SLC66A3

Summary

SLC66A3 (solute carrier family 66 member 3, HGNC:28503) is a protein-coding gene on chromosome 2p25.1, encoding Solute carrier family 66 member 3 (Q8N755).

Predicted to be located in membrane.

Source: NCBI Gene 130814 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_152391

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28503
Approved symbol	SLC66A3
Name	solute carrier family 66 member 3
Location	2p25.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC33602
Ensembl gene	ENSG00000162976
Ensembl biotype	protein_coding
Entrez	130814

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000295083, ENST00000402361, ENST00000428481, ENST00000441908, ENST00000445402, ENST00000445921, ENST00000464700, ENST00000476787, ENST00000487471, ENST00000496444

RefSeq mRNA: 4 — MANE Select: NM_152391 NM_001282710, NM_001282711, NM_001282712, NM_152391

CCDS: CCDS1679, CCDS62856, CCDS62857

Canonical transcript exons

ENST00000295083 — 7 exons

Exon	Start	End
ENSE00001070271	11164204	11164261
ENSE00001070275	11171925	11172045
ENSE00001255311	11160625	11160694
ENSE00001911849	11177737	11178856
ENSE00003487976	11160466	11160548
ENSE00003536674	11174968	11175009
ENSE00003848151	11155467	11155689

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 96.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3598 / max 169.6912, expressed in 1795 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18868	17.6857	1793
18869	0.6740	427

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.62	gold quality
secondary oocyte	CL:0000655	96.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.09	gold quality
monocyte	CL:0000576	95.78	gold quality
leukocyte	CL:0000738	95.72	gold quality
upper arm skin	UBERON:0004263	95.72	gold quality
layer of synovial tissue	UBERON:0007616	94.94	gold quality
decidua	UBERON:0002450	94.67	gold quality
germinal epithelium of ovary	UBERON:0001304	94.50	gold quality
calcaneal tendon	UBERON:0003701	94.43	gold quality
corpus epididymis	UBERON:0004359	94.18	gold quality
gall bladder	UBERON:0002110	93.93	gold quality
granulocyte	CL:0000094	93.77	gold quality
tibial nerve	UBERON:0001323	93.41	gold quality
right coronary artery	UBERON:0001625	93.37	gold quality
synovial joint	UBERON:0002217	93.34	gold quality
tendon of biceps brachii	UBERON:0008188	92.99	gold quality
descending thoracic aorta	UBERON:0002345	92.90	gold quality
tibia	UBERON:0000979	92.69	gold quality
adipose tissue	UBERON:0001013	92.56	gold quality
body of pancreas	UBERON:0001150	92.56	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.56	gold quality
palpebral conjunctiva	UBERON:0001812	92.30	gold quality
urethra	UBERON:0000057	92.20	gold quality
right adrenal gland cortex	UBERON:0035827	92.16	gold quality
parietal pleura	UBERON:0002400	91.75	gold quality
thoracic aorta	UBERON:0001515	91.64	gold quality
right adrenal gland	UBERON:0001233	91.59	gold quality
smooth muscle tissue	UBERON:0001135	91.54	gold quality
ascending aorta	UBERON:0001496	91.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting SLC66A3, 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-1252-5P	100.00	69.80	2774
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-217-5P	99.49	69.93	1419

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc66a3	ENSDARG00000054251
mus_musculus	Slc66a3	ENSMUSG00000045679
rattus_norvegicus	Slc66a3	ENSRNOG00000005126
drosophila_melanogaster	CG1265	FBGN0035517

Paralogs (1): MPDU1 (ENSG00000129255)

Protein

Protein identifiers

Solute carrier family 66 member 3 — Q8N755 (reviewed: Q8N755)

Alternative names: PQ-loop repeat-containing protein 3

All UniProt accessions (5): B5MC27, C9J4B6, Q8N755, G5E9P4, H7C493

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N755-1	1	yes
Q8N755-2	2

RefSeq proteins (4): NP_001269639, NP_001269640, NP_001269641, NP_689604* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006603	PQ-loop_rpt	Repeat
IPR016817	MannP-dilichol_defect-1	Family

Pfam: PF04193

UniProt features (7 total): transmembrane region 4, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N755-F1	91.94	0.81

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 165 (showing top): chr2p25, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOLDRATH_ANTIGEN_RESPONSE, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, LASTOWSKA_COAMPLIFIED_WITH_MYCN, GREENBAUM_E2A_TARGETS_DN, ONGUSAHA_TP53_TARGETS, RASHI_RESPONSE_TO_IONIZING_RADIATION_6, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, BERENJENO_TRANSFORMED_BY_RHOA_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC66A3	TMPPE	Q6ZT21	599
SLC66A3	TMEM41A	Q96HV5	558
SLC66A3	RMDN2	Q96LZ7	557
SLC66A3	BRD10	Q5HYC2	516
SLC66A3	NOL10	Q9BSC4	514
SLC66A3	HPCAL1	P37235	470
SLC66A3	KCNF1	Q9H3M0	447
SLC66A3	ATP6V1C2	Q8NEY4	433
SLC66A3	YIPF4	Q9BSR8	422
SLC66A3	DOLPP1	Q86YN1	417
SLC66A3	RASSF9	O75901	403
SLC66A3	PEX11G	Q96HA9	393
SLC66A3	TRAPPC6B	Q86SZ2	384
SLC66A3	MTMR10	Q9NXD2	379
SLC66A3	GTPBP6	O43824	376

IntAct

2 interactions, top by confidence:

A	B	Type	Score
	SLC66A3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (3): PQLC3 (Affinity Capture-MS), PQLC3 (Proximity Label-MS), PQLC3 (Affinity Capture-MS)

ESM2 similar proteins: A6NFX1, B0BMY1, D2HKB0, D3ZG27, D3ZH22, E7FB98, F1NJ67, O00219, P59266, Q17QZ3, Q1LZA0, Q28727, Q3T9M1, Q3UMZ3, Q4R581, Q5EAL3, Q5EB14, Q5R9A1, Q5RA57, Q5ZJX0, Q5ZKS8, Q60441, Q66H95, Q68F72, Q6AY78, Q6NTJ7, Q6ZP29, Q8BFQ6, Q8C4N4, Q8C6U2, Q8L9J7, Q8N755, Q8NEB5, Q8TB61, Q8TBR7, Q91W98, Q91WC7, Q91ZN5, Q92521, Q95KW8

Diamond homologs: O75352, Q8C6U2, Q8N755

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1251 predictions. Top by Δscore:

Variant	Effect	Δscore
2:11155685:GCAGG:G	donor_gain	1.0000
2:11155688:GG:G	donor_gain	1.0000
2:11155689:GG:G	donor_gain	1.0000
2:11160545:CAAG:C	donor_loss	1.0000
2:11160546:AAG:A	donor_loss	1.0000
2:11160547:AGGTA:A	donor_loss	1.0000
2:11160549:GT:G	donor_loss	1.0000
2:11160550:T:A	donor_loss	1.0000
2:11177731:TTTCA:T	acceptor_loss	1.0000
2:11177732:TTCA:T	acceptor_loss	1.0000
2:11177733:TCA:T	acceptor_loss	1.0000
2:11177734:CA:C	acceptor_loss	1.0000
2:11177735:A:AG	acceptor_gain	1.0000
2:11177735:AGTT:A	acceptor_loss	1.0000
2:11177736:G:GT	acceptor_gain	1.0000
2:11177736:GT:G	acceptor_gain	1.0000
2:11177736:GTT:G	acceptor_gain	1.0000
2:11177736:GTTC:G	acceptor_gain	1.0000
2:11155688:GGGTA:G	donor_loss	0.9900
2:11155689:GGTAA:G	donor_loss	0.9900
2:11155690:G:GG	donor_gain	0.9900
2:11155691:T:TC	donor_loss	0.9900
2:11172046:G:GG	donor_gain	0.9900
2:11177736:GTTCT:G	acceptor_gain	0.9900
2:11160461:TCCA:T	acceptor_loss	0.9800
2:11160462:CCA:C	acceptor_loss	0.9800
2:11160463:CAG:C	acceptor_loss	0.9800
2:11160464:A:AC	acceptor_loss	0.9800
2:11160465:G:GT	acceptor_loss	0.9800
2:11172808:TTTCC:T	donor_gain	0.9800

AlphaMissense

1287 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:11171952:A:C	S128R	0.988
2:11171954:T:A	S128R	0.988
2:11171954:T:G	S128R	0.988
2:11171943:A:C	S125R	0.987
2:11171945:C:A	S125R	0.987
2:11171945:C:G	S125R	0.987
2:11155580:A:C	S12R	0.985
2:11155582:C:A	S12R	0.985
2:11155582:C:G	S12R	0.985
2:11172006:A:C	S146R	0.975
2:11172008:T:A	S146R	0.975
2:11172008:T:G	S146R	0.975
2:11155667:A:C	S41R	0.969
2:11155669:T:A	S41R	0.969
2:11155669:T:G	S41R	0.969
2:11155609:G:C	K21N	0.965
2:11155609:G:T	K21N	0.965
2:11172018:T:A	W150R	0.961
2:11172018:T:C	W150R	0.961
2:11160547:A:C	Q75H	0.958
2:11160547:A:T	Q75H	0.958
2:11174972:A:C	R160S	0.958
2:11174972:A:T	R160S	0.958
2:11177771:T:A	N184K	0.958
2:11177771:T:G	N184K	0.958
2:11160524:G:A	E68K	0.957
2:11174974:T:A	I161K	0.957
2:11155679:G:A	E45K	0.956
2:11174971:G:C	R160T	0.956
2:11171957:G:C	K129N	0.955

dbSNP variants (sampled 300 via entrez): RS1000006177 (2:11161099 A>G), RS1000071511 (2:11153938 A>G), RS1000127867 (2:11156971 C>A), RS1000277274 (2:11162043 C>T), RS1000360592 (2:11168437 T>C), RS1000392984 (2:11168610 C>G,T), RS1000436419 (2:11177225 C>T), RS1000453210 (2:11165428 C>T), RS1000569947 (2:11166743 A>G), RS1000580810 (2:11171805 T>C,G), RS1000605410 (2:11160155 G>A), RS1000677400 (2:11161533 T>C,G), RS1000788703 (2:11166938 C>T), RS1001093525 (2:11178114 T>A,G), RS1001141887 (2:11170126 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010396_272	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-07
GCST90002401_416	Platelet distribution width	2.000000e-15
GCST90020025_1530	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST90020027_1589	Waist-hip index	4.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0007984	platelet component distribution width
EFO:0007788	BMI-adjusted waist-hip ratio

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 — SLC66 Lysosomal amino acid transporters

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
Benzo(a)pyrene	increases expression, increases methylation	3
methylmercuric chloride	decreases expression	2
sodium arsenite	increases expression, decreases expression	2
bisphenol S	affects cotreatment, decreases methylation, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
bisphenol A	decreases methylation	1
nickel sulfate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
eprenetapopt	affects expression, affects reaction	1
(+)-JQ1 compound	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	affects expression	1

Clinical trials (associated diseases)

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