SLC19A2

Summary

SLC19A2 (solute carrier family 19 member 2, HGNC:10938) is a protein-coding gene on chromosome 1q24.2, encoding Thiamine transporter 1 (O60779). High-affinity transporter for the intake of thiamine.

This gene encodes the thiamin transporter protein. Mutations in this gene cause thiamin-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural deafness. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10560 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thiamine-responsive megaloblastic anemia syndrome (Definitive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 449 total — 48 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006996

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10938
Approved symbol	SLC19A2
Name	solute carrier family 19 member 2
Location	1q24.2
Locus type	gene with protein product
Status	Approved
Aliases	THTR1, ThT1
Ensembl gene	ENSG00000117479
Ensembl biotype	protein_coding
OMIM	603941
Entrez	10560

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000236137, ENST00000367804, ENST00000643377, ENST00000646596, ENST00000954860

RefSeq mRNA: 2 — MANE Select: NM_006996 NM_001319667, NM_006996

CCDS: CCDS1280, CCDS81398

Canonical transcript exons

ENST00000236137 — 6 exons

Exon	Start	End
ENSE00000789594	169468644	169468836
ENSE00000789595	169469964	169470186
ENSE00000789596	169477155	169477757
ENSE00001021778	169468111	169468252
ENSE00001357740	169463909	169465977
ENSE00003821119	169485563	169485944

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7174 / max 215.6569, expressed in 1774 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15842	12.6875	1766
15838	0.7744	337
15841	0.5359	307
15837	0.5258	236
15840	0.0979	49
15839	0.0959	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.23	gold quality
oocyte	CL:0000023	97.50	gold quality
gastrocnemius	UBERON:0001388	96.64	gold quality
tibialis anterior	UBERON:0001385	96.10	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.94	gold quality
muscle of leg	UBERON:0001383	95.91	gold quality
biceps brachii	UBERON:0001507	95.87	gold quality
deltoid	UBERON:0001476	95.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.48	gold quality
muscle organ	UBERON:0001630	95.27	gold quality
skeletal muscle organ	UBERON:0014892	95.27	gold quality
mucosa of stomach	UBERON:0001199	94.86	gold quality
skeletal muscle tissue	UBERON:0001134	94.62	gold quality
buccal mucosa cell	CL:0002336	94.20	silver quality
body of tongue	UBERON:0011876	93.90	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.84	gold quality
diaphragm	UBERON:0001103	93.83	gold quality
vastus lateralis	UBERON:0001379	93.09	gold quality
choroid plexus epithelium	UBERON:0003911	92.67	gold quality
quadriceps femoris	UBERON:0001377	92.46	gold quality
palpebral conjunctiva	UBERON:0001812	92.27	gold quality
eye	UBERON:0000970	92.19	gold quality
pigmented layer of retina	UBERON:0001782	92.01	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.50	gold quality
amniotic fluid	UBERON:0000173	91.46	gold quality
lower lobe of lung	UBERON:0008949	91.44	gold quality
muscle tissue	UBERON:0002385	91.17	gold quality
left uterine tube	UBERON:0001303	91.15	gold quality
pericardium	UBERON:0002407	90.53	gold quality
placenta	UBERON:0001987	90.50	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

Upstream regulators (CollecTRI, top): KLF4, NR3C1, SP1, TP53

miRNA regulators (miRDB)

118 targeting SLC19A2, 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-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 40)

• the effect of mutations in SLC19A2 identical to those found in thiamine-responsive megaloblastic anemia syndrome (TRMA), on functional activity and membrane expression of the transporter. (PMID:12065289)
• insertion of the thiamine transporter 1 linkers into reduced folate carrier (D215-R263 Delta) at position 215 restored 60-80% of wild-type levels of transport (PMID:12227830)
• correlate structure with cellular expression profile and reveal a critical dependence on backbone integrity and microtubule-based trafficking processes for functional expression (PMID:12454006)
• the importance of GKLF, NF-1, and SP-1 in regulating the activity of the SLC19A2 promoter (PMID:12900388)
• hTHTR-2 is expressed along the human gastrointestinal tract and that expression of its protein in intestinal epithelia is mainly localized to the apical brush-border membrane domain (PMID:14615284)
• this functional characterization of the D93H mutation of THTR1 provides a molecular basis for Rogers syndrome (PMID:14622275)
• Missense mutation in the SLC19A2 gene is associated with thiamine-responsive megaloblastic anemia syndrome (PMID:14994241)
• Findings indicate that the RFC1 genotype is a possible susceptible gene marker for an increased neural tube defects risk in Chinese population. (PMID:15952116)
• Three genetic variants of SLC19A2 gene were identified in Wernicke Korsakoff syndrome patients. (PMID:16015585)
• differentiation of intestinal epithelial cells is associated with an up-regulation in thiamin uptake process which is mediated via transcriptional regulatory mechanisms that involve the SLC19A2 and SLC19A3 genes (PMID:16055442)
• analysis of targeting and trafficking of hTHTR1 and hTHTR2 in epithelial cells (PMID:16371350)
• We have identified a novel missense mutation (T158R) that was excluded in 100 control alleles. (PMID:16373304)
• Thiamine uptake by HEK-293 cells is mediated via a specific pH-dependent process, which involves both the hTHTR-1 and hTHTR-2. (PMID:16705148)
• results show spectrum of mutant phenotypes, underlining that thiamine-responsive megaloblastic anaemia can result from decreased thiamine transport underpinned by changes in THTR1 expression levels, cellular targeting and/or protein transport activity (PMID:17331069)
• THTR1 is involved in thiamine transport by retinal pigment epithelium. Mutations found in thiamine-responsive megaloblastic anemia impaired THTR1 expression/function. (PMID:17463047)
• Three infants with thiamine-responsive megaloblastic anemia were homozygous, and the parents were heterozygous for a c.196G>T mutation in the SLC19A2 gene on chromosome 1q23.3, which encodes a high-affinity thiamine transporter. (PMID:17659067)
• findings suggest that the RFC G80A polymorphism may influence outcome in childhood ALL patients being treated with methotrexate (PMID:19340000)
• Pancreatic beta cells and islets take up thiamine by a regulated THTR1/2-mediated process. (PMID:19423748)
• No SLC25A38 mutations were found among sixty CSA probands examined (PMID:19731322)
• Data show that MTHFR 677C>T and MTRR 66A>G polymorphisms are two independent risk factors for DS pregnancies in young women, but RFC-1 80G>A and MTR 2756A>G polymorphism are not independent risk factor. (PMID:20466634)
• Thiamine-responsive megaloblastic anaemia (TRMA), due to mutations in the thiamine transporter SLC19A2, is associated with the classical clinical triad of diabetes, deafness, and megaloblastic anaemia. (PMID:22369132)
• Thiamine-responsive megaloblastic anemia syndrome is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural hearing loss due to mutations in SLC 19A. (PMID:22876572)
• Glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. (PMID:23285265)
• study identified a compound heterozygous mutation p.Y81X/p.L457X (c.242insA/c.1370delT) in the SLC19A2 gene in two sisters with thiamine responsive megaloblastic anemia (PMID:23289844)
• A non-sense mutation SLC19A2 was found in four patients with Thiamine-responsive megaloblastic anemia, indicating its high frequency in Persian population. (PMID:23454484)
• Thiamine transporter 2 deficiency is a recessive disease caused by mutations in the SLC19A3 genes. (PMID:23589815)
• Here we describe for the first time Leber’s congenital amaurosis as the retinal phenotype and also report a novel point mutation in the SLC19A2 gene that co-segregated with the disease in a thiamine responsive megaloblastic anemia patient. (PMID:23638917)
• These findings demonstrate that the genes involved in dictating thiamine homeostasis, such as SLC19A2, SLC25A19 and TPK-1, were significantly up-regulated in clinical tissues and breast cancer cell lines. (PMID:23642734)
• study presents three thiamine-responsive megaloblastic anemia patients with a novel missense mutation in the SLC19A2 gene (c.382 G>A (p.E128K)). Administration of thiamine in patients with TRMA ameliorates the megaloblastic anemia and diabetes mellitus. (PMID:24072090)
• Missense mutations were found in the SLC19A2 gene of 4 Chinese patients with thiamine responsive megaloblastic anemia. (PMID:24355766)
• The present study confirms the variability of the clinical manifestations caused by the same mutation within patients with TRMA syndrome. (PMID:24357267)
• Allelic expression imbalance confirmed that cis variation at the human SLC35F3 locus influenced expression of that gene, and the allelic expression imbalance peak coincided with the hypertension peak. (PMID:24509276)
• the novel SLC19A2 mutation reported here may have contributed to the patient’s psychotic manifestations by an unknown mechanism (PMID:24520986)
• Individuals with genotype A80A for the SLC19A1 gene have a poor absorption of folate, altering the metabolism of folate and compromising the process of cell division promoting development of neuroblastoma. (PMID:24771227)
• A novel homozygous SLC19A2 gene mutation c.[205G>T], p.[(Val69Phe)] causing thiamine responsive megaloblastic anemia syndrome. (PMID:25707023)
• SLC19A2 mutation is associated with permanent neonatal diabetes mellitus. (PMID:28371426)
• A Novel Mutation of SLC19A2 in a Chinese Zhuang Ethnic Family with Thiamine-Responsive Megaloblastic Anemia.( (PMID:29969779)
• Study demonstrate that SLC19A2 deficit causes impaired insulin secretion in conjunction with mitochondrial dysfunction, loss of protection against oxidative stress, and cell cycle arrest. These findings link SLC19A2 mutations to autosomal dominant diabetes and suggest a role of SLC19A2 in beta-cell function and survival. (PMID:30833467)
• TRMA syndrome with a severe phenotype, cerebral infarction, and novel compound heterozygous SLC19A2 mutation: a case report. (PMID:31296181)
• Besides reporting a novel mutation of the causative gene SLC19A2, we wanted to emphasize this syndrome in the aspect of coexistence of insulin dependent diabetes, transfusion dependent anemia and thrombocytopenia. (PMID:31951336)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc19a2	ENSDARG00000059712
mus_musculus	Slc19a2	ENSMUSG00000040918
rattus_norvegicus	Slc19a2	ENSRNOG00000002839
drosophila_melanogaster	CG17036	FBGN0032449
drosophila_melanogaster	CG14694	FBGN0037845
drosophila_melanogaster	CG6574	FBGN0037846
caenorhabditis_elegans		WBGENE00007388
caenorhabditis_elegans		WBGENE00018138
caenorhabditis_elegans		WBGENE00044738

Paralogs (2): SLC19A3 (ENSG00000135917), SLC19A1 (ENSG00000173638)

Protein

Protein identifiers

Thiamine transporter 1 — O60779 (reviewed: O60779)

Alternative names: Solute carrier family 19 member 2, Thiamine carrier 1

All UniProt accessions (4): A0A024R8Y5, A0A024R928, A0A2R8Y5B5, O60779

UniProt curated annotations — full annotation on UniProt →

Function. High-affinity transporter for the intake of thiamine. Mediates H(+)-dependent pyridoxine transport.

Subunit / interactions. Interacts with TSPAN1; this interaction increases the stability of SLC19A2. Interacts with TMEM63B.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous; most abundant in skeletal and cardiac muscle. Medium expression in placenta, heart, liver and kidney, low in lung.

Disease relevance. Thiamine-responsive megaloblastic anemia syndrome (TRMA) [MIM:249270] An autosomal recessive disease characterized by megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Onset is typically between infancy and adolescence, but all of the cardinal findings are often not present initially. The anemia, and sometimes the diabetes, improves with high doses of thiamine. Other more variable features include optic atrophy, congenital heart defects, short stature, and stroke. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Pyridoxine transport is inhibited by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and carbonyl cyanide m-chlorophenylhydrazone (CCCP).

Similarity. Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60779-1	1	yes
O60779-2	2

RefSeq proteins (2): NP_001306596, NP_008927* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002666	Folate_carrier	Family
IPR028338	ThTr-1	Family
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF01770

Catalyzed reactions (Rhea), 2 shown:

• thiamine(out) + H(+)(in) = thiamine(in) + H(+)(out) (RHEA:71271)
• pyridoxine(out) + n H(+)(out) = pyridoxine(in) + n H(+)(in) (RHEA:76203)

UniProt features (72 total): helix 18, topological domain 13, transmembrane region 12, site 7, mutagenesis site 7, turn 4, sequence variant 3, modified residue 2, glycosylation site 2, strand 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8Z7Z	ELECTRON MICROSCOPY	3.23
8Z80	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60779-F1	80.99	0.54

Functional residue map

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

Catalytic / active sites (7): 104 (essential for pyridoxine transport); 105 (essential for pyridoxine transport); 109 (essential for pyridoxine transport); 111 (essential for pyridoxine transport); 112 (essential for pyridoxine transport); 186 (essential for pyridoxine transport); 191 (essential for pyridoxine transport)

