LDHA
protein-codinglactate dehydrogenase A
Gene summary
This gene encodes the A subunit of lactate dehydrogenase enzyme which catalyzes the reversible conversion of pyruvate to lactate with the concomitant oxidation of NADH to NAD in anaerobic glycolysis. The protein is found predominantly in skeletal muscle and belongs to the lactate dehydrogenase family. Mutations in this gene have been linked to exertional myoglobinuria. The human genome contains several non-transcribed pseudogenes of this gene. [provided by RefSeq, Sep 2023]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013047
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0013047
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013047
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0013047
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Dermatologic; Musculoskeletal; Renal
Intervention: Biochemical; Musculoskeletal; Renal
Rationale: Individuals can have exertional myoglobinuria, and renal failure has been reported, such that precautions (eg, involving exercise) may be beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LDHA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005566.4. 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 | 4 | 40 | 1 | 45 | ||
| missense | 1 | 82 | 3 | 1 | 87 | |
| nonsense | 3 | 1 | 4 | |||
| start loss | 0 | |||||
| frameshift | 3 | 3 | 2 | 8 | ||
| splice donor/acceptor (+/-2bp) | 3 | 3 | 6 | |||
| Total | 6 | 7 | 92 | 43 | 2 | 150 |
Highest pathogenic variant AF is 0.000047751404
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005557.1 | 7 | MANE Select | |
| Ensembl | ENSP00000395337.3 | 7 | MANE Select | |
| RefSeq | NP_001128711.1 | 6 | Standard | |
| RefSeq | NP_001158886.1 | 8 | 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)
- Central carbon metabolism in cancer - Homo sapiens (human)
- HIF-1 signaling pathway - Homo sapiens (human)
- Propanoate metabolism - Homo sapiens (human)
Biological Process
- response to hypoxia
- lactate metabolic process
- pyruvate metabolic process
- glycolytic process
- response to nutrient
Molecular Function
- L-lactate dehydrogenase activity
- protein binding
- kinase binding
- identical protein binding
- cadherin binding
Cellular Component
- nucleus
- cytosol
- membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000540430
- Coding exons
- 8
- Length
- 14038
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125748
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.58 | 133 | 195 | 0.681 | 0.0000103 | 2376 |
| Missense (PolyPhen) | 42 | 69.634 | 0.60315 | 896 | ||
| Synonymous | 0.669 | 59 | 65.9 | 0.895 | 0.00000332 | 697 |
| Loss of Function | 2.65 | 5 | 16.7 | 0.300 | 7.92e-7 | 210 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00035 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Disease
- DISEASE: Glycogen storage disease 11 (GSD11) [MIM:612933]: A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue. {ECO:0000269|PubMed:2334430}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.854
Intolerance Scores
- LoFtool
- 0.100
- RVIS EVS
- -0.4
- RVIS percentile EVS
- 26.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.986
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |