SLC3A2

Chr 11

solute carrier family 3 member 2

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

NCBI Gene: 6520 ENSG00000168003 UniProt: P08195 OMIM: 158070

The protein acts as a chaperone that facilitates formation and trafficking of amino acid transporter complexes to the cell membrane, partnering with various SLC7 family members to transport specific amino acids including neutral, dibasic, and anionic amino acids. Mutations cause autosomal recessive lysinuric protein intolerance, a rare disorder characterized by defective transport of dibasic amino acids (lysine, arginine, ornithine) leading to failure to thrive, protein aversion, hepatosplenomegaly, and potential pulmonary and renal complications. The gene is not highly constrained against loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Active trials

167

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.91

LOEUF

Mechanism· predicted

📖

GeneReview available — SLC3A2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.000

Z-score 1.94

OE 0.60 (0.40–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.15Z-score

OE missense 0.83 (0.75–0.91)

290 obs / 350.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.40–0.91)

0≤0.351.4

Missense OE?0.83 (0.75–0.91)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 16 / 26.8Missense obs/exp: 290 / 350.4Syn Z: 0.89

Background carrier burden — how many people carry a rare variant somewhere in SLC3A2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

893 rare PASS variants

Rare truncating (LoF)

1 in 330

161 rare PASS variants

Rare synonymous (reference)

1 in 160

389 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC3A2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 67	1 in 560
South Asian	~43k	1 in 46	1 in 370
Remaining (unassigned)	~30k	1 in 42	1 in 420
European (Finnish)	~27k	1 in 310	1 in 1,500
Admixed American	~22k	1 in 64	1 in 320
African / African American	~21k	1 in 44	1 in 850
East Asian	~20k	1 in 100	1 in 1,600
Ashkenazi Jewish	~13k	1 in 530	1 in 410
Middle Eastern	~2,884	1 in 98	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