Post-translational modifications (2): 1, 222

Glycosylation sites (2): 63, 314

Mutagenesis-validated functional residues (7):

Position	Phenotype
104	loss of pyridoxine transport; when associated with v-105; a-109; s-111; y-112; p-186 and f-191.
105	loss of pyridoxine transport; when associated with h-104; a-109; s-111; y-112; p-186 and f-191.
109	loss of pyridoxine transport; when associated with h-104; v-105; s-111; y-112; p-186 and f-191.
111	loss of pyridoxine transport; when associated with h-104; v-105; a-109; y-112; p-186 and f-191.
112	loss of pyridoxine transport; when associated with h-104; v-105; a-109; s-111; p-186 and f-191.
186	loss of pyridoxine transport; when associated with h-104; v-105; a-109; s-111; y-112 and f-191.
191	loss of pyridoxine transport; when associated with h-104; v-105; a-109; s-111; y-112 and p-186.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-196819	Vitamin B1 (thiamin) metabolism
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 319 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, SMID_BREAST_CANCER_LUMINAL_B_UP, GROSS_HYPOXIA_VIA_ELK3_UP

GO Biological Process (10): spermatogenesis (GO:0007283), thiamine diphosphate biosynthetic process (GO:0009229), thiamine transport (GO:0015888), pyridoxine transport (GO:0031923), thiamine-containing compound metabolic process (GO:0042723), thiamine transmembrane transport (GO:0071934), folic acid transport (GO:0015884), vitamin transmembrane transport (GO:0035461), vitamin transport (GO:0051180), transmembrane transport (GO:0055085)

GO Molecular Function (4): folic acid transmembrane transporter activity (GO:0008517), thiamine transmembrane transporter activity (GO:0015234), protein binding (GO:0005515), vitamin transmembrane transporter activity (GO:0090482)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vitamin transport	3
vitamin transmembrane transport	2
transport	2
vitamin transmembrane transporter activity	2
developmental process involved in reproduction	1
male gamete generation	1
thiamine diphosphate metabolic process	1
thiamine-containing compound biosynthetic process	1
organophosphate biosynthetic process	1
nitrogen compound transport	1
sulfur compound transport	1
organic hydroxy compound transport	1
vitamin B6 transport	1
sulfur compound metabolic process	1
pyrimidine-containing compound metabolic process	1
thiamine transport	1
azole transmembrane transport	1
pyrimidine-containing compound transmembrane transport	1
dicarboxylic acid transport	1
modified amino acid transport	1
transmembrane transport	1
cellular process	1
dicarboxylic acid transmembrane transporter activity	1
folic acid transport	1
modified amino acid transmembrane transporter activity	1
thiamine transmembrane transport	1
azole transmembrane transporter activity	1
sulfur compound transmembrane transporter activity	1
binding	1
transmembrane transporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

998 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC19A2	TPK1	Q9H3S4	748
SLC19A2	IER3IP1	Q9Y5U9	662
SLC19A2	TSPAN1	O60635	660
SLC19A2	SLC25A19	Q9HC21	654
SLC19A2	BTD	P43251	611
SLC19A2	RFX6	Q8HWS3	605
SLC19A2	WFS1	O76024	580
SLC19A2	SLC25A38	Q96DW6	570
SLC19A2	GLIS3	Q8NEA6	544
SLC19A2	INS	P01308	536
SLC19A2	ABCC8	Q09428	534
SLC19A2	PUS1	Q9Y606	529
SLC19A2	TKTL1	P51854	520
SLC19A2	TKTL2	Q9H0I9	518
SLC19A2	ABCB7	O75027	512

IntAct

119 interactions, top by confidence:

A	B	Type	Score
SLC19A2	ATP5F1B	psi-mi:“MI:0914”(association)	0.730
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
ATP5PB	SLC19A2	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
TSPAN1	SLC19A2	psi-mi:“MI:0915”(physical association)	0.600
TSPAN1	SLC19A2	psi-mi:“MI:0403”(colocalization)	0.600
SLC19A2	ENDOD1	psi-mi:“MI:0915”(physical association)	0.560
CERS2	SLC19A2	psi-mi:“MI:0915”(physical association)	0.550
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
SLC9A6	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
B4GALT3	SLC19A2	psi-mi:“MI:0914”(association)	0.530
P2RY1	SLC19A2	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
SLC5A5	SLC19A2	psi-mi:“MI:0914”(association)	0.530
TMEM63B	SLC19A2	psi-mi:“MI:0914”(association)	0.530

