SLC6A14

Summary

SLC6A14 (solute carrier family 6 member 14, HGNC:11047) is a protein-coding gene on chromosome Xq23, encoding Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) (Q9UN76). Amino acid transporter that plays an important role in the absorption of amino acids in the intestinal tract.

This gene encodes a member of the solute carrier family 6. Members of this family are sodium and chloride dependent neurotransmitter transporters. The encoded protein transports both neutral and cationic amino acids. This protein may also function as a beta-alanine carrier. Mutations in this gene may be associated with X-linked obesity. A pseudogene of this gene is found on chromosome X.

Source: NCBI Gene 11254 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cystic fibrosis (Supportive, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 117 total
• Phenotypes (HPO): 35
• Druggable target: yes
• MANE Select transcript: NM_007231

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11047
Approved symbol	SLC6A14
Name	solute carrier family 6 member 14
Location	Xq23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000268104
Ensembl biotype	protein_coding
OMIM	300444
Entrez	11254

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000463626, ENST00000598581, ENST00000905559, ENST00000961159, ENST00000961160, ENST00000961161

RefSeq mRNA: 1 — MANE Select: NM_007231 NM_007231

CCDS: CCDS14570

Canonical transcript exons

ENST00000598581 — 14 exons

Exon	Start	End
ENSE00002985627	116436606	116436757
ENSE00003049246	116442687	116442848
ENSE00003069914	116437790	116437955
ENSE00003082881	116455357	116455466
ENSE00003083297	116440966	116441097
ENSE00003092578	116454977	116455076
ENSE00003121256	116451442	116451670
ENSE00003127787	116444918	116445050
ENSE00003167269	116453017	116453142
ENSE00003197624	116457609	116457776
ENSE00003203705	116458809	116461458
ENSE00003211723	116454324	116454442
ENSE00003224435	116443643	116443790
ENSE00003224568	116446741	116446881

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 99.02.

FANTOM5 (CAGE): breadth broad, TPM avg 3.5958 / max 97.0385, expressed in 196 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197343	3.4206	193
197344	0.1151	85
197345	0.0601	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.02	gold quality
nasal cavity epithelium	UBERON:0005384	97.49	gold quality
nasal cavity mucosa	UBERON:0001826	94.01	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.85	gold quality
epithelium of bronchus	UBERON:0002031	91.89	gold quality
bronchus	UBERON:0002185	91.72	gold quality
lower lobe of lung	UBERON:0008949	91.44	gold quality
parotid gland	UBERON:0001831	91.12	gold quality
bronchial epithelial cell	CL:0002328	91.04	gold quality
amniotic fluid	UBERON:0000173	89.75	gold quality
epithelium of nasopharynx	UBERON:0001951	89.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.27	gold quality
saliva-secreting gland	UBERON:0001044	84.58	gold quality
minor salivary gland	UBERON:0001830	83.52	gold quality
trachea	UBERON:0003126	81.72	gold quality
epithelial cell of pancreas	CL:0000083	81.61	gold quality
sperm	CL:0000019	80.92	gold quality
visceral pleura	UBERON:0002401	80.84	gold quality
mouth mucosa	UBERON:0003729	80.29	gold quality
lung	UBERON:0002048	79.10	gold quality
male germ cell	CL:0000015	78.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.14	gold quality
pancreatic ductal cell	CL:0002079	77.40	silver quality
upper lobe of lung	UBERON:0008948	77.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.75	silver quality
upper lobe of left lung	UBERON:0008952	75.89	gold quality
epithelium of mammary gland	UBERON:0003244	75.22	gold quality
seminal vesicle	UBERON:0000998	74.85	gold quality
gingiva	UBERON:0001828	73.40	gold quality
mammary duct	UBERON:0001765	73.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	55.81
E-ANND-3	yes	21.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

137 targeting SLC6A14, 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-6867-5P	100.00	82.21	3464
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-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 19)

• SLC6A14 gene is an interesting novel candidate for obesity because it encodes an amino acid transporter, which potentially regulates tryptophan availability for serotonin synthesis and thus possibly affects appetite control. (PMID:14660752)
• association of the SLC6A14 gene locus with obesity. (PMID:15331564)
• The up-regulation of SLC6A14 may have a pathogenic role in colorectal neoplasms. (PMID:15905073)
• The SLC6A14 gene encodes the transport protein known as the beta-alanine carrier which, due to its broad substrate specificity, is likely to play an important role in absorption of essential nutrients and drugs. (PMID:18599538)
• The five gene transcripts (aldolase B, elafin, MST-1, simNIPhom and SLC6A14) were changed in patients with ulcerative colitis, and were related to the disease activity. (PMID:18700007)
• Single nucleotide polymorphism in SLC6A14 gene is associated with cystic fibrosis. (PMID:22466613)
• Very little is known about the role of SLC6A14 in PDAC and our results demonstrate that this target merits further investigation as a candidate transporter for functional imaging of pancreatic ductal adenocarcinoma . (PMID:26106611)
• SLC6A14 and 5-HTR2C polymorphisms are associated with food intake and nutritional status in children. (PMID:26160208)
• results indicate a significant correlation between T132903C and C109869T single nucleotide polymorphisms in the insulin receptor and solute carrier family 6 member 14 amino acid transporter(SLC6A14) genes with idiopathic infertility in Persian males (PMID:27172637)
• SLC6A14 was up-regulated several fold in patient-derived pancreatic cancer xenografts, primary tumour tissues and pancreatic cancer cells lines compared to normal pancreatic tissue or normal pancreatic epithelial cells (PMID:27747870)
• Together, these findings suggest that SLC6A14 activity plays a role in the modification of the initial stages of airway infection by altering the level of l-arginine in the airway surface liquid, which in turn affects the attachment of Pseudomonas aeruginosa. (PMID:29259090)
• Reprogramming of Amino Acid Transporters to Support Aspartate and Glutamate Dependency Sustains Endocrine Resistance in Breast Cancer. (PMID:31269432)
• New aspects of the human SLC6A14 structure-function relationship. (PMID:31373846)
• [SLC6A14, a modifier gene in cystic fibrosis].", trans “SLC6A14, un gene modificateur dans la mucoviscidose. (PMID:32146055)
• A flexible summary statistics-based colocalization method with application to the mucin cystic fibrosis lung disease modifier locus. (PMID:35065708)
• SLC6A14 Depletion Contributes to Amino Acid Starvation to Suppress EMT-Induced Metastasis in Gastric Cancer by Perturbing the PI3K/AKT/mTORC1 Pathway. (PMID:35865664)
• SLC6A14 facilitates epithelial cell ferroptosis via the C/EBPbeta-PAK6 axis in ulcerative colitis. (PMID:36272033)
• Machine learning identifies SLC6A14 as a novel biomarker promoting the proliferation and metastasis of pancreatic cancer via Wnt/beta-catenin signaling. (PMID:38267509)
• SLC6A14 promotes ulcerative colitis progression by facilitating NLRP3 inflammasome-mediated pyroptosis. (PMID:38314135)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
caenorhabditis_elegans		WBGENE00004905

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), SLC6A20 (ENSG00000163817), SLC6A18 (ENSG00000164363), SLC6A5 (ENSG00000165970), SLC6A19 (ENSG00000174358), SLC6A9 (ENSG00000196517), SLC6A17 (ENSG00000197106), (ENSG00000273554)

Protein

Protein identifiers

Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) — Q9UN76 (reviewed: Q9UN76)

Alternative names: Amino acid transporter ATB0+, Solute carrier family 6 member 14

All UniProt accessions (1): Q9UN76

UniProt curated annotations — full annotation on UniProt →

Function. Amino acid transporter that plays an important role in the absorption of amino acids in the intestinal tract. Mediates the uptake of a broad range of neutral and cationic amino acids (with the exception of proline) in a Na(+)/Cl(-)-dependent manner. Transports non-alpha-amino acids such as beta-alanine with low affinity, and has a higher affinity for dipolar and cationic amino acids such as leucine and lysine. Can also transport carnitine, butirylcarnitine and propionylcarnitine coupled to the transmembrane gradients of Na(+) and Cl(-).

Subcellular location. Membrane. Apical cell membrane.

Tissue specificity. Levels are highest in adult and fetal lung, in trachea and salivary gland. Lower levels detected in mammary gland, stomach and pituitary gland, and very low levels in colon, uterus, prostate and testis.

Disease relevance. Genetic variations in SLC6A14 may be associated with obesity in some populations, as shown by significant differences in allele frequencies between obese and non-obese individuals.

Miscellaneous. Transport inhibited by BCH (2-aminobicyclo-[2.2.1]-heptane-2-carboxylic acid).

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A14 subfamily.

