin	UBERON:0000014	47.49	gold quality
skin of abdomen	UBERON:0001416	46.89	gold quality
nipple	UBERON:0002030	46.65	silver quality
sural nerve	UBERON:0015488	46.60	gold quality
substantia nigra pars reticulata	UBERON:0001966	45.43	gold quality
right uterine tube	UBERON:0001302	45.27	silver quality
substantia nigra pars compacta	UBERON:0001965	44.99	gold quality
calcaneal tendon	UBERON:0003701	44.16	silver quality
deltoid	UBERON:0001476	43.66	gold quality
adult organism	UBERON:0007023	43.60	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
skeletal muscle tissue	UBERON:0001134	43.30	gold quality
skin of leg	UBERON:0001511	42.96	gold quality
pharyngeal mucosa	UBERON:0000355	42.81	gold quality
bone marrow cell	CL:0002092	42.58	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
gingiva	UBERON:0001828	42.37	gold quality
epithelium of nasopharynx	UBERON:0001951	42.06	gold quality
inferior vagus X ganglion	UBERON:0005363	41.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting AWAT1, 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-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-4421	97.99	64.89	701
HSA-MIR-5699-3P	97.81	65.00	861
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-3657	96.33	66.29	608
HSA-MIR-5002-3P	95.75	67.04	542

Literature-anchored findings (GeneRIF, showing 1)

• analysis of AWAT1 and AWAT2 substrate specificity and differentiation-specific expression pattern (PMID:15671038)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Awat1	ENSMUSG00000015665
rattus_norvegicus	Awat1	ENSRNOG00000026231
drosophila_melanogaster	CG1941	FBGN0033214
drosophila_melanogaster	Dgat2	FBGN0033215
drosophila_melanogaster	CG1946	FBGN0033216
caenorhabditis_elegans		WBGENE00010296
caenorhabditis_elegans		WBGENE00019464
caenorhabditis_elegans		WBGENE00020910
caenorhabditis_elegans		WBGENE00021818

Paralogs (6): DGAT2 (ENSG00000062282), MOGAT3 (ENSG00000106384), MOGAT1 (ENSG00000124003), AWAT2 (ENSG00000147160), MOGAT2 (ENSG00000166391), DGAT2L6 (ENSG00000184210)

Protein

Protein identifiers

Acyl-CoA wax alcohol acyltransferase 1 — Q58HT5 (reviewed: Q58HT5)

Alternative names: Diacylglycerol O-acyltransferase 2-like protein 3, Diacylglycerol acyltransferase 2, Long-chain-alcohol O-fatty-acyltransferase 1

All UniProt accessions (1): Q58HT5

UniProt curated annotations — full annotation on UniProt →

Function. Acyltransferase that catalyzes the formation of ester bonds between fatty alcohols and fatty acyl-CoAs to form wax monoesters. Shows a strong preference for decyl alcohol (C10), with less activity towards C16 and C18 alcohols. Shows a strong preference for saturated acyl-CoAs.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Predominantly expressed in skin, where it is limited to the sebaceous gland. Expressed in more mature, centrally located cells just before their rupture and sebum release. Also expressed in all tissues except spleen. Expressed at higher level in thymus, prostate and testis.

Similarity. Belongs to the diacylglycerol acyltransferase family.

RefSeq proteins (1): NP_001013597* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007130	DAGAT	Family

Pfam: PF03982

Enzyme classification (BRENDA):

• EC 2.3.1.75 — long-chain-alcohol O-fatty-acyltransferase (BRENDA: 24 organisms, 473 substrates, 10 inhibitors, 48 Km, 37 kcat entries)

Substrate kinetics (BRENDA)

17 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PALMITOYL-COA	0.0031–0.029	6
ARACHIDONOYL-COA	0.2263–0.2972	4
DECANOYL-COA	0.001–0.0176	4
EICOSAPENTAENOYL-COA	0.1016–0.1312	4
LAUROYL-COA	0.0001–0.0259	4
MYRISTOYL-COA	0.0039–0.0185	4
OCTADECATRIENOYL-COA	0.2809–0.2847	4
OCTANOYL-COA	0.0123–0.0299	4
STEAROYL-COA	0.0192–0.0759	4
11-CIS-RETINOL	0.0262	1
13-CIS-RETINOL	0.0352	1
9-CIS-RETINOL	0.0238	1
ALL-TRANS-RETINOL	0.0236	1
HEXADECANOL	0.044	1
HEXAN-1-OL	2.4	1

Catalyzed reactions (Rhea), 11 shown:

• hexadecan-1-ol + hexadecanoyl-CoA = hexadecyl hexadecanoate + CoA (RHEA:38167)
• 1,2-di-(9Z-octadecenoyl)-sn-glycerol + (9Z)-octadecenoyl-CoA = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38219)
• decan-1-ol + (9Z)-octadecenoyl-CoA = decyl (9Z)-octadecenoate + CoA (RHEA:38223)
• hexadecan-1-ol + (9Z)-octadecenoyl-CoA = hexadecyl (9Z)-octadecenoate + CoA (RHEA:38227)
• (9Z)-hexadecen-1-ol + (9Z)-octadecenoyl-CoA = 1-O-(9Z)-hexadecenyl (9Z)-octadecenoate + CoA (RHEA:38231)
• octadecan-1-ol + (9Z)-octadecenoyl-CoA = octadecyl (9Z)-octadecenoate + CoA (RHEA:38235)
• (9Z)-octadecen-1-ol + (9Z)-octadecenoyl-CoA = 1-O-(9Z)-octadecenyl (9Z)-octadecenoate + CoA (RHEA:38239)
• eicosan-1-ol + (9Z)-octadecenoyl-CoA = 1-O-eicosanyl (9Z)-octadecenoate + CoA (RHEA:38243)
• hexadecan-1-ol + (9Z)-hexadecenoyl-CoA = hexadecyl (9Z)-hexadecenoate + CoA (RHEA:38247)
• hexadecan-1-ol + octadecanoyl-CoA = hexadecyl octadecanoate + CoA (RHEA:38251)
• a long chain fatty alcohol + a fatty acyl-CoA = a long-chain alcohol wax ester + CoA (RHEA:38443)

UniProt features (3 total): transmembrane region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q58HT5-F1	93.13	0.83

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-2142753	Arachidonate metabolism
R-HSA-9640463	Wax biosynthesis
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8848584	Wax and plasmalogen biosynthesis
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 33 (showing top): GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_UNSATURATED_FATTY_ACID_METABOLIC_PROCESS, GOBP_FATTY_ACID_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_ARACHIDONATE_METABOLIC_PROCESS, GOBP_FATTY_ACID_DERIVATIVE_METABOLIC_PROCESS, DURCHDEWALD_SKIN_CARCINOGENESIS_UP, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOBP_FATTY_ACID_METABOLIC_PROCESS, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_O_ACYLTRANSFERASE_ACTIVITY

GO Biological Process (3): lipid metabolic process (GO:0006629), wax biosynthetic process (GO:0010025), arachidonate metabolic process (GO:0019369)

GO Molecular Function (4): long-chain-alcohol O-fatty-acyltransferase activity (GO:0047196), obsolete O-acyltransferase activity (GO:0008374), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of lipids	2
Fatty acid metabolism	1
Wax and plasmalogen biosynthesis	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
wax metabolic process	1
fatty acid derivative biosynthetic process	1
long-chain fatty acid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
catalytic activity	1
transferase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AWAT1	ELOVL2	Q9NXB9	866
AWAT1	SLC27A1	Q6PCB7	843
AWAT1	ELOVL3	Q9HB03	755
AWAT1	FABP4	P15090	741
AWAT1	DGAT1	O75907	733
AWAT1	ELOVL1	Q9BW60	718
AWAT1	ACSL5	Q9ULC5	638
AWAT1	SREBF1	P36956	601
AWAT1	SCD	O00767	576
AWAT1	PNPLA2	Q96AD5	575
AWAT1	MTTP	P55157	542
AWAT1	APOB	P04114	520
AWAT1	ACACA	Q13085	520
AWAT1	PPARA	Q07869	488
AWAT1	FAR2	Q96K12	471

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2ADU8, A2ADU9, A6QP72, F6ZFR0, O74850, O94361, P51658, Q08650, Q16635, Q22267, Q32LS6, Q3UN02, Q41745, Q4V8A1, Q4V9F0, Q502J0, Q54GC1, Q58HT5, Q58NB6, Q5F3X0, Q62730, Q6CF02, Q6E1M8, Q6E213, Q6IV76, Q6IV77, Q6IV78, Q6IV82, Q6IV83, Q6IV84, Q6IWY1, Q6P342, Q6PAZ3, Q6ZPD8, Q7TQA3, Q8LG50, Q8N3Y7, Q8TC12, Q8VD48, Q91WF0

Diamond homologs: A2ADU8, A2ADU9, A6QP72, K7K424, O74850, Q08650, Q28C88, Q2KHS5, Q3KPP4, Q3SYC2, Q4V9F0, Q54GC1, Q58HT5, Q5FVP8, Q5M7F4, Q5M8H5, Q6E1M8, Q6E213, Q6P342, Q6PAZ3, Q6ZPD8, Q70VZ7, Q70VZ8, Q75BY0, Q80W94, Q86VF5, Q91ZV4, Q96PD6, Q96PD7, Q96UY1, Q96UY2, Q9ASU1, Q9DCV3, A1A442, Q9ZVN2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

654 predictions. Top by Δscore:

Variant	Effect	Δscore
X:70236064:CTCA:C	acceptor_loss	1.0000
X:70236065:TCA:T	acceptor_loss	1.0000
X:70236066:CA:C	acceptor_loss	1.0000
X:70236068:GGT:G	acceptor_gain	1.0000
X:70236140:GTA:G	donor_loss	1.0000
X:70236141:TAAG:T	donor_loss	1.0000
X:70238206:CTTTA:C	acceptor_loss	1.0000
X:70238207:TTTA:T	acceptor_loss	1.0000
X:70238208:TTA:T	acceptor_loss	1.0000
X:70238209:TA:T	acceptor_loss	1.0000
X:70238211:GGT:G	acceptor_gain	1.0000
X:70240120:C:CA	acceptor_gain	1.0000
X:70240130:T:A	acceptor_gain	1.0000
X:70240133:CAGT:C	acceptor_loss	1.0000
X:70240134:A:AG	acceptor_gain	1.0000
X:70240134:AGTT:A	acceptor_gain	1.0000
X:70240134:AGTTG:A	acceptor_gain	1.0000
X:70240135:G:GA	acceptor_gain	1.0000
X:70240135:GT:G	acceptor_gain	1.0000
X:70240135:GTT:G	acceptor_gain	1.0000
X:70240135:GTTG:G	acceptor_gain	1.0000
X:70240135:GTTGG:G	acceptor_gain	1.0000
X:70234767:CATCT:C	donor_gain	0.9900
X:70234769:TCT:T	donor_gain	0.9900
X:70234772:G:GG	donor_gain	0.9900
X:70236061:T:TA	acceptor_gain	0.9900
X:70236064:CTCAG:C	acceptor_gain	0.9900
X:70236065:TCAG:T	acceptor_gain	0.9900
X:70236066:CAGGT:C	acceptor_gain	0.9900
X:70236067:A:AG	acceptor_gain	0.9900

AlphaMissense

2162 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:70238358:T:C	F203L	0.984
X:70238360:C:A	F203L	0.984
X:70238360:C:G	F203L	0.984
X:70239746:T:A	V215D	0.981
X:70240231:T:C	F310L	0.979
X:70240233:C:A	F310L	0.979
X:70240233:C:G	F310L	0.979
X:70239760:T:C	F220L	0.977
X:70239762:T:A	F220L	0.977
X:70239762:T:G	F220L	0.977
X:70238359:T:C	F203S	0.969
X:70238371:C:A	A207D	0.969
X:70237155:T:C	F123L	0.967
X:70237157:C:A	F123L	0.967
X:70237157:C:G	F123L	0.967
X:70237167:T:C	F127L	0.967
X:70237169:C:A	F127L	0.967
X:70237169:C:G	F127L	0.967
X:70237228:G:T	R147M	0.965
X:70236128:T:C	F82L	0.963
X:70236130:C:A	F82L	0.963
X:70236130:C:G	F82L	0.963
X:70237133:C:A	N115K	0.963
X:70237133:C:G	N115K	0.963
X:70237095:C:G	H103D	0.958
X:70237229:G:C	R147S	0.958
X:70237229:G:T	R147S	0.958
X:70238362:T:A	V204E	0.957
X:70239743:T:A	L214Q	0.954
X:70239755:T:C	F218S	0.953

dbSNP variants (sampled 300 via entrez): RS1000328209 (X:70236983 C>G), RS1000680637 (X:70237326 C>A), RS1000746534 (X:70239529 G>T), RS1000908598 (X:70237857 G>A,C,T), RS1001199372 (X:70236694 A>G), RS1002375937 (X:70237855 A>C), RS1002469992 (X:70234544 TG>T,TGG), RS1002667489 (X:70232766 TAAGGA>T), RS1002762080 (X:70235017 A>T), RS1002975897 (X:70239419 T>C), RS1003250808 (X:70239198 C>T), RS1005209484 (X:70238024 G>C), RS1006822624 (X:70239122 C>G), RS1007316386 (X:70240626 A>G), RS1007691882 (X:70240520 C>T)

Disease associations

OMIM: gene MIM:300924 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2375205 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
clothianidin	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Nickel	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2378918	Binding	Inhibition of human recombinant AWAT1 expressed in insect cell membrane using palmitoleyl alcohol and [14C]stearoyl coenzyme A as substrate after 10 to 15 mins by liquid scintillation counting	Identification and design of a novel series of MGAT2 inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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