LDHB

protein-coding

lactate dehydrogenase B

Gene summary

This gene encodes the B subunit of lactate dehydrogenase enzyme, which catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD+ in a post-glycolysis process. Alternatively spliced transcript variants have been found for this gene. Recent studies have shown that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is localized in the peroxisomes. Mutations in this gene are associated with lactate dehydrogenase B deficiency. Pseudogenes have been identified on chromosomes X, 5 and 13. [provided by RefSeq, Feb 2016]

MANE transcript

NM_002300.8

Inheritance

AR, AD

ClinVar variants

U:43B:5

Top phenotype

Lactate dehydrogenase B deficiency

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr12:21,635,342-21,757,857

External References & Databases

Ensembl (ENSG00000111716)

Transcript & Mutation Effects

hg38 • Region Span ~122.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

glycogen storage disease due to lactate dehydrogenase H-subunit deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013587

Submitter: PanelApp Australia

glycogen storage disease due to lactate dehydrogenase H-subunit deficiencySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0013587

Submitter: Orphanet

Clinical Genomic Database (CGD)

Lactate dehydrogenase B deficiencyAR

Manifestation: Biochemical

Intervention: General

Rationale: The clinical significance is unclear

Refs: 5119336; 6383647; 2334429; 70259; 10509905; 11509017

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LDHB variants in ClinVar

4 Conditions Cataloged

Glycogen storage disease due to lactate dehydrogenase H-subunit deficiencyTotal: 26

not specifiedTotal: 22

not providedTotal: 5

LDHB-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002300.8. 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			5 clinvar	1 clinvar	2 clinvar	8
missense			36 clinvar	1 clinvar		37
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar		1 clinvar	3
Total	0	0	43	2	3	48

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002300.8	RefSeq	NP_002291.1	7	MANE Select
ENST00000350669.5	Ensembl	ENSP00000229319.1	7	MANE Select
NM_001174097.3	RefSeq	NP_001167568.1	7	Standard
NM_001315537.2	RefSeq	NP_001302466.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyruvate metabolism - Homo sapiens (human)
Glycolysis / Gluconeogenesis - Homo sapiens (human)
Propanoate metabolism - Homo sapiens (human)
Cysteine and methionine metabolism - Homo sapiens (human)
Glucagon signaling pathway - Homo sapiens (human)

Biological Process

carbohydrate metabolic process
pyruvate metabolic process
oxidation-reduction process

Molecular Function

L-lactate dehydrogenase activity
protein binding
identical protein binding

Cellular Component

cytoplasm
cytosol
membrane
membrane raft
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396076
Coding exons: 7
Length: 122516
Individuals with no LoFs: 123796
Homozygous LoFs: 72
Heterozygous LoFs: 1880
Defined: 125748
p: 0.00779

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.913	149	184	0.811	0.00000949	2204
Missense (PolyPhen)		19	43.358	0.43822		647
Synonymous	0.783	58	66.1	0.877	0.00000356	641
Loss of Function	1.01	10	14.1	0.710	5.94e-7	185

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00092	0.00092	rare
Latino/Admixed American	0.052	0.052	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0069	0.0069	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00062	0.00062	rare
Other	0.0070	0.0069	notable

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Lactate dehydrogenase B deficiency (LDHBD) [MIM:614128]: A condition with no deleterious effects on health. LDHBD is of interest to laboratory medicine mainly because it can cause misdiagnosis in those disorders in which elevation of serum LDH is expected. {ECO:0000269|PubMed:10211631, ECO:0000269|PubMed:11509017, ECO:0000269|PubMed:1587525, ECO:0000269|PubMed:2334429, ECO:0000269|PubMed:8314553, ECO:0000269|PubMed:8462975, ECO:0000269|PubMed:8611651, ECO:0000269|PubMed:9929983, ECO:0000269|Ref.20}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.851

Intolerance Scores

LoFtool: 0.331
RVIS EVS: -0.25
RVIS percentile EVS: 35.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.993

Gene Damage Prediction

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