SLC25A4

Chr 4

solute carrier family 25 member 4

Also known as: AAC1, ANT, ANT 1, ANT1, MTDPS12, MTDPS12A, PEO2, PEO3

NCBI Gene: 291ENSG00000151729UniProt: P12235

This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein forms a homodimer embedded in the inner mitochondria membrane. Mutations in this gene have been shown to result in autosomal dominant progressive external opthalmoplegia and familial hypertrophic cardiomyopathy. [provided by RefSeq, Jun 2013]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtProgressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 2
UniProtMitochondrial DNA depletion syndrome 12B, cardiomyopathic type
UniProtMitochondrial DNA depletion syndrome 12A, cardiomyopathic type

Clinical highlights

Gene-disease validity (ClinGen)
Leigh syndrome · ADLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total
Interpreting a novel variant
Both dominant negative and loss of function mechanisms are described for this gene and which one applies is variant-dependent. Do not assume a null variant is — or isn't — the pathogenic class without checking the specific variant against curated evidence.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
35
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.64
LOEUF
DN/LOF*
Mechanism· annotated
📖
GeneReview available — SLC25A4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.64LOEUF
pLI 0.453
Z-score 2.33
OE 0.20 (0.08–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.87Z-score
OE missense 0.60 (0.51–0.71)
105 obs / 174.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.20 (0.08–0.64)
0≤0.351.4
Missense OE?0.60 (0.51–0.71)
0≤0.61.4
Synonymous OE?1.02
0≤1.21.6
LoF obs/exp: 2 / 9.9Missense obs/exp: 105 / 174.7Syn Z: -0.15

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SLC25A4 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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