SLC7A9

Chr 19ADAR

solute carrier family 7 member 9

Also known as: BAT1, CSNU3

NCBI Gene: 11136 ENSG00000021488 UniProt: P82251 OMIM: 604144

The encoded protein associates with SLC3A1 to form a functional transporter complex that mediates electrogenic exchange of cationic amino acids and neutral amino acids, and is required for reabsorption of L-cystine and dibasic amino acids in renal proximal tubules. Mutations cause cystinuria, leading to cystine stone formation in the urinary system due to impaired amino acid transport. Inheritance follows both autosomal dominant and autosomal recessive patterns depending on the specific mutation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that belongs to a family of light subunits of amino acid transporters. This protein plays a role in the high-affinity and sodium-independent transport of cystine and neutral and dibasic amino acids, and appears to function in the reabsorption of cystine in the kidney tubule. Mutations in this gene cause non-type I cystinuria, a disease that leads to cystine stones in the urinary system due to impaired transport of cystine and dibasic amino acids. Alternate transcript variants, which encode the same protein, have been found for this gene. [provided by RefSeq, Jul 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismAD/ARLOEUF 1.121 OMIM phenotype

Clinical Summary— SLC7A9

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Gene-Disease Validity (ClinGen)

cystinuria · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

92 unique Pathogenic / Likely Pathogenic· 175 VUS of 475 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SLC7A9

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?

1.12LOEUF

pLI 0.000

Z-score 1.12

OE 0.75 (0.51–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.81Z-score

OE missense 0.87 (0.78–0.96)

256 obs / 294.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.51–1.12)

0≤0.351.4

Missense OE?0.87 (0.78–0.96)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 17 / 22.8Missense obs/exp: 256 / 294.9Syn Z: 0.16

This gene — mechanism propensity

0.85top 5%

GOF

0.82top 10%

LOF

0.1697th %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

475 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35

Likely Pathogenic57

VUS175

Likely Benign93

Benign60

Conflicting41

Pathogenic

Likely Pathogenic

175

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	25	5	5	0	35
Likely Pathogenic	29	22	4	2	57
VUS	3	145	20	7	175
Likely Benign	0	5	40	48	93
Benign	0	0	51	9	60
Conflicting	—				41
Total	57	177	120	66	461

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap SLC7A9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →