SLC3A2

Chr 11

solute carrier family 3 member 2

Also known as: 4F2, 4F2HC, 4T2HC, CD98, CD98HC, MDU1, NACAE

This gene is a member of the solute carrier family and encodes a cell surface, transmembrane protein. The protein exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. The encoded transporter plays a role in regulation of intracellular calcium levels and transports L-type amino acids. Alternatively spliced transcript variants, encoding different isoforms, have been characterized. [provided by RefSeq, Nov 2010]

107
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical SummarySLC3A2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 77 VUS of 107 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

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.
0.91LOEUF
pLI 0.000
Z-score 1.94
OE 0.60 (0.400.91)
Tolerant

Typical tolerance to LoF variation

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.
1.15Z-score
OE missense 0.83 (0.750.91)
290 obs / 350.4 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.0.60 (0.400.91)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.750.91)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
01.21.6
LoF obs/exp: 16 / 26.8Missense obs/exp: 290 / 350.4Syn Z: 0.89

ClinVar Variant Classifications

107 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic3
VUS77
Likely Benign13
Benign6
8
Pathogenic
3
Likely Pathogenic
77
VUS
13
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
3
0
3
VUS
0
73
4
0
77
Likely Benign
0
6
1
6
13
Benign
0
1
2
3
6
Total080189107

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC3A2 · 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

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING
NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17
AdavosertibAfatinibAfatinib Dimaleate
Ann Arbor Stage I Small Lymphocytic LymphomaAnn Arbor Stage II Small Lymphocytic LymphomaChronic Lymphocytic Leukemia

Lenalidomide and Vaccine Therapy in Treating Patients With Early-Stage Asymptomatic Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ACTIVE NOT RECRUITING
NCT01351896Phase PHASE2National Cancer Institute (NCI)Started 2011-11-02
Biospecimen CollectionBone Marrow AspirationBone Marrow Biopsy
Very High Risk Acute Lymphoblastic LeukemiaCD19 CAR-T Therapy

Treatment of CD19 Chimeric Antigen Receptor T Cells for Pediatric Patients With CD19-positive B-cell Acute Lymphoblastic Leukemia Who Are Indicated for Hematopoietic Stem Cell Transplantation

RECRUITING
NCT06247501Phase PHASE2Seoul National University HospitalStarted 2024-01-19
SNUH-CD19-CAR-T
Locally Advanced Lung Non-Small Cell CarcinomaStage II Lung Cancer AJCC v8Stage IIA Lung Cancer AJCC v8

Papaverine in Combination With Chemoradiation for the Treatment of Stage II-III Non-small Cell Lung Cancer

RECRUITING
NCT05136846Phase PHASE1Ohio State University Comprehensive Cancer CenterStarted 2021-12-06
CarboplatinDurvalumabPaclitaxel
Obesity (Disorder)

Tirzepatide and Muscle Outcomes in Obesity

RECRUITING
NCT07373834Phase NAUniversity Medical Centre LjubljanaStarted 2026-01
TirzepatidePlacebo
X-Linked Myotubular Myopathy

Study of ASP2957 in Male Participants With X-linked Myotubular Myopathy Who Need Ventilators

RECRUITING
NCT07052929Phase PHASE1, PHASE2Astellas Gene TherapiesStarted 2025-12-15
ASP2957MethylprednisolonePrednisolone
Severe Combined Immunodeficiency

Autologous Gene Therapy for Artemis-Deficient SCID

RECRUITING
NCT03538899Phase PHASE1, PHASE2University of California, San FranciscoStarted 2018-05-31
AProArt-CD34CliniMACS® CD34 Reagent System cell sorter deviceBusulfan
Endometrial AdenocarcinomaEndometrial Mixed Cell AdenocarcinomaEndometrial Serous Adenocarcinoma

Testing the Combination of Olaparib and Durvalumab, Cediranib and Durvalumab, Olaparib and Capivasertib, and Cediranib Alone in Recurrent or Refractory Endometrial Cancer Following the Earlier Phase of the Study That Tested Olaparib and Cediranib in Comparison to Cediranib Alone, and Olaparib Alone

ACTIVE NOT RECRUITING
NCT03660826Phase PHASE2National Cancer Institute (NCI)Started 2018-09-27
Biospecimen CollectionBone Marrow AspirateBone Marrow Biopsy
Anatomic Stage IV Breast Cancer AJCC v8Invasive Breast CarcinomaMetastatic Triple-Negative Breast Carcinoma

Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer

RECRUITING
NCT03606967Phase PHASE2National Cancer Institute (NCI)Started 2021-04-13
Biopsy ProcedureBiospecimen CollectionCarboplatin
Bladder Urothelial CarcinomaStage IV Bladder Cancer AJCC v8Stage IVA Bladder Cancer AJCC v8

Radiation Therapy and Durvalumab With or Without Tremelimumab in Treating Participants With Unresectable, Locally Advanced, or Metastatic Bladder Cancer

ACTIVE NOT RECRUITING
NCT03601455Phase PHASE2Jonsson Comprehensive Cancer CenterStarted 2018-10-26
DurvalumabExternal Beam Radiation TherapyTremelimumab
BCLC Stage B Hepatocellular CarcinomaBCLC Stage C Hepatocellular CarcinomaLocally Advanced Hepatocellular Carcinoma

Durvalumab and Tremelimumab After Radioembolization for the Treatment of Unresectable, Locally Advanced Liver Cancer

ACTIVE NOT RECRUITING
NCT04605731Phase PHASE1City of Hope Medical CenterStarted 2021-08-03
DurvalumabTremelimumab
COPD

Respiratory Muscles in End-stage Lung Disease: Pathophysiological Processes & Clinical Consequences

NOT YET RECRUITING
NCT06935825University Medical Center GroningenStarted 2025-09-01