SLC7A9

Summary

SLC7A9 (solute carrier family 7 member 9, HGNC:11067) is a protein-coding gene on chromosome 19q13.11, encoding b(0,+)-type amino acid transporter 1 (P82251). Associates with SLC3A1 to form a functional transporter complex that mediates the electrogenic exchange between cationic amino acids and neutral amino acids, with a stoichiometry of 1:1.

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.

Source: NCBI Gene 11136 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cystinuria (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 31
• Clinical variants (ClinVar): 472 total — 35 pathogenic, 45 likely-pathogenic
• Phenotypes (HPO): 9
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_014270

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11067
Approved symbol	SLC7A9
Name	solute carrier family 7 member 9
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Aliases	BAT1
Ensembl gene	ENSG00000021488
Ensembl biotype	protein_coding
OMIM	604144
Entrez	11136

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000023064, ENST00000587772, ENST00000589659, ENST00000590341, ENST00000590465, ENST00000592232, ENST00000879205, ENST00000879206, ENST00000879207, ENST00000879208, ENST00000879209, ENST00000879210, ENST00000879211

RefSeq mRNA: 3 — MANE Select: NM_014270 NM_001126335, NM_001243036, NM_014270

CCDS: CCDS12425

Canonical transcript exons

ENST00000023064 — 13 exons

Exon	Start	End
ENSE00000428116	32864629	32864776
ENSE00001161393	32869686	32869767
ENSE00001387970	32868448	32868645
ENSE00003547002	32864096	32864338
ENSE00003548545	32830511	32830684
ENSE00003552605	32843855	32843951
ENSE00003560007	32858440	32858543
ENSE00003625809	32842168	32842317
ENSE00003650792	32833149	32833323
ENSE00003703148	32860606	32860650
ENSE00003704503	32862118	32862217
ENSE00003707322	32859841	32859964
ENSE00003709413	32862461	32862586

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 99.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2614 / max 121.7124, expressed in 35 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180399	0.2546	35
180398	0.0068	3

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.38	gold quality
secondary oocyte	CL:0000655	97.98	gold quality
jejunal mucosa	UBERON:0000399	97.46	gold quality
oocyte	CL:0000023	96.12	gold quality
nephron tubule	UBERON:0001231	96.05	gold quality
kidney epithelium	UBERON:0004819	95.89	gold quality
renal glomerulus	UBERON:0000074	95.85	gold quality
metanephric glomerulus	UBERON:0004736	95.82	gold quality
duodenum	UBERON:0002114	94.05	gold quality
adult organism	UBERON:0007023	90.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.90	gold quality
adult mammalian kidney	UBERON:0000082	88.42	gold quality
small intestine	UBERON:0002108	88.40	gold quality
cortex of kidney	UBERON:0001225	84.97	gold quality
kidney	UBERON:0002113	84.88	gold quality
right lobe of liver	UBERON:0001114	84.47	gold quality
liver	UBERON:0002107	80.76	gold quality
metanephros	UBERON:0000081	78.00	gold quality
jejunum	UBERON:0002115	74.05	gold quality
tibialis anterior	UBERON:0001385	72.15	silver quality
metanephros cortex	UBERON:0010533	67.30	gold quality
ventricular zone	UBERON:0003053	66.69	gold quality
renal medulla	UBERON:0000362	66.61	gold quality
pancreatic ductal cell	CL:0002079	65.22	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.67	gold quality
cerebellar hemisphere	UBERON:0002245	64.19	gold quality
cerebellar cortex	UBERON:0002129	64.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	63.82	gold quality
upper leg skin	UBERON:0004262	62.62	silver quality
intestine	UBERON:0000160	62.20	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	528.71
E-ANND-3	yes	4.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting SLC7A9, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-6776-3P	98.38	66.34	655

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 35)

