SLC14A2

Chr 18

solute carrier family 14 member 2

Also known as: HUT2, UT-A2, UT2, UTA, UTR, hUT-A6

The encoded protein mediates urea transport across the renal inner medullary collecting duct membrane, which is critical for the kidney's urinary concentrating mechanism. Mutations cause autosomal recessive renal tubular dysgenesis with severe polyhydramnios, oligohydramnios sequence, and neonatal renal failure. This gene shows minimal constraint against loss-of-function variants in the general population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
50
P/LP submissions
0%
P/LP missense
0.98
LOEUF
Multiple*
Mechanism· predicted
Clinical SummarySLC14A2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
48 unique Pathogenic / Likely Pathogenic· 146 VUS of 215 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.66
OE 0.73 (0.560.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.14Z-score
OE missense 1.02 (0.951.09)
534 obs / 525.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.73 (0.560.98)
00.351.4
Missense OE1.02 (0.951.09)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 33 / 45.0Missense obs/exp: 534 / 525.1Syn Z: -0.30
DN
0.7034th %ile
GOF
0.76top 25%
LOF
0.2777th %ile

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

GOFprediction above median
DNprediction 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

215 submitted variants in ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic2
VUS146
Likely Benign5
Benign1
46
Pathogenic
2
Likely Pathogenic
146
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
46
0
46
Likely Pathogenic
0
0
2
0
2
VUS
0
141
5
0
146
Likely Benign
0
3
1
1
5
Benign
0
1
0
0
1
Total0145541200

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC14A2 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC