AKR7A2

Summary

AKR7A2 (aldo-keto reductase family 7 member A2, HGNC:389) is a protein-coding gene on chromosome 1p36.13, encoding Aflatoxin B1 aldehyde reductase member 2 (O43488). Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate.

The protein encoded by this gene belongs to the aldo/keto reductase (AKR) superfamily and AKR7 family, which are involved in the detoxification of aldehydes and ketones. The AKR7 family consists of 3 genes that are present in a cluster on the p arm of chromosome 1. This protein, thought to be localized in the golgi, catalyzes the NADPH-dependent reduction of succinic semialdehyde to the endogenous neuromodulator, gamma-hydroxybutyrate. It may also function as a detoxication enzyme in the reduction of aflatoxin B1 and 2-carboxybenzaldehyde. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8574 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 82 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_003689

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:389
Approved symbol	AKR7A2
Name	aldo-keto reductase family 7 member A2
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	AFAR
Ensembl gene	ENSG00000053371
Ensembl biotype	protein_coding
OMIM	603418
Entrez	8574

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000235835, ENST00000330072, ENST00000481966, ENST00000489286, ENST00000492217

RefSeq mRNA: 2 — MANE Select: NM_003689 NM_001320979, NM_003689

CCDS: CCDS194

Canonical transcript exons

ENST00000235835 — 7 exons

Exon	Start	End
ENSE00000872932	19311827	19312144
ENSE00001188305	19303965	19304386
ENSE00001617062	19307314	19307410
ENSE00001736745	19308158	19308262
ENSE00003492361	19307002	19307101
ENSE00003495638	19306018	19306147
ENSE00003653261	19308455	19308642

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 96.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.5495 / max 289.6138, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10653	65.5495	1823

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.31	gold quality
duodenum	UBERON:0002114	96.29	gold quality
right adrenal gland	UBERON:0001233	96.03	gold quality
right adrenal gland cortex	UBERON:0035827	96.03	gold quality
right uterine tube	UBERON:0001302	95.63	gold quality
left adrenal gland	UBERON:0001234	95.23	gold quality
jejunal mucosa	UBERON:0000399	95.14	gold quality
left adrenal gland cortex	UBERON:0035825	95.07	gold quality
adult organism	UBERON:0007023	94.77	gold quality
adrenal cortex	UBERON:0001235	94.64	gold quality
adult mammalian kidney	UBERON:0000082	94.29	gold quality
endocervix	UBERON:0000458	94.24	gold quality
right lobe of liver	UBERON:0001114	93.86	gold quality
ectocervix	UBERON:0012249	93.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.78	gold quality
adrenal gland	UBERON:0002369	93.69	gold quality
transverse colon	UBERON:0001157	93.66	gold quality
left ovary	UBERON:0002119	93.14	gold quality
body of stomach	UBERON:0001161	93.12	gold quality
right ovary	UBERON:0002118	93.00	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.94	gold quality
body of pancreas	UBERON:0001150	92.92	gold quality
small intestine	UBERON:0002108	92.81	gold quality
apex of heart	UBERON:0002098	92.72	gold quality
gall bladder	UBERON:0002110	92.51	gold quality
bronchial epithelial cell	CL:0002328	92.24	gold quality
gastrocnemius	UBERON:0001388	92.23	gold quality
esophagus mucosa	UBERON:0002469	92.17	gold quality
muscle of leg	UBERON:0001383	92.11	gold quality
ventricular zone	UBERON:0003053	92.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

50 targeting AKR7A2, 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-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-4646-3P	98.65	66.98	693

Literature-anchored findings (GeneRIF, showing 8)