RefSeq proteins (1): NP_009162* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR037272	SNS_sf	Homologous_superfamily

Pfam: PF00209

Catalyzed reactions (Rhea), 12 shown:

• glycine(out) + chloride(out) + 2 Na(+)(out) = glycine(in) + chloride(in) + 2 Na(+)(in) (RHEA:70691)
• beta-alanine(out) + chloride(out) + 2 Na(+)(out) = beta-alanine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71247)
• L-leucine(out) + chloride(out) + 2 Na(+)(out) = L-leucine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71279)
• L-glutamine(out) + chloride(out) + 2 Na(+)(out) = L-glutamine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71283)
• L-arginine(out) + chloride(out) + 2 Na(+)(out) = L-arginine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71287)
• (R)-carnitine(out) + chloride(out) + 2 Na(+)(out) = (R)-carnitine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71291)
• O-propanoyl-(R)-carnitine(out) + chloride(out) + 2 Na(+)(out) = O-propanoyl-(R)-carnitine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71295)
• L-isoleucine(out) + chloride(out) + 2 Na(+)(out) = L-isoleucine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71299)
• L-methionine(out) + chloride(out) + 2 Na(+)(out) = L-methionine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71303)
• L-valine(out) + chloride(out) + 2 Na(+)(out) = L-valine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71307)
• L-alanine(out) + chloride(out) + 2 Na(+)(out) = L-alanine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71311)
• L-serine(out) + chloride(out) + 2 Na(+)(out) = L-serine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71315)

UniProt features (26 total): transmembrane region 12, glycosylation site 8, topological domain 3, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UN76-F1	89.48	0.74

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 (8): 155, 163, 174, 189, 197, 202, 230, 302

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-5619094	Variant SLC6A14 may confer susceptibility towards obesity
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: 281 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GCANCTGNY_MYOD_Q6, SP3_Q3, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, GOZGIT_ESR1_TARGETS_DN, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, CAGCTG_AP4_Q5, GOBP_AMINO_ACID_BETAINE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_CHLORIDE_TRANSPORT, GOBP_QUATERNARY_AMMONIUM_GROUP_TRANSPORT, TGCTGAY_UNKNOWN

GO Biological Process (12): beta-alanine transport (GO:0001762), amino acid transmembrane transport (GO:0003333), amino acid transport (GO:0006865), response to toxic substance (GO:0009636), alanine transport (GO:0032328), sodium ion transmembrane transport (GO:0035725), amino acid import across plasma membrane (GO:0089718), (R)-carnitine transmembrane transport (GO:1902270), glycine import across plasma membrane (GO:1903804), chloride transport (GO:0006821), aromatic amino acid transport (GO:0015801), branched-chain amino acid transport (GO:0015803)

GO Molecular Function (9): beta-alanine transmembrane transporter activity (GO:0001761), amino acid transmembrane transporter activity (GO:0015171), aromatic amino acid transmembrane transporter activity (GO:0015173), neutral, basic amino acid:sodium:chloride symporter activity (GO:0015374), branched-chain amino acid:sodium symporter activity (GO:0015657), alanine transmembrane transporter activity (GO:0022858), (R)-carnitine transmembrane transporter activity (GO:1901235), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (5): plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324), vesicle (GO:0031982), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
SLC-mediated transport of amino acids	1
SLC-mediated transmembrane transport	1
SLC transporter disorders	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
carboxylic acid transport	4
nitrogen compound transport	4
carboxylic acid transmembrane transporter activity	3
neutral amino acid transport	2
transmembrane transport	2
amino acid transmembrane transport	2
neutral L-amino acid transmembrane transporter activity	2
amino acid transport	1
transport	1
response to chemical	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
import across plasma membrane	1
(R)-carnitine transport	1
carnitine transmembrane transport	1
glycine transport	1
amino acid import across plasma membrane	1
carboxylic acid transmembrane transport	1
monoatomic anion transport	1
inorganic anion transport	1
beta-alanine transport	1
transmembrane transporter activity	1
aromatic amino acid transport	1
amino acid:sodium symporter activity	1
chloride transport	1
organic acid:sodium symporter activity	1
branched-chain amino acid transmembrane transporter activity	1
alanine transport	1
carnitine transmembrane transporter activity	1
(R)-carnitine transmembrane transport	1
secondary active transmembrane transporter activity	1
transporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1
membrane-bounded organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

980 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A14	SLC1A5	Q15758	944
SLC6A14	SLC7A6	Q92536	669
SLC6A14	SLC7A9	P82251	666
SLC6A14	SLC7A7	Q9UM01	655
SLC6A14	SLC26A9	Q7LBE3	652
SLC6A14	FFAR4	Q5NUL3	643
SLC6A14	SLC7A5	Q01650	640
SLC6A14	MC3R	P41968	627
SLC6A14	SLC38A2	Q96QD8	594
SLC6A14	NPC1	O15118	588
SLC6A14	PCSK1	P29120	586
SLC6A14	FTO	Q9C0B1	585
SLC6A14	SLC7A8	Q9UHI5	565
SLC6A14	SLC7A1	P30825	563
SLC6A14	SH2B1	Q9NRF2	548

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SLC6A14	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): SLC6A14 (Positive Genetic), SLC6A14 (Cross-Linking-MS (XL-MS)), ABCB1 (Affinity Capture-MS), ATP5I (Affinity Capture-MS), ATP5J2 (Affinity Capture-MS), ATP5J (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), ATP6V1A (Affinity Capture-MS), ATP6V1B2 (Affinity Capture-MS), BSG (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CANX (Affinity Capture-MS), CD55 (Affinity Capture-MS)

ESM2 similar proteins: A5PJX7, A7Y2W8, B3MRS1, B3NV41, B4MEG2, B4NDL8, B4PZQ4, O35316, O35899, O55192, O88576, P23975, P23977, P23978, P27799, P28572, P28573, P30531, P31641, P31643, P31645, P31646, P31647, P31648, P31649, P31650, P31651, P31652, P48055, P48056, P48057, P48065, P48066, P51143, P51905, Q00589, Q03614, Q28039, Q2PG55, Q5R6J1

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1510 predictions. Top by Δscore:

Variant	Effect	Δscore
X:116436700:G:GT	donor_gain	1.0000
X:116436748:G:GT	donor_gain	1.0000
X:116436754:GGAG:G	donor_gain	1.0000
X:116436755:G:GT	donor_gain	1.0000
X:116437789:GAAA:G	acceptor_gain	1.0000
X:116437953:G:GT	donor_gain	1.0000
X:116443632:A:AG	acceptor_gain	1.0000
X:116443633:T:G	acceptor_gain	1.0000
X:116443638:TTTAG:T	acceptor_loss	1.0000
X:116443639:TTAG:T	acceptor_loss	1.0000
X:116443641:A:AG	acceptor_gain	1.0000
X:116443642:G:GA	acceptor_gain	1.0000
X:116443642:GT:G	acceptor_gain	1.0000
X:116443642:GTA:G	acceptor_gain	1.0000
X:116443642:GTAA:G	acceptor_gain	1.0000
X:116443642:GTAAC:G	acceptor_gain	1.0000
X:116443786:TGGAA:T	donor_gain	1.0000
X:116443787:GGAA:G	donor_gain	1.0000
X:116443787:GGAAG:G	donor_gain	1.0000
X:116443788:G:GT	donor_gain	1.0000
X:116443788:GAA:G	donor_gain	1.0000
X:116443789:AA:A	donor_gain	1.0000
X:116443790:AG:A	donor_loss	1.0000
X:116443791:G:GG	donor_gain	1.0000
X:116443791:G:T	donor_loss	1.0000
X:116443792:T:G	donor_loss	1.0000
X:116444917:GTAAA:G	acceptor_gain	1.0000
X:116455353:TTAGG:T	acceptor_gain	1.0000
X:116455354:TAG:T	acceptor_loss	1.0000
X:116455355:AGGAG:A	acceptor_gain	1.0000

AlphaMissense

4208 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:116437856:T:A	W39R	0.999
X:116437856:T:C	W39R	0.999
X:116437858:G:C	W39C	0.999
X:116437858:G:T	W39C	0.999
X:116437915:T:A	N58K	0.999
X:116437915:T:G	N58K	0.999
X:116437925:T:C	F62L	0.999
X:116437927:T:A	F62L	0.999
X:116437927:T:G	F62L	0.999
X:116440971:T:C	F74L	0.999
X:116440973:C:A	F74L	0.999
X:116440973:C:G	F74L	0.999
X:116442797:T:A	W153R	0.999
X:116442797:T:C	W153R	0.999
X:116442799:G:C	W153C	0.999
X:116442799:G:T	W153C	0.999
X:116451445:T:A	W312R	0.999
X:116451445:T:C	W312R	0.999
X:116451583:A:C	S358R	0.999
X:116451585:C:A	S358R	0.999
X:116451585:C:G	S358R	0.999
X:116451607:T:C	F366L	0.999
X:116451609:T:A	F366L	0.999
X:116451609:T:G	F366L	0.999
X:116437847:C:A	R36S	0.998
X:116437848:G:C	R36P	0.998
X:116437893:G:A	G51E	0.998
X:116437904:G:A	G55R	0.998
X:116437904:G:C	G55R	0.998
X:116437905:G:A	G55E	0.998

