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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SLC25A36
solute carrier family 25 member 36
Chromosome 3 Β· 3q23
NCBI Gene: 55186Ensembl: ENSG00000114120.15HGNC: HGNC:25554UniProt: A0A384MEA9
27PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
pyrimidine nucleotide import into mitochondrionpyrimidine nucleotide transmembrane transporter activitymitochondrionmitochondrial inner membraneneurodegenerative diseasehyperinsulinemic hypoglycemia, familial, 8myotonic syndromecholelithiasis
✦AI Summary

SLC25A36 encodes a mitochondrial pyrimidine nucleotide transporter that mediates bidirectional transport of pyrimidine and guanine nucleotides across the inner mitochondrial membrane 1. The protein catalyzes antiport of cytosine, uracil, and guanine nucleotides (in deoxy and non-deoxy forms) at higher rates, with lower-rate uniport activity also documented 1. By exchanging intramitochondrial nucleotide mono- and diphosphates for cytosolic triphosphates, SLC25A36 supplies precursors essential for mitochondrial DNA and RNA synthesis while removing catabolic products 1. This nucleotide transport function is critical for mitochondrial genome maintenance and respiration regulation. Biallelic SLC25A36 mutations cause hyperinsulinism/hyperammonemia (HI/HA) syndrome, a severe metabolic disorder 23. Loss-of-function mutations reduce mitochondrial GTP content, leading to hyperactivation of glutamate dehydrogenase and excessive insulin secretion 2. Clinical manifestations include hyperinsulinism, hyperammonemia, seizures, hypothyroidism, and developmental delay 34. Emerging evidence suggests oral uridine supplementation may improve metabolic parameters and growth outcomes in affected patients 4. SLC25A36 was additionally identified among eight mitochondrial genes associated with calcific aortic valve disease pathogenesis 5, implicating nucleotide transport in valve disease mechanisms.

Sources cited
1
SLC25A36 transports pyrimidine nucleotides via antiport and uniport mechanisms; essential for mitochondrial DNA/RNA synthesis
PMID: 25320081
2
Biallelic SLC25A36 mutations cause hyperinsulinism/hyperammonemia syndrome by reducing mitochondrial GTP and hyperactivating glutamate dehydrogenase
PMID: 34971397
3
SLC25A36 deficiency presents with hyperinsulinism, hyperammonemia, seizures, and developmental outcomes in biallelic mutation carriers
PMID: 36695547
4
SLC25A36 deficiency causes metabolic and developmental dysfunction; uridine supplementation improves thyroid function and growth
PMID: 34576089
5
SLC25A36 identified as mitochondrial gene associated with calcific aortic valve disease pathogenesis
PMID: 39384885
Disease Associationsβ“˜21
neurodegenerative diseaseOpen Targets
0.52Moderate
hyperinsulinemic hypoglycemia, familial, 8Open Targets
0.51Moderate
myotonic syndromeOpen Targets
0.22Weak
cholelithiasisOpen Targets
0.19Weak
adolescent idiopathic scoliosisOpen Targets
0.05Suggestive
hyperinsulinismOpen Targets
0.02Suggestive
HyperammonemiaOpen Targets
0.02Suggestive
Acute hepatic failureOpen Targets
0.01Suggestive
Global developmental delayOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.00Suggestive
multiple myelomaOpen Targets
0.00Suggestive
hepatitis C virus induced hepatocellular carcinomaOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
cervical cancerOpen Targets
0.00Suggestive
Friedreich ataxiaOpen Targets
0.00Suggestive
metastatic prostate cancerOpen Targets
0.00Suggestive
Neurodevelopmental delayOpen Targets
0.00Suggestive
prostate cancerOpen Targets
0.00Suggestive
metastatic melanomaOpen Targets
0.00Suggestive
posterior cortical atrophyOpen Targets
0.00Suggestive
Hyperinsulinemic hypoglycemia, familial, 8UniProt
Pathogenic Variants2
NM_001104647.3(SLC25A36):c.284+3A>TPathogenic
Hyperinsulinemic hypoglycemia, familial, 8
β˜†β˜†β˜†β˜†2023
NM_001104647.3(SLC25A36):c.803dup (p.Ser269fs)Pathogenic
Hyperinsulinemic hypoglycemia, familial, 8
β˜†β˜†β˜†β˜†2023β†’ Residue 269
View on ClinVar β†—
Related Genes
SLC25A33Co-mentioned in literature20%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
50%
Ovary
43%
Brain
33%
Lung
27%
Liver
3%
Gene Interaction Network
Click a node to explore
SLC25A36SLC25A33
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q96CQ1
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.92LoF Tolerant
pLIβ“˜
0.02Tolerant
Observed/Expected LoF0.54 [0.33–0.92]
RankingsWhere SLC25A36 stands among ~20K protein-coding genes
  • #12,673of 20,598
    Most Researched27
  • #4,526of 5,498
    Most Pathogenic Variants2
  • #8,430of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedSLC25A36
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Multiomics identification of ALDH9A1 as a crucial immunoregulatory molecule involved in calcific aortic valve disease.
PMID: 39384885
Sci Rep Β· 2024
1.00
2
The human SLC25A33 and SLC25A36 genes of solute carrier family 25 encode two mitochondrial pyrimidine nucleotide transporters.
PMID: 25320081
J Biol Chem Β· 2014
0.90
3
Hyperinsulinism/hyperammonemia syndrome caused by biallelic SLC25A36 mutation.
PMID: 36695547
J Inherit Metab Dis Β· 2023
0.80
4
PNC2 (SLC25A36) Deficiency Associated With the Hyperinsulinism/Hyperammonemia Syndrome.
PMID: 34971397
J Clin Endocrinol Metab Β· 2022
0.70
5
Uridine Treatment of the First Known Case of SLC25A36 Deficiency.
PMID: 34576089
Int J Mol Sci Β· 2021
0.60