CBR4

protein-coding

carbonyl reductase 4, the group of Short chain dehydrogenase/reductase superfamily

Gene summary

Enables several functions, including 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; NADPH binding activity; and NADPH dehydrogenase (quinone) activity. Involved in several processes, including daunorubicin metabolic process; doxorubicin metabolic process; and protein tetramerization. Located in mitochondrial matrix. Part of oxidoreductase complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_032783.5

Inheritance

—

ClinVar variants

U:39B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.98

Max pathogenic AF

—

Genomic locus

chr4:168,863,770-169,010,275

External References & Databases

Ensembl (ENSG00000145439)

Transcript & Mutation Effects

hg38 • Region Span ~146.5 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 CBR4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 37

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032783.5. 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						0
missense			37 clinvar	2 clinvar		39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	39	2	0	41

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032783.5	RefSeq	NP_116172.2	5	MANE Select
ENST00000306193.8	Ensembl	ENSP00000303525.3	5	MANE Select
ENST00000504480.5	Ensembl	ENSP00000427615.1	4	Standard
ENST00000504480.6	Ensembl	ENSP00000427615.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Fatty acyl-CoA biosynthesis
Metabolism
Fatty acid metabolism

Biological Process

fatty acid biosynthetic process
daunorubicin metabolic process
doxorubicin metabolic process
protein homotetramerization
protein heterotetramerization

Molecular Function

NAD(P)H dehydrogenase (quinone) activity
protein binding
NADPH dehydrogenase (quinone) activity
3-oxoacyl-[acyl-carrier-protein] reductase (NADH) activity
quinone binding

Cellular Component

mitochondrial matrix
oxidoreductase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306193
Coding exons: 5
Length: 146506
Individuals with no LoFs: 125613
Homozygous LoFs: 0
Heterozygous LoFs: 134
Defined: 125747
p: 0.000533

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0768	120	122	0.980	0.00000575	1515
Missense (PolyPhen)		35	37.688	0.92868		471
Synonymous	0.145	44	45.2	0.973	0.00000220	475
Loss of Function	0.0477	8	8.15	0.982	3.60e-7	119

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.0036	0.0036	notable
European (Non-Finnish)	0.00030	0.00028	rare
South Asian	0.000065	0.000065	rare
Other	0.0018	0.0016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: The heterotetramer with HSD17B8 has NADH-dependent 3- ketoacyl-acyl carrier protein reductase activity, and thereby plays a role in mitochondrial fatty acid biosynthesis (PubMed:19571038, PubMed:25203508). Within the heterotetramer, HSD17B8 binds NADH; CBR4 binds NADPD (PubMed:25203508). The homotetramer has NADPH-dependent quinone reductase activity (PubMed:19000905). Both homotetramer and the heterotetramer have broad substrate specificity and can reduce 9,10- phenanthrenequinone, 1,4-benzoquinone and various other o-quinones and p-quinones (in vitro) (PubMed:19000905, PubMed:19571038, PubMed:25203508). {ECO:0000269|PubMed:19000905, ECO:0000269|PubMed:19571038, ECO:0000269|PubMed:25203508}.;

Intolerance Scores

LoFtool: 0.485
RVIS EVS: 0.31
RVIS percentile EVS: 72.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.145

Gene Damage Prediction

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