AKR7A3

Summary

AKR7A3 (aldo-keto reductase family 7 member A3, HGNC:390) is a protein-coding gene on chromosome 1p36.13, encoding Aldo-keto reductase family 7 member A3 (O95154). Catalyzes the NADPH-dependent reduction of various carbonyl-containing compounds, including aldehydes, ketones, and toxic products from cellular metabolism or environmental exposure.

Aldo-keto reductases, such as AKR7A3, are involved in the detoxification of aldehydes and ketones.

Source: NCBI Gene 22977 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_012067

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:390
Approved symbol	AKR7A3
Name	aldo-keto reductase family 7 member A3
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000162482
Ensembl biotype	protein_coding
OMIM	608477
Entrez	22977

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000361640, ENST00000894619, ENST00000894620, ENST00000894621

RefSeq mRNA: 1 — MANE Select: NM_012067 NM_012067

CCDS: CCDS193

Canonical transcript exons

ENST00000361640 — 7 exons

Exon	Start	End
ENSE00001465982	19282573	19282892
ENSE00001664415	19286185	19286372
ENSE00001675448	19283996	19284125
ENSE00001677350	19284686	19284785
ENSE00001750802	19285018	19285114
ENSE00001784129	19285888	19285992
ENSE00001845823	19288496	19288770

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 98.91.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0168 / max 9.4064, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201388	0.0168	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	98.91	gold quality
jejunal mucosa	UBERON:0000399	98.72	gold quality
body of pancreas	UBERON:0001150	97.94	gold quality
mucosa of transverse colon	UBERON:0004991	97.72	gold quality
right lobe of liver	UBERON:0001114	96.84	gold quality
ileal mucosa	UBERON:0000331	95.27	gold quality
pancreatic ductal cell	CL:0002079	94.52	gold quality
adult mammalian kidney	UBERON:0000082	94.39	gold quality
liver	UBERON:0002107	94.37	gold quality
cardia of stomach	UBERON:0001162	91.98	gold quality
body of stomach	UBERON:0001161	90.88	gold quality
gall bladder	UBERON:0002110	90.73	gold quality
jejunum	UBERON:0002115	90.55	gold quality
pylorus	UBERON:0001166	90.41	gold quality
renal medulla	UBERON:0000362	90.14	gold quality
small intestine	UBERON:0002108	89.80	gold quality
adult organism	UBERON:0007023	89.50	gold quality
nephron tubule	UBERON:0001231	89.36	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.27	gold quality
colonic mucosa	UBERON:0000317	88.97	gold quality
stomach	UBERON:0000945	88.94	gold quality
kidney	UBERON:0002113	88.87	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.13	gold quality
pancreas	UBERON:0001264	87.40	gold quality
fundus of stomach	UBERON:0001160	87.34	gold quality
kidney epithelium	UBERON:0004819	87.18	gold quality
transverse colon	UBERON:0001157	86.58	gold quality
cortex of kidney	UBERON:0001225	86.53	gold quality
rectum	UBERON:0001052	84.56	gold quality
renal glomerulus	UBERON:0000074	82.94	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	67.44
E-GEOD-81547	yes	18.45
E-ANND-3	yes	17.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting AKR7A3, 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-3065-3P	99.87	70.25	1407
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-4277	98.34	67.17	1323

Literature-anchored findings (GeneRIF, showing 1)

• Results demonstrate that Akr7a3 mRNA and protein levels are consistently co-expressed along with Akr1b10, in both experimental rat liver carcinogenesis and some human hepatocellular carcinoma samples. (PMID:29383608)

Cross-species orthologs

19 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:110366	ENSDARG00000004167
danio_rerio	akr1a1a	ENSDARG00000035257
danio_rerio	zgc:110782	ENSDARG00000044544
danio_rerio	zgc:101765	ENSDARG00000054934
danio_rerio	zgc:56622	ENSDARG00000099728
rattus_norvegicus	Akr7a3	ENSRNOG00000017899
drosophila_melanogaster	CG6083	FBGN0036183
drosophila_melanogaster	CG18547	FBGN0037973
drosophila_melanogaster	CG3397	FBGN0037975
caenorhabditis_elegans		WBGENE00003176
caenorhabditis_elegans		WBGENE00009980
caenorhabditis_elegans		WBGENE00009981
caenorhabditis_elegans		WBGENE00012722
caenorhabditis_elegans		WBGENE00012723
caenorhabditis_elegans		WBGENE00015307
caenorhabditis_elegans		WBGENE00015564
caenorhabditis_elegans		WBGENE00015565
caenorhabditis_elegans		WBGENE00016985
caenorhabditis_elegans		WBGENE00022887

Paralogs (16): AKR7A2 (ENSG00000053371), KCNAB2 (ENSG00000069424), AKR1B1 (ENSG00000085662), AKR1A1 (ENSG00000117448), AKR1D1 (ENSG00000122787), AKR1C2 (ENSG00000151632), AKR1E2 (ENSG00000165568), KCNAB1 (ENSG00000169282), KCNAB3 (ENSG00000170049), AKR1C1 (ENSG00000187134), AKR1C3 (ENSG00000196139), AKR1B10 (ENSG00000198074), AKR1C4 (ENSG00000198610), AKR7L (ENSG00000211454), AKR1B15 (ENSG00000227471), AKR1C8 (ENSG00000264006)

Protein

Protein identifiers

Aldo-keto reductase family 7 member A3 — O95154 (reviewed: O95154)

Alternative names: AFB1 aldehyde reductase 2, Aflatoxin B1 aldehyde reductase member 3

All UniProt accessions (2): A0A384MDN8, O95154

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NADPH-dependent reduction of various carbonyl-containing compounds, including aldehydes, ketones, and toxic products from cellular metabolism or environmental exposure. Can reduce the dialdehyde form of aflatoxin B1 (AFB1) into alcohol derivatives, via monoaldehydes intermediates. Can reduce the dialdehyde form of aflatoxin B1 (AFB1) into alcohol derivatives, via monoaldehydes intermediates, thus preventing the formation of protein adducts that contribute to AFB1-induced toxicity.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in colon, kidney, liver, pancreas, adenocarcinoma and endometrium.

Activity regulation. Inhibited by citrate.

Similarity. Belongs to the aldo/keto reductase family. Aldo/keto reductase 2 subfamily.

RefSeq proteins (1): NP_036199* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023210	NADP_OxRdtase_dom	Domain
IPR036812	NAD(P)_OxRdtase_dom_sf	Homologous_superfamily
IPR050523	AKR_Detox_Biosynth	Family

Pfam: PF00248

Catalyzed reactions (Rhea), 4 shown:

• a primary alcohol + NADP(+) = an aldehyde + NADPH + H(+) (RHEA:15937)
• aflatoxin B1 dialdehyde + NADPH + H(+) = aflatoxin B1 C(6a)-monoaldehyde + NADP(+) (RHEA:84055)
• aflatoxin B1 dialdehyde + NADPH + H(+) = aflatoxin B1 C(8)-monoaldehyde + NADP(+) (RHEA:84059)
• aflatoxin B1 C(6a)-monoaldehyde + NADPH + 2 H(+) = aflatoxin B1 triol + NADP(+) (RHEA:84063)

UniProt features (57 total): helix 18, binding site 15, strand 10, modified residue 3, sequence variant 3, turn 3, sequence conflict 2, chain 1, active site 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CLP	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95154-F1	96.49	0.96

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 (2): 49 (proton donor); 77 (lowers pka of active site tyr)

Ligand- & substrate-binding residues (15): 202; 208; 209; 222; 290; 294; 298; 17; 44; 49; 113; 143 …

Post-translational modifications (3): 6, 85, 227

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5423646	Aflatoxin activation and detoxification
R-HSA-1430728	Metabolism
R-HSA-211859	Biological oxidations

MSigDB gene sets: 77 (showing top): MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, GNF2_GSTM1, GNF2_HPN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, BROWNE_HCMV_INFECTION_48HR_DN, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GNF2_LCAT, GOBP_TOXIN_METABOLIC_PROCESS, GOBP_DETOXIFICATION, GNF2_HPX, GOBP_ALDEHYDE_METABOLIC_PROCESS, MODULE_88, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN

GO Biological Process (3): aldehyde metabolic process (GO:0006081), aflatoxin catabolic process (GO:0046223), response to toxic substance (GO:0009636)

GO Molecular Function (6): alcohol dehydrogenase (NADP+) activity (GO:0008106), electron transfer activity (GO:0009055), identical protein binding (GO:0042802), NADP+ binding (GO:0070401), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
metabolic process	1
mycotoxin catabolic process	1
aflatoxin metabolic process	1
response to chemical	1
alcohol dehydrogenase [NAD(P)+] activity	1
molecular_function	1
protein binding	1
anion binding	1
NADP binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

1421 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKR7A3	AKR1B1	P15121	823
AKR7A3	MSC	O60682	745
AKR7A3	AKR1A1	P14550	604
AKR7A3	PLA2G2A	P14555	557
AKR7A3	AKR1B10	O60218	552
AKR7A3	AKR1D1	P51857	545
AKR7A3	NQO1	P15559	515
AKR7A3	GSTA5	Q7RTV2	479
AKR7A3	EPHX1	P07099	465
AKR7A3	AKR1B15	C9JRZ8	464
AKR7A3	AKR1E2	Q96JD6	462
AKR7A3	CYP1A2	P05177	452
AKR7A3	GSTP1	P09211	437
AKR7A3	AKR1C3	P42330	425
AKR7A3	CYP1A1	P04798	411

IntAct

38 interactions, top by confidence:

A	B	Type	Score
AKR7A3	AKR7A2	psi-mi:“MI:0914”(association)	0.890
AKR7A3	AKR7A2	psi-mi:“MI:0915”(physical association)	0.890
AKR7A2	AKR7A3	psi-mi:“MI:0915”(physical association)	0.890
AKR7A3	AKR7A3	psi-mi:“MI:0915”(physical association)	0.800
AKR7A3	KRT31	psi-mi:“MI:0915”(physical association)	0.560
AKR7A3	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.560
FNDC11	AKR7A3	psi-mi:“MI:0914”(association)	0.530
TRABD	FCN1	psi-mi:“MI:0914”(association)	0.530
AKR7A3	ASAH1	psi-mi:“MI:0914”(association)	0.530
AKR7A3	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
CFTR	AKR7A3	psi-mi:“MI:0915”(physical association)	0.510
AKR7A3		psi-mi:“MI:0915”(physical association)	0.370
	AP3B1	psi-mi:“MI:0914”(association)	0.350
PRPS2	ARHGEF37	psi-mi:“MI:0914”(association)	0.350
AKR7A2	DCTN6	psi-mi:“MI:0914”(association)	0.350
HOGA1	AKR7A3	psi-mi:“MI:0914”(association)	0.350
TERF2IP	AKR7A3	psi-mi:“MI:0915”(physical association)	0.000
AKR7A3	KRT31	psi-mi:“MI:0915”(physical association)	0.000
AKR7A3	AKR7A3	psi-mi:“MI:0915”(physical association)	0.000
AKR7A2	AKR7A3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (36): AKR7A3 (Two-hybrid), AKR7A2 (Affinity Capture-MS), AKR7L (Affinity Capture-MS), COMMD9 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), TRMT11 (Affinity Capture-MS), DDRGK1 (Affinity Capture-MS), AKR7A3 (Two-hybrid), AKR7A3 (Two-hybrid), AKR7L (Affinity Capture-MS), AKR7A2 (Affinity Capture-MS), COMMD9 (Affinity Capture-MS), DDRGK1 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), AKR7A3 (Affinity Capture-MS)

ESM2 similar proteins: A1YER2, A1YFX9, A2T7G9, A6NNS2, B0BN93, B0BNF8, O22718, O35331, O35678, O75911, O77769, O80526, O88876, O95154, P11172, P14755, P15904, P84169, Q06136, Q15738, Q1RMJ5, Q28DS0, Q2KIJ5, Q2QNG7, Q2QZ86, Q3SZM9, Q3T067, Q3ZBE9, Q5E964, Q5I0K3, Q5PPL3, Q5R514, Q5R5C9, Q5RDZ2, Q6AY30, Q6UWP2, Q811X6, Q86WA6, Q8JGT5, Q8K183

Diamond homologs: A0A0F7TN16, A0A0U5GHU6, A0A5B8YXI2, C7ZBE5, C8VQ93, M2YJQ2, O43488, O95154, P25612, P38918, P42884, P43546, P43547, P47182, Q00049, Q00258, Q00727, Q01333, Q01752, Q07747, Q08361, Q6UEH5, Q75ZG2, Q8CG45, Q8CG76, M2YMU7, Q6Q875, Q75ZG3, Q8NHP1, P46905, P77735, Q40648, Q9P7U2, M3APK9, Q46851, Q8X529, V5NZC3, A2XRZ0, B8ASB2, B9WYE6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

726 predictions. Top by Δscore:

Variant	Effect	Δscore
1:19282889:CACC:C	acceptor_gain	1.0000
1:19282891:CC:C	acceptor_gain	1.0000
1:19282892:CC:C	acceptor_gain	1.0000
1:19282893:C:CC	acceptor_gain	1.0000
1:19283994:A:AT	donor_loss	1.0000
1:19283995:CCTGC:C	donor_loss	1.0000
1:19284121:AGTAG:A	acceptor_gain	1.0000
1:19284122:GTAG:G	acceptor_gain	1.0000
1:19284123:TAG:T	acceptor_gain	1.0000
1:19284124:AG:A	acceptor_gain	1.0000
1:19284126:C:CA	acceptor_loss	1.0000
1:19284126:C:CC	acceptor_gain	1.0000
1:19284680:GCTTA:G	donor_loss	1.0000
1:19284681:CTTA:C	donor_loss	1.0000
1:19284683:TAC:T	donor_loss	1.0000
1:19284684:A:AC	donor_gain	1.0000
1:19284684:ACCG:A	donor_loss	1.0000
1:19284685:C:CA	donor_loss	1.0000
1:19284685:C:CC	donor_gain	1.0000
1:19284688:ATT:A	donor_gain	1.0000
1:19284781:GCCCC:G	acceptor_gain	1.0000
1:19284782:CCCC:C	acceptor_gain	1.0000
1:19284782:CCCCC:C	acceptor_gain	1.0000
1:19284783:CCC:C	acceptor_gain	1.0000
1:19284783:CCCC:C	acceptor_gain	1.0000
1:19284784:CC:C	acceptor_gain	1.0000
1:19284784:CCC:C	acceptor_gain	1.0000
1:19284784:CCCTG:C	acceptor_loss	1.0000
1:19284785:CC:C	acceptor_gain	1.0000
1:19284786:C:CC	acceptor_gain	1.0000

AlphaMissense

2158 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:19285031:G:C	F197L	0.993
1:19285031:G:T	F197L	0.993
1:19285033:A:G	F197L	0.993
1:19284022:A:G	W270R	0.992
1:19284022:A:T	W270R	0.992
1:19286356:C:A	K77N	0.992
1:19286356:C:G	K77N	0.992
1:19284721:G:C	F223L	0.988
1:19284721:G:T	F223L	0.988
1:19284723:A:G	F223L	0.988
1:19285103:A:C	N173K	0.988
1:19285103:A:T	N173K	0.988
1:19284020:C:A	W270C	0.983
1:19284020:C:G	W270C	0.983
1:19285028:G:C	N198K	0.979
1:19285028:G:T	N198K	0.979
1:19288546:T:A	E55V	0.979
1:19285984:G:C	F137L	0.976
1:19285984:G:T	F137L	0.976
1:19285986:A:G	F137L	0.976
1:19288605:G:C	F35L	0.976
1:19288605:G:T	F35L	0.976
1:19288607:A:G	F35L	0.976
1:19288545:C:A	E55D	0.975
1:19288545:C:G	E55D	0.975
1:19288578:G:C	D44E	0.975
1:19288578:G:T	D44E	0.975
1:19284104:A:C	F242L	0.974
1:19284104:A:T	F242L	0.974
1:19284106:A:G	F242L	0.974

dbSNP variants (sampled 300 via entrez): RS1000234503 (1:19288888 C>G,T), RS1000681625 (1:19288090 G>A,T), RS1000859018 (1:19284421 C>T), RS1001293736 (1:19273736 G>A,C,T), RS1001689945 (1:19284886 C>A), RS1001753417 (1:19280353 G>A), RS1001912627 (1:19283828 C>A,T), RS1001966982 (1:19289571 A>G), RS1002367404 (1:19287363 T>C,G), RS1002492134 (1:19278757 G>A), RS1002691241 (1:19285810 G>A,C,T), RS1002802472 (1:19281468 C>A), RS1002860750 (1:19288174 C>T), RS1003452731 (1:19289287 A>C), RS1003525686 (1:19275205 G>A)

Disease associations

OMIM: gene MIM:608477 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003815_87	Late-onset Alzheimer’s disease	4.000000e-06
GCST007001_1	Cerebrospinal AB1-42 levels in normal cognition	5.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease
EFO:0004670	beta-amyloid 1-42 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2231198	AKR7A3		0.00	0
rs2013249	AKR7A3		0.00	0

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Chenodeoxycholic Acid	decreases expression, affects cotreatment	3
Tobacco Smoke Pollution	decreases expression	3
Cyclosporine	decreases expression, affects cotreatment	3
Deoxycholic Acid	affects cotreatment, decreases expression	2
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	2
Glycocholic Acid	affects cotreatment, decreases expression	2
Glycodeoxycholic Acid	affects cotreatment, decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
9,10-phenanthrenequinone	affects activity, increases reduction	1
triphenyl phosphate	affects expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
benzo(a)pyrene-1,6-quinone	affects activity, increases reduction	1
7-hydroxycoumarin	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
nefazodone	affects cotreatment, decreases expression	1
benzo(a)pyrene-7,8-dione	affects activity, affects cotreatment, increases reduction	1
2-palmitoylglycerol	increases expression	1
4-hydroxyequilenin-o-quinone	affects activity, affects cotreatment, increases reduction	1
abrine	decreases expression	1
Atazanavir Sulfate	affects cotreatment, decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	affects cotreatment, decreases expression	1
Ethanol	decreases expression	1
Chrysenes	increases reduction, affects activity	1

Clinical trials (associated diseases)

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