SLC25A10

Chr 17AR

solute carrier family 25 member 10

Also known as: DIC, MTDPS19

The protein catalyzes the electroneutral exchange of dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate across the mitochondrial inner membrane, supplying substrates essential for gluconeogenesis, fatty acid metabolism, urea synthesis, and sulfur metabolism. Mutations cause mitochondrial DNA depletion syndrome 19 through autosomal recessive inheritance. The pathogenic mechanism involves loss of function, disrupting critical mitochondrial substrate transport required for cellular metabolism.

Summary from RefSeq, OMIM, UniProt, Mechanism

Primary Disease Associations & Inheritance

?Mitochondrial DNA depletion syndrome 19MIM #618972
AR
0
Active trials
19
Pubs (1 yr)
28
P/LP submissions
8%
P/LP missense
1.16
LOEUF
DN
Mechanism· predicted
Clinical SummarySLC25A10
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 67 VUS of 135 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.16LOEUF
pLI 0.000
Z-score 1.08
OE 0.72 (0.461.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.63Z-score
OE missense 0.87 (0.770.99)
167 obs / 191.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.461.16)
00.351.4
Missense OE0.87 (0.770.99)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 12 / 16.8Missense obs/exp: 167 / 191.3Syn Z: 0.04
DN
0.86top 5%
GOF
0.79top 25%
LOF
0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

135 submitted variants in ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic7
VUS67
Likely Benign14
Benign4
Conflicting1
19
Pathogenic
7
Likely Pathogenic
67
VUS
14
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
18
0
19
Likely Pathogenic
2
1
4
0
7
VUS
0
59
8
0
67
Likely Benign
0
8
1
5
14
Benign
0
2
0
2
4
Conflicting
1
Total271317112

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC25A10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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