glycogen storage disease due to lactate dehydrogenase H-subunit deficiency

Summary

glycogen storage disease due to lactate dehydrogenase H-subunit deficiency (MONDO:0013587) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease due to lactate dehydrogenase H-subunit deficiency
Mondo ID	MONDO:0013587
MeSH	C563641
OMIM	614128
Orphanet	284435
UMLS	C3279904
MedGen	481534
GARD	0003161
Is cancer (heuristic)	no

Also known as: glycogenosis due to lactate dehydrogenase H-subunit deficiency · GSD due to lactate dehydrogenase H-subunit deficiency · lactate dehydrogenase B deficiency · lactate dehydrogenase deficiency type B · lactate dehydrogenase-B deficiency · LDH deficiency B · LDH-H subunit deficiency · LDHBD

Data availability: 31 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorder of glycogen metabolism › glycogen storage disease due to lactate dehydrogenase deficiency › glycogen storage disease due to lactate dehydrogenase H-subunit deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

31 retrieved; paginated sample, class counts are floors:

21 uncertain significance, 4 affects, 4 benign, 1 likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
882520	NM_002300.8(LDHB):c.130-8G>A	LDHB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14562	NM_002300.8(LDHB):c.515G>A (p.Arg172His)	LDHB	Affects	no assertion criteria provided
14563	NM_002300.8(LDHB):c.385A>C (p.Ser129Arg)	LDHB	Affects	no assertion criteria provided
14564	NM_002300.8(LDHB):c.19A>G (p.Lys7Glu)	LDHB	Affects	no assertion criteria provided
14565	NM_002300.8(LDHB):c.973T>C (p.Trp325Arg)	LDHB	Affects	no assertion criteria provided
308014	NM_002300.8(LDHB):c.*73T>C	LDHB	Uncertain significance	criteria provided, single submitter
308016	NM_002300.8(LDHB):c.749A>G (p.Asn250Ser)	LDHB	Uncertain significance	criteria provided, multiple submitters, no conflicts
308017	NM_002300.8(LDHB):c.727A>G (p.Ile243Val)	LDHB	Uncertain significance	criteria provided, single submitter
308018	NM_002300.8(LDHB):c.719A>G (p.Tyr240Cys)	LDHB	Uncertain significance	criteria provided, single submitter
308020	NM_002300.8(LDHB):c.621G>T (p.Val207=)	LDHB	Uncertain significance	criteria provided, single submitter
308021	NM_002300.8(LDHB):c.585C>T (p.Gly195=)	LDHB	Uncertain significance	criteria provided, single submitter
308022	NM_002300.8(LDHB):c.528T>A (p.Ala176=)	LDHB	Uncertain significance	criteria provided, single submitter
308024	NM_002300.8(LDHB):c.422-10A>G	LDHB	Uncertain significance	criteria provided, single submitter
308025	NM_002300.8(LDHB):c.421+7T>C	LDHB	Uncertain significance	criteria provided, single submitter
308026	NM_002300.8(LDHB):c.375C>T (p.Ile125=)	LDHB	Uncertain significance	criteria provided, single submitter
308028	NM_002300.8(LDHB):c.129+11A>G	LDHB	Uncertain significance	criteria provided, single submitter
3777092	NM_002300.8(LDHB):c.837+45A>G	LDHB	Uncertain significance	criteria provided, single submitter
880881	NM_002300.8(LDHB):c.826A>G (p.Thr276Ala)	LDHB	Uncertain significance	criteria provided, single submitter
880882	NM_002300.8(LDHB):c.782T>C (p.Ile261Thr)	LDHB	Uncertain significance	criteria provided, multiple submitters, no conflicts
880883	NM_002300.8(LDHB):c.767G>A (p.Ser256Asn)	LDHB	Uncertain significance	criteria provided, multiple submitters, no conflicts
882255	NM_002300.8(LDHB):c.523A>G (p.Met175Val)	LDHB	Uncertain significance	criteria provided, single submitter
882518	NM_002300.8(LDHB):c.210C>A (p.Ser70Arg)	LDHB	Uncertain significance	criteria provided, single submitter
882519	NM_002300.8(LDHB):c.178A>G (p.Lys60Glu)	LDHB	Uncertain significance	criteria provided, single submitter
882521	NM_002300.8(LDHB):c.-34A>G	LDHB	Uncertain significance	criteria provided, single submitter
883306	NM_002300.8(LDHB):c.-71C>G	LDHB	Uncertain significance	criteria provided, single submitter
884169	NM_002300.8(LDHB):c.843G>A (p.Met281Ile)	LDHB	Uncertain significance	criteria provided, single submitter
308015	NM_002300.8(LDHB):c.879A>G (p.Pro293=)	LDHB	Benign	criteria provided, multiple submitters, no conflicts
308019	NM_002300.8(LDHB):c.713+15A>G	LDHB	Benign	criteria provided, multiple submitters, no conflicts
308023	NM_002300.8(LDHB):c.472C>T (p.Arg158Cys)	LDHB	Likely benign	criteria provided, single submitter
308029	NM_002300.8(LDHB):c.-81G>C	LDHB	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
LDHB	Supportive	Autosomal dominant	glycogen storage disease due to lactate dehydrogenase H-subunit deficiency	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LDHB	Orphanet:284435	Glycogen storage disease due to lactate dehydrogenase H-subunit deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LDHB	HGNC:6541	ENSG00000111716	P07195	L-lactate dehydrogenase B chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LDHB	L-lactate dehydrogenase B chain	Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LDHB	Enzyme (other)	yes	1.1.1.27	Lactate/malate_DH_N, L-lactate/malate_DH, L-lactate_DH

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
heart right ventricle	1
lateral globus pallidus	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LDHB	293	ubiquitous	marker	renal medulla, heart right ventricle, lateral globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LDHB	734

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LDHB	P07195	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Pyruvate metabolism	1	407.9×	0.007	LDHB
Aerobic respiration and respiratory electron transport	1	88.5×	0.017	LDHB
Metabolism	1	11.6×	0.086	LDHB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pyruvate catabolic process	1	2106.5×	5e-04	LDHB
lactate metabolic process	1	1872.4×	5e-04	LDHB
NAD+ metabolic process	1	1872.4×	5e-04	LDHB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LDHB	2	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GOSSYPOL	3	LDHB
MOLIBRESIB	2	LDHB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
LDHB	77	Binding:73, ADMET:3, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LDHB	1.1.1.27	L-lactate dehydrogenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
GOSSYPOL	3	LDHB
MOLIBRESIB	2	LDHB

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	LDHB
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.