BDH2
protein-coding3-hydroxybutyrate dehydrogenase 2, the group of Short chain dehydrogenase/reductase superfamily
Gene summary
Enables 3-hydroxybutyrate dehydrogenase activity and NAD binding activity. Involved in epithelial cell differentiation and fatty acid beta-oxidation. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]
- DHRS6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.3 kbGenCC 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 BDH2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020139.4. 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 | 1 | 2 | |||
| missense | 37 | 1 | 38 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 42 | 0 | 2 | 44 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_064524.3 | 9 | MANE Select | |
| Ensembl | ENSP00000296424.4 | 9 | MANE Select | |
| Ensembl | ENSP00000427442.1 | 5 | Standard | |
| Ensembl | ENSP00000424173.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| bdh2 | Danio rerio | Structure: nucleate erythrocyte Quality: decreased occurrence abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Butanoate metabolism - Homo sapiens (human)
- Synthesis and degradation of ketone bodies - Homo sapiens (human)
- ketogenesis
- ketolysis
- Metabolism of lipids
Biological Process
- fatty acid beta-oxidation
- siderophore biosynthetic process
- epithelial cell differentiation
- heme metabolic process
- ketone body biosynthetic process
Molecular Function
- 3-hydroxybutyrate dehydrogenase activity
- oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor
- NAD binding
Cellular Component
- cytoplasm
- mitochondrion
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296424
- Coding exons
- 9
- Length
- 20449
- Individuals with no LoFs
- 125601
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 146
- Defined
- 125748
- p
- 0.000585
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.496 | 121 | 137 | 0.881 | 0.00000724 | 1604 |
| Missense (PolyPhen) | 59 | 57.587 | 1.0245 | 677 | ||
| Synonymous | 1.60 | 33 | 46.9 | 0.703 | 0.00000260 | 459 |
| Loss of Function | 0.525 | 12 | 14.1 | 0.849 | 6.65e-7 | 167 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00054 | 0.00054 | rare |
| Finnish | 0.0031 | 0.0030 | notable |
| European (Non-Finnish) | 0.00029 | 0.00028 | rare |
| South Asian | 0.00082 | 0.00082 | rare |
| Other | 0.00099 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Dehydrogenase that mediates the formation of 2,5- dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin and associates with LCN2, thereby playing a key role in iron homeostasis and transport. Also acts as a 3-hydroxybutyrate dehydrogenase (By similarity). {ECO:0000250, ECO:0000269|PubMed:16380372}.;
Recessive Scores
- pRec
- 0.136
Intolerance Scores
- LoFtool
- 0.873
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 68.13
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.978
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |