SLC6A20

Summary

SLC6A20 (solute carrier family 6 member 20, HGNC:30927) is a protein-coding gene on chromosome 3p21.31, encoding Sodium- and chloride-dependent transporter XTRP3 (Q9NP91). Mediates the Na(+)- and Cl(-)-dependent uptake of imino acids such as L-proline, N-methyl-L-proline and pipecolate as well as N-methylated amino acids.

Transport of small hydrophilic substances across cell membranes is mediated by substrate-specific transporter proteins which have been classified into several families of related genes. The protein encoded by this gene belongs to the sodium:neurotransmitter symporter (SNF) family and functions as a proline transporter expressed in kidney and small intestine. Mutations in this gene are associated with Hyperglycinuria and Iminoglycinuria.

Source: NCBI Gene 54716 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperglycinuria (Limited, GenCC)
• GWAS associations: 18
• Clinical variants (ClinVar): 295 total
• Phenotypes (HPO): 6
• MANE Select transcript: NM_020208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30927
Approved symbol	SLC6A20
Name	solute carrier family 6 member 20
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	XT3, Xtrp3, SIT1, IMINO
Ensembl gene	ENSG00000163817
Ensembl biotype	protein_coding
OMIM	605616
Entrez	54716

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000353278, ENST00000358525, ENST00000413781, ENST00000470226, ENST00000473146, ENST00000493980, ENST00000703343, ENST00000703344, ENST00000962428, ENST00000962429

RefSeq mRNA: 6 — MANE Select: NM_020208 NM_001385683, NM_001406066, NM_001406067, NM_001406069, NM_020208, NM_022405

CCDS: CCDS2730, CCDS43077, CCDS93258

Canonical transcript exons

ENST00000358525 — 11 exons

Exon	Start	End
ENSE00001078587	45772505	45772615
ENSE00001078588	45782083	45782223
ENSE00001078589	45775761	45775988
ENSE00001329465	45780009	45780100
ENSE00003489221	45765537	45765741
ENSE00003528777	45770209	45770371
ENSE00003584806	45759857	45760022
ENSE00003656198	45762913	45763072
ENSE00003786205	45771217	45771458
ENSE00003844483	45755449	45759127
ENSE00003845203	45796299	45796536

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 96.69.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2386 / max 81.9052, expressed in 77 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41902	0.1437	47
41901	0.0676	33
41904	0.0273	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	96.69	gold quality
choroid plexus epithelium	UBERON:0003911	92.35	gold quality
duodenum	UBERON:0002114	88.13	gold quality
jejunal mucosa	UBERON:0000399	87.71	gold quality
gall bladder	UBERON:0002110	85.19	gold quality
ileal mucosa	UBERON:0000331	84.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.44	gold quality
palpebral conjunctiva	UBERON:0001812	81.86	gold quality
epithelial cell of pancreas	CL:0000083	79.66	silver quality
tibial nerve	UBERON:0001323	77.04	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.01	gold quality
small intestine	UBERON:0002108	76.80	gold quality
secondary oocyte	CL:0000655	76.19	gold quality
islet of Langerhans	UBERON:0000006	75.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.77	gold quality
pancreatic ductal cell	CL:0002079	74.65	silver quality
pancreas	UBERON:0001264	72.18	gold quality
body of pancreas	UBERON:0001150	71.03	gold quality
jejunum	UBERON:0002115	68.77	gold quality
sural nerve	UBERON:0015488	68.41	gold quality
buccal mucosa cell	CL:0002336	67.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	67.73	gold quality
trigeminal ganglion	UBERON:0001675	67.03	gold quality
oocyte	CL:0000023	65.88	gold quality
nasal cavity epithelium	UBERON:0005384	65.57	silver quality
heart right ventricle	UBERON:0002080	65.07	gold quality
myocardium	UBERON:0002349	64.21	gold quality
left ventricle myocardium	UBERON:0006566	63.88	gold quality
endocervix	UBERON:0000458	63.87	gold quality
upper lobe of lung	UBERON:0008948	63.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	14.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting SLC6A20, 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-6758-5P	100.00	66.21	1470
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-376A-3P	99.06	69.17	1128

Literature-anchored findings (GeneRIF, showing 10)

