SLC36A3

Summary

SLC36A3 (solute carrier family 36 member 3, HGNC:19659) is a protein-coding gene on chromosome 5q33.1, encoding Proton-coupled amino acid transporter 3 (Q495N2).

Predicted to enable amino acid transmembrane transporter activity. Predicted to be involved in carboxylic acid transport and proton transmembrane transport. Predicted to be located in membrane. Predicted to be active in vacuolar membrane.

Source: NCBI Gene 285641 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_181774

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19659
Approved symbol	SLC36A3
Name	solute carrier family 36 member 3
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	PAT3, TRAMD2, tramdorin2
Ensembl gene	ENSG00000186334
Ensembl biotype	protein_coding
OMIM	608332
Entrez	285641

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000335230, ENST00000377713, ENST00000423071

RefSeq mRNA: 2 — MANE Select: NM_181774 NM_001145017, NM_181774

CCDS: CCDS4314, CCDS47316

Canonical transcript exons

ENST00000335230 — 10 exons

Exon	Start	End
ENSE00001335582	151296180	151296268
ENSE00001335654	151298593	151298683
ENSE00001845371	151276358	151277661
ENSE00001913463	151303227	151303766
ENSE00003500349	151287246	151287464
ENSE00003501121	151284044	151284210
ENSE00003504793	151288386	151288470
ENSE00003504898	151284613	151284711
ENSE00003529179	151281014	151281183
ENSE00003658245	151293364	151293459

Expression profiles

Bgee: expression breadth broad, 11 present calls, max score 77.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0127 / max 8.5706, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64358	0.0092	3
64357	0.0034	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.47	gold quality
testis	UBERON:0000473	68.98	gold quality
left testis	UBERON:0004533	68.71	gold quality
right testis	UBERON:0004534	67.80	gold quality
colonic epithelium	UBERON:0000397	45.40	gold quality
bone marrow cell	CL:0002092	44.71	gold quality
bone marrow	UBERON:0002371	43.90	gold quality
monocyte	CL:0000576	42.93	gold quality
leukocyte	CL:0000738	42.81	gold quality
granulocyte	CL:0000094	42.45	silver quality
sural nerve	UBERON:0015488	41.30	gold quality
calcaneal tendon	UBERON:0003701	39.86	gold quality
lower esophagus mucosa	UBERON:0035834	39.77	gold quality
ganglionic eminence	UBERON:0004023	38.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	38.95	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
skin of leg	UBERON:0001511	36.10	silver quality
mucosa of stomach	UBERON:0001199	35.92	silver quality
apex of heart	UBERON:0002098	35.90	gold quality
blood	UBERON:0000178	35.81	gold quality
zone of skin	UBERON:0000014	35.59	silver quality
superior frontal gyrus	UBERON:0002661	35.23	gold quality
popliteal artery	UBERON:0002250	35.20	gold quality
tibial artery	UBERON:0007610	35.15	gold quality
uterine cervix	UBERON:0000002	34.75	gold quality
vagina	UBERON:0000996	34.70	silver quality
skin of abdomen	UBERON:0001416	34.52	silver quality
right coronary artery	UBERON:0001625	34.38	gold quality
right adrenal gland cortex	UBERON:0035827	34.34	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting SLC36A3, 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-4425	100.00	67.59	1049
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-6513-5P	99.43	67.81	1071

Literature-anchored findings (GeneRIF, showing 2)

• PAT3 was isolated and identified, but its function is not yet known. (PMID:12809675)
• lysophosphatidic acid stimulates apical Cl(-)/OH(-) exchange activity and surface levels of SLC36A3 and SLC26A6 in intestinal epithelial cells (PMID:19910524)

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc38a5b	ENSDARG00000014587
mus_musculus	Slc36a3	ENSMUSG00000049491
rattus_norvegicus	Slc36a3	ENSRNOG00000021310
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), SLC36A1 (ENSG00000123643), SLC38A2 (ENSG00000134294), SLC38A4 (ENSG00000139209), SLC38A6 (ENSG00000139974), SLC38A10 (ENSG00000157637), SLC38A8 (ENSG00000166558), SLC38A11 (ENSG00000169507), SLC38A9 (ENSG00000177058), SLC36A4 (ENSG00000180773), SLC36A2 (ENSG00000186335), SLC38A3 (ENSG00000188338)

Protein

Protein identifiers

Proton-coupled amino acid transporter 3 — Q495N2 (reviewed: Q495N2)

Alternative names: Solute carrier family 36 member 3, Tramdorin-2

All UniProt accessions (1): Q495N2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Specifically expressed in testis.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q495N2-1	1	yes
Q495N2-2	2
Q495N2-3	3

RefSeq proteins (2): NP_001138489, NP_861439* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013057	AA_transpt_TM	Domain

Pfam: PF01490

UniProt features (35 total): topological domain 12, transmembrane region 11, sequence variant 5, compositionally biased region 2, splice variant 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q495N2-F1	84.61	0.64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 65 (showing top): GOCC_VACUOLAR_MEMBRANE, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_AMINO_ACID_TRANSPORT, E4F1_Q6, GOBP_ORGANIC_ANION_TRANSPORT, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_ORGANIC_CATION_TRANSPORT, GOBP_NEUTRAL_AMINO_ACID_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, GOMF_L_AMINO_ACID_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_AMINO_ACID_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (4): L-alanine transport (GO:0015808), glycine transport (GO:0015816), proline transmembrane transport (GO:0035524), proton transmembrane transport (GO:1902600)

GO Molecular Function (4): amino acid:proton symporter activity (GO:0005280), L-alanine transmembrane transporter activity (GO:0015180), glycine transmembrane transporter activity (GO:0015187), L-proline transmembrane transporter activity (GO:0015193)

GO Cellular Component (2): vacuolar membrane (GO:0005774), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nitrogen compound transport	2
L-amino acid transmembrane transporter activity	2
neutral L-amino acid transmembrane transporter activity	2
L-amino acid transport	1
alanine transport	1
neutral amino acid transport	1
carboxylic acid transport	1
amino acid transmembrane transport	1
carboxylic acid transmembrane transport	1
monoatomic cation transmembrane transport	1
amino acid:monoatomic cation symporter activity	1
solute:proton symporter activity	1
L-alanine transport	1
alanine transmembrane transporter activity	1
glycine transport	1
carboxylic acid transmembrane transporter activity	1
proline transmembrane transport	1
vacuole	1
bounding membrane of organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

541 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC36A3	PARVA	Q9NVD7	656
SLC36A3	LIMS1	P48059	642
SLC36A3	TLN1	Q9Y490	584
SLC36A3	ILK	P57043	584
SLC36A3	HMCN1	Q96RW7	564
SLC36A3	TLN2	Q9Y4G6	558
SLC36A3	HMCN2	Q8NDA2	556
SLC36A3	FERMT2	Q96AC1	536
SLC36A3	WDR35	Q9P2L0	504
SLC36A3	SLC6A19	Q695T7	477
SLC36A3	FNDC8	Q8TC99	461
SLC36A3	SLC6A18	Q96N87	461
SLC36A3	SLC6A20	Q9NP91	461
SLC36A3	SLC36A2	Q495M3	439
SLC36A3	DOCK1	Q14185	396

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SLC36A3	GNB3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): GNB3 (Affinity Capture-MS), GNB3 (Affinity Capture-MS)

ESM2 similar proteins: A7MBD8, O70247, P63115, P63116, P83740, Q08DX7, Q1EHB4, Q28728, Q2M3M2, Q2YDU8, Q495M3, Q495N2, Q49B93, Q4V8B1, Q5BL81, Q5FY69, Q5RAE3, Q5U4D8, Q6R4Q5, Q6YBV0, Q6ZMD2, Q7SYH5, Q7T384, Q811P0, Q8BHK3, Q8BYF6, Q8CH36, Q8CIW6, Q8K078, Q8K415, Q8K4D3, Q8N695, Q8R0G7, Q8VDT1, Q91Y63, Q924A5, Q96BD0, Q99N01, Q9BXS9, Q9D232

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1477 predictions. Top by Δscore:

Variant	Effect	Δscore
5:151277657:GACAC:G	acceptor_gain	1.0000
5:151277658:ACAC:A	acceptor_gain	1.0000
5:151277659:CAC:C	acceptor_gain	1.0000
5:151277659:CACC:C	acceptor_gain	1.0000
5:151277660:AC:A	acceptor_gain	1.0000
5:151277661:CC:C	acceptor_gain	1.0000
5:151277662:C:CC	acceptor_gain	1.0000
5:151277663:T:G	acceptor_loss	1.0000
5:151284707:ATCCC:A	acceptor_gain	1.0000
5:151284708:TCCC:T	acceptor_gain	1.0000
5:151284709:CCC:C	acceptor_gain	1.0000
5:151284709:CCCC:C	acceptor_gain	1.0000
5:151284710:CC:C	acceptor_gain	1.0000
5:151284710:CCC:C	acceptor_gain	1.0000
5:151284711:CC:C	acceptor_gain	1.0000
5:151284712:C:CC	acceptor_gain	1.0000
5:151284713:T:C	acceptor_loss	1.0000
5:151287231:C:A	donor_gain	1.0000
5:151287261:A:AC	donor_gain	1.0000
5:151287262:A:C	donor_gain	1.0000
5:151287279:C:CA	donor_gain	1.0000
5:151277667:A:AC	acceptor_gain	0.9900
5:151281012:A:AC	donor_gain	0.9900
5:151281013:C:CC	donor_gain	0.9900
5:151281013:CA:C	donor_gain	0.9900
5:151283854:C:A	donor_gain	0.9900
5:151284612:CCATA:C	donor_gain	0.9900
5:151284620:ACG:A	donor_gain	0.9900
5:151284621:CGC:C	donor_gain	0.9900
5:151284712:C:T	acceptor_gain	0.9900

AlphaMissense

3082 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:151287276:G:C	S226R	0.995
5:151287276:G:T	S226R	0.995
5:151287278:T:G	S226R	0.995
5:151284091:A:C	F309L	0.991
5:151284091:A:T	F309L	0.991
5:151284093:A:G	F309L	0.991
5:151277594:G:C	S404R	0.990
5:151277594:G:T	S404R	0.990
5:151277596:T:G	S404R	0.990
5:151284070:G:C	S316R	0.990
5:151284070:G:T	S316R	0.990
5:151284072:T:G	S316R	0.990
5:151284056:A:G	L321S	0.989
5:151284105:C:G	G305R	0.989
5:151284114:C:G	G302R	0.989
5:151284114:C:T	G302R	0.989
5:151284634:G:C	F262L	0.989
5:151284634:G:T	F262L	0.989
5:151284636:A:G	F262L	0.989
5:151277597:G:C	S403R	0.988
5:151277597:G:T	S403R	0.988
5:151277599:T:G	S403R	0.988
5:151277600:G:C	S402R	0.988
5:151277600:G:T	S402R	0.988
5:151277602:T:G	S402R	0.988
5:151296254:G:C	S78R	0.988
5:151296254:G:T	S78R	0.988
5:151296256:T:G	S78R	0.988
5:151284114:C:A	G302W	0.987
5:151298604:C:G	A70P	0.987

dbSNP variants (sampled 300 via entrez): RS1000067087 (5:151299242 CTCTCTCTCTCTCTCTCTCTCTCTA>C), RS1000123410 (5:151281556 G>A), RS1000124833 (5:151293202 T>C), RS1000153913 (5:151293642 A>G), RS1000416778 (5:151287681 C>T), RS1000476838 (5:151299272 A>C,G), RS1000653127 (5:151305300 G>A), RS1000678808 (5:151276840 C>T), RS1000787470 (5:151299177 C>T), RS1000856262 (5:151282835 C>T), RS1000908406 (5:151283101 G>A), RS1001106351 (5:151281426 A>G,T), RS1001223572 (5:151292076 G>T), RS1001274265 (5:151302251 C>G), RS1001326461 (5:151302689 A>G,T)

Disease associations

OMIM: gene MIM:608332 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004131_47	Inflammatory bowel disease	3.000000e-15
GCST004132_24	Crohn’s disease	2.000000e-19

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 — SLC36 family of proton-coupled amino acid transporters

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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