• a decreasing expression gradient of heterodimeric rBAT-b(0,+)AT along the proximal tubule is responsible for virtually all apical cystine reabsorption (PMID:12167606)
• in cystinuria, the detection rate for mutations in SLC7A9 in children was 25% in the SLC7A9 gene for non-type I chromosomes. (PMID:12234283)
• The finding of SLC7A9 mutations in all three subtypes underscores the complex interactions between specific cystinuria genes and other factors influencing cystine excretion. (PMID:12371955)
• Three novel SLC7A9 mutations were identified: two missense mutations (P261L and V330M) and one single base-pair deletion (1009 delA) (PMID:12820697)
• deletions in SLC7A9 in cystinuria (PMID:14531788)
• Mutations of this protein have a population-specific distribution among south-east Europeans living in Germany. (PMID:14991253)
• Mutational analysis should focus on this gene in inheritance of cytinuria. (PMID:15635077)
• Disease: cystinuria, type non-I.Deletion codon 50. (PMID:15818799)
• gene deletion , codon 423 in cystinuria, type non-1. (PMID:15818803)
• SLC3A1 and SLC7A9 mutations may have roles in cystinuria (PMID:16138908)
• Mutations of SLC7A9 for Japanese cystinuria patients are different from those reported for European and American population. (PMID:16609684)
• all carriers of a SLC7A9 mutation manifested cystinuria if their normal allele had non-wild type nucleotides in two or more of the identified polymorphic sites (PMID:16838140)
• a novel splice-acceptor site mutation in the SLC7A9 gene may have a role in cystinuria [case report] (PMID:17701443)
• To characterize the clinical features and analyze the genetic basis of cystinuria in an inbred Moslem Arab Israeli family. Sequencing of this gene revealed a missense mutation, P482L, in the homozygous state in all three affected sibs (PMID:17710781)
• Twenty-four novel mutations in a cohort of 85 patients by direct sequencing of the SLC3A1 and SLC7A9 cystinyuria genes are reported. (PMID:18752446)
• SLC3A1 and SLC7A9 mutations identified in 52 Greek cystinuria patients; in total 14 mutations were identified in SLC3A1 and 12 in SLC7A9. (PMID:18778962)
• Suggest that amino acid transporters B(0)AT1 and b(0,+)AT are involved in the reabsorption of L-citrulline in the kidney, at least in part, by mediating the apical membrane transport of L-citrulline in renal tubule cells. (PMID:19322909)
• Studies identified 6 different alleles in SLC3A1 and 2 in SLC7A9 accounting for a total of 25 copy number changes, 11 in SLC3A1 and 14 in SLC7A9. (PMID:19782624)
• In SLC7A9 gene, one large genomic rearrangement and 24 sequence variants are found in cystinuria patients. (PMID:21255007)
• We present six family members with a complex phenotypic profile of cystinuria based on mutations in SLC3A1 (type A) or SLC7A9 (type B). (PMID:24045899)
• Case Report: novel mutation of SLC7A9 gene in cystinuria. (PMID:25599739)
• Report no association of SLC7A9 mutations with clinical course of disease in cystinuria patients. (PMID:25964309)
• G105R but not R333W mutation found in Iranian cystinuria patients (PMID:26123750)
• Five SLC3A1 and SLC7A9 mutations appear to be responsible for the genetic basis of cystinuria in the Greek-Cypriot patients (PMID:26540609)
• A new variation in exon 4 of the SLC7A9 gene was identified in cystinuria patients, which was insertion of 1 adenine nucleotide between 2 cytosine nucleotides in position c.213-214insA. (PMID:28270646)
• Spectrum of SLC3A1 and SLC7A9 mutations in cystinuria patients presenting with prenatal hyperechoic colon has been described. (PMID:28646536)
• Thirteen pediatric patients with cystine stones were evaluated in our clinic between 2012 and 2015. Gene mutations in SLC3A1 and SLC7A9 were investigated (PMID:28689648)
• Analysis showing how different mutations in SLC3A1 and SLC7A9 affect severity of cystinuria. (PMID:28812535)
• Study shows that various computational tools were able to distinguish cystinuria-causing mutations from benign polymorphisms. Only missense mutation V142A had a benign effect on the protein structure and function of SLC7A9. The intron variant c.604+66C>G in SLC7A9 gene probably affected the splicing process. (PMID:30069816)
• A homozygous c.325G>A mutation in cationic amino cid transport proteins (SLC7A9) was identified in two patients, and six neutral and basic amino acid transporter protein (SLC3A1) mutations were found in five patients. (PMID:30146843)
• Structural basis for amino acid exchange by a human heteromeric amino acid transporter. (PMID:32817565)
• Clinical profile of a Polish cohort of children and young adults with cystinuria. (PMID:33349102)
• SLC7A9 as a Potential Biomarker for Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma. (PMID:34773193)
• Interpretation of SLC3A1 and SLC7A9 variants in cystinuria patients: The significance of the PM3 criterion and protein stability. (PMID:37439839)
• Population genetics analysis of SLC3A1 and SLC7A9 revealed the etiology of cystine stone may be more than what our current genetic knowledge can explain. (PMID:37561200)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc7a9	ENSDARG00000005894
mus_musculus	Slc7a9	ENSMUSG00000030492
rattus_norvegicus	Slc7a9	ENSRNOG00000012344
drosophila_melanogaster	mnd	FBGN0002778
drosophila_melanogaster	CG7255	FBGN0036493
drosophila_melanogaster	CG5535	FBGN0036764
drosophila_melanogaster	slif	FBGN0037203
drosophila_melanogaster	CG1607	FBGN0039844
caenorhabditis_elegans		WBGENE00000002
caenorhabditis_elegans		WBGENE00000003
caenorhabditis_elegans		WBGENE00000005
caenorhabditis_elegans	aat-9	WBGENE00000010
caenorhabditis_elegans		WBGENE00015197
caenorhabditis_elegans		WBGENE00017747

