BDH1

protein-coding

3-hydroxybutyrate dehydrogenase 1, the group of Short chain dehydrogenase/reductase superfamily

Gene summary

This gene encodes a member of the short-chain dehydrogenase/reductase gene family. The encoded protein forms a homotetrameric lipid-requiring enzyme of the mitochondrial membrane and has a specific requirement for phosphatidylcholine for optimal enzymatic activity. The encoded protein catalyzes the interconversion of acetoacetate and (R)-3-hydroxybutyrate, the two major ketone bodies produced during fatty acid catabolism. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_203314.3

Inheritance

ClinVar variants

U:58B:11

Top phenotype

BDH1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr3:197,509,783-197,573,323

External References & Databases

Ensembl (ENSG00000161267)

Transcript & Mutation Effects

hg38 • Region Span ~63.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BDH1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 57

BDH1-related disorderTotal: 8

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_203314.3. 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		2 clinvar	3
missense			56 clinvar	5 clinvar	4 clinvar	65
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	58	5	6	69

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 78 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_203314.3	RefSeq	NP_976059.1	6	MANE Select
ENST00000392379.6	Ensembl	ENSP00000376184.1	6	MANE Select
NM_004051.5	RefSeq	NP_004042.1	6	Standard
NM_203315.3	RefSeq	NP_976060.1	6	Standard

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)
Succinyl CoA: 3-ketoacid CoA transferase deficiency
Ketone Body Metabolism
Synthesis and Degradation of Ketone Bodies

Biological Process

ketone body biosynthetic process
ketone body catabolic process
oxidation-reduction process

Molecular Function

3-hydroxybutyrate dehydrogenase activity

Cellular Component

nucleoplasm
mitochondrion
mitochondrial matrix
matrix side of mitochondrial inner membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392379
Coding exons: 6
Length: 63541
Individuals with no LoFs: 125648
Homozygous LoFs: 0
Heterozygous LoFs: 100
Defined: 125748
p: 0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.413	212	230	0.923	0.0000149	2228
Missense (PolyPhen)		71	88.358	0.80355		887
Synonymous	-0.212	97	94.4	1.03	0.00000651	692
Loss of Function	0.488	12	14.0	0.859	7.56e-7	168

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0030	0.0030	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.269

Intolerance Scores

LoFtool: 0.134
RVIS EVS: 0.42
RVIS percentile EVS: 77.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.955

Gene Damage Prediction

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