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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC44A4
solute carrier family 44 member 4
Chromosome 6 · 6p21.33
NCBI Gene: 80736Ensembl: ENSG00000204385.14HGNC: HGNC:13941UniProt: A0A140VJH4
35PubMed Papers
1Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomeacetylcholine secretionthiamine pyrophosphate transmembrane transporter activityapical plasma membraneDeafness, autosomal dominant, 72
✦AI Summary

SLC44A4 encodes a thiamine pyrophosphate transporter (TPPT) that plays a critical role in colonic uptake of vitamin B1 from gut microbiota 1. The transporter demonstrates colon-specific expression along the gastrointestinal tract and is predominantly or solely responsible for carrier-mediated thiamine pyrophosphate (TPP) uptake in colonocytes 1. Mechanistically, SLC44A4 expression is regulated by transcription factors ELF3 and CREB-1, which drive basal promoter activity in colonic epithelial cells 2. The colon-specific expression pattern is controlled by epigenetic mechanisms, including histone modifications where histone H3 shows activating marks (trimethylation at lysine 4, acetylation at lysine 9) in colon but repressive marks (trimethylation at lysine 27) in other tissues 3. SLC44A4 expression can be downregulated by pathogenic factors, as demonstrated by EHEC infection reducing transporter expression through ERK1/2 and NF-κB signaling pathways 4. Beyond its physiological role, SLC44A4 knockout mice show increased susceptibility to colitis and inflammation, supporting genome-wide association studies identifying it as a potential colitis susceptibility gene 1. The transporter has also gained attention as a therapeutic target, with SLC44A4-targeted antibody-drug conjugates being developed for epithelial tumors, particularly pancreatic and prostate cancers 5.

Sources cited
1
SLC44A4 is the predominant or only transporter for colonic TPP uptake and knockout increases colitis susceptibility
PMID: 38713615
2
ELF3 and CREB-1 transcription factors regulate SLC44A4 basal promoter activity
PMID: 25715703
3
Colon-specific expression is controlled by histone modifications
PMID: 26901654
4
EHEC infection downregulates SLC44A4 through ERK1/2 and NF-κB pathways
PMID: 31639155
5
SLC44A4 is a target for antibody-drug conjugates in epithelial tumors
PMID: 27550944
Disease Associationsⓘ1
Deafness, autosomal dominant, 72UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CD80Protein interaction93%CD86Protein interaction83%SLC44A5Shared pathway75%SLC44A3Shared pathway75%SLC44A2Shared pathway60%SLC44A1Shared pathway60%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
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SLC44A4CD80CD86SLC44A5SLC44A3SLC44A2SLC44A1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q53GD3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.90LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.75 [0.62–0.90]
RankingsWhere SLC44A4 stands among ~20K protein-coding genes
  • #11,071of 20,598
    Most Researched35
  • #8,192of 17,882
    Most Constrained (LOEUF)0.90
Genes detectedSLC44A4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy.
PMID: 27646942
J Clin Oncol · 2017
1.00
2
Effect of knocking out mouse
PMID: 38713615
Am J Physiol Gastrointest Liver Physiol · 2024
0.90
3
Regulation of basal promoter activity of the human thiamine pyrophosphate transporter SLC44A4 in human intestinal epithelial cells.
PMID: 25715703
Am J Physiol Cell Physiol · 2015
0.80
4
Identification of novel diagnostic panel for mild cognitive impairment and Alzheimer's disease: findings based on urine proteomics and machine learning.
PMID: 37925455
Alzheimers Res Ther · 2023
0.70
5
The Discovery and Preclinical Development of ASG-5ME, an Antibody-Drug Conjugate Targeting SLC44A4-Positive Epithelial Tumors Including Pancreatic and Prostate Cancer.
PMID: 27550944
Mol Cancer Ther · 2016
0.60