CBR3

Summary

CBR3 (carbonyl reductase 3, HGNC:1549) is a protein-coding gene on chromosome 21q22.12, encoding Carbonyl reductase [NADPH] 3 (O75828). Catalyzes the NADPH-dependent reduction of carbonyl compounds to their corresponding alcohols.

Carbonyl reductase 3 catalyzes the reduction of a large number of biologically and pharmacologically active carbonyl compounds to their corresponding alcohols. The enzyme is classified as a monomeric NADPH-dependent oxidoreductase. CBR3 contains three exons spanning 11.2 kilobases and is closely linked to another carbonyl reductase gene - CBR1.

Source: NCBI Gene 874 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 56 total
• Druggable target: yes
• MANE Select transcript: NM_001236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1549
Approved symbol	CBR3
Name	carbonyl reductase 3
Location	21q22.12
Locus type	gene with protein product
Status	Approved
Aliases	SDR21C2
Ensembl gene	ENSG00000159231
Ensembl biotype	protein_coding
OMIM	603608
Entrez	874

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000290354, ENST00000926155

RefSeq mRNA: 1 — MANE Select: NM_001236 NM_001236

CCDS: CCDS13642

Canonical transcript exons

ENST00000290354 — 3 exons

Exon	Start	End
ENSE00001044173	36137825	36137932
ENSE00001044175	36135079	36135481
ENSE00001044176	36146076	36146562

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 98.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.6282 / max 336.8999, expressed in 1547 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188984	14.4004	1521
188983	1.2279	850

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	98.35	gold quality
gingiva	UBERON:0001828	98.14	gold quality
tendon of biceps brachii	UBERON:0008188	97.30	gold quality
tongue squamous epithelium	UBERON:0006919	95.93	gold quality
squamous epithelium	UBERON:0006914	94.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.47	gold quality
esophagus squamous epithelium	UBERON:0006920	93.72	gold quality
epithelium of esophagus	UBERON:0001976	93.58	gold quality
esophagus mucosa	UBERON:0002469	93.42	gold quality
cervix squamous epithelium	UBERON:0006922	93.35	gold quality
parotid gland	UBERON:0001831	92.97	gold quality
mouth mucosa	UBERON:0003729	92.84	gold quality
cartilage tissue	UBERON:0002418	92.78	gold quality
minor salivary gland	UBERON:0001830	92.21	gold quality
nasal cavity mucosa	UBERON:0001826	91.82	gold quality
saliva-secreting gland	UBERON:0001044	91.53	gold quality
cervix epithelium	UBERON:0004801	91.35	gold quality
tendon	UBERON:0000043	91.32	gold quality
mammalian vulva	UBERON:0000997	90.89	gold quality
oral cavity	UBERON:0000167	90.85	gold quality
lower esophagus mucosa	UBERON:0035834	90.75	gold quality
pharyngeal mucosa	UBERON:0000355	90.02	gold quality
calcaneal tendon	UBERON:0003701	89.89	gold quality
nasal cavity epithelium	UBERON:0005384	89.59	silver quality
penis	UBERON:0000989	88.99	gold quality
layer of synovial tissue	UBERON:0007616	88.90	gold quality
synovial joint	UBERON:0002217	88.87	gold quality
oviduct epithelium	UBERON:0004804	88.45	gold quality
mucosa of stomach	UBERON:0001199	88.17	gold quality
buccal mucosa cell	CL:0002336	87.86	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF6, NFE2L2

Literature-anchored findings (GeneRIF, showing 23)

