SLC36A1

Summary

SLC36A1 (solute carrier family 36 member 1, HGNC:18761) is a protein-coding gene on chromosome 5q33.1, encoding Proton-coupled amino acid transporter 1 (Q7Z2H8). Electrogenic proton/amino acid symporter with selectivity for small apolar L-amino acids, their D-enantiomers and selected amino acid derivatives such as 4-aminobutanoate/GABA.

This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 206358 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 188 total
• Phenotypes (HPO): 2
• Druggable target: yes
• MANE Select transcript: NM_078483

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18761
Approved symbol	SLC36A1
Name	solute carrier family 36 member 1
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	LYAAT-1, PAT1, TRAMD3
Ensembl gene	ENSG00000123643
Ensembl biotype	protein_coding
OMIM	606561
Entrez	206358

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 16 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000243389, ENST00000429484, ENST00000517628, ENST00000517945, ENST00000519829, ENST00000520111, ENST00000520701, ENST00000521351, ENST00000521925, ENST00000522185, ENST00000882825, ENST00000882826, ENST00000882827, ENST00000882828, ENST00000882829, ENST00000882830, ENST00000882831, ENST00000924342

RefSeq mRNA: 4 — MANE Select: NM_078483 NM_001308150, NM_001308151, NM_001349740, NM_078483

CCDS: CCDS4316, CCDS78073

Canonical transcript exons

ENST00000243389 — 11 exons

Exon	Start	End
ENSE00000841262	151473673	151473771
ENSE00000841263	151476590	151476756
ENSE00000906369	151487983	151492379
ENSE00000972907	151465074	151465169
ENSE00001085807	151467707	151467925
ENSE00001085809	151467199	151467283
ENSE00001828164	151447603	151447813
ENSE00003601539	151464514	151464602
ENSE00003627106	151463553	151463643
ENSE00003648343	151479320	151479489
ENSE00003665494	151458788	151458935

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 97.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5206 / max 196.5912, expressed in 1788 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59635	10.6563	1787
59636	0.4611	160
59638	0.1554	81
59645	0.1405	15
59637	0.0439	15
59644	0.0273	13
59634	0.0246	3
59646	0.0115	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	97.26	gold quality
duodenum	UBERON:0002114	95.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.20	gold quality
cerebellar cortex	UBERON:0002129	92.95	gold quality
cerebellar hemisphere	UBERON:0002245	92.95	gold quality
cerebellum	UBERON:0002037	92.55	gold quality
ileal mucosa	UBERON:0000331	92.06	gold quality
jejunum	UBERON:0002115	91.34	gold quality
trabecular bone tissue	UBERON:0002483	90.10	gold quality
trigeminal ganglion	UBERON:0001675	89.84	gold quality
tongue squamous epithelium	UBERON:0006919	89.47	gold quality
colonic mucosa	UBERON:0000317	89.09	gold quality
rectum	UBERON:0001052	88.68	gold quality
tendon of biceps brachii	UBERON:0008188	88.54	silver quality
mucosa of sigmoid colon	UBERON:0004993	88.42	gold quality
secondary oocyte	CL:0000655	88.25	gold quality
dorsal root ganglion	UBERON:0000044	88.23	gold quality
pons	UBERON:0000988	88.19	gold quality
sperm	CL:0000019	87.75	silver quality
male germ cell	CL:0000015	87.28	silver quality
cerebellar vermis	UBERON:0004720	86.81	gold quality
vena cava	UBERON:0004087	86.78	gold quality
bone element	UBERON:0001474	86.71	gold quality
paraflocculus	UBERON:0005351	86.52	gold quality
thymus	UBERON:0002370	86.44	silver quality
mucosa of transverse colon	UBERON:0004991	86.43	gold quality
cervix squamous epithelium	UBERON:0006922	86.37	gold quality
oocyte	CL:0000023	86.32	gold quality
visceral pleura	UBERON:0002401	86.32	gold quality
blood	UBERON:0000178	86.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.07
E-MTAB-9067	yes	4.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

172 targeting SLC36A1, 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-8485	100.00	77.57	4731
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-128-3P	99.95	71.17	2484