Paralogs (12): SLC7A2 (ENSG00000003989), SLC7A14 (ENSG00000013293), SLC7A8 (ENSG00000092068), SLC7A4 (ENSG00000099960), SLC7A6 (ENSG00000103064), SLC7A5 (ENSG00000103257), SLC7A10 (ENSG00000130876), SLC7A1 (ENSG00000139514), SLC7A11 (ENSG00000151012), SLC7A7 (ENSG00000155465), SLC7A13 (ENSG00000164893), SLC7A3 (ENSG00000165349)

Protein

Protein identifiers

b(0,+)-type amino acid transporter 1 — P82251 (reviewed: P82251)

Alternative names: Glycoprotein-associated amino acid transporter b0,+AT1, Solute carrier family 7 member 9

All UniProt accessions (2): P82251, K7EKD0

UniProt curated annotations — full annotation on UniProt →

Function. Associates with SLC3A1 to form a functional transporter complex that mediates the electrogenic exchange between cationic amino acids and neutral amino acids, with a stoichiometry of 1:1. Has system b(0,+)-like activity with high affinity for extracellular cationic amino acids and L-cystine and lower affinity for intracellular neutral amino acids. Substrate exchange is driven by high concentration of intracellular neutral amino acids and the intracellular reduction of L-cystine to L-cysteine. Required for reabsorption of L-cystine and dibasic amino acids across the brush border membrane in renal proximal tubules.

Subunit / interactions. Disulfide-linked heterodimer composed of the catalytic light chain subunit SLC7A9 and the heavy chain subunit SLC3A1. The heterodimer is the minimal functional unit. Assembles in heterotetramers (dimers of heterodimers) and higher order oligomers; the oligomerization is mediated by SLC3A1 likely to prevent degradation and facilitate heteromer trafficking to the plasma membrane. Interacts with CAV1.

Subcellular location. Apical cell membrane. Cell membrane.

Tissue specificity. Expressed in the brush border membrane in the kidney (at protein level). Kidney, small intestine, liver and placenta.

Disease relevance. Cystinuria (CSNU) [MIM:220100] An autosomal disorder characterized by impaired epithelial cell transport of cystine and dibasic amino acids (lysine, ornithine, and arginine) in the proximal renal tubule and gastrointestinal tract. The impaired renal reabsorption of cystine and its low solubility causes the formation of calculi in the urinary tract, resulting in obstructive uropathy, pyelonephritis, and, rarely, renal failure. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the amino acid-polyamine-organocation (APC) superfamily.

RefSeq proteins (3): NP_001119807, NP_001229965, NP_055085* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002293	AA/rel_permease1	Family
IPR050598	AminoAcid_Transporter	Family

Pfam: PF13520

Catalyzed reactions (Rhea), 6 shown:

• L-lysine(out) + L-arginine(in) = L-lysine(in) + L-arginine(out) (RHEA:70827)
• L-leucine(out) + L-arginine(in) = L-leucine(in) + L-arginine(out) (RHEA:71059)
• L-histidine(out) + L-arginine(in) = L-histidine(in) + L-arginine(out) (RHEA:71063)
• L-phenylalanine(out) + L-arginine(in) = L-phenylalanine(in) + L-arginine(out) (RHEA:71067)
• L-cysteine(out) + L-arginine(in) = L-cysteine(in) + L-arginine(out) (RHEA:71071)
• L-cystine(out) + L-arginine(in) = L-cystine(in) + L-arginine(out) (RHEA:71075)

UniProt features (131 total): sequence variant 49, helix 23, turn 13, transmembrane region 12, topological domain 11, mutagenesis site 10, strand 5, binding site 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6LI9	ELECTRON MICROSCOPY	2.3
6LID	ELECTRON MICROSCOPY	2.7
6YUP	ELECTRON MICROSCOPY	2.9
6YV1	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P82251-F1	85.26	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 43–47; 233

Post-translational modifications (1): 18

Disulfide bonds (1): 144

Mutagenesis-validated functional residues (10):

Position	Phenotype
230	abolishes amino acid transport activity.
233	complete loss of amino acid transport activity.
235	complete loss of amino acid transport activity.
237	reduces amino acid transport activity.
321	does not affect amino acid transport activity.
379	markedly reduces amino acid transport activity.
383	complete loss of amino acid transport activity.
386	loss of amino acid transport activity.
482	no effect on amino acid transport activity.
482	decreased amino acid transport activity.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-210991	Basigin interactions
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-5619113	Defective SLC3A1 causes cystinuria (CSNU)
R-HSA-5660883	Defective amino acid transport by SLC7A9 causes cystinuria (CSNU)
R-HSA-109582	Hemostasis
R-HSA-1643685	Disease
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 126 (showing top): AAGCAAT_MIR137, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, TGACCTY_ERR1_Q2, HNF1_Q6, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, CHX10_01, GOBP_ORGANIC_ACID_TRANSPORT, COUP_01, NKX62_Q2, GOBP_AMINO_ACID_TRANSPORT, GOBP_BASIC_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SULFUR_COMPOUND_TRANSPORT, HNF4_01, PPAR_DR1_Q2

GO Biological Process (8): amino acid transmembrane transport (GO:0003333), neutral amino acid transport (GO:0015804), L-cystine transport (GO:0015811), protein-containing complex assembly (GO:0065003), amino acid transport (GO:0006865), transmembrane transport (GO:0055085), L-alpha-amino acid transmembrane transport (GO:1902475), basic amino acid transmembrane transport (GO:1990822)

GO Molecular Function (9): neutral L-amino acid transmembrane transporter activity (GO:0015175), L-cystine transmembrane transporter activity (GO:0015184), antiporter activity (GO:0015297), peptide antigen binding (GO:0042605), protein heterodimerization activity (GO:0046982), broad specificity neutral L-amino acid:basic L-amino acid antiporter activity (GO:0180009), protein binding (GO:0005515), amino acid transmembrane transporter activity (GO:0015171), transmembrane transporter activity (GO:0022857)

GO Cellular Component (4): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), brush border membrane (GO:0031526), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
SLC transporter disorders	2
Cell surface interactions at the vascular wall	1
SLC-mediated transport of amino acids	1
Hemostasis	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
amino acid transmembrane transport	3
amino acid transport	2
transmembrane transport	2
neutral amino acid transport	2
L-amino acid transport	2
transport	2
sulfur amino acid transport	1
modified amino acid transport	1
cellular component assembly	1
protein-containing complex organization	1
cellular process	1
carboxylic acid transmembrane transport	1
basic amino acid transport	1
amino acid transmembrane transporter activity	1
sulfur amino acid transmembrane transporter activity	1
L-amino acid transmembrane transporter activity	1
L-cystine transport	1
modified amino acid transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
antigen binding	1
peptide binding	1
protein dimerization activity	1
basic amino acid transmembrane transporter activity	1
neutral L-amino acid transmembrane transporter activity	1
antiporter activity	1
binding	1
transmembrane transporter activity	1
transporter activity	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
brush border	1
apical plasma membrane	1
cell projection membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

982 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC7A9	SLC3A1	Q07837	998
SLC7A9	SLC3A2	P08195	824
SLC7A9	SLC6A19	Q695T7	748
SLC7A9	AIRE	O43918	743
SLC7A9	SLC6A14	Q9UN76	666
SLC7A9	SLC1A1	P43005	626
SLC7A9	SLC15A1	P46059	597
SLC7A9	SLC36A1	Q7Z2H8	547
SLC7A9	SLC6A20	Q9NP91	520
SLC7A9	SLC34A1	Q06495	519
SLC7A9	SLC1A5	Q15758	517
SLC7A9	SLC16A10	Q8TF71	511
SLC7A9	SHROOM3	Q8TF72	507
SLC7A9	SLC43A2	Q8N370	505
SLC7A9	SLC38A2	Q96QD8	495

IntAct

10 interactions, top by confidence:

A	B	Type	Score
SLC7A9	CREB3	psi-mi:“MI:0915”(physical association)	0.560
SLC3A1	SLC7A9	psi-mi:“MI:0407”(direct interaction)	0.520
TGM2	SLC7A9	psi-mi:“MI:0915”(physical association)	0.370
SLC7A9	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
SLC7A9	CDC7	psi-mi:“MI:0914”(association)	0.350
AGO2	NDUFA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (114): SLC7A9 (Two-hybrid), CREB3 (Two-hybrid), ABR (Affinity Capture-MS), ADAM15 (Affinity Capture-MS), AKAP11 (Affinity Capture-MS), AKAP12 (Affinity Capture-MS), ANKHD1 (Affinity Capture-MS), ANKRD44 (Affinity Capture-MS), AP5S1 (Affinity Capture-MS), ARFGEF1 (Affinity Capture-MS), ARFGEF2 (Affinity Capture-MS), KIAA1244 (Affinity Capture-MS), ARMC6 (Affinity Capture-MS), ATF6B (Affinity Capture-MS), ATG2B (Affinity Capture-MS)

ESM2 similar proteins: O04249, O65413, P23586, P46032, P46896, P58353, P82251, P82252, P93051, Q07423, Q0WP01, Q0WQ63, Q10710, Q10PW9, Q39228, Q3ECP7, Q41144, Q4F7G0, Q5Q0U0, Q6Z401, Q6ZKF0, Q7EZD7, Q851G4, Q8BN82, Q8GW61, Q8L7R8, Q8LBI9, Q8VZT3, Q8WMN1, Q93Y91, Q93YP9, Q94AZ2, Q94CI6, Q94CI7, Q94EC3, Q94EC4, Q94KE0, Q9FMX3, Q9FRL3, Q9LFB8

Diamond homologs: A1L3M3, D3ZMM8, O34739, P63115, P63116, P82251, P82252, Q01650, Q22397, Q28I80, Q59I64, Q5RAE3, Q5RAG7, Q5RKI7, Q63016, Q7YQK4, Q8BGK6, Q8MH63, Q8TCU3, Q91WN3, Q92536, Q9GIP4, Q9N1Q4, Q9N1R6, Q9NS82, Q9QXA6, Q9QXW9, Q9R0S5, Q9UHI5, Q9UM01, Q9UPY5, Q9WTR6, Q9WVR6, Q9Z127, Q9Z1K8, Q8VIE6, A0JNI9, A8I499, B0UYF2, B3TP03

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

472 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	35
Likely pathogenic	45
Uncertain significance	174
Likely benign	84
Benign	60

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068795	NC_000019.10:g.32833324del	Pathogenic
1071621	NM_014270.5(SLC7A9):c.501dup (p.Leu168fs)	Pathogenic
1179151	NM_014270.5(SLC7A9):c.1262_1263del (p.Ser421fs)	Pathogenic
1323616	NM_014270.5(SLC7A9):c.1400-2A>G	Pathogenic
1404775	NM_014270.5(SLC7A9):c.604+1G>A	Pathogenic
1452963	NM_014270.5(SLC7A9):c.157A>T (p.Lys53Ter)	Pathogenic
1459890	NC_000019.9:g.(?33324055)(33324229_?)del	Pathogenic
1687433	NM_014270.5(SLC7A9):c.730del (p.Glu244fs)	Pathogenic
2060879	NM_014270.5(SLC7A9):c.1445C>T (p.Pro482Leu)	Pathogenic
2425932	NC_000019.9:g.(?33349326)(33351576_?)del	Pathogenic
242913	NM_014270.5(SLC7A9):c.1224+4167_1324del	Pathogenic
2431528	NM_014270.5(SLC7A9):c.206G>A (p.Trp69Ter)	Pathogenic
2584401	NM_014270.5(SLC7A9):c.235+1del	Pathogenic
2683632	NM_014270.5(SLC7A9):c.459C>A (p.Cys153Ter)	Pathogenic
2762200	NM_014270.5(SLC7A9):c.23del (p.Lys8fs)	Pathogenic
288197	NM_014270.5(SLC7A9):c.614dup (p.Asn206fs)	Pathogenic
3359165	NM_014270.5(SLC7A9):c.74del (p.Ser25fs)	Pathogenic
3359173	NM_014270.5(SLC7A9):c.1399+1G>C	Pathogenic
3359175	NM_014270.5(SLC7A9):c.220dup (p.Val74fs)	Pathogenic
3359176	NM_014270.5(SLC7A9):c.1399+2T>C	Pathogenic
3359177	NM_014270.5(SLC7A9):c.785del (p.Leu262fs)	Pathogenic
3377378	NM_014270.5(SLC7A9):c.584G>A (p.Gly195Glu)	Pathogenic
4713802	NM_014270.5(SLC7A9):c.808dup (p.Met270fs)	Pathogenic
562455	NM_014270.5(SLC7A9):c.1353C>A (p.Tyr451Ter)	Pathogenic
5780	NM_014270.5(SLC7A9):c.508G>A (p.Val170Met)	Pathogenic
5786	NM_014270.5(SLC7A9):c.335dup (p.Ser113fs)	Pathogenic
5788	NM_014270.5(SLC7A9):c.131T>C (p.Ile44Thr)	Pathogenic
666217	NC_000019.10:g.(?32830600)(32868554_?)del	Pathogenic
804180	NM_014270.5(SLC7A9):c.525del (p.Ser174_Tyr175insTer)	Pathogenic
804193	NM_014270.5(SLC7A9):c.1399+2dup	Pathogenic

SpliceAI

1814 predictions. Top by Δscore:

Variant	Effect	Δscore
19:32830798:AGAC:A	donor_gain	1.0000
19:32833147:A:AC	donor_gain	1.0000
19:32833148:C:CC	donor_gain	1.0000
19:32833242:C:CA	donor_gain	1.0000
19:32833270:C:CT	acceptor_gain	1.0000
19:32833276:C:CT	acceptor_gain	1.0000
19:32833277:A:T	acceptor_gain	1.0000
19:32842162:GCTTA:G	donor_loss	1.0000
19:32842163:CTTA:C	donor_loss	1.0000
19:32842164:TTACC:T	donor_loss	1.0000
19:32842165:TACCT:T	donor_loss	1.0000
19:32842166:ACCTT:A	donor_loss	1.0000
19:32842167:C:A	donor_loss	1.0000
19:32842316:CC:C	acceptor_gain	1.0000
19:32842317:CCTAA:C	acceptor_gain	1.0000
19:32859836:CTCA:C	donor_loss	1.0000
19:32859838:CA:C	donor_loss	1.0000
19:32859839:A:AC	donor_gain	1.0000
19:32859839:A:AG	donor_loss	1.0000
19:32859839:AC:A	donor_gain	1.0000
19:32859840:C:CC	donor_gain	1.0000
19:32859840:C:T	donor_loss	1.0000
19:32859840:CC:C	donor_gain	1.0000
19:32859840:CCA:C	donor_gain	1.0000
19:32859960:GGTTT:G	acceptor_gain	1.0000
19:32859961:GTTTC:G	acceptor_loss	1.0000
19:32859962:TTT:T	acceptor_gain	1.0000
19:32859962:TTTC:T	acceptor_loss	1.0000
19:32859963:TT:T	acceptor_gain	1.0000
19:32859964:TC:T	acceptor_loss	1.0000

AlphaMissense

3154 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:32862119:A:G	W235R	0.998
19:32862119:A:T	W235R	0.998
19:32864717:G:C	F49L	0.998
19:32864717:G:T	F49L	0.998
19:32864719:A:G	F49L	0.998
19:32859845:G:T	A290D	0.997
19:32862121:C:T	G234E	0.997
19:32864234:A:G	W114R	0.997
19:32864234:A:T	W114R	0.997
19:32864293:C:T	G94E	0.997
19:32864659:A:G	W69R	0.997
19:32864659:A:T	W69R	0.997
19:32864725:C:A	G47W	0.997
19:32843931:C:G	R333P	0.996
19:32858440:C:G	R326T	0.996
19:32860621:A:G	L245P	0.996
19:32860638:A:C	N239K	0.996
19:32860638:A:T	N239K	0.996
19:32862567:G:C	N166K	0.996
19:32862567:G:T	N166K	0.996
19:32864248:G:T	A109D	0.996
19:32864294:C:A	G94W	0.996
19:32864646:C:T	G73E	0.996
19:32864647:C:G	G73R	0.996
19:32864647:C:T	G73R	0.996
19:32864718:A:C	F49C	0.996
19:32864724:C:T	G47E	0.996
19:32833209:C:G	G447R	0.995
19:32858462:C:A	G319W	0.995
19:32859939:C:G	G259R	0.995

dbSNP variants (sampled 300 via entrez): RS1000001946 (19:32832841 C>A), RS1000016932 (19:32868117 G>A), RS1000047882 (19:32868325 A>T), RS1000105492 (19:32833877 G>C), RS1000355801 (19:32859035 T>A,C), RS1000379218 (19:32845559 T>A,C), RS1000409336 (19:32864414 G>A,C), RS1000439618 (19:32832597 AAAAAAAAG>A), RS1000456746 (19:32834290 C>T), RS1000488848 (19:32847265 G>A), RS1000566292 (19:32870608 G>A), RS1000636012 (19:32869444 T>C), RS1000744974 (19:32865217 T>C), RS1000912905 (19:32854003 A>G), RS1000961762 (19:32860500 T>A,C)

Disease associations

OMIM: gene MIM:604144 | disease phenotypes: MIM:220100, MIM:158810, MIM:173900

GenCC curated gene-disease

Disease	Classification	Inheritance
cystinuria	Definitive	Autosomal recessive
cystinuria type B	Supportive	Semidominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
cystinuria	Definitive	AR

Mondo (4): cystinuria (MONDO:0009067), Bethlem myopathy 1A (MONDO:0024530), polycystic kidney disease 1 (MONDO:0008263), cystinuria type B (MONDO:0019746)

Orphanet (2): Cystinuria (Orphanet:214), Bethlem muscular dystrophy (Orphanet:610)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000083	Renal insufficiency
HP:0000787	Nephrolithiasis
HP:0003131	Cystinuria
HP:0003268	Argininuria
HP:0003297	Hyperlysinuria
HP:0003532	Ornithinuria

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000649_8	Chronic kidney disease	3.000000e-15
GCST000651_3	Creatinine levels	5.000000e-11
GCST001073_2	Urinary metabolites	6.000000e-27
GCST002364_33	Urinary metabolites (H-NMR features)	1.000000e-33
GCST002364_34	Urinary metabolites (H-NMR features)	2.000000e-33
GCST002364_35	Urinary metabolites (H-NMR features)	1.000000e-33
GCST003372_60	Glomerular filtration rate (creatinine)	2.000000e-13
GCST003401_26	Glomerular filtration rate in non diabetics (creatinine)	3.000000e-12
GCST004292_13	Glomerular filtration rate (creatinine)	2.000000e-12
GCST005649_1	Urinary metabolite ratios in chronic kidney disease	1.000000e-18
GCST005649_10	Urinary metabolite ratios in chronic kidney disease	2.000000e-23
GCST005649_11	Urinary metabolite ratios in chronic kidney disease	3.000000e-22
GCST005649_12	Urinary metabolite ratios in chronic kidney disease	6.000000e-22
GCST005649_13	Urinary metabolite ratios in chronic kidney disease	2.000000e-19
GCST005649_14	Urinary metabolite ratios in chronic kidney disease	5.000000e-19
GCST005649_2	Urinary metabolite ratios in chronic kidney disease	3.000000e-17
GCST005649_3	Urinary metabolite ratios in chronic kidney disease	8.000000e-17
GCST005649_4	Urinary metabolite ratios in chronic kidney disease	9.000000e-17
GCST005651_7	Urinary metabolite levels in chronic kidney disease	5.000000e-12
GCST005666_2	Fractional excretion of metabolites in chronic kidney disease	2.000000e-09
GCST005985_58	Creatinine levels	1.000000e-08
GCST007344_103	Estimated glomerular filtration rate	3.000000e-17
GCST007876_146	Estimated glomerular filtration rate	9.000000e-28
GCST007877_22	Creatinine levels	1.000000e-12
GCST008971_59	Urate levels	9.000000e-12
GCST009733_114	Urinary metabolite levels in chronic kidney disease	2.000000e-23
GCST009733_40	Urinary metabolite levels in chronic kidney disease	4.000000e-21
GCST009733_82	Urinary metabolite levels in chronic kidney disease	9.000000e-12
GCST009735_19	Urinary metabolite modules (eigenmetabolites) in chronic kidney disease	2.000000e-17
GCST012020_538	Serum metabolite levels	2.000000e-21

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0005116	urinary metabolite measurement
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003555	Cystinuria	C12.050.351.968.419.815.885.250; C12.200.777.419.815.885.250; C12.950.419.815.885.250; C16.320.831.885.250
C536326	Polycystic kidney disease, type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC7 family

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, increases methylation	3
Benzo(a)pyrene	affects methylation, decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
potassium perchlorate	decreases expression	1
quercitrin	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
perfluorooctane sulfonic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
2-amino-3-(2-amino-2-carboxyethylsulfanyl-mercuricsulfanyl)-propionic acid	increases uptake, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Cystine	affects cotreatment, increases uptake	1
Methapyrilene	increases methylation	1
Quercetin	decreases expression	1
Silicon Dioxide	increases expression	1
Valproic Acid	decreases expression	1
Zidovudine	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0E71	GM16753	Transformed cell line	Female

Clinical trials (associated diseases)

21 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02125721	PHASE4	COMPLETED	Effect of Increasing Doses of Cystine Binding Thiol Drugs on Cystine Capacity in Patients With Cystinuria
NCT02910531	PHASE2	COMPLETED	Lipoic Acid Supplement for Cystine Stone
NCT02942420	PHASE2	UNKNOWN	Bucillamine Phase 2 Trial in Patients With Cystinuria
NCT03663855	PHASE2	COMPLETED	Effect of Increasing Doses of Tiopronin on Cystine Capacity in Patients With Cystinuria
NCT04818034	PHASE2	COMPLETED	The Effect of Sodium-glucose Cotransporter (SGLT) 2 Inhibitors on Cystine Stone Formation: A Preliminary Study
NCT05058859	PHASE2	WITHDRAWN	Long Term Clinical Efficacy of Sodium-glucose Cotransporter-2 (SGLT-2) Inhibitor in Cystinurics
NCT04137978	PHASE2/PHASE3	WITHDRAWN	Study Evaluating Patients With Cystinuria
NCT04147871	PHASE2/PHASE3	WITHDRAWN	Study Evaluating Patients With Cystinuria and Efficacy and Safety Exploratory Study in the Youngest Children
NCT00381849	PHASE1/PHASE2	COMPLETED	Use of an Herbal Preparation to Prevent and Dissolve Kidney Stones
NCT00169806	Not specified	ACTIVE_NOT_RECRUITING	Randall’s Plaque Study: Pathogenesis and Relationship to Nephrolithiasis
NCT00588562	Not specified	RECRUITING	Rare Kidney Stone Consortium Patient Registry
NCT02026388	Not specified	RECRUITING	Rare Kidney Stone Consortium Biobank
NCT02120105	Not specified	COMPLETED	Cystine Capacity Clinical Study (CysCap)
NCT02124395	Not specified	COMPLETED	Health-related Quality of Life in Rare Kidney Stone
NCT02538016	Not specified	COMPLETED	TCUPS- Tolvaptan Use in Cystinuria and Urolithiasis: A Pilot Study
NCT02780297	Not specified	RECRUITING	Prospective Research Rare Kidney Stones (ProRKS)
NCT03539926	Not specified	UNKNOWN	This Study Evaluates the Superiority of Daily Self-pH Monitorization of Lit-control®pH Meter Compared to the Monitorization of Reactive Strips (Standard of Care).
NCT03836144	Not specified	COMPLETED	Effect of Urine Alkalinazation on Urinary Inflammatory Markers in Patients With Cystinuria
NCT05048563	Not specified	COMPLETED	Registry of Thiola EC Therapy
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT04020159	Not specified	UNKNOWN	Global Registry for COL6-related Dystrophies