• structure and tissue-related expression of AFAR genes on chromosome 1 (PMID:12879023)
• The human aldo-keto reductase AKR7A2 has been proposed previously to catalyze the NADPH-dependent reduction of succinic semialdehyde (SSA) to gamma-Hydroxybutyrate in human brain (PMID:17591773)
• The human AFAR gene family maps to a genomic region in 1p36 of frequent hemizygous deletions in various human cancers. (PMID:18752886)
• Aflatoxin B(1) aldehyde reductase (AKR7A2) was confirmed to be only highly expressed in pancreatic cancer, not in normal adjacent pancreas and benign tumors. (PMID:19077459)
• induced expression in human monocytes following exposure to Aflatoxin B1 (PMID:25027672)
• AKR7A2 contributes to protection against MG-induced toxicity. (PMID:25451587)
• AKR7A2 physically interacts with CYGB. (PMID:28536627)
• expression in cardiomyocytes is mediated by NF-kappaB through conserved response elements in the proximal gene promoter region (PMID:30817976)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	akr1a1a	ENSDARG00000035257
danio_rerio	zgc:56622	ENSDARG00000099728
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

Paralogs (16): KCNAB2 (ENSG00000069424), AKR1B1 (ENSG00000085662), AKR1A1 (ENSG00000117448), AKR1D1 (ENSG00000122787), AKR1C2 (ENSG00000151632), AKR7A3 (ENSG00000162482), AKR1E2 (ENSG00000165568), KCNAB1 (ENSG00000169282), KCNAB3 (ENSG00000170049), AKR1C1 (ENSG00000187134), AKR1C3 (ENSG00000196139), AKR1B10 (ENSG00000198074), AKR1C4 (ENSG00000198610), AKR7L (ENSG00000211454), AKR1B15 (ENSG00000227471), AKR1C8 (ENSG00000264006)

Protein

Protein identifiers

Aflatoxin B1 aldehyde reductase member 2 — O43488 (reviewed: O43488)

Alternative names: AFB1 aldehyde reductase 1, Aldoketoreductase 7, Succinic semialdehyde reductase

All UniProt accessions (5): O43488, H3BLU7, H7C4Q7, H7C5H7, V9HWA2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. May have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad substrate specificity. Has NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen.

Subunit / interactions. Homodimer.

Subcellular location. Mitochondrion. Golgi apparatus. Cytoplasm.

Tissue specificity. Detected in brain, liver, small intestine and testis, and at lower levels in heart, prostate, skeletal muscle and spleen. Detected in kidney proximal and distal tubules, endothelial cells lining the Bowman’s capsules and some cysts. Detected at low levels in lung and pancreas (at protein level). Widely expressed.

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

RefSeq proteins (2): NP_001307908, NP_003680* (*=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), 1 shown:

• 4-hydroxybutanoate + NADP(+) = succinate semialdehyde + NADPH + H(+) (RHEA:26381)

UniProt features (54 total): helix 18, binding site 10, strand 9, sequence variant 7, modified residue 4, turn 2, transit peptide 1, chain 1, site 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2BP1	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43488-F1	93.45	0.89

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

Ligand- & substrate-binding residues (10): 263; 318–326; 359; 72; 141; 171–172; 197; 226–236; 250; 260

Post-translational modifications (4): 40, 128, 236, 255

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: 216 (showing top): MORF_MTA1, MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, MORF_HDAC1, MORF_HDAC2, GOBP_KETONE_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, ROSS_LEUKEMIA_WITH_MLL_FUSIONS, MORF_BUB3, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, MORF_RFC4, MORF_PRKDC

GO Biological Process (5): carbohydrate metabolic process (GO:0005975), aldehyde metabolic process (GO:0006081), lipid metabolic process (GO:0006629), daunorubicin metabolic process (GO:0044597), doxorubicin metabolic process (GO:0044598)

GO Molecular Function (5): aldose reductase (NADPH) activity (GO:0004032), electron transfer activity (GO:0009055), phenanthrene-9,10-epoxide hydrolase activity (GO:0019119), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (5): cytoplasm (GO:0005737), mitochondrion (GO:0005739), 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
cytoplasm	3
primary metabolic process	2
glycoside metabolic process	2
polyketide metabolic process	2
ketone metabolic process	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
metabolic process	1
primary alcohol metabolic process	1
tertiary alcohol metabolic process	1
alcohol dehydrogenase (NADP+) activity	1
molecular_function	1
phenanthrene-epoxide hydrolase activity	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
endomembrane system	1
extracellular vesicle	1

Protein interactions and networks

STRING

1707 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKR7A2	AKR1B1	P15121	885
AKR7A2	AKR1A1	P14550	780
AKR7A2	ALDH5A1	P51649	719
AKR7A2	AKR1B10	O60218	692
AKR7A2	PLA2G2A	P14555	597
AKR7A2	AKR1C3	P42330	579
AKR7A2	AKR1C4	P17516	544
AKR7A2	AKR1C1	P52896	544
AKR7A2	CBR1	P16152	543
AKR7A2	AKR1D1	P51857	519
AKR7A2	ADHFE1	Q8IWW8	519
AKR7A2	AKR1B15	C9JRZ8	518
AKR7A2	NQO1	P15559	508
AKR7A2	EPHX1	P07099	501
AKR7A2	TMEM14A	Q9Y6G1	494

IntAct

82 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
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
ZBTB1	AKR7A2	psi-mi:“MI:0915”(physical association)	0.670
AKR7A2	ZBTB1	psi-mi:“MI:0915”(physical association)	0.670
CYGB	AKR7A2	psi-mi:“MI:0914”(association)	0.570
CYGB	AKR7A2	psi-mi:“MI:0915”(physical association)	0.570
AKR7A2	APBB2	psi-mi:“MI:0915”(physical association)	0.560
AKR7A2		psi-mi:“MI:0915”(physical association)	0.560
AKR7A2	ATXN3	psi-mi:“MI:0915”(physical association)	0.560
PCNA	POM121C	psi-mi:“MI:0914”(association)	0.550
LEO1	SUPT5H	psi-mi:“MI:0914”(association)	0.530
SMC1A	PDS5B	psi-mi:“MI:0914”(association)	0.530
	MYL12B	psi-mi:“MI:0914”(association)	0.460
	AKR7A2	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
AKR7A2	AKR7A2	psi-mi:“MI:0915”(physical association)	0.370
CEP70	AKR7A2	psi-mi:“MI:0915”(physical association)	0.370
Snw1	AKR7A2	psi-mi:“MI:0914”(association)	0.350
CTR9	POLR2B	psi-mi:“MI:0914”(association)	0.350

BioGRID (91): AKR7A2 (Two-hybrid), AKR7A2 (Affinity Capture-MS), AKR7A3 (Two-hybrid), AKR7A2 (Co-fractionation), DUSP12 (Co-fractionation), PSMC1 (Co-fractionation), AKR7A2 (Affinity Capture-MS), AKR7A2 (Affinity Capture-MS), AKR7A2 (Affinity Capture-MS), AKR7A2 (Affinity Capture-MS), AKR7A2 (Affinity Capture-MS), AKR7A2 (Affinity Capture-MS), AKR7A2 (Affinity Capture-MS), AKR7A2 (Affinity Capture-MS), AKR7A2 (Affinity Capture-MS)

ESM2 similar proteins: A4FV98, A6NKP2, A6QLY2, O18735, O43488, O75382, O75648, O77485, O77486, O88676, P04626, P23764, P25325, P34059, P52848, Q02353, Q0VD18, Q10836, Q10981, Q10982, Q28113, Q32KH5, Q32KJ6, Q3U129, Q3UHN9, Q4R766, Q571E4, Q5I0D5, Q5RB73, Q5RJL2, Q6AYT7, Q6P988, Q7RTV5, Q7Z4H8, Q8CIW5, Q8K093, Q8N2K0, Q8WNQ7, Q96AZ1, Q96SL4

