mitochondrial DNA depletion syndrome 18

disease

On this page

Also known as MTDPS18

Summary

mitochondrial DNA depletion syndrome 18 (MONDO:0032932) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial DNA depletion syndrome 18
Mondo ID	MONDO:0032932
OMIM	618811
DOID	DOID:0070449
UMLS	C5394140
MedGen	1713890
GARD	0025777
Is cancer (heuristic)	no

Also known as: MTDPS18

Data availability: 6 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 18

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

6 retrieved; paginated sample, class counts are floors:

3 benign, 1 conflicting classifications of pathogenicity, 1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
827876	NM_030631.4(SLC25A21):c.695A>G (p.Lys232Arg)	SLC25A21	Pathogenic	no assertion criteria provided
1687162	NM_030631.4(SLC25A21):c.532C>T (p.Arg178Ter)	SLC25A21	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3367058	NM_030631.4(SLC25A21):c.43C>T (p.Arg15Trp)	SLC25A21	Uncertain significance	criteria provided, single submitter
1332980	NM_030631.4(SLC25A21):c.441A>G (p.Gln147=)	SLC25A21	Benign	criteria provided, multiple submitters, no conflicts
1332981	NM_030631.4(SLC25A21):c.270+15C>T	SLC25A21	Benign	criteria provided, multiple submitters, no conflicts
1332982	NM_030631.4(SLC25A21):c.71-21_71-20insC	SLC25A21	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
SLC25A21	Moderate	Autosomal recessive	mitochondrial DNA depletion syndrome 18	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
SLC25A21	HGNC:14411	ENSG00000183032	Q9BQT8	Mitochondrial 2-oxodicarboxylate carrier	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC25A21	Mitochondrial 2-oxodicarboxylate carrier	Transports dicarboxylates across the inner membranes of mitochondria by a counter-exchange mechanism.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC25A21	Other/Unknown	no		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
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC25A21	165	broad	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC25A21	877

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC25A21	Q9BQT8	88.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Lysine catabolism	1	1142.0×	9e-04	SLC25A21

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitochondrial alpha-ketoglutarate transmembrane transport	1	8426.0×	4e-04	SLC25A21
obsolete lysine catabolic process	1	2407.4×	6e-04	SLC25A21
lipid transport	1	263.3×	0.004	SLC25A21

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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
SLC25A21	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ALLICIN	2	SLC25A21

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC25A21	2	Binding:2

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

1 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)
ALLICIN	2	SLC25A21

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	SLC25A21
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.

Cohort genes: SLC25A21