dbSNP variants (sampled 300 via entrez): RS1000290686 (X:116456823 T>C), RS1000955912 (X:116438291 A>G), RS1001091871 (X:116437947 A>G), RS1001915485 (X:116443162 A>C), RS1004113241 (X:116437124 T>G), RS1004288188 (X:116458606 A>C), RS1004587727 (X:116436776 C>A,T), RS1005802368 (X:116435181 C>T), RS1005854317 (X:116434875 C>T), RS1006093973 (X:116443782 A>G), RS1006372258 (X:116444367 T>A,C), RS1006735587 (X:116461563 G>A), RS1006760348 (X:116439160 A>G), RS1007627278 (X:116441725 A>C), RS1008296130 (X:116437847 C>A,T)

Disease associations

OMIM: gene MIM:300444 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cystic fibrosis	Supportive	Autosomal recessive

Mondo (1): cystic fibrosis (MONDO:0009061)

Orphanet (0):

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Nephrolithiasis
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001508	Failure to thrive
HP:0001738	Exocrine pancreatic insufficiency
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002035	Rectal prolapse
HP:0002099	Asthma
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002570	Steatorrhea
HP:0002724	Recurrent Aspergillus infections
HP:0002726	Recurrent Staphylococcus aureus infections
HP:0002783	Recurrent lower respiratory tract infections
HP:0002842	Recurrent Burkholderia cepacia infections
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003251	Male infertility
HP:0004401	Meconium ileus
HP:0005376	Recurrent Haemophilus influenzae infections
HP:0006536	Airway obstruction
HP:0012236	Elevated sweat chloride

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003143_1	Lung disease severity in cystic fibrosis	5.000000e-10
GCST003143_2	Lung disease severity in cystic fibrosis	5.000000e-08
GCST003143_3	Lung disease severity in cystic fibrosis	1.000000e-09
GCST003143_4	Lung disease severity in cystic fibrosis	5.000000e-06
GCST003143_5	Lung disease severity in cystic fibrosis	3.000000e-08
GCST003143_6	Lung disease severity in cystic fibrosis	9.000000e-06
GCST007367_5	Meconium ileus in cystic fibrosis	2.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007744	lung disease severity measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4680044 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Glycine transporter subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
α-methyl-D,L-tryptophan	Inhibition	3.6	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, decreases expression, increases expression	8
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
bisphenol A	increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Genistein	increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
urushiol	increases expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
formononetin	decreases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects localization, increases expression, affects cotreatment	1
sodium arsenite	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cyfluthrin	decreases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Allergens	increases abundance, increases expression, affects cotreatment	1
Ampicillin	increases expression	1
Asbestos	affects expression	1
Vehicle Emissions	affects cotreatment, increases abundance, increases expression	1
Azathioprine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	increases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylstilbestrol	increases expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 6 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4670320	Binding	Substrate activity at SLC6A14 (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of glycine uptake incubated for 10 mins by HPLC/MS/MS analysis	Bifunctional and Unusual Amino Acid β- or γ-Ester Prodrugs of Nucleoside Analogues for Improved Affinity to ATB and Enhanced Metabolic Stability: An Application to Floxuridine. — J Med Chem
CHEMBL4670321	ADMET	Substrate activity at SLC6A14 (unknown origin) expressed in Xenopus laevis oocytes assessed as ABT0+ mediated drug uptake at 0.5 mM incubated for 10 mins by HPLC analysis	Bifunctional and Unusual Amino Acid β- or γ-Ester Prodrugs of Nucleoside Analogues for Improved Affinity to ATB and Enhanced Metabolic Stability: An Application to Floxuridine. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4W7	LS180-SLC6A14-KO-c13	Cancer cell line	Female
CVCL_D4W8	LS180-SLC6A14-KO-c5	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	PHASE4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	PHASE4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	PHASE4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	PHASE4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	PHASE4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	PHASE4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	PHASE4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	PHASE4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	PHASE4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	PHASE4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	PHASE4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	PHASE4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	PHASE4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	PHASE4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	PHASE4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	PHASE4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	PHASE4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	PHASE4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	PHASE4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	PHASE4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	PHASE4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	PHASE4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	PHASE4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	PHASE4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	PHASE4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	PHASE4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	PHASE4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	PHASE4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	PHASE4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	PHASE4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	PHASE4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	PHASE4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	PHASE4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis