AWAT2

gene
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Also known as MFAT

Summary

AWAT2 (acyl-CoA wax alcohol acyltransferase 2, HGNC:23251) is a protein-coding gene on chromosome Xq13.1, encoding Acyl-CoA wax alcohol acyltransferase 2 (Q6E213). Acyltransferase that catalyzes the formation of ester bonds between fatty alcohols and fatty acyl-CoAs to form wax monoesters.

This gene encodes an enzyme belonging to the diacylglycerol acyltransferase family. This enzyme produces wax esters by the esterification of long chain (or wax) alcohols with acyl-CoA-derived fatty acids. It functions in lipid metabolism in the skin, mostly in undifferentiated peripheral sebocytes. This enzyme may also have acyl-CoA:retinol acyltransferase activities, where it catalyzes the synthesis of diacylglycerols and retinyl esters.

Source: NCBI Gene 158835 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 33 total — 1 pathogenic
  • Druggable target: yes
  • MANE Select transcript: NM_001002254

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:23251
Approved symbolAWAT2
Nameacyl-CoA wax alcohol acyltransferase 2
LocationXq13.1
Locus typegene with protein product
StatusApproved
AliasesMFAT
Ensembl geneENSG00000147160
Ensembl biotypeprotein_coding
OMIM300925
Entrez158835

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000276101, ENST00000440401, ENST00000443056, ENST00000949827

RefSeq mRNA: 1 — MANE Select: NM_001002254 NM_001002254

CCDS: CCDS35320

Canonical transcript exons

ENST00000276101 — 8 exons

ExonStartEnd
ENSE000009790157004392670043996
ENSE000011631367004435270044462
ENSE000014182707004054270041622
ENSE000014637897004984870049938
ENSE000017112917004306970043243
ENSE000017962977004218770042386
ENSE000035209417004177370041962
ENSE000036420017004347870043682

Expression profiles

Bgee: expression breadth broad, 28 present calls, max score 83.04.

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
quadriceps femorisUBERON:000137783.04gold quality
cerebellar vermisUBERON:000472082.54gold quality
thymusUBERON:000237082.10gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099170.80gold quality
skin of abdomenUBERON:000141660.98gold quality
zone of skinUBERON:000001456.51gold quality
skin of legUBERON:000151153.13gold quality
right testisUBERON:000453449.60gold quality
left testisUBERON:000453347.41gold quality
testisUBERON:000047346.98gold quality
sural nerveUBERON:001548843.75gold quality
right lungUBERON:000216742.34gold quality
ventricular zoneUBERON:000305340.62silver quality
upper lobe of left lungUBERON:000895238.80gold quality
calcaneal tendonUBERON:000370138.19gold quality
bone marrow cellCL:000209238.10gold quality
lungUBERON:000204837.89gold quality
lower esophagus mucosaUBERON:003583437.56gold quality
ganglionic eminenceUBERON:000402337.54silver quality
muscle tissueUBERON:000238537.34silver quality
colonic epitheliumUBERON:000039737.20gold quality
cortical plateUBERON:000534336.47gold quality
skeletal muscle tissueUBERON:000113435.28gold quality
granulocyteCL:000009434.93gold quality
smooth muscle tissueUBERON:000113534.90silver quality
vermiform appendixUBERON:000115434.74gold quality
bone marrowUBERON:000237134.27silver quality
adrenal tissueUBERON:001830333.36gold quality
hindlimb stylopod muscleUBERON:000425232.15gold quality
tonsilUBERON:000237232.13gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3no2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting AWAT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4283100.0066.422097
HSA-MIR-3925-3P100.0069.951237
HSA-MIR-340-5P100.0072.504437
HSA-MIR-318599.9968.121959
HSA-MIR-453199.9969.703181
HSA-MIR-185-3P99.9567.011743
HSA-MIR-3934-3P99.7665.511351
HSA-MIR-4524A-3P99.7266.852406
HSA-MIR-6762-3P99.6666.941188
HSA-MIR-6512-3P99.6566.071468
HSA-MIR-6720-5P99.6566.221459
HSA-MIR-182799.6368.573265
HSA-MIR-9851-3P99.6369.681110
HSA-MIR-451699.6167.783390
HSA-MIR-6716-5P99.5668.621244
HSA-MIR-444199.4966.563216
HSA-MIR-889-5P99.4168.751025
HSA-MIR-431699.3765.751360
HSA-MIR-593-5P99.3469.50965
HSA-MIR-450699.3467.47526
HSA-MIR-472199.2666.05818
HSA-MIR-5584-3P99.2368.791351
HSA-MIR-125399.1267.081688
HSA-MIR-443499.1067.011984
HSA-MIR-570399.1067.092053
HSA-MIR-470599.1069.101091
HSA-MIR-371A-5P99.0866.511914
HSA-MIR-4717-3P99.0666.341072
HSA-MIR-670-3P99.0368.882404
HSA-MIR-92299.0267.231838

Literature-anchored findings (GeneRIF, showing 3)

  • analysis of AWAT1 and AWAT2 substrate specificity and differentiation-specific expression pattern (PMID:15671038)
  • MFAT is a multifunctional acyltransferase that likely plays an important role in lipid metabolism in human skin. (PMID:16106050)
  • Expression of Acyl-CoA wax-alcohol acyltransferase 2 (AWAT2) by human and rabbit meibomian glands and meibocytes. (PMID:34838721)

Cross-species orthologs

9 orthologs

OrganismSymbolGene ID
mus_musculusAwat2ENSMUSG00000031220
rattus_norvegicusAwat2ENSRNOG00000003030
drosophila_melanogasterCG1941FBGN0033214
drosophila_melanogasterDgat2FBGN0033215
drosophila_melanogasterCG1946FBGN0033216
caenorhabditis_elegansWBGENE00010296
caenorhabditis_elegansWBGENE00019464
caenorhabditis_elegansWBGENE00020910
caenorhabditis_elegansWBGENE00021818

Paralogs (6): DGAT2 (ENSG00000062282), MOGAT3 (ENSG00000106384), MOGAT1 (ENSG00000124003), MOGAT2 (ENSG00000166391), DGAT2L6 (ENSG00000184210), AWAT1 (ENSG00000204195)

Protein

Protein identifiers

Acyl-CoA wax alcohol acyltransferase 2Q6E213 (reviewed: Q6E213)

Alternative names: 11-cis-specific retinyl-ester synthase, Acyl-CoA retinol O-fatty-acyltransferase, Diacylglycerol O-acyltransferase 2-like protein 4, Diacylglycerol O-acyltransferase candidate 4, Long-chain-alcohol O-fatty-acyltransferase 2, Multifunctional O-acyltransferase, Wax synthase

All UniProt accessions (2): Q6E213, H0YAL0

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 preference for medium chain acyl-CoAs from C12 to C16 in length and fatty alcohols shorter than C20, as the acyl donors and acceptors, respectively. Also possesses acyl-CoA retinol acyltransferase (ARAT) activity that preferentially esterifies 11-cis-retinol, a chromophore precursor of bleached opsin pigments in cone cells. Shows higher catalytic efficiency toward 11-cis-retinol versus 9-cis-retinol, 13-cis-retinol, and all-trans-retinol substrates.

Subunit / interactions. Monomer.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in skin, where it is primarily restricted to undifferentiated peripheral sebocytes. Also expressed at lower level in other tissues except pancreas.

Activity regulation. 11-cis retinoids act as allosteric modulators of acyl-CoA retinol O-fatty-acyltransferase (ARAT) activity by suppressing esterification of 9-cis, 13-cis, or all-trans retinols concurrently increasing the enzyme specificity toward 11-cis isomer.

Similarity. Belongs to the diacylglycerol acyltransferase family.

RefSeq proteins (1): NP_001002254* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR007130DAGATFamily

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.

SubstrateKm (mM)Measurements
PALMITOYL-COA0.0031–0.0296
ARACHIDONOYL-COA0.2263–0.29724
DECANOYL-COA0.001–0.01764
EICOSAPENTAENOYL-COA0.1016–0.13124
LAUROYL-COA0.0001–0.02594
MYRISTOYL-COA0.0039–0.01854
OCTADECATRIENOYL-COA0.2809–0.28474
OCTANOYL-COA0.0123–0.02994
STEAROYL-COA0.0192–0.07594
11-CIS-RETINOL0.02621
13-CIS-RETINOL0.03521
9-CIS-RETINOL0.02381
ALL-TRANS-RETINOL0.02361
HEXADECANOL0.0441
HEXAN-1-OL2.41

Catalyzed reactions (Rhea), 12 shown:

  • an acyl-CoA + a 1,2-diacyl-sn-glycerol = a triacyl-sn-glycerol + CoA (RHEA:10868)
  • all-trans-retinol + an acyl-CoA = an all-trans-retinyl ester + CoA (RHEA:11488)
  • a 2-acylglycerol + an acyl-CoA = a 1,2-diacyl-sn-glycerol + CoA (RHEA:32947)
  • 1-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoyl-CoA = 1,2-di-(9Z-octadecenoyl)-glycerol + CoA (RHEA:37915)
  • 2-(9Z-octadecenoyl)-glycerol + hexadecanoyl-CoA = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + CoA (RHEA:38071)
  • 1,2-di-(9Z-octadecenoyl)-sn-glycerol + hexadecanoyl-CoA = 1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + CoA (RHEA:38163)
  • hexadecan-1-ol + hexadecanoyl-CoA = hexadecyl hexadecanoate + CoA (RHEA:38167)
  • hexadecane-1,2-diol + hexadecanoyl-CoA = 2-hydroxyhexadecyl hexadecanoate + CoA (RHEA:38171)
  • all-trans-retinol + hexadecanoyl-CoA = all-trans-retinyl hexadecanoate + CoA (RHEA:38175)
  • 1,2-di-(9Z-octadecenoyl)-sn-glycerol + (9Z)-octadecenoyl-CoA = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38219)
  • 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)

UniProt features (4 total): transmembrane region 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q6E213-F194.340.86

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

IDPathway
R-HSA-1482883Acyl chain remodeling of DAG and TAG
R-HSA-2187335The retinoid cycle in cones (daylight vision)
R-HSA-9640463Wax biosynthesis
R-HSA-1430728Metabolism
R-HSA-1483206Glycerophospholipid biosynthesis
R-HSA-1483257Phospholipid metabolism
R-HSA-2187338Visual phototransduction
R-HSA-556833Metabolism of lipids
R-HSA-8848584Wax and plasmalogen biosynthesis
R-HSA-9709957Sensory Perception

MSigDB gene sets: 50 (showing top): GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RETINOL_METABOLIC_PROCESS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_NEUTRAL_LIPID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_NEUTRAL_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_FATTY_ACID_DERIVATIVE_BIOSYNTHETIC_PROCESS, KEGG_GLYCEROLIPID_METABOLISM, GOBP_FATTY_ACID_DERIVATIVE_METABOLIC_PROCESS, GOBP_ISOPRENOID_METABOLIC_PROCESS, GOBP_PRIMARY_ALCOHOL_METABOLIC_PROCESS, GOBP_ALCOHOL_METABOLIC_PROCESS

GO Biological Process (6): retinoid metabolic process (GO:0001523), lipid metabolic process (GO:0006629), monoacylglycerol biosynthetic process (GO:0006640), wax biosynthetic process (GO:0010025), acylglycerol acyl-chain remodeling (GO:0036155), retinol metabolic process (GO:0042572)

GO Molecular Function (7): 2-acylglycerol O-acyltransferase activity (GO:0003846), diacylglycerol O-acyltransferase activity (GO:0004144), long-chain-alcohol O-fatty-acyltransferase activity (GO:0047196), retinol O-fatty-acyltransferase activity (GO:0050252), 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-7 pathways:

CategoryPathways
Metabolism of lipids2
Glycerophospholipid biosynthesis1
Visual phototransduction1
Wax and plasmalogen biosynthesis1
Phospholipid metabolism1
Sensory Perception1
Metabolism1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
acylglycerol O-acyltransferase activity2
acyltransferase activity, transferring groups other than amino-acyl groups2
diterpenoid metabolic process1
primary metabolic process1
monoacylglycerol metabolic process1
acylglycerol biosynthetic process1
wax metabolic process1
fatty acid derivative biosynthetic process1
acylglycerol metabolic process1
retinoid metabolic process1
primary alcohol metabolic process1
hormone metabolic process1
olefinic compound metabolic process1
retinol metabolic process1
catalytic activity1
transferase activity1
organelle membrane1
nuclear outer membrane-endoplasmic reticulum membrane network1
endoplasmic reticulum subcompartment1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
cellular anatomical structure1

Protein interactions and networks

STRING

590 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
AWAT2ICAM1P05362892
AWAT2ENY2Q9NPA8821
AWAT2ZDHHC4Q9NPG8802
AWAT2NSL1Q96IY1727
AWAT2CMC2Q9NRP2666
AWAT2PROCRQ9UNN8634
AWAT2NXT2Q9NPJ8542
AWAT2CD36P16671531
AWAT2SCARB2Q14108528
AWAT2SCARB1Q8WTV0524
AWAT2FBXO8Q9NRD0523
AWAT2FAM162AQ96A26507
AWAT2ALBP02768458
AWAT2FAR2Q96K12458
AWAT2PECAM1P16284457

IntAct

2 interactions, top by confidence:

ABTypeScore
AWAT2HPCAL1psi-mi:“MI:0914”(association)0.350

BioGRID (4): AWAT2 (Positive Genetic), UBE3A (Affinity Capture-MS), HERC3 (Affinity Capture-MS), HPCAL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVX0, A2ADU8, A2ADU9, A2Y075, A6QP72, O82232, P34655, P55017, P55018, P56508, P59158, P68178, P68179, Q0DKW8, Q0VBW2, Q22701, Q3ZCB2, Q53GD3, Q54RZ2, Q5REK4, Q5RJI2, Q5TYP8, Q66I68, Q6DK93, Q6DK99, Q6E1M8, Q6E213, Q6GMG8, Q6GZQ0, Q6NUC1, Q6P828, Q6PCW6, Q6ZPD8, Q8H5T6, Q8NG11, Q8QZY6, Q8S5M8, Q91VA1, Q9ARD5, Q9BYD5

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

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

ClassificationCount (floor)
Pathogenic1
Likely pathogenic0
Uncertain significance25
Likely benign3
Benign0

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
1526803GRCh37/hg19 Xq11.1-21.1(chrX:61877278-79123671)Pathogenic

SpliceAI

1124 predictions. Top by Δscore:

VariantEffectΔscore
X:70041959:CCGA:Cacceptor_gain1.0000
X:70041960:CGAC:Cacceptor_gain1.0000
X:70041963:C:CCacceptor_gain1.0000
X:70041967:C:CTacceptor_gain1.0000
X:70041968:A:Tacceptor_gain1.0000
X:70041976:CAG:Cacceptor_gain1.0000
X:70041977:A:Tacceptor_gain1.0000
X:70041978:G:Cacceptor_gain1.0000
X:70041978:G:GCacceptor_gain1.0000
X:70042181:ACTC:Adonor_loss1.0000
X:70042182:CT:Cdonor_loss1.0000
X:70042183:TCAC:Tdonor_loss1.0000
X:70042184:CACC:Cdonor_loss1.0000
X:70042185:A:ACdonor_gain1.0000
X:70042186:C:CCdonor_gain1.0000
X:70042186:C:CGdonor_loss1.0000
X:70042319:C:CTacceptor_gain1.0000
X:70042358:C:CTacceptor_gain1.0000
X:70042358:C:Tacceptor_gain1.0000
X:70042383:CACC:Cacceptor_gain1.0000
X:70042385:CC:Cacceptor_gain1.0000
X:70042386:CC:Cacceptor_gain1.0000
X:70042387:C:CCacceptor_gain1.0000
X:70043241:CCC:Cacceptor_gain1.0000
X:70043242:CCC:Cacceptor_gain1.0000
X:70043683:C:CCacceptor_gain1.0000
X:70044346:GCTTA:Gdonor_loss1.0000
X:70044347:CTTAC:Cdonor_loss1.0000
X:70044348:TTA:Tdonor_loss1.0000
X:70044349:TACC:Tdonor_loss1.0000

AlphaMissense

2180 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
X:70041865:A:CF315L0.972
X:70041865:A:TF315L0.972
X:70041867:A:GF315L0.972
X:70042359:A:CF225L0.970
X:70042359:A:TF225L0.970
X:70042361:A:GF225L0.970
X:70043092:A:CF208L0.969
X:70043092:A:TF208L0.969
X:70043094:A:GF208L0.969
X:70041853:C:AK319N0.963
X:70041853:C:GK319N0.963
X:70043498:C:AR151I0.961
X:70043935:G:CF86L0.956
X:70043935:G:TF86L0.956
X:70043937:A:GF86L0.956
X:70043497:T:AR151S0.953
X:70043497:T:GR151S0.953
X:70041962:A:TV283D0.947
X:70043557:A:CF131L0.941
X:70043557:A:TF131L0.941
X:70043559:A:GF131L0.941
X:70043569:G:CF127L0.941
X:70043569:G:TF127L0.941
X:70043571:A:GF127L0.941
X:70042213:G:TP274H0.940
X:70044385:A:GW55R0.940
X:70044385:A:TW55R0.940
X:70041878:A:GL311P0.938
X:70043498:C:GR151T0.938
X:70042367:A:CY223D0.937

dbSNP variants (sampled 300 via entrez): RS1000110599 (X:70051476 A>AC), RS1000279198 (X:70041475 C>T), RS1000405795 (X:70050187 G>A), RS1000797425 (X:70041131 G>A), RS1001570251 (X:70048407 T>G), RS1001786052 (X:70042237 G>A), RS1001957712 (X:70050728 C>T), RS1002308976 (X:70045492 G>A), RS1002915408 (X:70043862 C>A), RS1002961269 (X:70046742 T>G), RS1003213524 (X:70044249 C>A), RS1003777779 (X:70042756 G>A), RS1004189924 (X:70040149 A>G,T), RS1004244049 (X:70040667 G>A), RS1004370168 (X:70048818 G>A)

Disease associations

OMIM: gene MIM:300925 | 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): CHEMBL2375204 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases methylation1
Atrazineincreases expression1
Benzo(a)pyrenedecreases methylation, increases methylation1
Cadmiumdecreases expression, increases abundance1
Endosulfandecreases expression1
Phthalic Acidsdecreases expression1
Smokeincreases expression1
Aflatoxin B1increases methylation1
Cadmium Chloridedecreases expression, increases abundance1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL2378804BindingInhibition of human recombinant AWAT2 expressed in insect cell membrane using cetyl alcohol and [14C]oleoyl coenzyme A as substrate after 10 to 15 mins by liquid scintillation countingIdentification 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.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.