AKR7L

Summary

AKR7L (aldo-keto reductase family 7 like (gene/pseudogene), HGNC:24056) is a protein-coding gene on chromosome 1p36.13, encoding Aflatoxin B1 aldehyde reductase member 4 (Q8NHP1). Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol.

This gene is one of three aldo-keto reductase genes that are present in a cluster on the p arm of chromosome 1. The encoded proteins are involved in the reduction of the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. It has been speculated that this family member encodes a selenoprotein, which includes a selenocysteine (Sec) residue in lieu of a UGA translational termination codon. However, there is no evidence that such a protein is produced in vivo. The alternative interpretation is that this family member is a segregating pseudogene, where some individuals have an allele that encodes a functional enzyme, while other individuals have an allele encoding a protein that is predicted to be non-functional.

Source: NCBI Gene 246181 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 6 total — 1 pathogenic

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24056
Approved symbol	AKR7L
Name	aldo-keto reductase family 7 like (gene/pseudogene)
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	AFAR3
Ensembl gene	ENSG00000211454
Ensembl biotype	protein_coding
OMIM	608478
Entrez	246181

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_LoF, 1 retained_intron

ENST00000429712, ENST00000457194, ENST00000493176

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000429712 — 7 exons

Exon	Start	End
ENSE00001504261	19269272	19269371
ENSE00001627290	19269583	19269679
ENSE00001719156	19273861	19274194
ENSE00001755337	19267103	19267461
ENSE00003476553	19270748	19270935
ENSE00003675263	19268572	19268701
ENSE00003715904	19270451	19270555

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 95.35.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	95.35	gold quality
right lobe of liver	UBERON:0001114	93.11	gold quality
liver	UBERON:0002107	90.53	gold quality
body of pancreas	UBERON:0001150	87.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.43	gold quality
mucosa of transverse colon	UBERON:0004991	85.17	gold quality
body of stomach	UBERON:0001161	84.93	gold quality
small intestine	UBERON:0002108	84.57	gold quality
stomach	UBERON:0000945	82.00	gold quality
fundus of stomach	UBERON:0001160	81.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.64	gold quality
transverse colon	UBERON:0001157	78.52	gold quality
adult mammalian kidney	UBERON:0000082	78.37	gold quality
cortex of kidney	UBERON:0001225	76.91	gold quality
pancreas	UBERON:0001264	76.78	gold quality
metanephros cortex	UBERON:0010533	76.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.01	gold quality
cerebellar hemisphere	UBERON:0002245	74.77	gold quality
kidney	UBERON:0002113	74.76	gold quality
cerebellar cortex	UBERON:0002129	74.70	gold quality
cerebellum	UBERON:0002037	74.66	gold quality
intestine	UBERON:0000160	74.14	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.94	gold quality
rectum	UBERON:0001052	73.46	gold quality
gall bladder	UBERON:0002110	72.69	gold quality
mucosa of stomach	UBERON:0001199	72.06	gold quality
colon	UBERON:0001155	70.49	gold quality
skin of leg	UBERON:0001511	66.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	66.92	gold quality
nucleus accumbens	UBERON:0001882	66.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.24

Regulation

Is transcription factor: no

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	akr7a3	ENSDARG00000016649
mus_musculus	Akr7a5	ENSMUSG00000028743
rattus_norvegicus	Akr7a2	ENSRNOG00000017780
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

Paralogs (16): AKR7A2 (ENSG00000053371), 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), AKR1B15 (ENSG00000227471), AKR1C8 (ENSG00000264006)

Protein

Protein identifiers

Aflatoxin B1 aldehyde reductase member 4 — Q8NHP1 (reviewed: Q8NHP1)

Alternative names: AFB1 aldehyde reductase 3, Aldoketoreductase 7-like

All UniProt accessions (0):

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Tissue specificity. Mainly expressed in uterus.

Polymorphism. The sequence shown in this entry differs from the translation of the reference genome assembly (GRCh38/hg38) due to a nonsense variant creating stop codon at position 106 in the reference genome. This sequence carries a selenocysteine-insertion element (SECIS)-like structure that during translation may recode an in-frame TGA-stop codon to a selenocysteine. However, there is no evidence that such a protein is produced in vivo. The sequence shown in this entry is that of variant p.Ter106Arg. This variant has a frequency of about 3% in the human population according to the Genome Aggregation Database (gnomAD v3.1.2).

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NHP1-1	1	yes
Q8NHP1-3	2

RefSeq proteins (0): (*=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

UniProt features (17 total): binding site 8, sequence variant 3, chain 1, active site 1, site 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHP1-F1	95.89	0.95

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 (8): 44; 113; 143–144; 169; 198–208; 222; 232; 290–298

Post-translational modifications (1): 85

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5423646	Aflatoxin activation and detoxification

MSigDB gene sets: 17 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, WCTCNATGGY_UNKNOWN, GATA1_01, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS, chr1p36, GOMF_ALCOHOL_DEHYDROGENASE_NADPPLUS_ACTIVITY, REACTOME_AFLATOXIN_ACTIVATION_AND_DETOXIFICATION, GOMF_ALCOHOL_DEHYDROGENASE_NAD_P_PLUS_ACTIVITY, GOMF_OXIDOREDUCTASE_ACTIVITY, MEBARKI_HCC_PROGENITOR_FZD8CRD_DN, BUSSLINGER_GASTRIC_PARIETAL_CELLS, BUSSLINGER_DUODENAL_LATE_IMMATURE_ENTEROCYTES, DESCARTES_FETAL_PANCREAS_ACINAR_CELLS, E2F_Q2, CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN

GO Biological Process (0):

GO Molecular Function (2): oxidoreductase activity (GO:0016491), alcohol dehydrogenase (NADP+) activity (GO:0008106)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062), nuclear envelope (GO:0005635), smooth endoplasmic reticulum (GO:0005790), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Biological oxidations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
catalytic activity	1
alcohol dehydrogenase [NAD(P)+] activity	1
intracellular anatomical structure	1
extracellular vesicle	1
nucleus	1
organelle envelope	1
endoplasmic reticulum	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

10 interactions, top by confidence:

A	B	Type	Score
PEF1	PDCD6	psi-mi:“MI:0914”(association)	0.900
AKR7A3	AKR7A2	psi-mi:“MI:0914”(association)	0.890
AKR7A3	ASAH1	psi-mi:“MI:0914”(association)	0.530
SCRIB	CHD2	psi-mi:“MI:0914”(association)	0.350
AKR7L	KIF2A	psi-mi:“MI:0914”(association)	0.350
AKR7A2	DCTN6	psi-mi:“MI:0914”(association)	0.350
KCTD13	SMTN	psi-mi:“MI:0914”(association)	0.350

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, M2YMU7, O43488, O95154, P25612, P38918, P42884, P43546, P43547, P47182, Q00049, Q00258, Q00727, Q01333, Q01752, Q07747, Q08361, Q6Q875, Q6UEH5, Q75ZG2, Q75ZG3, Q8CG45, Q8CG76, Q8NHP1, A0A3B1EFQ1, A0QJ99, A2XRZ0, A2XRZ6, B8ASB2, C6TBN2, F4HPY8, K3VD70, O14125, O14295, O22707

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1228381	GRCh37/hg19 1p36.13-36.12(chr1:16785250-23491592)x1	Pathogenic

SpliceAI

989 predictions. Top by Δscore:

Variant	Effect	Δscore
1:19267458:CACC:C	acceptor_gain	1.0000
1:19267460:CC:C	acceptor_gain	1.0000
1:19267461:CC:C	acceptor_gain	1.0000
1:19267462:C:CC	acceptor_gain	1.0000
1:19268697:AGAAG:A	acceptor_gain	1.0000
1:19268698:GAAG:G	acceptor_gain	1.0000
1:19268699:AAG:A	acceptor_gain	1.0000
1:19268700:AG:A	acceptor_gain	1.0000
1:19268701:GCTG:G	acceptor_loss	1.0000
1:19268702:C:CC	acceptor_gain	1.0000
1:19268703:T:G	acceptor_loss	1.0000
1:19268707:C:CT	acceptor_gain	1.0000
1:19268708:A:T	acceptor_gain	1.0000
1:19268709:G:C	acceptor_gain	1.0000
1:19268709:G:GC	acceptor_gain	1.0000
1:19268715:A:AC	acceptor_gain	1.0000
1:19269270:A:AC	donor_gain	1.0000
1:19269271:C:CT	donor_gain	1.0000
1:19269274:ATT:A	donor_gain	1.0000
1:19269276:T:TA	donor_gain	1.0000
1:19269294:A:AC	donor_gain	1.0000
1:19269295:C:CC	donor_gain	1.0000
1:19269581:ACCAG:A	donor_gain	1.0000
1:19269582:CCAGC:C	donor_gain	1.0000
1:19269676:TGCC:T	acceptor_gain	1.0000
1:19269678:CC:C	acceptor_gain	1.0000
1:19269679:CC:C	acceptor_gain	1.0000
1:19269680:C:CA	acceptor_loss	1.0000
1:19269680:C:CC	acceptor_gain	1.0000
1:19269681:T:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000526528 (1:19273545 A>G), RS1001293736 (1:19273736 G>A,C,T), RS1001857246 (1:19269182 G>A), RS1002788470 (1:19266584 G>T), RS1002902932 (1:19266317 G>GTTTA,GTTTC), RS1003525686 (1:19275205 G>A), RS1003850561 (1:19265732 G>C,T), RS1005015505 (1:19265696 T>G), RS1005646816 (1:19272952 C>G,T), RS1005861520 (1:19271920 A>G), RS1006026288 (1:19267014 A>G), RS1006102320 (1:19268301 G>C), RS1006549563 (1:19266643 A>G), RS1007659974 (1:19272218 C>A), RS1008383430 (1:19274447 C>A,G,T)

Disease associations

OMIM: gene MIM:608478 | 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
GCST000597_10	Brain structure	1.000000e-07
GCST007001_1	Cerebrospinal AB1-42 levels in normal cognition	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
aristolochic acid I	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
fipronil	affects cotreatment, decreases expression	1
DEET	affects cotreatment, decreases expression	1
Xylitol	increases expression	1
Oleic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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