BioGRID (337): SLC19A2 (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), DNASE1L2 (Affinity Capture-MS), PPIE (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), PPIE (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), DNASE1L2 (Affinity Capture-MS)

ESM2 similar proteins: A2AVZ9, A4IHK6, A4QN56, A5D7V7, B0S5Y3, B2RXV4, B5X4H8, O00400, O60779, O75387, P41438, P58355, P60815, Q04991, Q0VC03, Q0VCM6, Q1JPD8, Q28FF3, Q4LE88, Q4R877, Q569T7, Q5BK75, Q5E9R1, Q5R542, Q5RBM3, Q5RF58, Q62866, Q6AYY8, Q6GMG6, Q6N075, Q6PB15, Q71B07, Q8BSM7, Q8CGA3, Q8N370, Q8NBI5, Q91X85, Q921Y4, Q944P0, Q99J27

Diamond homologs: O45166, O60779, P41438, P41440, Q17766, Q22931, Q4R877, Q62866, Q99PL8, Q9BZV2, Q9EQN9, P42557, Q53S99, Q559K0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of ATP by chemiosmotic coupling	5	37.6×	2e-05
Cristae formation	5	22.8×	1e-04
Class A/1 (Rhodopsin-like receptors)	13	12.7×	7e-09
Mitochondrial biogenesis	5	11.1×	2e-03
GPCR ligand binding	11	9.3×	4e-06
Peptide ligand-binding receptors	8	7.8×	3e-04
G alpha (q) signalling events	10	7.5×	4e-05
Signaling by GPCR	12	6.3×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
complement receptor mediated signaling pathway	5	54.0×	3e-06
proton motive force-driven ATP synthesis	5	38.6×	1e-05
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	10	21.0×	8e-09
positive regulation of cytosolic calcium ion concentration	14	15.8×	1e-10
phospholipase C-activating G protein-coupled receptor signaling pathway	12	15.2×	6e-09
proton motive force-driven mitochondrial ATP synthesis	5	12.7×	2e-03
calcium-mediated signaling	7	12.3×	1e-04
adenylate cyclase-activating G protein-coupled receptor signaling pathway	9	9.8×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	48
Likely pathogenic	10
Uncertain significance	162
Likely benign	178
Benign	12

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1178328	NM_006996.3(SLC19A2):c.697C>T (p.Gln233Ter)	Pathogenic
1454060	NM_006996.3(SLC19A2):c.620_624dup (p.Pro209fs)	Pathogenic
2114203	NM_006996.3(SLC19A2):c.1351_1360del (p.Glu451fs)	Pathogenic
2202878	NM_006996.3(SLC19A2):c.1223+1G>A	Pathogenic
2202880	NM_006996.3(SLC19A2):c.196G>T (p.Glu66Ter)	Pathogenic
2425678	NC_000001.10:g.(?169435087)(169455004_?)del	Pathogenic
2425679	NC_000001.10:g.(?169454781)(169455004_?)del	Pathogenic
2505911	NM_006996.3(SLC19A2):c.1160G>A (p.Trp387Ter)	Pathogenic
2693922	NM_006996.3(SLC19A2):c.1171dup (p.Ala391fs)	Pathogenic
2710969	NM_006996.3(SLC19A2):c.497T>A (p.Leu166Ter)	Pathogenic
2734015	NM_006996.3(SLC19A2):c.1370del (p.Phe456_Leu457insTer)	Pathogenic
2734016	NM_006996.3(SLC19A2):c.1189A>T (p.Arg397Ter)	Pathogenic
2734017	NM_006996.3(SLC19A2):c.759dup (p.Glu254Ter)	Pathogenic
2750526	NM_006996.3(SLC19A2):c.673C>T (p.Gln225Ter)	Pathogenic
2779982	NM_006996.3(SLC19A2):c.358G>T (p.Gly120Ter)	Pathogenic
2796384	NM_006996.3(SLC19A2):c.903G>A (p.Trp301Ter)	Pathogenic
2820387	NM_006996.3(SLC19A2):c.555G>A (p.Trp185Ter)	Pathogenic
2833242	NM_006996.3(SLC19A2):c.999del (p.Asn333fs)	Pathogenic
2833923	NM_006996.3(SLC19A2):c.902G>A (p.Trp301Ter)	Pathogenic
2840207	NM_006996.3(SLC19A2):c.678_679del (p.Arg226fs)	Pathogenic
2846261	NM_006996.3(SLC19A2):c.597del (p.Val200fs)	Pathogenic
2854646	NM_006996.3(SLC19A2):c.148G>T (p.Glu50Ter)	Pathogenic
2855932	NM_006996.3(SLC19A2):c.556_557insTTGGT (p.Ser186fs)	Pathogenic
2859272	NM_006996.3(SLC19A2):c.391del (p.Tyr131fs)	Pathogenic
3247981	NC_000001.10:g.(?169439182)(169447015_?)del	Pathogenic
3247982	NC_000001.10:g.(?169435087)(169439444_?)del	Pathogenic
3247983	NC_000001.10:g.(?169446833)(169454047_?)del	Pathogenic
3255578	NM_006996.3(SLC19A2):c.566_567delinsTCT (p.Ser189fs)	Pathogenic
3643123	NM_006996.3(SLC19A2):c.1223+1G>T	Pathogenic
3646475	NM_006996.3(SLC19A2):c.382G>T (p.Glu128Ter)	Pathogenic

SpliceAI

1048 predictions. Top by Δscore:

Variant	Effect	Δscore
1:169468107:TTA:T	donor_loss	1.0000
1:169468108:TAC:T	donor_loss	1.0000
1:169468109:A:AG	donor_loss	1.0000
1:169468110:CCTG:C	donor_loss	1.0000
1:169468248:GAAAA:G	acceptor_gain	1.0000
1:169468249:AAAA:A	acceptor_gain	1.0000
1:169468250:AAA:A	acceptor_gain	1.0000
1:169468250:AAACT:A	acceptor_loss	1.0000
1:169468251:AA:A	acceptor_gain	1.0000
1:169468253:C:CA	acceptor_loss	1.0000
1:169468253:C:CC	acceptor_gain	1.0000
1:169468254:T:C	acceptor_gain	1.0000
1:169468254:T:TC	acceptor_gain	1.0000
1:169468264:A:C	acceptor_gain	1.0000
1:169468642:A:AC	donor_gain	1.0000
1:169468643:C:CC	donor_gain	1.0000
1:169468643:CGTTG:C	donor_gain	1.0000
1:169468751:C:CT	acceptor_gain	1.0000
1:169468752:A:T	acceptor_gain	1.0000
1:169469962:A:AC	donor_gain	1.0000
1:169469962:AC:A	donor_gain	1.0000
1:169469963:C:CC	donor_gain	1.0000
1:169469963:CC:C	donor_gain	1.0000
1:169470101:C:CT	acceptor_gain	1.0000
1:169470102:A:T	acceptor_gain	1.0000
1:169485564:T:TA	donor_gain	1.0000
1:169485565:C:A	donor_gain	1.0000
1:169465978:C:CC	acceptor_gain	0.9900
1:169468108:TA:T	donor_gain	0.9900
1:169468109:A:AC	donor_gain	0.9900

AlphaMissense

3187 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:169477477:C:G	R162P	0.997
1:169468241:G:T	A412D	0.995
1:169470090:A:G	W302R	0.995
1:169470090:A:T	W302R	0.995
1:169470093:A:G	W301R	0.995
1:169470093:A:T	W301R	0.995
1:169477543:G:T	A140D	0.995
1:169485645:C:T	G41D	0.995
1:169468202:C:T	G425D	0.994
1:169477668:T:A	K98N	0.994
1:169477668:T:G	K98N	0.994
1:169485646:C:G	G41R	0.994
1:169468195:A:C	N427K	0.993
1:169468195:A:T	N427K	0.993
1:169470036:A:G	W320R	0.993
1:169470036:A:T	W320R	0.993
1:169468204:A:C	F424L	0.992
1:169468204:A:T	F424L	0.992
1:169468206:A:G	F424L	0.992
1:169468214:G:T	A421D	0.992
1:169477663:A:T	V100D	0.992
1:169485611:G:C	F52L	0.992
1:169485611:G:T	F52L	0.992
1:169485613:A:G	F52L	0.992
1:169470071:C:T	G308D	0.991
1:169477555:G:T	A136D	0.991
1:169477641:G:C	S107R	0.991
1:169477641:G:T	S107R	0.991
1:169477643:T:G	S107R	0.991
1:169468184:G:T	A431D	0.990

dbSNP variants (sampled 300 via entrez): RS1000230073 (1:169476354 T>C), RS1000304891 (1:169475878 T>C), RS1000361639 (1:169483460 T>C), RS1000582129 (1:169475969 G>C), RS1000671246 (1:169468609 T>A,C), RS1001321069 (1:169464970 G>C), RS1001342907 (1:169472005 A>G), RS1001375633 (1:169472309 G>A), RS1001624959 (1:169465296 C>A), RS1001853470 (1:169477531 T>C), RS1002119159 (1:169469006 A>C), RS1002305755 (1:169477958 G>C), RS1002376588 (1:169470739 G>A), RS1002514382 (1:169481281 T>G), RS1002645378 (1:169487732 G>C)

Disease associations

OMIM: gene MIM:603941 | disease phenotypes: MIM:128600, MIM:249270

GenCC curated gene-disease

Disease	Classification	Inheritance
thiamine-responsive megaloblastic anemia syndrome	Definitive	Autosomal recessive

Mondo (4): ear malformation (MONDO:0007500), thiamine-responsive megaloblastic anemia syndrome (MONDO:0009575), sensorineural hearing loss disorder (MONDO:0020678), monogenic diabetes (MONDO:0015967)

Orphanet (2): Thiamine-responsive megaloblastic anemia syndrome (Orphanet:49827), Rare genetic diabetes mellitus (Orphanet:183625)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000407	Sensorineural hearing impairment
HP:0000546	Retinal degeneration
HP:0000548	Cone/cone-rod dystrophy
HP:0000556	Retinal dystrophy
HP:0000572	Visual loss
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000819	Diabetes mellitus
HP:0000951	Abnormality of the skin
HP:0000980	Pallor
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001297	Stroke
HP:0001609	Hoarse voice
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001695	Cardiac arrest
HP:0001696	Situs inversus totalis
HP:0001873	Thrombocytopenia
HP:0001889	Megaloblastic anemia
HP:0001924	Sideroblastic anemia
HP:0002014	Diarrhea
HP:0002020	Gastroesophageal reflux
HP:0002039	Anorexia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001253_1	Venous thromboembolism	2.000000e-26
GCST008461_2	Plasma factor V levels in venous thrombosis	8.000000e-12

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536510	Thiamine responsive megaloblastic anemia syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3079 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 413 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1318296	AMPROLIUM	2	413

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC19 family of vitamin transporters

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.12	Ki	7600	nM	AMPROLIUM

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
amprolium	213091: Antiparasitic activity against thiamine transporter of Eimeria tenella	ki	7.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects expression	4
Tetrachlorodibenzodioxin	affects expression, increases expression	4
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	4
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Estradiol	increases expression, affects cotreatment	2
Cyclosporine	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
arsenite	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
iodopravadoline	decreases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
elesclomol	decreases reaction, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Acetylcysteine	decreases reaction, increases expression	1
Air Pollutants	decreases expression, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 1 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL814138	Functional	Antiparasitic activity against thiamine transporter of chicken intestine	Parasite enzymes as potential targets for antiparasitic chemotherapy. — J Med Chem
CHEMBL814139	Binding	Antiparasitic activity against thiamine transporter of Eimeria tenella	Parasite enzymes as potential targets for antiparasitic chemotherapy. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4IJ	HCT116-SLC19A2-KO-c5	Cancer cell line	Male
CVCL_D4IK	HCT116-SLC19A2-KO-c8	Cancer cell line	Male
CVCL_TL79	HAP1 SLC19A2 (-) 1	Cancer cell line	Male
CVCL_TL80	HAP1 SLC19A2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01655212	PHASE3	TERMINATED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment in a Randomized Controlled Trial
NCT02005822	PHASE3	COMPLETED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment
NCT03374514	PHASE3	UNKNOWN	Cochlear Electrical Impedance and the Effect of Topical Dexamethasone on Cochlear Implant Surgery
NCT02497690	PHASE2	COMPLETED	Effectiveness of Therapy Via Telemedicine Following Cochlear Implants
NCT03107871	PHASE2	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants
NCT04120116	PHASE2	COMPLETED	FX-322 in Adults With Stable Sensorineural Hearing Loss
NCT05061758	PHASE2	WITHDRAWN	A Trial of LY3056480 in Patients With SNLH
NCT07364747	PHASE2	RECRUITING	Protective Effect of Acetylcysteine Against Cisplatinum-Induced Ototoxicity: A Randomized Controlled Trial
NCT06976658	PHASE2	RECRUITING	Glucokinase Activator in Monogenic Diabetes
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT01795144	PHASE1	COMPLETED	Incretin Regulation of Insulin Secretion in Monogenic Diabetes
NCT06431698	Not specified	UNKNOWN	CORRECTION OF EAR DEFORMITIES IN NEWBORNS BY MODELING, COMPARISON OF TWO PROTOCOLS
NCT07154667	Not specified	RECRUITING	Evaluation of the Auryzon™ EAR 2.0 System in Ear Reconstruction
NCT02693704	PHASE2/PHASE3	COMPLETED	Evaluation of a Binaural Spatialization Method for Hearing Aids
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01267994	PHASE1/PHASE2	COMPLETED	A Clinical Trial of Anakinra for Steroid-Resistant Autoimmune Inner Ear Disease
NCT01902914	PHASE1/PHASE2	UNKNOWN	Effectiveness of P02 Digital Hearing Aids
NCT02038972	PHASE1/PHASE2	COMPLETED	Safety of Autologous Stem Cell Infusion for Children With Acquired Hearing Loss
NCT02616172	PHASE1/PHASE2	SUSPENDED	Autologous Bone Marrow Harvest and Transplant for Sensorineural Hearing Loss
NCT03616223	PHASE1/PHASE2	COMPLETED	FX-322 in Sensorineural Hearing Loss
NCT04129775	PHASE1/PHASE2	COMPLETED	OTO-413 in Subjects With Speech-in-Noise Hearing Impairment
NCT04462198	PHASE1/PHASE2	COMPLETED	Phase I/IIa Study Evaluating Safety and Efficacy of an Intratympanic Dose of PIPE-505 in Subjects With Hearing Loss
NCT07032038	PHASE1/PHASE2	NOT_YET_RECRUITING	First In Human Randomised Trial of Rincell-1 in Adults With a Cochlear Implant
NCT06025097	EARLY_PHASE1	COMPLETED	Intra-Tympanic Steroid With PRP Combination in Sensorineural Hearing Loss and Tinnitus.
NCT06707389	EARLY_PHASE1	NOT_YET_RECRUITING	Autologous Blood Monocyte Vesicles for the Treatment of Sudden Deafness
NCT07472023	EARLY_PHASE1	ENROLLING_BY_INVITATION	Regenerative Medicine and Stem Cell-Based Interventions for Inner Ear Trauma, Tinnitus, and Sensorineural Hearing Loss
NCT00023036	Not specified	COMPLETED	Clinical and Genetic Analysis of Enlarged Vestibular Aqueducts
NCT00023049	Not specified	COMPLETED	Genetic Analysis of Hereditary Disorders of Hearing and Balance
NCT00261768	Not specified	COMPLETED	Efficacy of Digital Noise Reduction Strategies: A Hearing Aid Trial
NCT00589511	Not specified	COMPLETED	Nucleus Freedom Cochlear Implant System Pediatric Post-approval Study
NCT00678899	Not specified	COMPLETED	Evaluation of the Nucleus Hybrid™ L24 Cochlear Implant System
NCT00787189	Not specified	COMPLETED	Study of Low Level Laser Therapy and Word Recognition in Hearing Impaired Individuals
NCT01184248	Not specified	COMPLETED	The Effect of Sound Stimulation on Pure-tone Hearing Threshold
NCT01434446	Not specified	COMPLETED	The Effect of Sound Stimulation on Hearing Ability
NCT01749592	Not specified	COMPLETED	Single-sided Deafness and Cochlear Implants
NCT01781039	Not specified	COMPLETED	Investigation of Anatomical Correlates of Speech Discrimination
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02093806	Not specified	UNKNOWN	Clinical Applications of Round Window Imaging Anatomy in Cochlear Implant Surgery
NCT02252601	Not specified	UNKNOWN	Evaluation of the High Frequency Digit Triplet Test in Cystic Fibrosis
NCT02584361	Not specified	UNKNOWN	Cochlear Implant and Vestibular Function.