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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SLC35A4
solute carrier family 35 member A4
Chromosome 5 · 5q31.3
NCBI Gene: 113829Ensembl: ENSG00000176087.17HGNC: HGNC:20753UniProt: Q96G79
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
Golgi membraneprotein bindingtransmembrane transporter activityGolgi apparatushepatitis B virus infectionneoplasmhepatocellular carcinomarenal cell carcinoma
✦AI Summary

SLC35A4 is a Golgi membrane transporter that mediates CDP-ribitol import, a critical substrate for ribitol phosphate incorporation into α-dystroglycan glycans 1. The protein functions redundantly with SLC35A1 for CDP-ribitol transport, with its smaller binding pocket restricting substrate specificity compared to the promiscuous SLC35A1 1. SLC35A4 does not transport CMP-sialic acid, UDP-galactose, or UDP-N-acetylglucosamine 21. Beyond its canonical transporter role, SLC35A4 exhibits dual-coding capacity: its upstream ORF encodes a functional inner mitochondrial membrane microprotein (SLC35A4-MP) that regulates cellular respiration and ATP generation 3. An alternative ORF produces AltSLC35A4, also localized to the inner mitochondrial membrane 4. Both the reference SLC35A4 protein and AltSLC35A4 protect against oxidative stress, with SLC35A4 showing dramatic translational upregulation during sodium arsenite-induced oxidative stress via upstream ORF-dependent mechanisms 4. At the Golgi, SLC35A4 associates with nucleotide sugar transporters SLC35A2 and SLC35A3, modulating their subcellular distribution and forming multi-enzyme complexes that facilitate N-glycan synthesis 25.

Sources cited
1
SLC35A4 mediates CDP-ribitol transport to the Golgi in redundancy with SLC35A1; smaller binding pocket restricts substrate specificity
PMID: 34015330
2
SLC35A4 localizes to Golgi with even number of transmembrane domains; does not transport CMP-sialic acid, UDP-galactose, or UDP-N-acetylglucosamine; modulates SLC35A2/SLC35A3 complex trafficking
PMID: 28167211
3
SLC35A4 upstream ORF encodes a 103-amino acid functional microprotein in the inner mitochondrial membrane that regulates cellular respiration
PMID: 38580077
4
SLC35A4 exhibits dual-coding nature producing reference protein and AltSLC35A4; both protect against oxidative stress with reference protein showing translational upregulation during oxidative stress
PMID: 40545711
5
SLC35A4 forms multi-enzyme/multi-transporter complexes with other nucleotide sugar transporters (SLC35A2, SLC35A3) in Golgi membranes
PMID: 30737517
Disease Associationsⓘ20
hepatitis B virus infectionOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
renal cell carcinomaOpen Targets
0.01Suggestive
osteosarcomaOpen Targets
0.01Suggestive
obesityOpen Targets
0.01Suggestive
fibrosarcomaOpen Targets
0.01Suggestive
brain neoplasmOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
gastric carcinomaOpen Targets
0.01Suggestive
oral squamous cell carcinomaOpen Targets
0.01Suggestive
ovarian cancerOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.01Suggestive
multiple myelomaOpen Targets
0.00Suggestive
acute myeloid leukemiaOpen Targets
0.00Suggestive
colorectal carcinomaOpen Targets
0.00Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.00Suggestive
lung adenocarcinomaOpen Targets
0.00Suggestive
supranuclear palsy, progressive, 1Open Targets
0.00Suggestive
uterine cancerOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SLC35A5Shared pathway75%SLC35A3Shared pathway60%SLC35A2Shared pathway60%SLC35A1Shared pathway57%SLC35E3Shared pathway40%C1GALT1C1LShared pathway25%
Tissue Expression6 tissues
Heart
100%
Lung
88%
Liver
74%
Ovary
46%
Brain
35%
Bone Marrow
25%
Gene Interaction Network
Click a node to explore
SLC35A4SLC35A5SLC35A3SLC35A2SLC35A1SLC35E3C1GALT1C1L
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q96G79
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.79LoF Tolerant
pLIⓘ
0.13Tolerant
Observed/Expected LoF0.45 [0.27–0.79]
RankingsWhere SLC35A4 stands among ~20K protein-coding genes
  • #14,542of 20,598
    Most Researched19
  • #6,575of 17,882
    Most Constrained (LOEUF)0.79
Genes detectedSLC35A4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The promiscuous binding pocket of SLC35A1 ensures redundant transport of CDP-ribitol to the Golgi.
PMID: 34015330
J Biol Chem · 2021
1.00
2
An Inner Mitochondrial Membrane Microprotein from the SLC35A4 Upstream ORF Regulates Cellular Metabolism.
PMID: 38580077
J Mol Biol · 2024
0.90
3
The dual-coding gene SLC35A4 protects against oxidative stress.
PMID: 40545711
Protein Sci · 2025
0.80
4
An insight into the orphan nucleotide sugar transporter SLC35A4.
PMID: 28167211
Biochim Biophys Acta Mol Cell Res · 2017
0.70
5
Bioorthogonal photocatalytic proximity labeling in primary living samples.
PMID: 38548729
Nat Commun · 2024
0.60