Encephalopathy due to beta-mercaptolactate-cysteine disulfiduria

Summary

Encephalopathy due to beta-mercaptolactate-cysteine disulfiduria (MONDO:0009585) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 24

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

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

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0000348	High forehead	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000444	Convex nasal ridge	Frequent (30-79%)
HP:0000463	Anteverted nares	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000958	Dry skin	Frequent (30-79%)
HP:0001166	Arachnodactyly	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001852	Sandal gap	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002353	EEG abnormality	Frequent (30-79%)
HP:0002857	Genu valgum	Frequent (30-79%)
HP:0002983	Micromelia	Frequent (30-79%)
HP:0100720	Hypoplasia of the ear cartilage	Frequent (30-79%)
HP:0000069	Abnormality of the ureter	Occasional (5-29%)
HP:0001513	Obesity	Occasional (5-29%)
HP:0001537	Umbilical hernia	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	encephalopathy due to beta-mercaptolactate-cysteine disulfiduria
Mondo ID	MONDO:0009585
MeSH	C563085
OMIM	249650
Orphanet	1035
UMLS	C0796055
MedGen	208661
GARD	0000654
Is cancer (heuristic)	no

Also known as: 3-mercaptopyruvate sulfurtransferase deficiency · Ampola syndrome · Beta-mercaptolactate cysteine disulfiduria · MCDU · mercaptolactate-cysteine disulfiduria

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › encephalopathy due to beta-mercaptolactate-cysteine disulfiduria

Related subtypes (81): Huntington disease and related disorders, agenesis of the corpus callosum with peripheral neuropathy, striatonigral degeneration, angioid streaks of choroid, amyotrophic lateral sclerosis-parkinsonism-dementia complex, inherited Creutzfeldt-Jakob disease, mitochondrial DNA depletion syndrome 4a, cerebellar ataxia-hypogonadism syndrome, myoclonic cerebellar dyssynergia, cerebral sclerosis similar to Pelizaeus-Merzbacher disease, Chediak-Higashi syndrome, PEHO syndrome, deafness dystonia syndrome, Kennedy disease, fatal familial insomnia, Huntington disease-like 1, neuronal intranuclear inclusion disease, ataxia-telangiectasia-like disorder, radiation sensitivity/chromosome instability syndrome, autosomal dominant, Huntington disease-like 2, microphthalmia-brain atrophy syndrome, neurodegenerative syndrome due to cerebral folate transport deficiency, hereditary sensory neuropathy-deafness-dementia syndrome, infantile cerebellar-retinal degeneration, Alzheimer disease 17, hypotonia, infantile, with psychomotor retardation and characteristic facies, Alzheimer disease 18, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, severe neurodegenerative syndrome with lipodystrophy, developmental and epileptic encephalopathy, 35, combined oxidative phosphorylation deficiency 29, neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, neuronal ceroid lipofuscinosis, frontotemporal dementia with motor neuron disease, frontotemporal dementia, GM2 gangliosidosis, attenuated Chédiak-Higashi syndrome, autosomal recessive cerebral atrophy, neurodegeneration with brain iron accumulation, fatal post-viral neurodegenerative disorder, ferro-cerebro-cutaneous syndrome, PRKAR1B-related neurodegenerative dementia with intermediate filaments, ITM2B amyloidosis, corticobasal syndrome, infantile-onset axonal motor and sensory neuropathy-optic atrophy-neurodegenerative syndrome, recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome, posterior cortical atrophy, progressive supranuclear palsy, leukodystrophy, hereditary spastic paraplegia, facial onset sensory and motor neuronopathy, X-linked neurodegenerative syndrome, Bertini type, X-linked neurodegenerative syndrome, Hamel type, boylan dew greco syndrome, hereditary motor neuron disease, neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, frontotemporal dementia and/or amyotrophic lateral sclerosis, neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities, neurodegeneration with ataxia and late-onset optic atrophy, neurodegeneration, childhood-onset, with cerebellar atrophy, neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, neurodegeneration, infantile-onset, biotin-responsive, hereditary optic atrophy, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome, familial Alzheimer disease, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, hereditary cerebellar ataxia, DCTN1-related neurodegeneration, early-childhood-onset neurodegeneration with retinitis pigmentosa, sensorineural hearing loss, and demyelinating peripheral neuropathy, TUBB4A-related neurologic disorder, neurodegeneration, childhood-onset, with progressive microcephaly, neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, neurodegeneration and seizures due to copper transport defect, neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, neurodegenerative disorder, X-linked, female-restricted, with parkinsonism and cognitive impairment, neurodegenerative disorder with cerebellar and caudate atrophy, APP-related brain and vascular amyloidosis

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

1 retrieved; paginated sample, class counts are floors:

1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
684529	NM_021126.8(MPST):c.314A>G (p.Tyr105Cys)	MPST	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · 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
MPST	No Known Disease Relationship	Autosomal recessive	encephalopathy due to beta-mercaptolactate-cysteine disulfiduria

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
MPST	HGNC:7223	ENSG00000128309	P25325	3-mercaptopyruvate sulfurtransferase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MPST	3-mercaptopyruvate sulfurtransferase	Transfer of a sulfur ion to cyanide or to other thiol compounds.

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)
MPST	Enzyme (other)	yes	2.8.1.2	Thiosulphate_STrfase_CS, Rhodanese-like_dom, Rhodanese-like_dom_sf

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
mucosa of transverse colon	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MPST	280	ubiquitous	marker	mucosa of transverse colon, right lobe of liver, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MPST	1,151

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MPST	P25325	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Degradation of cysteine and homocysteine	1	951.7×	0.004	MPST
Sulfur amino acid metabolism	1	571.0×	0.004	MPST
Metabolism of amino acids and derivatives	1	67.6×	0.020	MPST
Metabolism	1	11.6×	0.086	MPST

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
cyanate catabolic process	1	8426.0×	5e-04	MPST
hydrogen sulfide biosynthetic process	1	5617.3×	5e-04	MPST
sulfur amino acid catabolic process	1	4213.0×	5e-04	MPST
transsulfuration	1	4213.0×	5e-04	MPST
spinal cord development	1	510.7×	0.003	MPST
liver development	1	221.7×	0.005	MPST
response to toxic substance	1	210.7×	0.005	MPST
kidney development	1	140.4×	0.007	MPST

Therapeutics

Drug target analysis

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

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
MPST	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MPST	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MPST	2.8.1.2	3-mercaptopyruvate sulfurtransferase

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	1	MPST
D	Druggable family + AlphaFold only, no drug	0
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)
MPST	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.