SLC25A13

Chr 7AR

solute carrier family 25 member 13

Mitochondrial electrogenic aspartate/glutamate antiporter that favors efflux of aspartate and entry of glutamate and proton within the mitochondria as part of the malate-aspartate shuttle (PubMed:11566871, PubMed:38937634, PubMed:38945283, PubMed:39419476). Substrate exchange across the membrane occurs consecutively with one substrate being transported first, then dissociating from the substrate binding site before the second substrate binds for transport in the opposite direction (PubMed:38937634). Also mediates the uptake of L-cysteinesulfinate (3-sulfino-L-alanine) by mitochondria in exchange for L-glutamate and proton (PubMed:11566871). Can also exchange L-cysteinesulfinate with aspartate in their anionic form without any proton translocation (PubMed:11566871). Lacks transport activity towards gamma-aminobutyric acid (GABA) (PubMed:38945283)

Primary Disease Associations & Inheritance

Citrullinemia, adult-onset type IIMIM #603471

Citrullinemia, type II, neonatal-onsetMIM #605814

UniProtCitrin deficiency, adolescent or adult onset

UniProtCitrin deficiency, neonatal or infantile onset

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— SLC25A13

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Gene-Disease Validity (ClinGen)

citrin deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Some data sources returned errors (2)

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clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.24LOEUF

pLI 0.000

Z-score 0.33

OE 0.94 (0.73–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.30Z-score

OE missense 0.96 (0.87–1.04)

348 obs / 364.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.94 (0.73–1.24)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.87–1.04)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98

0≤1.21.6

LoF obs/exp: 38 / 40.3Missense obs/exp: 348 / 364.4Syn Z: 0.22