CBR1

protein-coding

carbonyl reductase 1, the group of Short chain dehydrogenase/reductase superfamily

Gene summary

The protein encoded by this gene belongs to the short-chain dehydrogenases/reductases (SDR) family, which function as NADPH-dependent oxidoreductases having wide specificity for carbonyl compounds, such as quinones, prostaglandins, and various xenobiotics. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2013]

Previous symbols:

MANE transcript

NM_001757.4

Inheritance

—

ClinVar variants

U:46B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr21:36,069,941-36,073,166

External References & Databases

Ensembl (ENSG00000159228)

Transcript & Mutation Effects

hg38 • Region Span ~3.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CBR1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001757.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			46 clinvar	3 clinvar		49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	46	3	1	50

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001757.4	RefSeq	NP_001748.1	3	MANE Select
ENST00000290349.11	Ensembl	ENSP00000290349.6	3	MANE Select
NM_001286789.2	RefSeq	NP_001273718.1	3	Standard
ENST00000399191.3	Ensembl	ENSP00000382143.3	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Folate biosynthesis - Homo sapiens (human)
Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics
Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
Arachidonic acid metabolism - Homo sapiens (human)
Doxorubicin Pathway, Pharmacokinetics

Biological Process

drug metabolic process
cyclooxygenase pathway
epithelial cell differentiation
vitamin K metabolic process
oxidation-reduction process

Molecular Function

carbonyl reductase (NADPH) activity
oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
15-hydroxyprostaglandin dehydrogenase (NADP+) activity
prostaglandin-E2 9-reductase activity

Cellular Component

cytosol
extracellular exosome
extracellular vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000290349
Coding exons: 3
Length: 3226
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125748
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0906	164	161	1.02	0.00000813	1788
Missense (PolyPhen)		45	45.21	0.99535		553
Synonymous	-1.53	87	70.6	1.23	0.00000394	568
Loss of Function	0.460	7	8.44	0.829	4.44e-7	92

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00014	0.000092	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00053	0.00052	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione. {ECO:0000269|PubMed:15799708, ECO:0000269|PubMed:17912391, ECO:0000269|PubMed:18449627, ECO:0000269|PubMed:18826943}.;

Recessive Scores

pRec: 0.267

Intolerance Scores

LoFtool: 0.372
RVIS EVS: -0.03
RVIS percentile EVS: 51.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium