mitochondrial DNA depletion syndrome 19

Summary

mitochondrial DNA depletion syndrome 19 (MONDO:0033545) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial DNA depletion syndrome 19
Mondo ID	MONDO:0033545
OMIM	618972
DOID	DOID:0070450
UMLS	C5436514
MedGen	1770258
GARD	0018370
Is cancer (heuristic)	no

Also known as: MTDPS19

Data availability: 5 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › mitochondrial oxidative phosphorylation disorder › mitochondrial DNA depletion syndrome › mitochondrial DNA depletion syndrome 19

Related subtypes (20): Sengers syndrome, mitochondrial DNA depletion syndrome 1, mitochondrial DNA depletion syndrome, myopathic form, mitochondrial DNA depletion syndrome 4b, mitochondrial DNA depletion syndrome 11, mitochondrial DNA deletion syndrome with progressive myopathy, mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive, mitochondrial DNA depletion syndrome 14B (cardioencephalomyopathic type), mitochondrial DNA depletion syndrome 15 (hepatocerebral type), mitochondrial DNA depletion syndrome 12A (cardiomyopathic type), autosomal dominant, mitochondrial DNA depletion syndrome, encephalomyopathic form, mitochondrial dna depletion syndrome 16B (neuroophthalmic type), mitochondrial DNA depletion syndrome 20 (mngie type), mitochondrial DNA depletion syndrome 16 (hepatic type), mitochondrial DNA depletion syndrome 17, mitochondrial DNA depletion syndrome 18, mitochondrial DNA depletion syndrome, hepatocerebral form, AFG3L2-related optic atrophy and/or spastic ataxia spectrum, mitochondrial dna depletion syndrome 21, mitochondrial dna depletion syndrome 14A (encephalomyopathic type)

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 likely pathogenic, 1 uncertain significance, 1 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
974801	NM_012140.5(SLC25A10):c.[657C>T;763-37G>A]		Pathogenic	no assertion criteria provided
3780613	NM_012140.5(SLC25A10):c.329-2A>T	SLC25A10	Likely pathogenic	criteria provided, single submitter
446175	NM_012140.5(SLC25A10):c.304A>T (p.Lys102Ter)	SLC25A10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3065487	NM_012140.5(SLC25A10):c.534+5G>T	SLC25A10	Uncertain significance	criteria provided, single submitter
446188	NM_012140.5(SLC25A10):c.763-37G>A	SLC25A10	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
SLC25A10	Moderate	Autosomal recessive	mitochondrial DNA depletion syndrome 19	3

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
SLC25A10	HGNC:10980	ENSG00000183048	Q9UBX3	Mitochondrial dicarboxylate carrier	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC25A10	Mitochondrial dicarboxylate carrier	Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across the mitochondrial inner membrane.

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC25A10	Transporter	yes		MCP, MCP_transmembrane, MCP_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
liver	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
SLC25A10	133	ubiquitous	marker	right lobe of liver, mucosa of transverse colon, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC25A10	1,394

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC25A10	Q9UBX3	77.53

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Sulfide oxidation to sulfate	1	1903.3×	7e-04	SLC25A10
Organic anion transport by SLC5/17/25 transporters	1	1427.5×	7e-04	SLC25A10

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
thiosulfate transport	1	16852.0×	4e-04	SLC25A10
malate transmembrane transport	1	16852.0×	4e-04	SLC25A10
oxaloacetate transport	1	8426.0×	4e-04	SLC25A10
dicarboxylic acid transport	1	5617.3×	4e-04	SLC25A10
obsolete sulfide oxidation, using sulfide:quinone oxidoreductase	1	5617.3×	4e-04	SLC25A10
glyceraldehyde-3-phosphate biosynthetic process	1	4213.0×	4e-04	SLC25A10
succinate transmembrane transport	1	4213.0×	4e-04	SLC25A10
phosphate ion transmembrane transport	1	1203.7×	0.001	SLC25A10
sulfate transmembrane transport	1	1203.7×	0.001	SLC25A10
gluconeogenesis	1	324.1×	0.004	SLC25A10
lipid transport	1	263.3×	0.004	SLC25A10
monoatomic ion transport	1	156.0×	0.006	SLC25A10

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
SLC25A10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	SLC25A10
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)
SLC25A10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.