LDHA

lactate dehydrogenase A

Basic information

Region (hg38): 11:18394560-18408425

Links

ENSG00000134333 ∙ NCBI:3939 ∙ OMIM:150000 ∙ HGNC:6535 ∙ Uniprot:P00338 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease XI	AR	Biochemical; Musculoskeletal; Renal	Individuals can have exertional myoglobinuria, and renal failure has been reported, such that precautions (eg, involving exercise) may be beneficial	Biochemical; Dermatologic; Musculoskeletal; Renal	7449146; 3092644; 3383424; 2334430; 1959923; 1999544

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LDHA gene.

• Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LDHA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	25	4	32
missense		1	51	1	1	54
nonsense	2					2
start loss						0
frameshift	1		2			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			5	4		9
non coding			23	29	27	79
Total	3	2	80	55	32

Variants in LDHA

This is a list of pathogenic ClinVar variants found in the LDHA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-18394597-T-C		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Jan 12, 2018)
11-18394766-A-C			Benign (Jul 02, 2019)
11-18396036-G-A			Benign (Jul 07, 2018)
11-18396179-A-T			Likely benign (Jun 21, 2019)
11-18396211-G-T			Likely benign (Jun 21, 2019)
11-18396556-A-AC			Uncertain significance (Sep 16, 2018)
11-18396809-C-G		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency • LDHA-related disorder	Likely benign (Dec 02, 2021)
11-18396849-A-G		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Sep 11, 2023)
11-18396850-C-T		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Nov 09, 2023)
11-18396872-T-C		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Apr 28, 2017)
11-18396881-A-C		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Likely benign (Mar 02, 2023)
11-18396889-A-G		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Jan 13, 2018)
11-18396894-A-G		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency • Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
11-18396895-C-G		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Aug 16, 2022)
11-18396895-C-T		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Feb 28, 2022)
11-18396899-C-G		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Likely benign (May 28, 2022)
11-18396899-C-T		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Conflicting classifications of pathogenicity (Dec 22, 2023)
11-18396925-T-C		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Dec 07, 2023)
11-18396959-C-G		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Dec 10, 2021)
11-18396963-A-G		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Apr 18, 2023)
11-18396968-G-A		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Jul 12, 2022)
11-18396968-GGTAA-G		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Uncertain significance (Jan 29, 2024)
11-18396970-T-C		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Likely pathogenic (Jun 03, 2022)
11-18396985-C-T		Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Likely benign (Aug 17, 2023)
11-18397138-A-G			Likely benign (Sep 22, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LDHA	protein_coding	protein_coding	ENST00000540430	8	14038

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0692	0.928	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.58	133	195	0.681	0.0000103	2376
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000412	0.000412
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000795	0.0000791
Middle Eastern	0.000109	0.000109
South Asian	0.000261	0.000261
Other	0.000348	0.000326

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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);Cysteine and methionine metabolism - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Glutaminolysis and Cancer;Cori Cycle;HIF1A and PPARG regulation of glycolysis;Photodynamic therapy-induced HIF-1 survival signaling;fig-met-1-last-solution;Amino Acid metabolism;Pathways in clear cell renal cell carcinoma;PI3K-AKT-mTOR - VitD3 Signalling;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Glycolysis and Gluconeogenesis;hypoxia-inducible factor in the cardivascular system;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;Glycolysis Gluconeogenesis;lactate fermentation (reoxidation of cytosolic NADH);The citric acid (TCA) cycle and respiratory electron transport;TCR;Metabolism;Methionine Cysteine metabolism;Propanoate metabolism;EGFR1;Pyruvate metabolism;Validated targets of C-MYC transcriptional activation;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

• pRec: 0.854

Intolerance Scores

• loftool: 0.100
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.53

Haploinsufficiency Scores

• pHI: 0.430
• hipred: Y
• hipred_score: 0.604
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ldha
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; immune system phenotype; respiratory system phenotype; liver/biliary system phenotype; neoplasm

Gene ontology

• Biological process: response to hypoxia;lactate metabolic process;pyruvate metabolic process;glycolytic process;response to nutrient;response to glucose;NAD metabolic process;response to hydrogen peroxide;positive regulation of apoptotic process;response to estrogen;post-embryonic animal organ development;response to cAMP;oxidation-reduction process
• Cellular component: nucleus;cytosol;membrane;extracellular exosome
• Molecular function: L-lactate dehydrogenase activity;protein binding;kinase binding;identical protein binding;cadherin binding;NAD binding