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, A0A3B1EFQ1, A2XRZ0, A2XRZ6, B8ASB2, B9WYE6, C6TBN2, F4HPY8, G2TRN6, K3VD70, O05408, O14295

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TNFR1-induced NF-kappa-B signaling pathway	5	32.9×	4e-05
Regulation of TNFR1 signaling	6	26.3×	2e-05
SARS-CoV-2 activates/modulates innate and adaptive immune responses	5	8.8×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	6	34.4×	1e-05
positive regulation of canonical NF-kappaB signal transduction	7	7.9×	7e-03
DNA repair	7	7.0×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	67
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
59922	GRCh38/hg38 1p36.13(chr1:19093306-20063342)x1	Pathogenic

SpliceAI

742 predictions. Top by Δscore:

Variant	Effect	Δscore
1:19304383:CACC:C	acceptor_gain	1.0000
1:19304384:ACCC:A	acceptor_loss	1.0000
1:19304385:CC:C	acceptor_gain	1.0000
1:19304386:CC:C	acceptor_gain	1.0000
1:19304387:C:CA	acceptor_loss	1.0000
1:19306012:GGTTA:G	donor_loss	1.0000
1:19306013:GTTA:G	donor_loss	1.0000
1:19306014:TTA:T	donor_loss	1.0000
1:19306015:TACC:T	donor_loss	1.0000
1:19306041:TCC:T	donor_gain	1.0000
1:19306143:AGAAG:A	acceptor_gain	1.0000
1:19306144:GAAG:G	acceptor_gain	1.0000
1:19306145:AAG:A	acceptor_gain	1.0000
1:19306145:AAGCT:A	acceptor_gain	1.0000
1:19306146:AG:A	acceptor_gain	1.0000
1:19306146:AGCT:A	acceptor_loss	1.0000
1:19306146:AGCTG:A	acceptor_gain	1.0000
1:19306147:GC:G	acceptor_loss	1.0000
1:19306147:GCT:G	acceptor_gain	1.0000
1:19306148:C:CC	acceptor_gain	1.0000
1:19306148:CTGT:C	acceptor_gain	1.0000
1:19306150:G:C	acceptor_gain	1.0000
1:19306150:G:GC	acceptor_gain	1.0000
1:19306153:C:CT	acceptor_gain	1.0000
1:19306154:A:T	acceptor_gain	1.0000
1:19306997:CTCA:C	donor_loss	1.0000
1:19306998:TCAC:T	donor_loss	1.0000
1:19307000:A:AC	donor_gain	1.0000
1:19307001:C:CC	donor_gain	1.0000
1:19307006:T:TA	donor_gain	1.0000

AlphaMissense

2328 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:19308626:C:A	K105N	0.998
1:19308626:C:G	K105N	0.998
1:19306044:A:G	W298R	0.996
1:19306044:A:T	W298R	0.996
1:19307399:G:C	N201K	0.996
1:19307399:G:T	N201K	0.996
1:19307324:G:C	N226K	0.995
1:19307324:G:T	N226K	0.995
1:19306144:G:C	F264L	0.994
1:19306144:G:T	F264L	0.994
1:19306146:A:G	F264L	0.994
1:19307037:G:C	F251L	0.994
1:19307037:G:T	F251L	0.994
1:19307039:A:G	F251L	0.994
1:19308233:G:C	N172K	0.994
1:19308233:G:T	N172K	0.994
1:19308520:G:C	H141D	0.993
1:19308627:T:A	K105M	0.993
1:19306042:C:A	W298C	0.992
1:19306042:C:G	W298C	0.992
1:19307002:C:G	R263P	0.992
1:19308520:G:T	H141N	0.992
1:19307101:C:T	G230E	0.991
1:19308627:T:G	K105T	0.991
1:19307331:G:T	A224D	0.990
1:19311896:A:G	Y77H	0.990
1:19311997:C:T	G43D	0.990
1:19307098:C:T	G231D	0.989
1:19308158:C:A	Q197H	0.989
1:19308158:C:G	Q197H	0.989

dbSNP variants (sampled 300 via entrez): RS1000083657 (1:19310817 T>G), RS1000348737 (1:19304993 T>G), RS1000444243 (1:19310455 T>C), RS1000538528 (1:19311456 G>A,C), RS1000665176 (1:19306125 C>G,T), RS1001182856 (1:19311668 T>C,G), RS1001252631 (1:19311593 G>A,C,T), RS1001266486 (1:19305196 T>C), RS1001512741 (1:19310964 C>T), RS1001607592 (1:19310730 G>A), RS1001844822 (1:19312113 G>A,C,T), RS1002154399 (1:19307195 A>G), RS1002223873 (1:19305776 A>G), RS1002573547 (1:19302637 A>C,G), RS1003291936 (1:19302837 T>G)

Disease associations

OMIM: gene MIM:603418 | disease phenotypes: MIM:239510, MIM:605909, MIM:614507

GenCC curated gene-disease

Mondo (3): hyperprolinemia type 2 (MONDO:0009401), autosomal recessive early-onset Parkinson disease 6 (MONDO:0011613), DDOST-congenital disorder of glycosylation (MONDO:0013789)

Orphanet (3): Young-onset Parkinson disease (Orphanet:2828), DDOST-CDG (Orphanet:300536), Hyperprolinemia type 2 (Orphanet:79101)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006585_566	Blood protein levels	2.000000e-24
GCST007001_1	Cerebrospinal AB1-42 levels in normal cognition	5.000000e-07
GCST008758_46	Pre-treatment viral load in HIV-1 infection	2.000000e-17
GCST009733_75	Urinary metabolite levels in chronic kidney disease	0.000000e+00
GCST009735_22	Urinary metabolite modules (eigenmetabolites) in chronic kidney disease	2.000000e-26

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0010125	viral load
EFO:0005116	urinary metabolite measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C538385	Hyperprolinemia type 2 (supp.)
C565276	Parkinson Disease 6, Autosomal Recessive Early-Onset (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067037 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1043657	AKR7A2		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.82	Kd	152.4	nM	CHEMBL5653589
6.71	ED50	192.6	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147834: Binding affinity to human AKR7A2 incubated for 45 mins by Kinobead based pull down assay	kd	0.1524	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression, decreases expression (+1 more)	4
4-hydroxy-2-nonenal	increases expression, affects reaction, increases response to substance, affects response to substance, decreases response to substance	3
7-hydroxycoumarin	affects reaction, increases response to substance, increases expression	3
Cyclosporine	affects cotreatment, decreases expression	3
9,10-phenanthrenequinone	increases reduction, affects activity	2
bisphenol A	affects expression, affects cotreatment, decreases methylation	2
sodium arsenite	decreases expression, increases expression	2
Chenodeoxycholic Acid	affects cotreatment, decreases expression	2
Deoxycholic Acid	affects cotreatment, decreases expression	2
Doxorubicin	increases metabolic processing, decreases expression, increases phosphorylation	2
Glycochenodeoxycholic Acid	decreases expression, affects cotreatment	2
Glycocholic Acid	affects cotreatment, decreases expression	2
Glycodeoxycholic Acid	affects cotreatment, decreases expression	2
Hydrogen Peroxide	increases chemical synthesis, increases reduction, increases expression, increases response to substance, affects activity (+1 more)	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Pyruvaldehyde	decreases response to substance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
16-ketoestrone	increases reduction	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
succinic semialdehyde	increases reduction	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(a)pyrene-3,6-quinone	affects activity, affects cotreatment, increases reduction	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650876	Binding	Binding affinity to human AKR7A2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D2HZ	Abcam Raji AKR7A2 KO	Cancer cell line	Male
CVCL_UQ10	Abcam Jurkat AKR7A2 KO	Cancer cell line	Male
CVCL_WQ94	Abcam K-562 AKR7A2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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