Literature-anchored findings (GeneRIF, showing 19)

• PAT1 expressed exclusively in apical membrane of Caco-2 cells. hPAT1 may be responsible for H(+)-coupled amino acid transport expressed in apical membrane of Caco-2 cells. (PMID:12527723)
• A high-capacity imino acid carrier localized at the small intestinal luminal membrane that transports nutrients and amino acids and imino acids. (PMID:15521011)
• Amino acid uptake via hPAT1 is inhibited by activators of the cAMP pathway indirectly through inhibition of NHE3 activity. (PMID:15754324)
• PAT1a, which is 99.0% identical to protein interacting with APP tail 1 (PAT1), is a functional link between the transport and processing of beta-amyloid precursor protein APP and its two paralogs APLP1 and APLP2 in vivo. (PMID:17050537)
• His-55 might be responsible for binding and translocation of H+ in the course of cellular amino acid uptake by PAT1. (PMID:18230330)
• This study is the first to demonstrate both taurine uptake via PAT1 and functional expression of PAT1 at the apical membrane of the intestinal epithelium. (PMID:19074966)
• Data conclude that hPAT1 might be responsible for the intestinal absorption of beta-GPA thereby allowing its oral administration. (PMID:19358571)
• The role of N-glycosylation in transport function and surface targeting of the human solute carrier PAT1 (PMID:19409386)
• a disulfide bridge is essential for the transport function of the human proton-coupled amino acid transporter hPAT1 (PMID:19549785)
• In human cells, SLC36A1 localized on intracellular membranes is required for amino acid-dependent mTORC1 activation and cell proliferation. SLC36A1 also has similar in vivo growth regulatory activity to fly SLC36 AAAPs when expressed in Drosophila. (PMID:20498635)
• PATs function as part of an amino acid-sensing engine that drives mTORC1 activation from endosomal and lysosomal membranes (PMID:22574197)
• In hPAT1 expressing oocytes Gly-Tyr, Gly-Pro, and Gly-Phe inhibited currents induced by drug substances. (PMID:22853447)
• estrogen attenuates the activity of PAT1 by directly closing PAT1 (PMID:22975709)
• Data suggest that PAT1 in enterocytes is responsible for intestinal absorption of some of the alkaloids from areca nut (i.e., arecaidine, guvacine, isoguvacine). (PMID:23488788)
• Sertraline is an apparent non-competitive inhibitor of PAT1-mediated transport. (PMID:23962042)
• Data indicate that the glycosylation-deficient mutant of amino acid transporter PAT1 (PAT1(3)(NQ) ) is unstable and is degraded mainly via the endoplasmic reticulum-associated degradation pathway in HEK293 cells. (PMID:28117901)
• A mechanism through which amino acids may suppress the expression of PAT1 on lysosomes by inducing protein cleavage to remove a targeting signal. (PMID:28670736)
• Increasing the PAT1 level does not readily increase the mTORC1 activity. The lysosomal PAT1 was increased by starvation and decreased by nutrient replenishment. The lysosomal PAT1 plays a negative role on the mTORC1 activity. (PMID:30253187)
• SLC36A1-mTORC1 signaling drives acquired resistance to CDK4/6 inhibitors. (PMID:31555743)

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc36a1	ENSDARG00000075618
mus_musculus	Slc36a1	ENSMUSG00000020261
rattus_norvegicus	Slc36a1	ENSRNOG00000065424
drosophila_melanogaster	CG16700	FBGN0030816
drosophila_melanogaster	CG4991	FBGN0030817
drosophila_melanogaster	CG13384	FBGN0032036
drosophila_melanogaster	polyph	FBGN0033572
drosophila_melanogaster	VGAT	FBGN0033911
drosophila_melanogaster	acs	FBGN0035300
drosophila_melanogaster	CG7888	FBGN0036116
drosophila_melanogaster	CG32079	FBGN0052079
drosophila_melanogaster	CG32081	FBGN0052081
drosophila_melanogaster	mah	FBGN0285912
caenorhabditis_elegans		WBGENE00006783
caenorhabditis_elegans	slc-36.4	WBGENE00010421
caenorhabditis_elegans	Y18D10A.23	WBGENE00012487
caenorhabditis_elegans		WBGENE00012629
caenorhabditis_elegans		WBGENE00012804
caenorhabditis_elegans		WBGENE00019837
caenorhabditis_elegans		WBGENE00020837

Paralogs (15): SLC38A5 (ENSG00000017483), SLC32A1 (ENSG00000101438), SLC38A7 (ENSG00000103042), SLC38A1 (ENSG00000111371), SLC38A2 (ENSG00000134294), SLC38A4 (ENSG00000139209), SLC38A6 (ENSG00000139974), SLC38A10 (ENSG00000157637), SLC38A8 (ENSG00000166558), SLC38A11 (ENSG00000169507), SLC38A9 (ENSG00000177058), SLC36A4 (ENSG00000180773), SLC36A3 (ENSG00000186334), SLC36A2 (ENSG00000186335), SLC38A3 (ENSG00000188338)

Protein

Protein identifiers

Proton-coupled amino acid transporter 1 — Q7Z2H8 (reviewed: Q7Z2H8)

Alternative names: Solute carrier family 36 member 1

All UniProt accessions (7): E5RG64, E5RHG5, E5RI40, E7EW39, Q7Z2H8, H0YB60, H0YBS2

UniProt curated annotations — full annotation on UniProt →

Function. Electrogenic proton/amino acid symporter with selectivity for small apolar L-amino acids, their D-enantiomers and selected amino acid derivatives such as 4-aminobutanoate/GABA. May be involved in the efflux from the lysosomal compartment of neutral amino acids resulting from proteolysis. May play a role in specifying sites for exocytosis in neurons.

Subcellular location. Cell membrane. Apical cell membrane. Lysosome membrane.

Similarity. Belongs to the amino acid/polyamine transporter 2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z2H8-1	1	yes
Q7Z2H8-3	2
Q7Z2H8-4	3

RefSeq proteins (4): NP_001295079, NP_001295080, NP_001336669, NP_510968* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013057	AA_transpt_TM	Domain

Pfam: PF01490

Catalyzed reactions (Rhea), 9 shown:

• L-serine(in) + H(+)(in) = L-serine(out) + H(+)(out) (RHEA:28887)
• glycine(in) + H(+)(in) = glycine(out) + H(+)(out) (RHEA:28899)
• D-alanine(in) + H(+)(in) = D-alanine(out) + H(+)(out) (RHEA:28903)
• 4-aminobutanoate(in) + H(+)(in) = 4-aminobutanoate(out) + H(+)(out) (RHEA:28915)
• L-proline(out) + H(+)(out) = L-proline(in) + H(+)(in) (RHEA:28963)
• L-alanine(in) + H(+)(in) = L-alanine(out) + H(+)(out) (RHEA:29443)
• beta-alanine(in) + H(+)(in) = beta-alanine(out) + H(+)(out) (RHEA:29459)
• D-proline(out) + H(+)(out) = D-proline(in) + H(+)(in) (RHEA:70643)
• D-serine(out) + H(+)(out) = D-serine(in) + H(+)(in) (RHEA:70647)

UniProt features (41 total): topological domain 12, transmembrane region 11, sequence conflict 4, glycosylation site 3, splice variant 3, mutagenesis site 3, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z2H8-F1	84.95	0.66

Functional residue map

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

Disulfide bonds (1): 180–329

Glycosylation sites (3): 174, 183, 470

Mutagenesis-validated functional residues (3):

Position	Phenotype
180	loss amino acid:proton symporter activity. no effect on localization to the plasma membrane.
329	loss amino acid:proton symporter activity. no effect on localization to the plasma membrane.
473	no effect on amino acid:proton symporter activity. no effect on localization to the plasma membrane.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-428559	Proton-coupled neutral amino acid transporters
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 206 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_VACUOLAR_MEMBRANE, CGGAARNGGCNG_UNKNOWN, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, PATIL_LIVER_CANCER, USF_01, CASORELLI_APL_SECONDARY_VS_DE_NOVO_UP, GOBP_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SULFUR_COMPOUND_TRANSPORT, LIAO_METASTASIS, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOCC_APICAL_PLASMA_MEMBRANE

