Histiocytoid cardiomyopathy

Summary

Histiocytoid cardiomyopathy (MONDO:0010771) is a disease with 5 cohort genes and 3 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 5
• ClinVar variants: 5
• Phenotypes (HPO): 44
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

44 HPO clinical features (Orphanet curated; top 44 by frequency):

HPO ID	Term	Frequency
HP:0001649	Tachycardia	Very frequent (80-99%)
HP:0004755	Supraventricular tachycardia	Frequent (30-79%)
HP:0004756	Ventricular tachycardia	Frequent (30-79%)
HP:0000961	Cyanosis	Occasional (5-29%)
HP:0000980	Pallor	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001635	Congestive heart failure	Occasional (5-29%)
HP:0001640	Cardiomegaly	Occasional (5-29%)
HP:0001678	Atrioventricular block	Occasional (5-29%)
HP:0001716	Wolff-Parkinson-White syndrome	Occasional (5-29%)
HP:0001945	Fever	Occasional (5-29%)
HP:0002013	Vomiting	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0002329	Drowsiness	Occasional (5-29%)
HP:0002401	Stroke-like episode	Occasional (5-29%)
HP:0002789	Tachypnea	Occasional (5-29%)
HP:0003546	Exercise intolerance	Occasional (5-29%)
HP:0011712	Right bundle branch block	Occasional (5-29%)
HP:0011716	Junctional ectopic tachycardia	Occasional (5-29%)
HP:0012735	Cough	Occasional (5-29%)
HP:0000107	Renal cyst	Very rare (<1-4%)
HP:0000147	Polycystic ovaries	Very rare (<1-4%)
HP:0000175	Cleft palate	Very rare (<1-4%)
HP:0000238	Hydrocephalus	Very rare (<1-4%)
HP:0000485	Megalocornea	Very rare (<1-4%)
HP:0000568	Microphthalmia	Very rare (<1-4%)
HP:0000648	Optic atrophy	Very rare (<1-4%)
HP:0001250	Seizure	Very rare (<1-4%)
HP:0001254	Lethargy	Very rare (<1-4%)
HP:0001274	Agenesis of corpus callosum	Very rare (<1-4%)
HP:0001629	Ventricular septal defect	Very rare (<1-4%)
HP:0001907	Thromboembolism	Very rare (<1-4%)
HP:0001943	Hypoglycemia	Very rare (<1-4%)
HP:0002301	Hemiplegia	Very rare (<1-4%)
HP:0002438	Cerebellar malformation	Very rare (<1-4%)
HP:0003128	Lactic acidosis	Very rare (<1-4%)
HP:0004749	Atrial flutter	Very rare (<1-4%)
HP:0005110	Atrial fibrillation	Very rare (<1-4%)
HP:0005165	Shortened PR interval	Very rare (<1-4%)
HP:0005950	Laryngeal web	Very rare (<1-4%)
HP:0007185	Loss of consciousness	Very rare (<1-4%)
HP:0007707	Congenital aphakia	Very rare (<1-4%)
HP:0007957	Corneal opacity	Very rare (<1-4%)
HP:0100598	Pulmonary edema	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	histiocytoid cardiomyopathy
Mondo ID	MONDO:0010771
MeSH	C535584
OMIM	500000
Orphanet	137675
DOID	DOID:0080198
ICD-11	1870618141
NCIT	C45745
UMLS	C1708371
MedGen	310844
GARD	0009511
Is cancer (heuristic)	no

Also known as: Arachnocytosis of the myocardium · congenital cardiomyopathy · foamy myocardial transformation of infancy · focal lipid cardiomyopathy · histiocytoid cardiomyopathy · infantile cardiomyopathy with histiocytoid change · infantile histiocytoid cardiomyopathy · infantile xanthomatous cardiomyopathy · isolated Cardiac lipidosis · myocardial hamartoma · oncocytic cardiomyopathy · Purkinje cell hamartoma

Data availability: 5 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › histiocytoid cardiomyopathy

Related subtypes (13): oxoglutaricaciduria, multiple acyl-CoA dehydrogenase deficiency, inborn mitochondrial myopathy, HSD10 mitochondrial disease, hypotonia-cystinuria syndrome, fumaric aciduria, 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, mitochondrial pyruvate carrier deficiency, mitochondrial oxidative phosphorylation disorder, mitochondrial membrane transport disorder, inherited lipoic acid biosynthesis defect, pyruvate dehydrogenase deficiency, OPA1-related optic atrophy with or without extraocular features

Subtypes (1): cardiac lipidosis, familial

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

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 likely benign, 1 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
9589	NC_012920.1(MT-TL1):m.3243A>G	MT-TL1	Pathogenic	reviewed by expert panel
190302	NM_001135998.3(NDUFB11):c.262C>T (p.Arg88Ter)	NDUFB11	Pathogenic	criteria provided, multiple submitters, no conflicts
9640	NC_012920.1(MT-ATP8):m.8528T>C	MT-ATP6	Likely pathogenic	reviewed by expert panel
9684	NC_012920.1(MT-CYB):m.15498G>A	MT-CYB	Uncertain significance	criteria provided, single submitter
254142	NM_001162529.3(FAM135A):c.474C>G (p.Tyr158Ter)	FAM135A	Likely benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 18 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDUFB11	Orphanet:2556	Microphthalmia with linear skin defects syndrome
NDUFB11	Orphanet:2609	Isolated complex I deficiency
MT-ATP6	Orphanet:104	Leber hereditary optic neuropathy
MT-ATP6	Orphanet:225154	Familial infantile bilateral striatal necrosis
MT-ATP6	Orphanet:254913	Isolated ATP synthase deficiency
MT-ATP6	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ATP6	Orphanet:320360	MT-ATP6-related mitochondrial spastic paraplegia
MT-ATP6	Orphanet:397750	Periodic paralysis with later-onset distal motor neuropathy
MT-ATP6	Orphanet:644	NARP syndrome
MT-CYB	Orphanet:104	Leber hereditary optic neuropathy
MT-CYB	Orphanet:137675	Histiocytoid cardiomyopathy
MT-CYB	Orphanet:1460	Isolated complex III deficiency
MT-TL1	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-TL1	Orphanet:324525	Hypertrophic cardiomyopathy with kidney anomalies due to mitochondrial DNA mutation
MT-TL1	Orphanet:480	Kearns-Sayre syndrome
MT-TL1	Orphanet:550	MELAS
MT-TL1	Orphanet:551	MERRF
MT-TL1	Orphanet:663	Mitochondrial DNA-related progressive external ophthalmoplegia

Cohort genes → proteins

5 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NDUFB11	HGNC:20372	ENSG00000147123	Q9NX14	NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial	clinvar
FAM135A	HGNC:21084	ENSG00000082269	Q9P2D6	Protein FAM135A	clinvar
MT-ATP6	HGNC:7414	ENSG00000198899	P00846	ATP synthase F(0) complex subunit a	clinvar
MT-CYB	HGNC:7427	ENSG00000198727	P00156	Cytochrome b	clinvar
MT-TL1	HGNC:7490	ENSG00000209082		mitochondrially encoded tRNA-Leu (UUA/G) 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDUFB11	NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial	Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.
MT-ATP6	ATP synthase F(0) complex subunit a	Subunit a, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of th…
MT-CYB	Cytochrome b	Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 5 · Druggable fraction: 0.0

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
Other/Unknown	5	1.8×	0.054

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NDUFB11	Other/Unknown	no		NADH_UbQ_OxRdtase_ESSS_su
FAM135A	Other/Unknown	no		DUF676_lipase-like, DUF3657, AB_hydrolase_fold
MT-ATP6	Other/Unknown	no		ATP_synth_F0_asu, ATP_synth_F0_asu_AS, F0_ATP_A_sf
MT-CYB	Other/Unknown	no		Cyt_b/b6_N, Cyt_b/b6_C, Di-haem_cyt_TM
MT-TL1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

5 cohort genes 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	2
gastrocnemius	1
hindlimb stylopod muscle	1
esophagus squamous epithelium	1
gingiva	1
gingival epithelium	1
descending thoracic aorta	1
left uterine tube	1
mucosa of stomach	1
pituitary gland	1
zone of skin	1
caudate nucleus	1
frontal cortex	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDUFB11	287	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius
FAM135A	265	ubiquitous	marker	esophagus squamous epithelium, gingival epithelium, gingiva
MT-ATP6	134	ubiquitous	marker	mucosa of stomach, left uterine tube, descending thoracic aorta
MT-CYB	134	ubiquitous	marker	apex of heart, pituitary gland, zone of skin
MT-TL1	118	ubiquitous	marker	frontal cortex, right frontal lobe, caudate nucleus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MT-CYB	3,317
MT-ATP6	2,869
NDUFB11	1,844
FAM135A	577
MT-TL1	0

Intra-cohort edges

A	B	Sources
MT-ATP6	MT-CYB	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MT-ATP6	P00846	10
NDUFB11	Q9NX14	7
MT-CYB	P00156	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FAM135A	Q9P2D6	60.24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitochondrial translation termination	2	54.9×	0.003	MT-ATP6, MT-CYB
Respiratory electron transport	2	47.6×	0.003	NDUFB11, MT-CYB
Aerobic respiration and respiratory electron transport	2	44.3×	0.003	NDUFB11, MT-ATP6
Formation of ATP by chemiosmotic coupling	1	142.8×	0.023	MT-ATP6
Complex III assembly	1	109.8×	0.024	MT-CYB
Cristae formation	1	86.5×	0.025	MT-ATP6
RND1 GTPase cycle	1	66.4×	0.028	FAM135A
Mitochondrial biogenesis	1	42.0×	0.035	MT-ATP6
Complex I biogenesis	1	41.4×	0.035	NDUFB11
Mitochondrial protein degradation	1	28.6×	0.045	MT-ATP6
Metabolism	2	5.8×	0.047	NDUFB11, MT-ATP6
Organelle biogenesis and maintenance	1	16.5×	0.064	MT-ATP6
Metabolism of proteins	1	3.1×	0.286	MT-ATP6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to hyperoxia	2	561.7×	9e-05	MT-ATP6, MT-CYB
proton motive force-driven mitochondrial ATP synthesis	2	131.7×	9e-04	NDUFB11, MT-ATP6
response to D-galactosamine	1	4213.0×	0.002	MT-CYB
response to cobalamin	1	2106.5×	0.002	MT-CYB
electron transport coupled proton transport	1	1053.2×	0.004	MT-CYB
response to mercury ion	1	601.9×	0.006	MT-CYB
response to glucagon	1	421.3×	0.007	MT-CYB
response to copper ion	1	383.0×	0.007	MT-CYB
mitochondrial electron transport, ubiquinol to cytochrome c	1	324.1×	0.007	MT-CYB
proton motive force-driven ATP synthesis	1	200.6×	0.010	MT-ATP6
response to cadmium ion	1	183.2×	0.010	MT-CYB
animal organ regeneration	1	150.5×	0.012	MT-CYB
cellular respiration	1	108.0×	0.015	MT-CYB
response to calcium ion	1	79.5×	0.018	MT-CYB
proton transmembrane transport	1	78.0×	0.018	MT-ATP6
aerobic respiration	1	62.0×	0.021	NDUFB11
response to toxic substance	1	52.7×	0.023	MT-CYB
response to ethanol	1	36.6×	0.032	MT-CYB
response to hypoxia	1	23.9×	0.045	MT-CYB
lipid metabolic process	1	22.9×	0.045	FAM135A
response to xenobiotic stimulus	1	17.3×	0.057	MT-CYB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 2 of 5 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NDUFB11	0	0
FAM135A	0	0
MT-ATP6	0	0
MT-CYB	0	0
MT-TL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NDUFB11	4	Binding:4
MT-ATP6	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	0
E	Difficult family or no structure, no drug	5	NDUFB11, FAM135A, MT-ATP6, MT-CYB, MT-TL1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NDUFB11	4	—
FAM135A	0	—
MT-ATP6	1	—
MT-CYB	0	—
MT-TL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05658965	Not specified	RECRUITING	KIDSHEART AND BRAIN : Early EEG Surgery Congenital Heart Disease Predict Onset of Neurodevelopmental Disorders
NCT06818760	Not specified	RECRUITING	Remote Monitoring in Pregnant Women With Congenital Heart Disease Using Wrist Wearables
NCT07437261	Not specified	COMPLETED	Neuropsychomotor Development From Ages 6 to 18 in Children With Early Surgically Treated Congenital Heart Disease