SLC28A3

Chr 9

solute carrier family 28 member 3

Also known as: CNT3

NCBI Gene: 64078ENSG00000197506UniProt: Q9HAS3OMIM: 608269

The SLC28A3 protein is a sodium-dependent nucleoside transporter that regulates cellular nucleoside homeostasis and transport of pyrimidine and purine nucleosides across cell membranes. Mutations cause autosomal recessive microcephaly, seizures, and developmental delay. The gene shows very low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.24
Clinical Summary— SLC28A3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 84 VUS of 138 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.24LOEUF
pLI 0.000
Z-score 0.34
OE 0.94 (0.72–1.24)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.07Z-score
OE missense 0.85 (0.77–0.93)
321 obs / 379.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.94 (0.72–1.24)
0≤0.351.4
Missense OE0.85 (0.77–0.93)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 36 / 38.3Missense obs/exp: 321 / 379.4Syn Z: 0.64
DN
0.77top 25%
GOF
0.73top 25%
LOF
0.2777th %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

138 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic4
VUS84
Likely Benign7
Benign4
23
Pathogenic
4
Likely Pathogenic
84
VUS
7
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
4
0
4
VUS
0
81
3
0
84
Likely Benign
0
6
1
0
7
Benign
0
1
0
3
4
Total088313122

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC28A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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