SLC17A4

Chr 6

solute carrier family 17 member 4

Also known as: KAIA2138

NCBI Gene: 10050ENSG00000146039UniProt: Q9Y2C5

Phosphate homeostasis is maintained by regulating intake, intestinal absorption, bone deposition and resorption, and renal excretion of phosphate. The central molecule in the control of phosphate excretion from the kidney is the sodium/phosphate cotransporter NPT1 (SLC17A1; MIM 182308), which is located in the renal proximal tubule. NPT1 uses the transmembrane electrochemical potential gradient of sodium to transport phosphate across the cell membrane. SLC17A4 is a similar sodium/phosphate cotransporter in the intestinal mucosa that plays an important role in the absorption of phosphate from the intestine (summary by Shibui et al., 1999 [PubMed 10319585]).[supplied by OMIM, Feb 2011]

78
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC17A4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 66 VUS of 78 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.08LOEUF
pLI 0.000
Z-score 1.27
OE 0.72 (0.49–1.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.09Z-score
OE missense 0.98 (0.89–1.09)
261 obs / 265.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.72 (0.49–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.89–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 17 / 23.6Missense obs/exp: 261 / 265.0Syn Z: 0.13

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS66
Likely Benign3
Benign2
Conflicting2
4
Pathogenic
1
Likely Pathogenic
66
VUS
3
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
63
3
0
66
Likely Benign
0
3
0
0
3
Benign
0
1
1
0
2
Conflicting
—2
Total0679078

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC17A4 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Thyroid Hormone Transporters.
Groeneweg S et al.·Endocr Rev
2020Review
Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.
Teumer A et al.·Nat Commun
2018Meta-analysis
Epigenetic signatures of gestational diabetes mellitus on cord blood methylation.
Haertle L et al.·Clin Epigenetics
2017
A prognostic signature consisting of metabolism-related genes and SLC17A4 serves as a potential biomarker of immunotherapeutic prediction in prostate cancer.
Li H et al.·Front Immunol
2022
Exome sequencing and array-based comparative genomic hybridisation analysis of preferential 6-methylmercaptopurine producers.
Chua EW et al.·Pharmacogenomics J
2015
The Genetic Basis of Thyroid Function: Novel Findings and New Approaches.
Kuś A et al.·J Clin Endocrinol Metab
2020Review
Integrative causal inference and predictive modeling reveal the iron-related gene SLC17A4 as a key biomarker in chronic rhinosinusitis.
Lv J et al.·Front Immunol
2026Functional
Phenotype-Genotype Correlation Applying a Cocktail Approach and an Exome Chip Analysis Reveals Further Variants Contributing to Variation of Drug Metabolism.
Böhm R et al.·Clin Pharmacol Ther
2024
Sequencing of 2 subclinical atherosclerosis candidate regions in 3669 individuals: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
Bis JC et al.·Circ Cardiovasc Genet
2014Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools