SLC29A4

Chr 7

solute carrier family 29 member 4

Also known as: ENT4, PMAT

NCBI Gene: 222962ENSG00000164638UniProt: Q7RTT9

This gene encodes a member of the SLC29A/ENT transporter protein family. The encoded membrane protein catalyzes the reuptake of monoamines into presynaptic neurons, thus determining the intensity and duration of monoamine neural signaling. It has been shown to transport several compounds, including serotonin, dopamine, and the neurotoxin 1-methyl-4-phenylpyridinium. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

0
Active trials
40
Pathogenic / LP
217
ClinVar variants
5
Pubs (1 yr)
-1.0
Missense Z
0.92
LOEUF
Clinical Summary— SLC29A4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 146 VUS of 217 total submissions
📖
GeneReview available — SLC29A4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.92LOEUF
pLI 0.000
Z-score 1.82
OE 0.56 (0.35–0.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.00Z-score
OE missense 1.15 (1.06–1.24)
420 obs / 366.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.56 (0.35–0.92)
0≤0.351.4
Missense OE1.15 (1.06–1.24)
0≤0.61.4
Synonymous OE1.69
0≤1.21.6
LoF obs/exp: 11 / 19.7Missense obs/exp: 420 / 366.1Syn Z: -7.15
DNGOF
DN
0.77top 25%
GOF
0.75top 25%
LOF
0.2385th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

217 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic3
VUS146
Likely Benign18
Benign11
Conflicting2
37
Pathogenic
3
Likely Pathogenic
146
VUS
18
Likely Benign
11
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
3
0
3
VUS
0
130
16
0
146
Likely Benign
0
6
1
11
18
Benign
0
3
1
7
11
Conflicting
—2
Total01395818217

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

SLC29A4 · 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 →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated Analysis of Slow Transit Constipation and Colorectal Cancer Reveals the Co-Pathogenic Targets and Their Potential Clinical Value.
Wang Y et al.·Cancer Invest
2025
Druggable Targets for Postpartum Depression: A Mendelian Randomization and Colocalization Study.
Wu S et al.·Cell Mol Neurobiol
2025
Identification of clinical and pharmacogenetic factors influencing metformin response in Type 2 diabetes mellitus.
Pérez-Gómez N et al.·Pharmacogenomics
2023
Update on drug-drug interaction at organic cation transporters: mechanisms, clinical impact, and proposal for advanced in vitro testing.
Koepsell H·Expert Opin Drug Metab Toxicol
2021Review
COVID-19 severity gradient differentially dysregulates clinically relevant drug processing genes in nasopharyngeal swab samples.
Nwabufo CK et al.·Br J Clin Pharmacol
2024
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Uncovering Functional Contributions of PMAT (Slc29a4) to Monoamine Clearance Using Pharmacobehavioral Tools.
Beaver JN et al.·Cells
2022Open AccessFunctional
Estradiol reduced 5-HT reuptake by downregulating the gene expression of Plasma Membrane Monoamine Transporter (PMAT, Slc29a4) through estrogen receptor β and the MAPK/ERK signaling pathway.
Gu Y et al.·Eur J Pharmacol
2022
Clinically significant findings of high-risk mutations in human SLC29A4 gene associated with diabetes mellitus type 2 in Pakistani population.
Moeez S et al.·J Biomol Struct Dyn
2022
Deletion of murine slc29a4 modifies vascular responses to adenosine and 5-hydroxytryptamine in a sexually dimorphic manner.
Wei R et al.·Physiol Rep
2020Open Access
Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: An IMI DIRECT Study.
Dawed AY et al.·Diabetes Care
2019
Top 5 resultsSearch Europe PMC ↗

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