Myoglobinuria, acute recurrent, autosomal recessive

Summary

Myoglobinuria, acute recurrent, autosomal recessive (MONDO:0009992) is a disease caused by LPIN1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: LPIN1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 289

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myoglobinuria, acute recurrent, autosomal recessive
Mondo ID	MONDO:0009992
MeSH	C564832
OMIM	268200
UMLS	C1849386
MedGen	340308
GARD	0018251
Is cancer (heuristic)	no

Also known as: myoglobinuria, acute recurrent, autosomal recessive

Data availability: 289 ClinVar variants · 5 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 › hereditary recurrent myoglobinuria › myoglobinuria, acute recurrent, autosomal recessive

Related subtypes (1): myoglobinuria, recurrent

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

289 retrieved; paginated sample, class counts are floors:

175 uncertain significance, 35 conflicting classifications of pathogenicity, 24 benign, 19 likely benign, 13 likely pathogenic, 11 pathogenic, 7 pathogenic/likely pathogenic, 5 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3006629	NM_001349206.2(LPIN1):c.835del (p.Ser279fs)	LOC126806147	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
807626	NM_001349206.2(LPIN1):c.942del (p.Pro315fs)	LOC126806147	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1050803	NM_001349206.2(LPIN1):c.1276C>T (p.Arg426Ter)	LPIN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1205474	NM_001349206.2(LPIN1):c.181C>T (p.Arg61Ter)	LPIN1	Pathogenic	criteria provided, multiple submitters, no conflicts
1323246	NM_001349206.2(LPIN1):c.1564C>T (p.Gln522Ter)	LPIN1	Pathogenic	criteria provided, single submitter
1465375	NM_001349206.2(LPIN1):c.1807-2A>G	LPIN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2444342	NM_001349206.2(LPIN1):c.1029del (p.Gln344fs)	LPIN1	Pathogenic	criteria provided, multiple submitters, no conflicts
280315	NM_001349206.2(LPIN1):c.1363_1364dup (p.Asp455fs)	LPIN1	Pathogenic	criteria provided, multiple submitters, no conflicts
3584334	NM_001349206.2(LPIN1):c.1807-1G>A	LPIN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3584358	NM_001349206.2(LPIN1):c.2621+1G>A	LPIN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3775683	NM_001349206.2(LPIN1):c.288+2dup	LPIN1	Pathogenic	criteria provided, single submitter
4080003	NM_001349206.2(LPIN1):c.221_222del (p.Val74fs)	LPIN1	Pathogenic	criteria provided, single submitter
4910	NM_001349206.2(LPIN1):c.643G>T (p.Glu215Ter)	LPIN1	Pathogenic	no assertion criteria provided
4911	NM_001349206.2(LPIN1):c.1270C>T (p.Arg424Ter)	LPIN1	Pathogenic	criteria provided, multiple submitters, no conflicts
4912	NM_001349206.2(LPIN1):c.2509C>T (p.Arg837Ter)	LPIN1	Pathogenic	criteria provided, single submitter
4913	NM_145693.2(LPIN1):c.2295-?_2513+?del	LPIN1	Pathogenic	no assertion criteria provided
4914	NM_001349206.2(LPIN1):c.1549+2T>C	LPIN1	Pathogenic	no assertion criteria provided
666366	NM_001349206.2(LPIN1):c.2057_2075dup (p.Gly693fs)	LPIN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1349474	NM_001349206.2(LPIN1):c.1887-1G>C	LPIN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3338439	GRCh37/hg19 2p25.1(chr2:11959558-11959775)x0	LPIN1	Likely pathogenic	no assertion criteria provided
3584302	NM_001349206.2(LPIN1):c.288G>A (p.Gln96=)	LPIN1	Likely pathogenic	criteria provided, single submitter
3584304	NM_001349206.2(LPIN1):c.472del (p.Arg158fs)	LPIN1	Likely pathogenic	criteria provided, single submitter
3584307	NM_001349206.2(LPIN1):c.704_705del (p.Glu235fs)	LPIN1	Likely pathogenic	criteria provided, single submitter
3584310	NM_001349206.2(LPIN1):c.957G>T (p.Lys319Asn)	LPIN1	Likely pathogenic	criteria provided, single submitter
3584331	NM_145693.4(LPIN1):c.1532_1535del	LPIN1	Likely pathogenic	criteria provided, single submitter
3584345	NM_001349206.2(LPIN1):c.2201_2204del (p.Lys734fs)	LPIN1	Likely pathogenic	criteria provided, single submitter
3584347	NM_001349206.2(LPIN1):c.2241dup (p.Val748fs)	LPIN1	Likely pathogenic	criteria provided, single submitter
3584356	NM_001349206.2(LPIN1):c.2518G>A (p.Asp840Asn)	LPIN1	Likely pathogenic	criteria provided, single submitter
3779819	NM_001349206.2(LPIN1):c.193-2A>T	LPIN1	Likely pathogenic	criteria provided, single submitter
3779820	NM_001349206.2(LPIN1):c.625del (p.Gln209fs)	LPIN1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
LPIN1	Definitive	Autosomal recessive	myoglobinuria, acute recurrent, autosomal recessive	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LPIN1	Orphanet:99845	Genetic recurrent myoglobinuria

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
LPIN1	HGNC:13345	ENSG00000134324	Q14693	Phosphatidate phosphatase LPIN1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LPIN1	Phosphatidate phosphatase LPIN1	Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis and therefore controls…

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)
LPIN1	Enzyme (other)	yes	3.1.3.4	Lipin_N, LNS2, LIPIN

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
lower esophagus mucosa	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LPIN1	297	ubiquitous	marker	sperm, male germ cell, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LPIN1	1,992

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LPIN1	Q14693	60.88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. 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
Synthesis of PE	1	878.5×	0.007	LPIN1
Depolymerization of the Nuclear Lamina	1	761.3×	0.007	LPIN1
Triglyceride biosynthesis	1	671.8×	0.007	LPIN1
Triglyceride metabolism	1	671.8×	0.007	LPIN1
Nuclear Envelope Breakdown	1	456.8×	0.007	LPIN1
Synthesis of PC	1	407.9×	0.007	LPIN1
Mitotic Prophase	1	368.4×	0.007	LPIN1
Glycerophospholipid biosynthesis	1	335.9×	0.007	LPIN1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	215.5×	0.009	LPIN1
Phospholipid metabolism	1	200.3×	0.009	LPIN1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	196.9×	0.009	LPIN1
Epigenetic regulation by WDR5-containing histone modifying complexes	1	154.3×	0.011	LPIN1
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	82.8×	0.019	LPIN1
Epigenetic regulation of gene expression	1	71.4×	0.020	LPIN1
M Phase	1	66.0×	0.020	LPIN1
Cell Cycle, Mitotic	1	48.2×	0.026	LPIN1
Cell Cycle	1	36.0×	0.033	LPIN1
Metabolism of lipids	1	31.6×	0.035	LPIN1
Gene expression (Transcription)	1	17.8×	0.059	LPIN1
Metabolism	1	11.6×	0.086	LPIN1

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
negative regulation of phosphatidic acid biosynthetic process	1	16852.0×	7e-04	LPIN1
triglyceride mobilization	1	4213.0×	0.001	LPIN1
phosphatidylethanolamine metabolic process	1	3370.4×	0.001	LPIN1
phosphatidic acid metabolic process	1	2808.7×	0.001	LPIN1
mitotic nuclear membrane disassembly	1	1872.4×	0.001	LPIN1
negative regulation of myelination	1	1872.4×	0.001	LPIN1
fatty acid catabolic process	1	1296.3×	0.001	LPIN1
triglyceride biosynthetic process	1	732.7×	0.002	LPIN1
animal organ regeneration	1	601.9×	0.002	LPIN1
cellular response to insulin stimulus	1	170.2×	0.007	LPIN1
positive regulation of cold-induced thermogenesis	1	163.6×	0.007	LPIN1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	LPIN1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LPIN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LPIN1	3.1.3.4	phosphatidate phosphatase

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

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	LPIN1
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LPIN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.