• carbonyl reductase has an important function in modifying the metastatic behavior of malignant tumors. (PMID:10728668)
• Decreased Carbonyl Reductase expression in epithelial ovarian cancer is associated with RLN metastasis and poor survival (PMID:11592776)
• The common carbonyl reductase 3 (CBR3)valine244methionine polymorphism encodes for CBR3 isoforms with distinctive enzymatic properties, as revealed in DNA variation panels from 10 ethnic groups. (PMID:15537833)
• There was a trend toward an association between the CBR3 V244M polymorphism and the risk of CHf (PMID:18457324)
• These results suggested that hCBR3 and hCBR1 play distinct physiological roles. (PMID:18493841)
• Polymorphisms in CBR3 may explain interindividual and interethnic variability of doxorubicin pharmacokinetics and pharmacodynamics. (PMID:18551042)
• CBR3 polymorphisms have no significant influence on the pharmacokinetics of doxorubicin in Asian breast cancer patients. (PMID:19016765)
• identified the promoter of human CBR3. Liver samples from black donors showed higher relative CBR3 mRNA levels than samples from whites (PMID:19590938)
• analysis of the structural basis for substrate specificity in human monomeric carbonyl reductases CBR3 (PMID:19841672)
• The CBR3 distal promoter contains an activating cis-regulatory element that is responsive to Trichostatin A (TSA) treatment according to promoter reporter assays in HEK 293 cells. (PMID:20494980)
• CBR3 is regulated via NRF2-dependent signaling pathways, a finding and plays an important role in the cellular response to oxidative stress. (PMID:20806931)
• a physiological role of CBR1, but not for CBR3, in S-nitrosoglutathione reduction and thus ultimately in regulation of NO signaling (PMID:21256830)
• Computational searches identify a conserved antioxidant response element(ARE) in the distal carbonyl reductase 3 (CBR3) promoter region. (PMID:22001310)
• CBR3 polymorphisms contribute to increased cardiomyopathy risk associated with anthracycline treatment of childhood cancer. (PMID:22124095)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• CBR3 is a novel target gene of inflammatory stimuli; elucidation of its detailed role in inflammation deserves further investigation. (PMID:22425771)
• genetic polymorphism in the CBR3 gene conferred risk of type 2 diabetes and insulin resistance in Chinese. The association was probably mediated through modulation of adipogenesis. (PMID:22527884)
• Variants of CBR3 and GSTP1 enzymes may be associated with changes in short-term functional cardiac parameters. (PMID:23182048)
• No significant correlation between cardiotoxicity and SNPs within the CBR pathway. Further investigation into CBR SNPs in a larger adult sample is needed. (PMID:26563179)
• association of SNPs in ABCB1 and CBR3 with chronic cardiotoxicity in a cohort of breast cancer patients treated with anthracyclines. (PMID:26799497)
• patients with advanced stage retinoblastoma had higher levels of PlncRNA-1 expression than patients with early stage retinoblastoma. There was an inverse correlation between PlncRNA-1 expression and CBR3 expression in retinoblastoma tissues, and PlncRNA-1 negatively regulated mRNA and protein expressions of CBR3. (PMID:30096220)
• CBR3 730G>A is significantly associated with recurrence- free survival in patients who received intravesical chemotherapy with pirarubicin after complete transurethral resection. (PMID:30125887)
• Long noncoding RNA CBR3 antisense RNA 1 promotes the aggressive phenotypes of nonsmallcell lung cancer by sponging microRNA5093p and competitively upregulating HDAC9 expression. (PMID:32945466)

Cross-species orthologs

28 orthologs

Organism	Symbol	Gene ID
danio_rerio	zmp:0000001048	ENSDARG00000016213
danio_rerio	cbr1l	ENSDARG00000021149
danio_rerio	zgc:101858	ENSDARG00000035129
danio_rerio	zgc:65997	ENSDARG00000043562
danio_rerio	zgc:163083	ENSDARG00000099873
danio_rerio	zgc:92161	ENSDARG00000101749
danio_rerio	zgc:123284	ENSDARG00000102720
danio_rerio	zgc:112146	ENSDARG00000104829
mus_musculus	Cbr3	ENSMUSG00000022947
rattus_norvegicus	Cbr3	ENSRNOG00000001701
drosophila_melanogaster	CG7601	FBGN0027583
drosophila_melanogaster	CG12171	FBGN0037354
drosophila_melanogaster	CG3699	FBGN0040349
drosophila_melanogaster	CG31546	FBGN0051546
drosophila_melanogaster	CG31548	FBGN0051548
drosophila_melanogaster	CG31549	FBGN0051549
drosophila_melanogaster	CG13377	FBGN0261446
caenorhabditis_elegans		WBGENE00000970
caenorhabditis_elegans		WBGENE00000975
caenorhabditis_elegans		WBGENE00000981
caenorhabditis_elegans		WBGENE00000993
caenorhabditis_elegans		WBGENE00008985
caenorhabditis_elegans		WBGENE00008986
caenorhabditis_elegans		WBGENE00011424
caenorhabditis_elegans	Y47G6A.21	WBGENE00021646
caenorhabditis_elegans	Y47G6A.22	WBGENE00021647
caenorhabditis_elegans		WBGENE00022809
caenorhabditis_elegans		WBGENE00219274

Paralogs (13): RDH8 (ENSG00000080511), DHRS7 (ENSG00000100612), DHRS2 (ENSG00000100867), DHRS7B (ENSG00000109016), HSD11B1 (ENSG00000117594), HSDL2 (ENSG00000119471), DHRS4 (ENSG00000157326), DHRS1 (ENSG00000157379), CBR1 (ENSG00000159228), HSD11B1L (ENSG00000167733), DHRS7C (ENSG00000184544), DHRS4L2 (ENSG00000187630), DHRS11 (ENSG00000278535)

Protein

Protein identifiers

Carbonyl reductase [NADPH] 3 — O75828 (reviewed: O75828)

Alternative names: NADPH-dependent carbonyl reductase 3, Quinone reductase CBR3, Short chain dehydrogenase/reductase family 21C member 2

All UniProt accessions (2): O75828, V9HW40

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NADPH-dependent reduction of carbonyl compounds to their corresponding alcohols. Has low NADPH-dependent oxidoreductase activity. Acts on several orthoquinones, acts as well on non-quinone compounds, such as isatin or on the anticancer drug oracin. Best substrates for CBR3 is 1,2- naphthoquinone, hence could play a role in protection against cytotoxicity of exogenous quinones. Exerts activity toward ortho-quinones but not paraquinones. No endogenous substrate for CBR3 except isatin has been identified.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in ovary, pancreas, intestine, colon, kidney, brain, thymus, lung, heart, liver, spleen, leukocyte, prostate and testis.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family.

RefSeq proteins (1): NP_001227* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR020904	Sc_DH/Rdtase_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR045313	CBR1-like	Family

Pfam: PF00106

Enzyme classification (BRENDA):

• EC 1.1.1.184 — carbonyl reductase (NADPH) (BRENDA: 40 organisms, 630 substrates, 214 inhibitors, 373 Km, 209 kcat entries)

Substrate kinetics (BRENDA)

114 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MENADIONE	—	31
NADPH	0.0021–10.27	26
2-HYDROXYACETOPHENONE	0.59–10.27	24
4-BENZOYLPYRIDINE	—	19
ISATIN	0.0008–4	19
9,10-PHENANTHRENEQUINONE	0.002–0.078	17
DAUNORUBICIN	0.043–3	13
DOXORUBICIN	0.041–0.335	13
4-NITROBENZALDEHYDE	0.12–1.1	9
NADH	0.062–8.67	9
1,4-NAPHTHOQUINONE	0.0073–0.54	6
PROSTAGLANDIN E2	0.03–0.32	6
2,3-HEXANEDIONE	0.06–0.62	5
ETHYL 4-CHLORO-3-OXOBUTANOATE	0.0026–4.6	5
S-NITROSOGLUTATHIONE	0.028–2.93	5

Catalyzed reactions (Rhea), 2 shown:

• a secondary alcohol + NADP(+) = a ketone + NADPH + H(+) (RHEA:19257)
• a quinone + NADPH + H(+) = a quinol + NADP(+) (RHEA:46164)

UniProt features (44 total): helix 13, strand 9, binding site 7, sequence variant 6, mutagenesis site 3, modified residue 2, initiator methionine 1, chain 1, active site 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2HRB	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75828-F1	96.66	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 (1): 194 (proton acceptor)

Ligand- & substrate-binding residues (7): 10–34; 38–42; 63–64; 90; 140; 194–198; 239

Post-translational modifications (2): 2, 30

Mutagenesis-validated functional residues (3):

Position	Phenotype
142	modest increase in carbonyl reductase (nadph) activity toward 1,2-naphthoquinone.
230	decreased carbonyl reductase (nadph) activity toward 1,2-naphthoquinone and isatin.
236	significant decreased of the km value for isatin.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-1430728	Metabolism
R-HSA-211859	Biological oxidations

MSigDB gene sets: 189 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, REACTOME_BIOLOGICAL_OXIDATIONS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_KETONE_METABOLIC_PROCESS, GOMF_STEROID_DEHYDROGENASE_ACTIVITY_ACTING_ON_THE_CH_OH_GROUP_OF_DONORS_NAD_OR_NADP_AS_ACCEPTOR, MODULE_99, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_NAD_P_H, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS, BURTON_ADIPOGENESIS_5, YAMAZAKI_TCEB3_TARGETS_DN, chr21q22

GO Biological Process (3): xenobiotic metabolic process (GO:0006805), phylloquinone catabolic process (GO:0042376), cognition (GO:0050890)

GO Molecular Function (8): 3-beta-hydroxysteroid 3-dehydrogenase (NADP+) activity (GO:0000253), carbonyl reductase (NADPH) activity (GO:0004090), NADPH dehydrogenase (quinone) activity (GO:0008753), NADPH binding (GO:0070402), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor (GO:0016655)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

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	3
metabolic process	1
cellular response to xenobiotic stimulus	1
vitamin K catabolic process	1
nervous system process	1
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
alcohol dehydrogenase (NADP+) activity	1
NAD(P)H dehydrogenase (quinone) activity	1
NADPH dehydrogenase activity	1
anion binding	1
NADP binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
oxidoreductase activity, acting on NAD(P)H	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3303 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CBR3	AKR1A1	P14550	912
CBR3	AKR1B1	P15121	799
CBR3	NQO1	P15559	614
CBR3	CBR4	Q8N4T8	596
CBR3	GSTP1	P09211	595
CBR3	SLC28A3	Q9HAS3	551
CBR3	SLC22A16	Q86VW1	499
CBR3	HSD17B2	P37059	489
CBR3	AKR1C3	P42330	465
CBR3	CYP2B6	P20813	461
CBR3	CYP3A4	P05184	459
CBR3	SARDH	Q9UL12	452
CBR3	AKR1C1	P52896	438
CBR3	AKR7A2	O43488	431
CBR3	SYDE2	Q5VT97	430

IntAct

40 interactions, top by confidence:

A	B	Type	Score
CBR3	SDCBP	psi-mi:“MI:0915”(physical association)	0.780
SDCBP	CBR3	psi-mi:“MI:0915”(physical association)	0.780
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CBR3	CBR1	psi-mi:“MI:0914”(association)	0.710
CBR3	CBR1	psi-mi:“MI:0915”(physical association)	0.710
CBR3	BICD2	psi-mi:“MI:0915”(physical association)	0.560
CBR3	LDLR	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
NDUFS3	ACOT7	psi-mi:“MI:0914”(association)	0.350
USP3	EIF3F	psi-mi:“MI:0914”(association)	0.350
IMMP1L	EIF1AY	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
S	COPE	psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350
ZBTB18	CBR3	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
PINK1	A2ML1	psi-mi:“MI:0914”(association)	0.350
UPK1A	A2ML1	psi-mi:“MI:0914”(association)	0.350
SARAF	A2ML1	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
SGK1	CBR3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (51): CBR3 (Affinity Capture-MS), SDCBP (Two-hybrid), CBR3 (Affinity Capture-MS), BTBD9 (Affinity Capture-MS), RABIF (Co-fractionation), CBR3 (Proximity Label-MS), CBR1 (Affinity Capture-MS), LDLR (Affinity Capture-MS), MKI67 (Affinity Capture-MS), RPS10 (Affinity Capture-MS), CCNL2 (Affinity Capture-MS), CBR3 (Affinity Capture-MS), SDCBP (Two-hybrid), CBR1 (Affinity Capture-MS), BTBD9 (Affinity Capture-MS)

ESM2 similar proteins: A6QP05, B0BNF8, B2GV72, O00764, O14756, O35331, O54753, O54909, O75452, O75828, O88451, P16152, P17516, P42330, P46597, P47727, P47844, P48758, P50170, P52895, P55006, P80508, Q04828, Q1XAA8, Q28960, Q3SZD7, Q3SZM9, Q3T001, Q3U0B3, Q3ZBV9, Q5R7C9, Q5RCU5, Q5REQ0, Q6SKR2, Q6UWP2, Q6W8P9, Q71R50, Q8C436, Q8HZJ0, Q8K183

Diamond homologs: A0A017SEY2, A0A023I4F1, A0A0C6DRT7, A0A1B7YCL6, A0A2P1DP77, A0A345BJN5, A0A482ND39, A0A4P8DJW5, A0A5B8YU33, A0AAW1NHX6, A2RVM0, B2X050, B6H062, B6HLP6, B8M9L2, C8V3Y7, D7UQ42, F4JJR8, G1XTZ5, G3Y422, G4MVZ5, G9N4A1, G9N4A6, I1S2J3, O48741, O75828, O80333, P00335, P0DXW2, P15428, P16232, P19992, P21218, P28845, P42317, P50199, P50203, P51975, P70684, P9WEF8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

322 predictions. Top by Δscore:

Variant	Effect	Δscore
21:36135429:G:GT	donor_gain	1.0000
21:36135478:AAGA:A	donor_gain	1.0000
21:36135479:AGA:A	donor_gain	1.0000
21:36135480:GA:G	donor_gain	1.0000
21:36135480:GAG:G	donor_gain	1.0000
21:36135482:G:GG	donor_gain	1.0000
21:36137819:T:A	acceptor_gain	1.0000
21:36137822:AAGGT:A	acceptor_gain	1.0000
21:36137823:A:AG	acceptor_loss	1.0000
21:36137823:A:G	acceptor_gain	1.0000
21:36137824:G:GA	acceptor_loss	1.0000
21:36137824:GGT:G	acceptor_gain	1.0000
21:36137930:ATGG:A	donor_loss	1.0000
21:36137933:GT:G	donor_loss	1.0000
21:36135429:GGA:G	donor_gain	0.9900
21:36135430:GAG:G	donor_gain	0.9900
21:36137822:A:AG	acceptor_gain	0.9900
21:36137822:AAG:A	acceptor_gain	0.9900
21:36137823:AG:A	acceptor_gain	0.9900
21:36137823:AGGT:A	acceptor_gain	0.9900
21:36137824:G:GG	acceptor_gain	0.9900
21:36137824:GG:G	acceptor_gain	0.9900
21:36137824:GGTG:G	acceptor_gain	0.9900
21:36137824:GGTGA:G	acceptor_gain	0.9900
21:36137933:G:GG	donor_gain	0.9900
21:36146074:A:AG	acceptor_gain	0.9900
21:36146075:G:GG	acceptor_gain	0.9900
21:36135432:G:GG	donor_gain	0.9800
21:36135477:CAAGA:C	donor_gain	0.9800
21:36137932:GGT:G	donor_gain	0.9800

AlphaMissense

1833 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:36146093:A:C	S139R	0.970
21:36146095:T:A	S139R	0.970
21:36146095:T:G	S139R	0.970
21:36146201:T:C	F175L	0.957
21:36146203:T:A	F175L	0.957
21:36146203:T:G	F175L	0.957
21:36146243:T:A	W189R	0.954
21:36146243:T:C	W189R	0.954
21:36137878:T:C	F115L	0.943
21:36137880:T:A	F115L	0.943
21:36137880:T:G	F115L	0.943
21:36135277:T:C	F29L	0.942
21:36135279:C:A	F29L	0.942
21:36135279:C:G	F29L	0.942
21:36146089:T:A	N137K	0.939
21:36146089:T:G	N137K	0.939
21:36135367:T:C	F59L	0.936
21:36135369:C:A	F59L	0.936
21:36135369:C:G	F59L	0.936
21:36135459:C:A	N89K	0.936
21:36135459:C:G	N89K	0.936
21:36146245:G:C	W189C	0.932
21:36146245:G:T	W189C	0.932
21:36146350:T:A	N224K	0.929
21:36146350:T:G	N224K	0.929
21:36146277:G:A	G200E	0.897
21:36137932:G:T	G133W	0.896
21:36146276:G:T	G200W	0.892
21:36135418:T:C	F76L	0.891
21:36135420:C:A	F76L	0.891

dbSNP variants (sampled 300 via entrez): RS1000526584 (21:36142317 A>C), RS1000846926 (21:36136543 T>C), RS1000868433 (21:36142541 G>T), RS1000877726 (21:36141241 G>A,C), RS1000983859 (21:36136929 C>G), RS1001023105 (21:36141719 T>G), RS1001246453 (21:36135544 G>A,C), RS1001296979 (21:36135761 A>C), RS1001587369 (21:36141148 G>A), RS1002473475 (21:36136413 A>C,G), RS1002557241 (21:36140103 G>A), RS1002721140 (21:36146870 C>A,T), RS1002888001 (21:36143796 C>G,T), RS1002913599 (21:36145556 T>G), RS1002940953 (21:36146768 T>G)

Disease associations

OMIM: gene MIM:603608 | 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
GCST001482_6	Lumbar spine bone mineral density	9.000000e-07
GCST006585_114	Blood protein levels	3.000000e-160

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6008 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1056892	Toxicity	3	anthracyclines and related substances	Heart Failure;Neoplasms
rs112783657	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs74743371	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs8133052	Efficacy,Toxicity	3	doxorubicin	Breast Neoplasms;Neutropenia

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1056892	CBR3	3	2.75	1	anthracyclines and related substances
rs2835285	CBR3		0.00	0
rs4987121	CBR3		0.00	0
rs8133052	CBR3	3	5.75	1	doxorubicin

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
5.02	Kd	9521	nM	CHEMBL5653589
5.02	ED50	9521	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 44 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	2148003: Binding affinity to human CBR3 incubated for 45 mins by Kinobead based pull down assay	kd	9.5207	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
sulforaphane	increases expression	2
entinostat	increases expression, affects cotreatment	2
Bortezomib	increases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
methyleugenol	increases expression	1
9,10-phenanthrenequinone	increases metabolic processing	1
bisphenol A	increases expression	1
diethyl maleate	decreases reaction, increases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
benzo(k)fluoranthene	increases expression	1
pregna-4,17-diene-3,16-dione	increases expression	1
benzo(e)pyrene	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment	1
celastrol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
glycidamide	increases expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases expression, decreases reaction	1
gedunin	increases expression	1
2-palmitoylglycerol	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004501	Binding	Binding affinity to human recombinant carbonyl reductase 3 expressed in Escherichia coli assessed as thermal shift by differential scanning fluorimetry in absence of cofactor	Discovery of a potent and selective inhibitor for human carbonyl reductase 1 from propionate scanning applied to the macrolide zearalenone. — Bioorg Med Chem

Clinical trials (associated diseases)

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