SLC25A25

Chr 9

solute carrier family 25 member 25

Also known as: MCSC, PCSCL, SCAMC-2, SCAMC2

NCBI Gene: 114789ENSG00000148339UniProt: Q6KCM7OMIM: 608745

This mitochondrial carrier protein functions as a calcium-dependent ATP-magnesium/inorganic phosphate antiporter that transports adenyl nucleotides across the inner mitochondrial membrane to regulate cellular energy metabolism. Mutations in SLC25A25 cause autosomal dominant disease, though the specific clinical phenotype is not established from the provided data. The protein is required for proper left-right body axis patterning during development.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
MultiplemechanismLOEUF 0.58
Clinical Summary— SLC25A25
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 47 VUS of 102 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.024
Z-score 3.03
OE 0.31 (0.18–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.65Z-score
OE missense 0.73 (0.66–0.82)
224 obs / 305.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.18–0.58)
0≤0.351.4
Missense OE0.73 (0.66–0.82)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 7 / 22.5Missense obs/exp: 224 / 305.3Syn Z: 0.51
DN
0.84top 10%
GOF
0.81top 10%
LOF
0.2679th %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

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic1
VUS47
Likely Benign1
Benign1
40
Pathogenic
1
Likely Pathogenic
47
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
39
0
40
Likely Pathogenic
0
0
1
0
1
VUS
1
43
3
0
47
Likely Benign
0
0
0
1
1
Benign
0
0
0
1
1
Total14443290

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC25A25 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients