AKR1C8

Summary

AKR1C8 (aldo-keto reductase family 1 member C8, HGNC:23469) is a protein-coding gene on chromosome 10p15.1, encoding Aldo-keto reductase family 1 member C8 (Q5T2L2).

Predicted to enable aldo-keto reductase (NADPH) activity and estradiol 17-beta-dehydrogenase [NAD(P)+] activity. Predicted to be involved in prostaglandin biosynthetic process. Predicted to be located in cytoplasm.

Source: NCBI Gene 340811 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001395972

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23469
Approved symbol	AKR1C8
Name	aldo-keto reductase family 1 member C8
Location	10p15.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000264006
Ensembl biotype	protein_coding
Entrez	340811

Gene structure

Transcript identifiers

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

ENST00000578467, ENST00000584929, ENST00000648824, ENST00000650030

RefSeq mRNA: 1 — MANE Select: NM_001395972 NM_001395972

CCDS: CCDS91207

Canonical transcript exons

ENST00000648824 — 9 exons

Exon	Start	End
ENSE00003831942	5161856	5161972
ENSE00003833891	5160812	5160889
ENSE00003834526	5162853	5163020
ENSE00003835563	5159883	5160005
ENSE00003836125	5157635	5157800
ENSE00003837835	5155675	5155757
ENSE00003839032	5158600	5158709
ENSE00003978319	5185012	5185150
ENSE00003978320	5153920	5154182

Expression profiles

Bgee: expression breadth broad, 56 present calls, max score 88.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0737 / max 46.0029, expressed in 14 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108072	0.0737	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.86	gold quality
right lobe of liver	UBERON:0001114	88.09	gold quality
liver	UBERON:0002107	85.96	gold quality
granulocyte	CL:0000094	59.71	gold quality
calcaneal tendon	UBERON:0003701	59.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	54.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	50.82	gold quality
subcutaneous adipose tissue	UBERON:0002190	48.97	gold quality
heart left ventricle	UBERON:0002084	48.84	gold quality
blood	UBERON:0000178	45.69	gold quality
adipose tissue	UBERON:0001013	45.31	gold quality
colonic epithelium	UBERON:0000397	44.60	gold quality
heart	UBERON:0000948	43.97	gold quality
right atrium auricular region	UBERON:0006631	43.19	gold quality
kidney	UBERON:0002113	43.04	gold quality
adult mammalian kidney	UBERON:0000082	42.75	gold quality
bone marrow cell	CL:0002092	41.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	41.15	gold quality
cortex of kidney	UBERON:0001225	41.01	gold quality
omental fat pad	UBERON:0010414	40.78	gold quality
thoracic mammary gland	UBERON:0005200	40.37	gold quality
corpus callosum	UBERON:0002336	40.14	gold quality
bone marrow	UBERON:0002371	39.81	silver quality
right lung	UBERON:0002167	39.79	silver quality
right testis	UBERON:0004534	39.47	gold quality
right uterine tube	UBERON:0001302	38.67	silver quality
sural nerve	UBERON:0015488	37.82	gold quality
upper lobe of left lung	UBERON:0008952	37.78	silver quality
testis	UBERON:0000473	37.51	gold quality
left testis	UBERON:0004533	37.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.91

Regulation

Is transcription factor: no

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	Akr1c15	ENSRNOG00000021735
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), AKR7A3 (ENSG00000162482), AKR1E2 (ENSG00000165568), KCNAB1 (ENSG00000169282), KCNAB3 (ENSG00000170049), AKR1C1 (ENSG00000187134), AKR1C3 (ENSG00000196139), AKR1B10 (ENSG00000198074), AKR1C4 (ENSG00000198610), AKR7L (ENSG00000211454), AKR1B15 (ENSG00000227471)

Protein

Protein identifiers

Aldo-keto reductase family 1 member C8 — Q5T2L2 (reviewed: Q5T2L2)

Alternative names: Aldo-keto reductase family 1 member C-like protein 1

All UniProt accessions (2): A0A3B3IRI8, Q5T2L2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Similarity. Belongs to the aldo/keto reductase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5T2L2-1	1	yes
Q5T2L2-3	2

RefSeq proteins (1): NP_001382901* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018170	Aldo/ket_reductase_CS	Conserved_site
IPR020471	AKR	Family
IPR023210	NADP_OxRdtase_dom	Domain
IPR036812	NAD(P)_OxRdtase_dom_sf	Homologous_superfamily
IPR044482	AKR1C	Family

Pfam: PF00248

UniProt features (13 total): binding site 6, splice variant 2, site 2, chain 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T2L2-F1	95.88	0.94

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 (3): 58 (proton donor); 57 (important for substrate specificity); 87 (lowers pka of active site tyr)

Ligand- & substrate-binding residues (6): 25–27; 53; 120; 169–170; 193; 271–283

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, chr10p15, GOBP_STEROID_METABOLIC_PROCESS, GOBP_ALCOHOL_METABOLIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY, GOBP_HORMONE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_METABOLIC_PROCESS, GSE22601_DOUBLE_NEGATIVE_VS_IMMATURE_CD4_SP_THYMOCYTE_DN

GO Biological Process (4): alcohol metabolic process (GO:0006066), steroid metabolic process (GO:0008202), monocarboxylic acid metabolic process (GO:0032787), hormone metabolic process (GO:0042445)

GO Molecular Function (2): oxidoreductase activity (GO:0016491), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
small molecule metabolic process	1
lipid metabolic process	1
carboxylic acid metabolic process	1
metabolic process	1
regulation of hormone levels	1
catalytic activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKR1C8	ASAH2B	P0C7U1	433
AKR1C8	TRIM2	Q9C040	422
AKR1C8	HMSD	A8MTL9	417
AKR1C8	AKR7A3	O95154	405
AKR1C8	TSPAN32	Q96QS1	399
AKR1C8	HOXA2	O43364	350
AKR1C8	GGT1	P19440	324
AKR1C8	GGTLC3	B5MD39	323
AKR1C8	FOXP2	O15409	280
AKR1C8	GGT2P	P36268	273
AKR1C8	TNXB	P22105	271
AKR1C8	GFI1	Q99684	269
AKR1C8	KCNAB3	O43448	204
AKR1C8	GDI2	P50395	204
AKR1C8	GLYCTK	Q8IVS8	204
AKR1C8	ADORA2A	P29274	204

IntAct

17 interactions, top by confidence:

A	B	Type	Score
CASP6	AKR1C8	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	AKR1C8	psi-mi:“MI:0915”(physical association)	0.560
SH3GLB1	AKR1C8	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	AKR1C8	psi-mi:“MI:0915”(physical association)	0.560
AKR1C8	COQ8A	psi-mi:“MI:0915”(physical association)	0.560
TRIM55	AKR1C8	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A2XRZ0, D3ZF77, O08782, O22707, O60218, P02532, P05980, P07943, P15121, P15122, P16116, P17264, P17516, P21300, P23457, P38918, P40691, P42330, P45376, P45377, P51652, P51857, P52895, P52897, P52898, P70694, P80276, P80508, P97382, Q04828, Q1XAA8, Q5R7C9, Q5REQ0, Q5T2L2, Q640V9, Q6AYQ2, Q6GML7, Q6W8P9, Q7XT99, Q84M96

Diamond homologs: A0A1D5XGW0, A0A1X9QHJ0, A0A2P1GIY9, A0A9E7S518, A0A9E7S5B9, B4F9A4, B9VRJ2, C9JRZ8, D3ZF77, E7C196, H9JTG9, M9PF61, O08782, O32210, O34678, O49133, O60218, O70473, O80944, P02532, P05980, P07943, P0DKI7, P0DXG9, P0DXH7, P14065, P14550, P15121, P15122, P16116, P17264, P17516, P21300, P23457, P23901, P26690, P28475, P31867, P42330, P45376

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2151 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:5162967:G:C	F49L	0.961
10:5162967:G:T	F49L	0.961
10:5162969:A:G	F49L	0.961
10:5162865:G:C	F83L	0.951
10:5162865:G:T	F83L	0.951
10:5162867:A:G	F83L	0.951
10:5185033:A:C	F24L	0.888
10:5185033:A:T	F24L	0.888
10:5185035:A:G	F24L	0.888
10:5161883:G:C	F117L	0.885
10:5161883:G:T	F117L	0.885
10:5161885:A:G	F117L	0.885
10:5162955:A:C	D53E	0.885
10:5162955:A:T	D53E	0.885
10:5162968:A:G	F49S	0.866
10:5162965:C:G	R50P	0.863
10:5162853:C:A	K87N	0.857
10:5162853:C:G	K87N	0.857
10:5161958:G:C	F92L	0.853
10:5161958:G:T	F92L	0.853
10:5161960:A:G	F92L	0.853
10:5162877:T:A	R79S	0.845
10:5162877:T:G	R79S	0.845
10:5161889:A:C	D115E	0.842
10:5161889:A:T	D115E	0.842
10:5162956:T:A	D53V	0.813
10:5162869:A:T	I82K	0.793
10:5162884:A:T	V77D	0.793
10:5185034:A:G	F24S	0.793
10:5162983:G:T	A44D	0.792

dbSNP variants (sampled 300 via entrez): RS1000018894 (10:5146545 T>A,C), RS1000019874 (10:5184023 T>C), RS1000068057 (10:5146845 A>C,G), RS1000075824 (10:5179540 G>A,C), RS1000107726 (10:5156709 G>A,C), RS1000186364 (10:5116731 T>A), RS1000205404 (10:5160525 T>C), RS1000207925 (10:5124763 G>A,C), RS1000240819 (10:5125011 A>T), RS1000291752 (10:5135218 G>A,T), RS1000435805 (10:5165482 T>C), RS1000476320 (10:5184346 C>T), RS1000477130 (10:5130168 A>C), RS1000487113 (10:5115983 T>C), RS1000647223 (10:5155619 A>G)

Disease associations

OMIM: gene `` | 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
GCST005024_79	Pursuit maintenance gain	2.000000e-07
GCST009391_19	Metabolite levels	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
perfluorooctane sulfonic acid	decreases expression	1
fipronil	decreases expression, affects cotreatment	1
Benzo(a)pyrene	increases methylation	1
DEET	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Tobacco Smoke Pollution	increases expression	1
Okadaic Acid	decreases expression	1
beta-Naphthoflavone	increases expression	1

Clinical trials (associated diseases)

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