• Using homology modeling we identified two highly conserved Na(+)-binding sites and a putative Cl(-)-binding site of SLC6A20. (PMID:19657969)
• genetic association studies in two populations, European/Rotterdam and Chinese Han/Shanghai: Data suggest that an SNP in SLC6A20 (rs13062383) is associated with predisposition of type 2 diabetes. [META-ANALYSIS] (PMID:24958070)
• SIT1, B(0)AT1 and ACE2 were co-localized in the brush-border membrane of small intestine enterocytes. (PMID:25534429)
• Imputed meta-analysis revealed that 13 SLC6A20 SNPs were significantly associated with Hirschsprung disease. In further subgroup analysis, SLC6A20 polymorphisms appeared to have increased associations with Long-Segment Hirschsprung disease. (PMID:26049783)
• SIT1 is not expressed in small intestine of human newborns. (PMID:30160974)
• Associations of SLC6A20 genetic polymorphisms with Hirschsprung’s disease in a Southern Chinese population. (PMID:31358688)
• Genome and epigenome editing identify CCR9 and SLC6A20 as target genes at the 3p21.31 locus associated with severe COVID-19. (PMID:33619245)
• Integrative approach identifies SLC6A20 and CXCR6 as putative causal genes for the COVID-19 GWAS signal in the 3p21.31 locus. (PMID:34425859)
• SIT1 transporter as a potential novel target in treatment of COVID-19. (PMID:34969185)
• Characterization and substrate specificity of the Na+ coupled IMINO transport system in apical brush border membranes of epithelial cells. Identically found in kidney proximal tubule. (PMID:3571270)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc6a20b	ENSMUSG00000025243
mus_musculus	Slc6a20a	ENSMUSG00000036814
rattus_norvegicus	Slc6a20b	ENSRNOG00000006010
rattus_norvegicus	Slc6a20a	ENSRNOG00000068642

Paralogs (19): SLC6A13 (ENSG00000010379), SLC6A7 (ENSG00000011083), SLC6A16 (ENSG00000063127), SLC6A15 (ENSG00000072041), SLC6A2 (ENSG00000103546), SLC6A4 (ENSG00000108576), SLC6A12 (ENSG00000111181), SLC6A8 (ENSG00000130821), SLC6A6 (ENSG00000131389), SLC6A11 (ENSG00000132164), SLC6A3 (ENSG00000142319), SLC6A1 (ENSG00000157103), SLC6A18 (ENSG00000164363), SLC6A5 (ENSG00000165970), SLC6A19 (ENSG00000174358), SLC6A9 (ENSG00000196517), SLC6A17 (ENSG00000197106), SLC6A14 (ENSG00000268104), (ENSG00000273554)

Protein

Protein identifiers

Sodium- and chloride-dependent transporter XTRP3 — Q9NP91 (reviewed: Q9NP91)

Alternative names: Sodium/imino-acid transporter 1, Solute carrier family 6 member 20, Transporter rB21A homolog

All UniProt accessions (2): A0A8V8TQV4, Q9NP91

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the Na(+)- and Cl(-)-dependent uptake of imino acids such as L-proline, N-methyl-L-proline and pipecolate as well as N-methylated amino acids. Also transports glycine, regulates proline and glycine homeostasis in the brain playing a role in the modulation of NMDAR currents.

Subcellular location. Apical cell membrane.

Tissue specificity. Kidney and small intestine. Expressed in the S3 segment of the proximal tubule. Expressed in neurons.

Disease relevance. Hyperglycinuria (HGLY) [MIM:138500] A condition characterized by excess of glycine in the urine. In some cases it is associated with renal colic and renal oxalate stones. The disease is caused by variants affecting the gene represented in this entry. Iminoglycinuria (IG) [MIM:242600] A disorder of renal tubular reabsorption of glycine and imino acids (proline and hydroxyproline), marked by excessive levels of all three substances in the urine. The disease is caused by variants affecting the gene represented in this entry. Haploinsufficiency of SLC6A20 combined with deficiency of the neutral amino acid transporter SLC6A19 or partially inactivating mutations in SLC36A2, is responsible for iminoglycinuria. Additional polymorphisms and mutations in SLC6A18 can contribute to the IG phenotype in some families.

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A20 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NP91-1	1, XT3, V1	yes
Q9NP91-2	2, XT3a, V2

RefSeq proteins (6): NP_001372612, NP_001392995, NP_001392996, NP_001392998, NP_064593, NP_071800 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR002438	Neutral_aa_SLC6	Family
IPR037272	SNS_sf	Homologous_superfamily

Pfam: PF00209

Catalyzed reactions (Rhea), 7 shown:

• glycine(out) + chloride(out) + 2 Na(+)(out) = glycine(in) + chloride(in) + 2 Na(+)(in) (RHEA:70691)
• glycine betaine(out) + chloride(out) + 2 Na(+)(out) = glycine betaine(in) + chloride(in) + 2 Na(+)(in) (RHEA:70735)
• L-proline(out) + chloride(out) + 2 Na(+)(out) = L-proline(in) + chloride(in) + 2 Na(+)(in) (RHEA:71263)
• L-pipecolate(out) + chloride(out) + 2 Na(+)(out) = L-pipecolate(in) + chloride(in) + 2 Na(+)(in) (RHEA:71267)
• sarcosine(out) + chloride(out) + 2 Na(+)(out) = sarcosine(in) + chloride(in) + 2 Na(+)(in) (RHEA:72227)
• N-methyl-L-proline(out) + chloride(out) + 2 Na(+)(out) = N-methyl-L-proline(in) + chloride(in) + 2 Na(+)(in) (RHEA:72231)
• 2-methyl-2-(methylamino)propanoate(out) + chloride(out) + 2 Na(+)(out) = 2-methyl-2-(methylamino)propanoate(in) + chloride(in) + 2 Na(+)(in) (RHEA:72235)

UniProt features (91 total): helix 33, turn 14, topological domain 13, transmembrane region 12, strand 11, glycosylation site 2, sequence variant 2, sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
7Y75	ELECTRON MICROSCOPY	3.1
7Y76	ELECTRON MICROSCOPY	3.2
8P31	ELECTRON MICROSCOPY	3.24
8P30	ELECTRON MICROSCOPY	3.29
8I91	ELECTRON MICROSCOPY	3.3
8WM3	ELECTRON MICROSCOPY	3.34
8P2Y	ELECTRON MICROSCOPY	3.46
8P2Z	ELECTRON MICROSCOPY	3.5
8P2X	ELECTRON MICROSCOPY	3.59
8P2W	ELECTRON MICROSCOPY	3.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP91-F1	93.25	0.85

Functional residue map

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

Glycosylation sites (2): 131, 357

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-5619101	Variant SLC6A20 affecting neurotransmitter transport contributes towards hyperglycinuria (HG) and iminoglycinuria (IG)
R-HSA-5660686	Variant SLC6A20 affecting amino acid transport contributes towards hyperglycinuria (HG) and iminoglycinuria (IG)
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425366
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: 356 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, GOBP_T_CELL_HOMEOSTASIS, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GGGTGGRR_PAX4_03, RODRIGUES_NTN1_TARGETS_DN, GOBP_AMINO_ACID_BETAINE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, MODULE_118

GO Biological Process (12): amino acid transport (GO:0006865), glycine transport (GO:0015816), proline transport (GO:0015824), amino-acid betaine transport (GO:0015838), sodium ion transmembrane transport (GO:0035725), amino acid import across plasma membrane (GO:0089718), transport across blood-brain barrier (GO:0150104), glycine import across plasma membrane (GO:1903804), L-isoleucine import across plasma membrane (GO:1903806), L-proline import across plasma membrane (GO:1904271), proline import across plasma membrane (GO:1905647), transmembrane transport (GO:0055085)

GO Molecular Function (11): proline:sodium symporter activity (GO:0005298), amino acid transmembrane transporter activity (GO:0015171), neutral L-amino acid transmembrane transporter activity (GO:0015175), L-isoleucine transmembrane transporter activity (GO:0015188), L-proline transmembrane transporter activity (GO:0015193), amino-acid betaine transmembrane transporter activity (GO:0015199), solute:sodium symporter activity (GO:0015370), protein binding (GO:0005515), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857), metal ion binding (GO:0046872)

GO Cellular Component (3): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
SLC transporter disorders	2
SLC-mediated transport of amino acids	1
SLC-mediated transmembrane transport	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
neutral amino acid transport	3
amino acid import across plasma membrane	3
transport	2
amino acid transmembrane transport	2
proline transmembrane transport	2
neutral L-amino acid transmembrane transporter activity	2
L-amino acid transmembrane transporter activity	2
carboxylic acid transport	1
nitrogen compound transport	1
L-amino acid transport	1
quaternary ammonium group transport	1
modified amino acid transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
import across plasma membrane	1
vascular transport	1
glycine transport	1
carboxylic acid transmembrane transport	1
L-alpha-amino acid transmembrane transport	1
isoleucine transmembrane transport	1
L-proline transmembrane transport	1
proline import across plasma membrane	1
cellular process	1
amino acid:sodium symporter activity	1
organic acid:sodium symporter activity	1
carboxylic acid transmembrane transporter activity	1
transmembrane transporter activity	1
amino acid transmembrane transporter activity	1
branched-chain amino acid transmembrane transporter activity	1
quaternary ammonium group transmembrane transporter activity	1
amino-acid betaine transport	1
modified amino acid transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1
solute:monoatomic cation symporter activity	1
binding	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
cation binding	1
membrane	1

Protein interactions and networks

STRING

834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A20	ACE2	Q9BYF1	986
SLC6A20	SLC36A2	Q495M3	959
SLC6A20	XYLT2	Q9H1B5	919
SLC6A20	LZTFL1	Q9NQ48	840
SLC6A20	FYCO1	Q9BQS8	785
SLC6A20	CXCR6	O00574	678
SLC6A20	CCR9	P51686	665
SLC6A20	XYLT1	Q86Y38	644
SLC6A20	XCR1	P46094	642
SLC6A20	ACKR2	O00590	584
SLC6A20	DPP9	Q86TI2	568
SLC6A20	SLC7A9	P82251	520
SLC6A20	HAND1	O96004	507
SLC6A20	SLC36A1	Q7Z2H8	489
SLC6A20	ACE	P12821	480

IntAct

39 interactions, top by confidence:

A	B	Type	Score
KRTAP10-8	SLC6A20	psi-mi:“MI:0915”(physical association)	0.720
SLC6A20	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
SLC6A20	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	SLC6A20	psi-mi:“MI:0915”(physical association)	0.560
SLC6A20	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
SLC6A20	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
SLC6A20	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
SLC6A20		psi-mi:“MI:0915”(physical association)	0.560
	SLC6A20	psi-mi:“MI:0915”(physical association)	0.560
SLC6A20	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	SLC6A20	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	SLC6A20	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-5	SLC6A20	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	SLC6A20	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	SLC6A20	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	SLC6A20	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	SLC6A20	psi-mi:“MI:0915”(physical association)	0.560
SLC6A20	TLCD2	psi-mi:“MI:0914”(association)	0.350
SLC6A20	EI24	psi-mi:“MI:0914”(association)	0.350

BioGRID (82): SLC6A20 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP1-1 (Two-hybrid), CYSRT1 (Two-hybrid), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid), ATP8A1 (Affinity Capture-MS), GPR89A (Affinity Capture-MS)

ESM2 similar proteins: A7Y2W8, B3MRS1, B3NV41, B4GVM9, B4JMC1, B4L7U0, B4MEG2, B4NDL8, B4PZQ4, B4R4T6, G5EBN9, O18875, O35316, O35899, O55192, P23975, P23977, P23978, P28570, P30531, P31641, P31643, P31645, P31646, P31647, P31648, P31649, P31650, P31652, P48057, P48066, P51143, P51905, Q00589, Q01959, Q03614, Q29GB8, Q60857, Q61327, Q64093

Diamond homologs: A5PJX7, A7Y2W8, A7Y2X0, B3MRS1, B3NV41, B4GVM9, B4JMC1, B4L7U0, B4MEG2, B4NDL8, B4PZQ4, B4R4T6, G5EBN9, O18875, O35316, O35899, O45813, O55192, O76689, O88575, O88576, P23975, P23977, P23978, P27799, P27922, P28570, P28571, P28572, P28573, P30531, P31641, P31643, P31645, P31646, P31647, P31648, P31649, P31650, P31651

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	219
Likely benign	30
Benign	36

Top pathogenic / likely-pathogenic (0)

SpliceAI

2443 predictions. Top by Δscore:

Variant	Effect	Δscore
3:45759852:GATA:G	donor_loss	1.0000
3:45759853:ATAC:A	donor_loss	1.0000
3:45759854:TAC:T	donor_loss	1.0000
3:45759855:A:T	donor_loss	1.0000
3:45759883:T:TA	donor_gain	1.0000
3:45760018:CAAAT:C	acceptor_gain	1.0000
3:45760022:TC:T	acceptor_loss	1.0000
3:45760023:C:CC	acceptor_gain	1.0000
3:45760023:CT:C	acceptor_loss	1.0000
3:45760024:T:A	acceptor_loss	1.0000
3:45760027:T:TC	acceptor_gain	1.0000
3:45762914:T:TA	donor_gain	1.0000
3:45765533:TGA:T	donor_loss	1.0000
3:45765536:C:CT	donor_loss	1.0000
3:45765548:T:TA	donor_gain	1.0000
3:45771215:A:AC	donor_gain	1.0000
3:45771216:C:CC	donor_gain	1.0000
3:45771216:CTT:C	donor_gain	1.0000
3:45771218:T:TA	donor_gain	1.0000
3:45796294:CTCA:C	donor_loss	1.0000
3:45796295:TCA:T	donor_loss	1.0000
3:45796296:CA:C	donor_loss	1.0000
3:45796297:A:C	donor_loss	1.0000
3:45796298:C:G	donor_loss	1.0000
3:45760019:AAAT:A	acceptor_gain	0.9900
3:45760020:AAT:A	acceptor_gain	0.9900
3:45760021:AT:A	acceptor_gain	0.9900
3:45760025:A:C	acceptor_gain	0.9900
3:45760027:T:C	acceptor_gain	0.9900
3:45762911:ACCT:A	donor_gain	0.9900

AlphaMissense

3867 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:45796335:A:G	W29R	0.999
3:45796335:A:T	W29R	0.999
3:45771267:G:C	F295L	0.998
3:45771267:G:T	F295L	0.998
3:45771269:A:G	F295L	0.998
3:45771279:G:C	S291R	0.998
3:45771279:G:T	S291R	0.998
3:45771281:T:G	S291R	0.998
3:45771431:A:G	W241R	0.998
3:45771431:A:T	W241R	0.998
3:45775976:A:G	W123R	0.998
3:45775976:A:T	W123R	0.998
3:45796327:G:C	F31L	0.998
3:45796327:G:T	F31L	0.998
3:45796329:A:G	F31L	0.998
3:45796331:C:G	R30P	0.998
3:45782216:G:C	F43L	0.997
3:45782216:G:T	F43L	0.997
3:45782218:A:G	F43L	0.997
3:45796328:A:C	F31C	0.997
3:45759869:C:A	W539C	0.996
3:45759869:C:G	W539C	0.996
3:45765622:G:C	S406R	0.996
3:45765622:G:T	S406R	0.996
3:45765624:T:G	S406R	0.996
3:45765715:G:C	F375L	0.996
3:45765715:G:T	F375L	0.996
3:45765717:A:G	F375L	0.996
3:45771252:G:C	F300L	0.996
3:45771252:G:T	F300L	0.996

dbSNP variants (sampled 300 via entrez): RS1000064072 (3:45789985 C>T), RS1000113903 (3:45777220 A>G), RS1000137169 (3:45777969 C>T), RS1000155214 (3:45767372 GA>G,GAA), RS1000315855 (3:45758216 T>C), RS1000375175 (3:45761313 G>A), RS1000387657 (3:45789710 C>A,T), RS1000400055 (3:45764509 C>G,T), RS1000415149 (3:45790334 T>C), RS1000651921 (3:45759743 G>A,T), RS1000697943 (3:45773987 C>T), RS1000752005 (3:45773669 T>C), RS1000859479 (3:45795755 CAG>C), RS1000890328 (3:45784084 C>T), RS1001000619 (3:45767168 C>T)

Disease associations

OMIM: gene MIM:605616 | disease phenotypes: MIM:138500, MIM:242600

GenCC curated gene-disease

Disease	Classification	Inheritance
hyperglycinuria	Limited	Autosomal recessive

Mondo (4): hyperglycinuria (MONDO:0007677), iminoglycinuria (MONDO:0009448), hereditary ataxia (MONDO:0100309), intellectual disability (MONDO:0001071)

Orphanet (3): Iminoglycinuria (Orphanet:42062), Hereditary ataxia (Orphanet:183518), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0002154	Hyperglycinemia
HP:0003080	Hydroxyprolinuria
HP:0003108	Hyperglycinuria
HP:0003137	Prolinuria
HP:0003260	Hydroxyprolinemia
HP:0008358	Hyperprolinemia

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST001073_5	Urinary metabolites	3.000000e-19
GCST001536_5	Immune reponse to smallpox (secreted TNF-alpha)	2.000000e-07
GCST001999_7	Adverse response to chemotherapy (neutropenia/leucopenia) (paclitaxel)	4.000000e-06
GCST002481_7	Acne (severe)	3.000000e-06
GCST002658_2	Hirschsprung disease	3.000000e-06
GCST003119_14	Urinary metabolites	8.000000e-22
GCST003119_3	Urinary metabolites	8.000000e-60
GCST006976_4	Macular thickness	1.000000e-71
GCST010698_35	Subcortical volume (min-P)	2.000000e-35
GCST010699_82	Brain morphology (min-P)	3.000000e-15
GCST010701_19	Cortical surface area (MOSTest)	5.000000e-08
GCST010702_119	Subcortical volume (MOSTest)	2.000000e-09
GCST010703_230	Brain morphology (MOSTest)	1.000000e-12
GCST012251_14	Macular telangiectasia type 2	1.000000e-09
GCST012252_5	Macular telangiectasia type 2	6.000000e-10
GCST012399_1	COVID-19	3.000000e-16
GCST90000255_22	Severe COVID-19 infection with respiratory failure (analysis I)	1.000000e-10
GCST90000256_1	Severe COVID-19 infection with respiratory failure (analysis II)	9.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0005116	urinary metabolite measurement
EFO:0004346	neuroimaging measurement
EFO:1002009	macular telangiectasia type 2

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C563009	Glycinuria with or without Oxalate Urolithiasis (supp.)
C531684	Hereditary spinal ataxia (supp.)
C536285	Iminoglycinuria (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 — Neutral amino acid transporter subfamily

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
terbufos	increases methylation	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Cannabidiol	increases expression	1
Fonofos	increases methylation	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Rifampin	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Palmitic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
beta-Naphthoflavone	increases expression	1
Permethrin	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4W9	LS180-SLC6A20-KO-c2	Cancer cell line	Female
CVCL_D4WA	LS180-SLC6A20-KO-c4	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01360164	PHASE1/PHASE2	UNKNOWN	Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Hereditary Ataxia
NCT00004306	Not specified	COMPLETED	Clinical and Molecular Correlations in Spinocerebellar Ataxia Type 10 (SCA10)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04750850	Not specified	COMPLETED	Core Stability Exercises and Hereditary Ataxia
NCT05160870	Not specified	UNKNOWN	Genotype-phenotype Correlation and Pathogenic Mechanism in Hereditary Ataxia
NCT05160883	Not specified	UNKNOWN	Neuroimaging Changes in Hereditary Ataxia
NCT06034886	Not specified	AVAILABLE	Expanded Access Protocol of Troriluzole in Patients With Spinocerebellar Ataxia (SCA)
NCT06152133	Not specified	COMPLETED	Telerehabilitation, Core Stability Exercises and Hereditary Ataxia (TRCore-ataxia)
NCT06267222	Not specified	ENROLLING_BY_INVITATION	Trans-spinal Electrical Stimulation in Individuals With Spinocerebellar Ataxia
NCT07092358	Not specified	RECRUITING	Hereditary Ataxia Research on Multi-Omics and Neuroclinical Insights in the Yangtze Delta
NCT07200505	Not specified	NOT_YET_RECRUITING	Telerehabilitation for Core Stability and Strength in Hereditary Ataxia
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study