SLC36A4

Summary

SLC36A4 (solute carrier family 36 member 4, HGNC:19660) is a protein-coding gene on chromosome 11q21, encoding Neutral amino acid uniporter 4 (Q6YBV0). Uniporter that mediates the transport of neutral amino acids like L-tryptophan, proline and alanine.

SLC36A4 belongs to the SLC36 family of amino acid transporters based on sequence similarity with other family members (e.g., SLC36A1; MIM 606561). SLC36 proteins contain about 500 amino acids and have 9 to 11 transmembrane domains. Unlike other SLC36 family members, which are proton-coupled amino acid transporters, SLC36A4 is a high-affinity/low-capacity non-proton-coupled amino acid transporter (Pillai and Meredith, 2011 [PubMed 21097500]).

Source: NCBI Gene 120103 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 87 total
• MANE Select transcript: NM_152313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19660
Approved symbol	SLC36A4
Name	solute carrier family 36 member 4
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	PAT4, FLJ38932
Ensembl gene	ENSG00000180773
Ensembl biotype	protein_coding
OMIM	613760
Entrez	120103

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000326402, ENST00000524875, ENST00000526735, ENST00000527503, ENST00000527743, ENST00000529184, ENST00000534116, ENST00000918109, ENST00000962040, ENST00000962041

RefSeq mRNA: 2 — MANE Select: NM_152313 NM_001286139, NM_152313

CCDS: CCDS66202, CCDS8291

Canonical transcript exons

ENST00000326402 — 11 exons

Exon	Start	End
ENSE00001229919	93154108	93154277
ENSE00001229937	93165918	93166016
ENSE00001229942	93167944	93168171
ENSE00001229994	93144174	93148844
ENSE00002151705	93197778	93197991
ENSE00003516419	93184430	93184520
ENSE00003518043	93162706	93162875
ENSE00003520854	93182806	93182894
ENSE00003524311	93185691	93185814
ENSE00003640140	93180797	93180881
ENSE00003657350	93181691	93181786

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 94.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1065 / max 639.6168, expressed in 1716 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121820	7.9109	1635
121819	3.5111	1314
121817	0.3478	74
121818	0.3367	124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	94.30	gold quality
monocyte	CL:0000576	91.78	gold quality
leukocyte	CL:0000738	90.95	gold quality
cartilage tissue	UBERON:0002418	88.50	gold quality
bone marrow cell	CL:0002092	88.12	gold quality
adrenal tissue	UBERON:0018303	87.84	gold quality
ventricular zone	UBERON:0003053	87.60	gold quality
epithelial cell of pancreas	CL:0000083	85.88	gold quality
ganglionic eminence	UBERON:0004023	85.74	gold quality
bone marrow	UBERON:0002371	85.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.90	gold quality
mucosa of stomach	UBERON:0001199	84.67	gold quality
cortical plate	UBERON:0005343	84.67	gold quality
stromal cell of endometrium	CL:0002255	84.66	gold quality
right lung	UBERON:0002167	83.24	gold quality
smooth muscle tissue	UBERON:0001135	82.76	gold quality
pancreas	UBERON:0001264	82.76	gold quality
endothelial cell	CL:0000115	82.07	gold quality
cerebellar cortex	UBERON:0002129	81.77	gold quality
vermiform appendix	UBERON:0001154	81.76	gold quality
calcaneal tendon	UBERON:0003701	81.76	gold quality
cerebellar hemisphere	UBERON:0002245	81.71	gold quality
prefrontal cortex	UBERON:0000451	81.59	gold quality
cerebellum	UBERON:0002037	81.40	gold quality
blood	UBERON:0000178	81.22	gold quality
popliteal artery	UBERON:0002250	81.08	gold quality
tibial artery	UBERON:0007610	81.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.81	gold quality
left ovary	UBERON:0002119	80.49	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	12.26
E-MTAB-6524	no	107.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

188 targeting SLC36A4, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
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-4481	100.00	66.42	1669
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 3)

• SLC36A4 has a similar in vivo growth regulatory activity to fly SLC36 family members when expressed in Drosophila and is also required for amino acid-dependent mTORC1 activation, and mTORC1-regulated proliferation in human cells. (PMID:20498635)
• SLC36A4 (hPAT4) is a high affinity amino acid transporter when expressed in Xenopus laevis oocytes. (PMID:21097500)
• Data predict that colorectal cancer cells with high PAT4 expression will be more resistant to depletion of serine and glutamine, allowing them to survive and outgrow neighbouring normal and tumorigenic cells. (PMID:26434594)

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc36a4	ENSDARG00000039661
mus_musculus	Slc36a4	ENSMUSG00000043885
rattus_norvegicus	Slc36a4	ENSRNOG00000011455
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), SLC36A3 (ENSG00000186334), SLC36A2 (ENSG00000186335), SLC38A3 (ENSG00000188338)

Protein

Protein identifiers

Neutral amino acid uniporter 4 — Q6YBV0 (reviewed: Q6YBV0)

Alternative names: Solute carrier family 36 member 4

All UniProt accessions (3): E9PID7, E9PN09, Q6YBV0

UniProt curated annotations — full annotation on UniProt →

Function. Uniporter that mediates the transport of neutral amino acids like L-tryptophan, proline and alanine. The transport activity is sodium ions-independent, electroneutral and therefore functions via facilitated diffusion.

Subunit / interactions. Interacts with CRYBA1.

Subcellular location. Lysosome membrane.

Tissue specificity. Expressed in retinal pigmented epithelial cells.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q6YBV0-1	1	yes
Q6YBV0-2	2

RefSeq proteins (2): NP_001273068, NP_689526* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013057	AA_transpt_TM	Domain

Pfam: PF01490

Catalyzed reactions (Rhea), 3 shown:

• L-alanine(in) = L-alanine(out) (RHEA:70719)
• L-tryptophan(in) = L-tryptophan(out) (RHEA:70947)
• L-proline(in) = L-proline(out) (RHEA:73811)

UniProt features (20 total): transmembrane region 10, sequence variant 3, sequence conflict 3, chain 1, modified residue 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6YBV0-F1	82.07	0.62

Functional residue map

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

Post-translational modifications (1): 1

Glycosylation sites (1): 495

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-71240	Tryptophan catabolism
R-HSA-1430728	Metabolism
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 167 (showing top): GOCC_VACUOLAR_MEMBRANE, REACTOME_TRYPTOPHAN_CATABOLISM, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_ORGANIC_CATION_TRANSPORT, CUI_TCF21_TARGETS_2_DN, VECCHI_GASTRIC_CANCER_EARLY_DN, GOBP_IMPORT_INTO_CELL, GOBP_NEUTRAL_AMINO_ACID_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, LINDGREN_BLADDER_CANCER_CLUSTER_1_DN, NUYTTEN_NIPP1_TARGETS_DN, GOMF_L_AMINO_ACID_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (7): amino acid transmembrane transport (GO:0003333), L-alanine transport (GO:0015808), proline transport (GO:0015824), tryptophan transport (GO:0015827), L-proline import across plasma membrane (GO:1904271), L-tryptophan transmembrane transport (GO:1904556), amino acid transport (GO:0006865)

GO Molecular Function (4): L-alanine transmembrane transporter activity (GO:0015180), L-proline transmembrane transporter activity (GO:0015193), L-tryptophan transmembrane transporter activity (GO:0015196), symporter activity (GO:0015293)

GO Cellular Component (5): lysosomal membrane (GO:0005765), vacuolar membrane (GO:0005774), plasma membrane (GO:0005886), lysosome (GO:0005764), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
SLC-mediated transport of amino acids	1
Metabolism of amino acids and derivatives	1
Transport of small molecules	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
L-amino acid transmembrane transporter activity	3
amino acid transport	2
L-amino acid transport	2
tryptophan transport	2
transmembrane transport	1
alanine transport	1
neutral amino acid transport	1
aromatic amino acid transport	1
L-proline transmembrane transport	1
proline import across plasma membrane	1
L-alpha-amino acid transmembrane transport	1
transport	1
L-alanine transport	1
alanine transmembrane transporter activity	1
neutral L-amino acid transmembrane transporter activity	1
proline transmembrane transport	1
aromatic 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
membrane	1
cell periphery	1
lytic vacuole	1
cellular anatomical structure	1

Protein interactions and networks

STRING

771 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC36A4	RAB1A	P11476	935
SLC36A4	RPTOR	Q8N122	702
SLC36A4	RRAGB	Q5VZM2	635
SLC36A4	SLC38A2	Q96QD8	611
SLC36A4	RRAGC	Q9HB90	604
SLC36A4	MTOR	P42345	602
SLC36A4	RRAGD	Q9NQL2	599
SLC36A4	SLC38A9	Q8NBW4	598
SLC36A4	EIF4EBP1	Q13541	593
SLC36A4	RPS6	P08227	566
SLC36A4	LIMS1	P48059	561
SLC36A4	RPS6KB1	P23443	559
SLC36A4	RRAGA	Q7L523	534
SLC36A4	RHEB	Q15382	526
SLC36A4	MTNR1B	P49286	506

IntAct

3 interactions, top by confidence:

A	B	Type	Score
	NPC1	psi-mi:“MI:0914”(association)	0.350
SLC36A4	GNAI2	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): SLC36A4 (Co-fractionation), SPPL2A (Co-fractionation), SLC36A4 (Co-fractionation), SLC36A4 (Co-fractionation), SLC36A4 (Co-fractionation), SLC36A4 (Co-fractionation), SLC36A4 (Co-fractionation), GNAI2 (Affinity Capture-MS), WIBG (Affinity Capture-MS), RNF5 (Affinity Capture-MS), SLC36A4 (Affinity Capture-RNA)

ESM2 similar proteins: A2SWM2, A2WSD3, A2WSD8, A2YZ24, A6QQU6, A8MRY9, B3LFA3, F4JKQ7, O77592, Q0D7E4, Q0J349, Q3SWX0, Q5A5P7, Q5KQN0, Q5M7K3, Q5R7Q3, Q5RD30, Q6AXR5, Q6K1C4, Q6P499, Q6YBV0, Q6YC49, Q7Z5S9, Q7ZU13, Q8AVC3, Q8BGN5, Q8CH36, Q8GWX2, Q8GYS1, Q8H184, Q8H4H5, Q8L783, Q8L7A0, Q8L9J7, Q8LR09, Q8N8Q9, Q8R1T4, Q8VEH0, Q8W0K2, Q93890

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

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RAB12	“down-regulates quantity by destabilization”	SLC36A4	relocalization
SLC36A4	“up-regulates quantity”	tryptophan	relocalization
SLC36A4	“up-regulates quantity”	proline	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2012 predictions. Top by Δscore:

Variant	Effect	Δscore
11:93154106:A:AC	donor_gain	1.0000
11:93154107:C:CC	donor_gain	1.0000
11:93162872:GGACC:G	acceptor_loss	1.0000
11:93162874:ACCTA:A	acceptor_loss	1.0000
11:93162875:CCTA:C	acceptor_loss	1.0000
11:93162876:CTAA:C	acceptor_loss	1.0000
11:93162877:T:C	acceptor_loss	1.0000
11:93165917:C:T	donor_loss	1.0000
11:93165917:CCA:C	donor_gain	1.0000
11:93165917:CCACT:C	donor_gain	1.0000
11:93166012:ATGTT:A	acceptor_gain	1.0000
11:93166013:TGTT:T	acceptor_gain	1.0000
11:93166015:TT:T	acceptor_gain	1.0000
11:93166016:TCTA:T	acceptor_loss	1.0000
11:93166017:C:CC	acceptor_gain	1.0000
11:93166017:C:CG	acceptor_loss	1.0000
11:93168187:A:T	acceptor_gain	1.0000
11:93180795:A:AC	donor_gain	1.0000
11:93180796:C:CC	donor_gain	1.0000
11:93180877:CACTC:C	acceptor_gain	1.0000
11:93180879:CTC:C	acceptor_gain	1.0000
11:93181685:ACTT:A	donor_loss	1.0000
11:93181686:CTT:C	donor_loss	1.0000
11:93181687:TTACC:T	donor_loss	1.0000
11:93181688:TAC:T	donor_loss	1.0000
11:93181689:A:AC	donor_gain	1.0000
11:93181689:A:AG	donor_loss	1.0000
11:93181689:AC:A	donor_gain	1.0000
11:93181689:ACCG:A	donor_gain	1.0000
11:93181689:ACCGC:A	donor_gain	1.0000

AlphaMissense

3315 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:93167974:A:C	S246R	1.000
11:93167974:A:T	S246R	1.000
11:93167976:T:G	S246R	1.000
11:93148673:C:T	G460E	0.999
11:93148674:C:G	G460R	0.999
11:93148674:C:T	G460R	0.999
11:93148777:G:C	S425R	0.999
11:93148777:G:T	S425R	0.999
11:93148779:T:G	S425R	0.999
11:93148780:G:C	S424R	0.999
11:93148780:G:T	S424R	0.999
11:93148782:T:G	S424R	0.999
11:93148783:G:C	S423R	0.999
11:93148783:G:T	S423R	0.999
11:93148785:T:G	S423R	0.999
11:93148793:C:T	G420E	0.999
11:93148794:C:G	G420R	0.999
11:93148794:C:T	G420R	0.999
11:93162735:G:C	S336R	0.999
11:93162735:G:T	S336R	0.999
11:93162737:T:G	S336R	0.999
11:93165929:C:G	G286R	0.999
11:93165939:A:C	F282L	0.999
11:93165939:A:T	F282L	0.999
11:93165941:A:G	F282L	0.999
11:93180836:A:C	C167W	0.999
11:93180844:C:G	G165R	0.999
11:93180844:C:T	G165R	0.999
11:93182880:G:C	S95R	0.999
11:93182880:G:T	S95R	0.999

dbSNP variants (sampled 300 via entrez): RS1000063508 (11:93191714 T>C), RS1000076210 (11:93171908 T>A,C), RS1000149545 (11:93172184 G>A), RS1000243005 (11:93152638 T>C), RS1000342341 (11:93145390 A>C), RS1000344792 (11:93182070 T>C), RS1000400010 (11:93195634 C>G,T), RS1000501379 (11:93150561 C>A), RS1000507532 (11:93199491 T>C), RS1000539300 (11:93181580 T>C), RS1000555111 (11:93199962 C>T), RS1000572431 (11:93152220 C>G,T), RS1000664362 (11:93193467 T>G), RS1000676537 (11:93181852 T>C), RS1000685287 (11:93190862 C>G,T)

Disease associations

OMIM: gene MIM:613760 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001762_819	Obesity-related traits	2.000000e-06
GCST002034_2	Adverse response to radiation therapy	5.000000e-08
GCST002934_1	Zinc levels	2.000000e-07
GCST007576_247	Chronotype	8.000000e-13
GCST007576_391	Chronotype	3.000000e-10
GCST011494_56	Daytime nap	5.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0007828	daytime rest measurement

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

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
jinfukang	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases expression	1
Phthalic Acids	decreases methylation	1
Dihydrotestosterone	increases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Cyclosporine	increases expression	1
Asbestos, Crocidolite	decreases methylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4MT	HCT116-SLC36A4-KO-c3	Cancer cell line	Male
CVCL_D4MU	HCT116-SLC36A4-KO-c5	Cancer cell line	Male
CVCL_TN33	HAP1 SLC36A4 (-) 1	Cancer cell line	Male
CVCL_TN34	HAP1 SLC36A4 (-) 2	Cancer cell line	Male
CVCL_TN35	HAP1 SLC36A4 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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