GO Biological Process (11): monoatomic ion transport (GO:0006811), amino acid transport (GO:0006865), taurine transmembrane transport (GO:0015734), L-alanine transport (GO:0015808), glycine transport (GO:0015816), proline transport (GO:0015824), alanine transport (GO:0032328), proline transmembrane transport (GO:0035524), amino acid import across plasma membrane (GO:0089718), proton transmembrane transport (GO:1902600), neutral amino acid transport (GO:0015804)

GO Molecular Function (12): amino acid:proton symporter activity (GO:0005280), proline:proton symporter activity (GO:0005297), amino acid transmembrane transporter activity (GO:0015171), L-alanine transmembrane transporter activity (GO:0015180), glycine transmembrane transporter activity (GO:0015187), L-proline transmembrane transporter activity (GO:0015193), ABC-type taurine transporter transporter activity (GO:0015411), alanine transmembrane transporter activity (GO:0022858), protein binding (GO:0005515), proton transmembrane transporter activity (GO:0015078), neutral L-amino acid transmembrane transporter activity (GO:0015175), symporter activity (GO:0015293)

GO Cellular Component (7): lysosomal membrane (GO:0005765), vacuolar membrane (GO:0005774), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), lysosome (GO:0005764), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transport of amino acids	2
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nitrogen compound transport	4
neutral amino acid transport	4
amino acid transmembrane transport	3
carboxylic acid transmembrane transporter activity	3
neutral L-amino acid transmembrane transporter activity	3
transport	2
L-amino acid transport	2
alanine transport	2
carboxylic acid transport	2
L-amino acid transmembrane transporter activity	2
alkanesulfonate transmembrane transport	1
carboxylic acid transmembrane transport	1
import across plasma membrane	1
monoatomic cation transmembrane transport	1
amino acid transport	1
amino acid:monoatomic cation symporter activity	1
solute:proton symporter activity	1
amino acid:proton symporter activity	1
transmembrane transporter activity	1
L-alanine transport	1
alanine transmembrane transporter activity	1
glycine transport	1
proline transmembrane transport	1
taurine transmembrane transporter activity	1
ABC-type alkanesulfonate transporter transporter activity	1
binding	1
monoatomic cation transmembrane transporter activity	1
proton transmembrane transport	1
amino acid transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
lysosome	1
lytic vacuole membrane	1
vacuole	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
apical part of cell	1

Protein interactions and networks

STRING

1184 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC36A1	RRAGC	Q9HB90	849
SLC36A1	SLC38A9	Q8NBW4	680
SLC36A1	SLC38A2	Q96QD8	655
SLC36A1	RPS6	P08227	634
SLC36A1	RRAGB	Q5VZM2	633
SLC36A1	RRAGD	Q9NQL2	624
SLC36A1	RPS6KB1	P23443	615
SLC36A1	SLC38A7	Q9NVC3	613
SLC36A1	MTOR	P42345	612
SLC36A1	SLC15A1	P46059	597
SLC36A1	EIF4EBP1	Q13541	591
SLC36A1	PIKFYVE	Q9Y2I7	587
SLC36A1	RRAGA	Q7L523	577
SLC36A1	SLC3A2	P08195	565
SLC36A1	SLC66A1	Q6ZP29	565

IntAct

11 interactions, top by confidence:

A	B	Type	Score
TUSC5	SLC36A1	psi-mi:“MI:0915”(physical association)	0.560
APP	SLC36A1	psi-mi:“MI:0915”(physical association)	0.560
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
SLC36A1	NRAS	psi-mi:“MI:0914”(association)	0.350
SLC36A1	ATP5PD	psi-mi:“MI:0914”(association)	0.350
TUSC5	SLC36A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): SLC36A1 (Affinity Capture-MS), SLC36A1 (Synthetic Growth Defect), SLC36A1 (Synthetic Growth Defect), SLC36A1 (Affinity Capture-MS), TUSC5 (Two-hybrid), SLC36A1 (Affinity Capture-RNA), SLC36A1 (Affinity Capture-RNA), SLC36A1 (Affinity Capture-MS), ATP5H (Affinity Capture-MS), UBB (Affinity Capture-MS), UBC (Affinity Capture-MS), ATP5J (Affinity Capture-MS), ATP5O (Affinity Capture-MS), ATP5E (Affinity Capture-MS), ATP5EP2 (Affinity Capture-MS)

ESM2 similar proteins: A1L3M3, D3ZMM8, O43511, O65413, O70247, P0AAE2, P0AAE3, P0AAE4, P23586, P37460, P63115, P63116, P82251, P82252, Q10PW9, Q28I80, Q41144, Q495M3, Q58CV5, Q59I64, Q5Q0U0, Q5RAE3, Q5U4D8, Q6Z401, Q7SY29, Q7Z2H8, Q8BGK6, Q8BHK3, Q8BN82, Q8K415, Q8K4D3, Q8N695, Q8TED4, Q924A5, Q92536, Q94AZ2, Q9LRB5, Q9MZD1, Q9N1Q4, Q9N1R6

Diamond homologs: F4ILY9, Q7Z2H8, Q9FKY3, Q9SF09, Q9SVG0, Q495M3, Q495N2, Q4KL91, Q4V8B1, Q6YBV0, Q811P0, Q8BHK3, Q8CH36, Q8K415, Q8K4D3, Q924A5, Q9VT04, Q9W056, P50944, Q9LXF8, F4J1Q9, Q4V5R4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SLC36A1	“up-regulates quantity”	glycine	relocalization
SLC36A1	“up-regulates quantity”	alanine	relocalization
SLC36A1	“up-regulates quantity”	proline	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	29
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

2317 predictions. Top by Δscore:

Variant	Effect	Δscore
5:151437165:G:GT	donor_gain	1.0000
5:151437175:GC:G	donor_gain	1.0000
5:151437176:C:G	donor_gain	1.0000
5:151458918:TCA:T	donor_gain	1.0000
5:151458936:G:GG	donor_gain	1.0000
5:151464492:T:A	acceptor_gain	1.0000
5:151464499:A:AG	acceptor_gain	1.0000
5:151464500:A:G	acceptor_gain	1.0000
5:151464503:T:G	acceptor_gain	1.0000
5:151465064:A:AG	acceptor_gain	1.0000
5:151465065:C:G	acceptor_gain	1.0000
5:151465068:TTCCA:T	acceptor_loss	1.0000
5:151465069:TCCA:T	acceptor_loss	1.0000
5:151465070:CCAGG:C	acceptor_loss	1.0000
5:151465071:CAGGC:C	acceptor_loss	1.0000
5:151465072:A:AG	acceptor_gain	1.0000
5:151465072:AG:A	acceptor_gain	1.0000
5:151465072:AGGCT:A	acceptor_gain	1.0000
5:151465073:G:GT	acceptor_gain	1.0000
5:151465073:GG:G	acceptor_gain	1.0000
5:151465073:GGC:G	acceptor_gain	1.0000
5:151465073:GGCT:G	acceptor_gain	1.0000
5:151465073:GGCTG:G	acceptor_gain	1.0000
5:151465166:GAAGG:G	donor_loss	1.0000
5:151465167:A:T	donor_gain	1.0000
5:151465167:AAGG:A	donor_loss	1.0000
5:151465170:G:GA	donor_loss	1.0000
5:151465171:T:G	donor_loss	1.0000
5:151467191:A:AG	acceptor_gain	1.0000
5:151467198:GACGT:G	acceptor_gain	1.0000

AlphaMissense

3111 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:151467893:A:C	S231R	0.999
5:151467895:C:A	S231R	0.999
5:151467895:C:G	S231R	0.999
5:151464526:A:C	S83R	0.998
5:151464528:C:A	S83R	0.998
5:151464528:C:G	S83R	0.998
5:151473748:T:C	F267L	0.997
5:151473750:T:A	F267L	0.997
5:151473750:T:G	F267L	0.997
5:151488042:A:C	S407R	0.997
5:151488044:C:A	S407R	0.997
5:151488044:C:G	S407R	0.997
5:151488045:A:C	S408R	0.997
5:151488047:C:A	S408R	0.997
5:151488047:C:G	S408R	0.997
5:151488048:A:C	S409R	0.997
5:151488050:C:A	S409R	0.997
5:151488050:C:G	S409R	0.997
5:151476680:A:C	S305R	0.996
5:151476682:C:A	S305R	0.996
5:151476682:C:G	S305R	0.996
5:151488153:G:C	G444R	0.996
5:151467260:T:C	F161L	0.995
5:151467262:T:A	F161L	0.995
5:151467262:T:G	F161L	0.995
5:151488033:G:C	G404R	0.995
5:151488154:G:A	G444D	0.995
5:151463632:G:C	A75P	0.994
5:151464517:G:C	G80R	0.994
5:151464561:C:G	C94W	0.994

dbSNP variants (sampled 300 via entrez): RS1000003823 (5:151444547 G>A), RS1000054441 (5:151444364 A>G,T), RS1000074003 (5:151419299 C>T), RS1000079137 (5:151447975 C>A,T), RS1000089491 (5:151489420 A>G), RS1000108945 (5:151378085 C>G), RS1000110586 (5:151486875 A>C), RS1000115210 (5:151496178 A>G), RS1000130226 (5:151367352 C>A,G,T), RS1000141941 (5:151553873 G>C), RS1000176320 (5:151468909 A>C), RS1000177480 (5:151466129 G>C,T), RS1000215787 (5:151383504 A>G,T), RS1000229022 (5:151372977 T>A), RS1000244755 (5:151417773 A>C,G,T)

Disease associations

OMIM: gene MIM:606561 | disease phenotypes: MIM:617769, MIM:138500, MIM:242600, MIM:209850

GenCC curated gene-disease

Mondo (4): spinocerebellar ataxia 45 (MONDO:0033480), hyperglycinuria (MONDO:0007677), iminoglycinuria (MONDO:0009448), autism (MONDO:0005260)

Orphanet (2): Spinocerebellar ataxia type 45 (Orphanet:589527), Iminoglycinuria (Orphanet:42062)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0003108	Hyperglycinuria
HP:0000717	Autism

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004631_22	Basophil percentage of white cells	5.000000e-09
GCST004634_26	Basophil percentage of granulocytes	4.000000e-09
GCST90002379_128	Basophil count	2.000000e-12
GCST90002380_155	Basophil percentage of white cells	6.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0005090	basophil count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
C563009	Glycinuria with or without Oxalate Urolithiasis (supp.)
C536285	Iminoglycinuria (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1914279 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC36 family of proton-coupled amino acid transporters

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
17β-estradiol	Inhibition	5.2	pIC50
ethinylestradiol	Inhibition	4.6	pIC50
diclofenac	Inhibition	3.57	pIC50
flurbiprofen	Inhibition	3.55	pIC50
ibuprofen	Inhibition	3.02	pIC50
5-hydroxy-L-tryptophan	Inhibition	3.0	pKi
indole-3-propionic acid	Inhibition	2.3	pKi
L-tryptophan	Inhibition	2.3	pKi
5-hydroxytryptamine	Inhibition	2.2	pKi

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Acetaminophen	increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Tretinoin	increases expression	2
dicrotophos	increases expression	1
sodium bichromate	decreases expression	1
sodium arsenite	increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Angiotensin-Converting Enzyme Inhibitors	increases expression	1
Atrazine	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	increases expression	1
Oxygen	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	decreases expression	1
Cyclosporine	increases methylation	1
Cadmium Chloride	decreases expression	1
Thapsigargin	decreases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1919336	Binding	Inhibition of human PAT1-mediated L-[3H]proline uptake in human Caco2 cells after 10 mins by liquid scintillation counting	Three-dimensional quantitative structure-activity relationship analyses of substrates of the human proton-coupled amino acid transporter 1 (hPAT1). — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4MR	HCT116-SLC36A1-KO-c1	Cancer cell line	Male
CVCL_D4MS	HCT116-SLC36A1-KO-c11	Cancer cell line	Male
CVCL_TN32	HAP1 SLC36A1 (-) 1	Cancer cell line	Male
CVCL_XT27	HAP1 SLC36A1 (-) 2	Cancer cell line	Male
CVCL_XT28	HAP1 SLC36A1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms