SLC25A19

Summary

SLC25A19 (solute carrier family 25 member 19, HGNC:14409) is a protein-coding gene on chromosome 17q25.1, encoding Mitochondrial thiamine pyrophosphate carrier (Q9HC21). Mitochondrial transporter mediating uptake of thiamine diphosphate into mitochondria. It is a selective cancer dependency (DepMap: 10.6% of cell lines).

This gene encodes a mitochondrial protein that is a member of the solute carrier family. Although this protein was initially thought to be the mitochondrial deoxynucleotide carrier involved in the uptake of deoxynucleotides into the matrix of the mitochondria, further studies have demonstrated that this protein instead functions as the mitochondrial thiamine pyrophosphate carrier, which transports thiamine pyrophosphates into mitochondria. Mutations in this gene cause microcephaly, Amish type, a metabolic disease that results in severe congenital microcephaly, severe 2-ketoglutaric aciduria, and death within the first year. Multiple alternatively spliced variants, encoding the same protein, have been identified for this gene.

Source: NCBI Gene 60386 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Amish lethal microcephaly (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 164 total — 8 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 54
• Cancer dependency (DepMap): dependent in 10.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001126121

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14409
Approved symbol	SLC25A19
Name	solute carrier family 25 member 19
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	DNC, MUP1, TPC
Ensembl gene	ENSG00000125454
Ensembl biotype	protein_coding
OMIM	606521
Entrez	60386

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 44 protein_coding, 1 retained_intron

ENST00000320362, ENST00000375261, ENST00000402418, ENST00000416858, ENST00000442286, ENST00000579207, ENST00000579228, ENST00000580151, ENST00000580273, ENST00000580994, ENST00000581988, ENST00000582778, ENST00000582822, ENST00000583332, ENST00000584438, ENST00000895817, ENST00000895818, ENST00000895819, ENST00000895820, ENST00000895821, ENST00000895822, ENST00000895823, ENST00000895824, ENST00000895825, ENST00000895826, ENST00000895827, ENST00000895828, ENST00000895829, ENST00000895830, ENST00000921219, ENST00000921220, ENST00000921221, ENST00000921222, ENST00000921223, ENST00000921224, ENST00000921225, ENST00000921226, ENST00000921227, ENST00000921228, ENST00000956596, ENST00000956597, ENST00000956598, ENST00000956599, ENST00000956600, ENST00000956601

RefSeq mRNA: 3 — MANE Select: NM_001126121 NM_001126121, NM_001126122, NM_021734

CCDS: CCDS11720

Canonical transcript exons

ENST00000416858 — 8 exons

Exon	Start	End
ENSE00000855717	75277353	75277483
ENSE00000855718	75278152	75278335
ENSE00001172339	75272992	75273639
ENSE00001241203	75286633	75286802
ENSE00001346381	75288502	75288591
ENSE00002236834	75289354	75289433
ENSE00003619602	75286304	75286459
ENSE00003784932	75283423	75283593

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 89.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7596 / max 108.3331, expressed in 1716 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168059	8.7596	1716

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	89.10	gold quality
right testis	UBERON:0004534	88.65	gold quality
testis	UBERON:0000473	87.73	gold quality
stromal cell of endometrium	CL:0002255	87.09	gold quality
right adrenal gland cortex	UBERON:0035827	87.00	gold quality
left adrenal gland cortex	UBERON:0035825	86.55	gold quality
right adrenal gland	UBERON:0001233	86.02	gold quality
left adrenal gland	UBERON:0001234	86.02	gold quality
vermiform appendix	UBERON:0001154	85.98	gold quality
adrenal cortex	UBERON:0001235	85.82	gold quality
granulocyte	CL:0000094	85.60	gold quality
mucosa of transverse colon	UBERON:0004991	85.38	gold quality
apex of heart	UBERON:0002098	85.24	gold quality
adrenal gland	UBERON:0002369	85.21	gold quality
lymph node	UBERON:0000029	85.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.82	gold quality
bone marrow cell	CL:0002092	84.38	gold quality
pancreatic ductal cell	CL:0002079	84.30	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.02	gold quality
gastrocnemius	UBERON:0001388	83.77	gold quality
adult organism	UBERON:0007023	83.72	gold quality
muscle of leg	UBERON:0001383	83.29	gold quality
leukocyte	CL:0000738	83.07	gold quality
monocyte	CL:0000576	83.06	gold quality
oocyte	CL:0000023	82.91	gold quality
tibialis anterior	UBERON:0001385	82.82	silver quality
spleen	UBERON:0002106	82.14	gold quality
caecum	UBERON:0001153	81.67	gold quality
tendon of biceps brachii	UBERON:0008188	81.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN

miRNA regulators (miRDB)

27 targeting SLC25A19, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-2276-5P	96.27	65.85	937
HSA-MIR-4793-3P	94.87	65.85	896

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 10.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 14)

• mutant protein lacks the normal transport activity, implying that failed deoxynucleotide transport across the inner mitochondrial membrane causes Amiah microcephaly (MCPHA) (PMID:12185364)
• mitochondria of Slc25a19(-/-) and Amish lethal microcephaly cells have undetectable and markedly reduced thiamine pyrophosphate content, respectively (PMID:17035501)
• We review the evidence that the function of the SLC25A19 gene product, previously identified as the mitochondrial deoxyribonucleotide carrier (DNC), is actually the transport of thiamine pyrophosphate.[review] (PMID:18280798)
• a pathogenic missense mutation in the SLC25A19 gene was identifiedin 4 patients who suffered from recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy (PMID:19798730)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• 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)
• Characterization of the SLC25A19 promoter and demonstration of an essential role for NF-Y in its basal activity. (PMID:23872534)
• Chronic alcohol exposure negatively impacts pancreatic mitochondrial thiamin pyrophosphate transport, and this effect is exerted, at least in part, at the level of Slc25a19 transcription and appears to involve an epigenetic mechanism. (PMID:26316591)
• Among 6 residues predicted by the docking model ( Thr(29), Arg(30), Ile(33), Ser(34), Asp(37) and Phe(298)), only Ile(33), Ser(34) and Asp(37) were critical for function. Ser(34) did not affect translation/stability. Ile(33) and Asp(37) mutants decreased this parameter andwere expressed less in mitochondria. A polar residue was needed at position 34. His(137) and Lys(291) are needed for delivery to mitochondria. (PMID:27188525)
• Pancreatic acinar cells Mitochondrial Thiamin Pyrophosphate uptake process is adaptively regulated by the prevailing thiamin level and this regulation is exerted at the level of transcription of the SLC25A19 gene and involves transcription factor binding affinity/epigenetic mechanisms. (PMID:28729247)
• Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4. (PMID:34587972)
• Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature. (PMID:35102031)
• miR-122-5p is involved in posttranscriptional regulation of the mitochondrial thiamin pyrophosphate transporter (SLC25A19) in pancreatic acinar cells. (PMID:37529835)
• SLC25A19 is required for NADH homeostasis and mitochondrial respiration. (PMID:38944213)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a19	ENSDARG00000100385
mus_musculus	Slc25a19	ENSMUSG00000020744
rattus_norvegicus	Slc25a19	ENSRNOG00000003918
rattus_norvegicus		ENSRNOG00000089437
drosophila_melanogaster	Tpc2	FBGN0035078
drosophila_melanogaster	Tpc1	FBGN0037852
caenorhabditis_elegans		WBGENE00016588

Paralogs (49): SLC25A13 (ENSG00000004864), SLC25A5 (ENSG00000005022), SLC25A39 (ENSG00000013306), SLC25A40 (ENSG00000075303), SLC25A3 (ENSG00000075415), SLC25A43 (ENSG00000077713), SLC25A24 (ENSG00000085491), SLC25A1 (ENSG00000100075), SLC25A17 (ENSG00000100372), SLC25A14 (ENSG00000102078), SLC25A15 (ENSG00000102743), SLC25A11 (ENSG00000108528), UCP1 (ENSG00000109424), SLC25A36 (ENSG00000114120), SLC25A12 (ENSG00000115840), SLC25A2 (ENSG00000120329), SLC25A51 (ENSG00000122696), SLC25A16 (ENSG00000122912), SLC25A35 (ENSG00000125434), SLC25A23 (ENSG00000125648), SLC25A47 (ENSG00000140107), SLC25A52 (ENSG00000141437), SLC25A38 (ENSG00000144659), SLC25A26 (ENSG00000144741), SLC25A48 (ENSG00000145832), SLC25A37 (ENSG00000147454), SLC25A25 (ENSG00000148339), SLC25A31 (ENSG00000151475), SLC25A4 (ENSG00000151729), SLC25A27 (ENSG00000153291), SLC25A28 (ENSG00000155287), SLC25A44 (ENSG00000160785), SLC25A45 (ENSG00000162241), SLC25A34 (ENSG00000162461), SLC25A32 (ENSG00000164933), SLC25A6 (ENSG00000169100), SLC25A33 (ENSG00000171612), SLC25A30 (ENSG00000174032), UCP3 (ENSG00000175564), UCP2 (ENSG00000175567)

Protein

Protein identifiers

Mitochondrial thiamine pyrophosphate carrier — Q9HC21 (reviewed: Q9HC21)

Alternative names: Mitochondrial thiamine pyrophosphate transporter, Mitochondrial uncoupling protein 1, Solute carrier family 25 member 19

All UniProt accessions (10): Q9HC21, J3KRY6, J3KS44, J3KSB1, J3KSI7, J3KTL0, J3QL84, J3QLV3, J3QS02, Q5JPC1

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial transporter mediating uptake of thiamine diphosphate into mitochondria. It is not clear if the antiporter activity is affected by the membrane potential or by the proton electrochemical gradient.

Subcellular location. Mitochondrion membrane.

Tissue specificity. Expressed in all tissues examined except for placenta. Highest levels in colon, kidney, lung, testis, spleen, and brain.

Disease relevance. Microcephaly, Amish type (MCPHA) [MIM:607196] A disorder characterized by severe congenital microcephaly and severe 2-ketoglutaric aciduria leading to death within the first year. The disease is caused by variants affecting the gene represented in this entry. Thiamine metabolism dysfunction syndrome 4, bilateral striatal degeneration and progressive polyneuropathy type (THMD4) [MIM:613710] A disease characterized by recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the mitochondrial carrier (TC 2.A.29) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HC21-1	1	yes
Q9HC21-2	2

RefSeq proteins (3): NP_001119593, NP_001119594, NP_068380 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002067	MCP	Family
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily

Pfam: PF00153

Catalyzed reactions (Rhea), 1 shown:

• thiamine phosphate(out) + thiamine diphosphate(in) = thiamine phosphate(in) + thiamine diphosphate(out) (RHEA:73383)

UniProt features (27 total): mutagenesis site 10, transmembrane region 6, sequence variant 3, repeat 3, chain 1, short sequence motif 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HC21-F1	85.23	0.46

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): 51

Mutagenesis-validated functional residues (10):

Position	Phenotype
29	does not affect thiamine pyrophosphate transmembrane transporter activity.
30	does not affect thiamine pyrophosphate transmembrane transporter activity.
33	decreases thiamine pyrophosphate transmembrane transporter activity.
34	decreases thiamine pyrophosphate transmembrane transporter activity.
37	decreases thiamine pyrophosphate transmembrane transporter activity.
82	does not affect thiamine pyrophosphate transmembrane transporter activity.
137	decreases thiamine pyrophosphate transmembrane transporter activity. does not affect protein expression.
231	does not affect thiamine pyrophosphate transmembrane transporter activity.
291	decreases thiamine pyrophosphate transmembrane transporter activity. does not affect protein expression.
298	does not affect thiamine pyrophosphate transmembrane transporter activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-196819	Vitamin B1 (thiamin) metabolism

MSigDB gene sets: 268 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, YY1_Q6, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_QUATERNARY_AMMONIUM_GROUP_TRANSPORT, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_VITAMIN_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SULFUR_COMPOUND_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE

GO Biological Process (5): thiamine diphosphate biosynthetic process (GO:0009229), deoxynucleotide transport (GO:0030302), thiamine pyrophosphate transmembrane transport (GO:0030974), thiamine-containing compound metabolic process (GO:0042723), transmembrane transport (GO:0055085)

GO Molecular Function (4): thiamine transmembrane transporter activity (GO:0015234), antiporter activity (GO:0015297), deoxynucleotide transmembrane transporter activity (GO:0030233), thiamine pyrophosphate transmembrane transporter activity (GO:0090422)

GO Cellular Component (5): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
thiamine transmembrane transport	2
intracellular membrane-bounded organelle	2
thiamine diphosphate metabolic process	1
thiamine-containing compound biosynthetic process	1
organophosphate biosynthetic process	1
nucleotide transport	1
carbohydrate derivative transport	1
quaternary ammonium group transport	1
organophosphate ester transport	1
sulfur compound metabolic process	1
pyrimidine-containing compound metabolic process	1
transport	1
cellular process	1
vitamin transmembrane transporter activity	1
azole transmembrane transporter activity	1
sulfur compound transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
nucleotide transmembrane transporter activity	1
deoxynucleotide transport	1
thiamine transmembrane transporter activity	1
organophosphate ester transmembrane transporter activity	1
quaternary ammonium group transmembrane transporter activity	1
thiamine pyrophosphate transmembrane transport	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

1329 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A19	ATP5PD	O75947	845
SLC25A19	ALDH7A1	P49419	788
SLC25A19	CIDEA	O60543	754
SLC25A19	PDE4D	Q08499	750
SLC25A19	SLC19A3	Q9BZV2	747
SLC25A19	PDE4A	P27815	739
SLC25A19	PDE4B	Q07343	730
SLC25A19	TPK1	Q9H3S4	717
SLC25A19	PDE1B	Q01064	674
SLC25A19	SLC19A2	O60779	654
SLC25A19	PDE4C	Q08493	646
SLC25A19	TMOD1	P28289	594
SLC25A19	DFFB	O76075	561
SLC25A19	DFFA	O00273	546
SLC25A19	ALDOB	P05062	545

IntAct

72 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
	XPO1	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
COX15	SLC25A3	psi-mi:“MI:0914”(association)	0.530
Cep152	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
Cdk1	IFT88	psi-mi:“MI:0914”(association)	0.350
ZWINT	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
RETREG2	SLC27A2	psi-mi:“MI:0914”(association)	0.350
HUWE1	NCOA4	psi-mi:“MI:0914”(association)	0.350
Tubgcp5	TUBG1	psi-mi:“MI:0914”(association)	0.350
POLR3E	BDP1	psi-mi:“MI:0914”(association)	0.350
GEMIN7	CSNK1D	psi-mi:“MI:0914”(association)	0.350
Phospho1	SLC4A2	psi-mi:“MI:0914”(association)	0.350
CLTB	WNK1	psi-mi:“MI:0914”(association)	0.350
PCDHB15	HLA-A	psi-mi:“MI:0914”(association)	0.350
CHST15	SLC43A3	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
PB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAIP1	COQ9	psi-mi:“MI:0914”(association)	0.350
ATAD3A	TMEM223	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
PCDHB3	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (91): SLC25A19 (Affinity Capture-RNA), SLC25A19 (Affinity Capture-RNA), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS), SLC25A19 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K309, A0A1D6N272, A3KPP4, G3XP90, G3YD89, O13844, P04575, P04633, P12234, P12242, P16036, P33303, Q08DK7, Q0VCH6, Q1LZB3, Q27257, Q29RM1, Q3KQZ1, Q3TZX3, Q505J6, Q58DS3, Q5HZE0, Q5IS35, Q5NVC1, Q5R7W2, Q5SWT3, Q6AYL0, Q6DFK2, Q6P036, Q6P316, Q7K566, Q8BGP6, Q8BL03, Q8BZ09, Q8N8R3, Q8TBP6, Q8VEM8, Q93XM7, Q99JD3, Q9BSK2

Diamond homologs: A0A1D6N272, A1DI57, A2ASZ8, A2CEQ0, A2R5A0, A3LVX1, A4RF23, A5DIS9, A5DX39, A6RF73, A6SL61, A7ER02, A7TIQ0, B4FIJ0, F4JU70, O04619, O94370, O95847, P29518, P49382, Q05AQ3, Q0CEN9, Q0P483, Q0UUH1, Q1E7P0, Q29RM1, Q2HFL6, Q2UCW8, Q3ZBJ8, Q4X022, Q54VS7, Q552L9, Q55E45, Q59Q36, Q5AVW1, Q5IS35, Q5NVC1, Q5PQ27, Q5XH95, Q5XHA0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	3
Uncertain significance	65
Likely benign	44
Benign	22

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1695338	NM_001126121.2(SLC25A19):c.576G>C (p.Gln192His)	Pathogenic
1695340	NM_001126121.2(SLC25A19):c.745T>A (p.Phe249Ile)	Pathogenic
1695341	NM_001126121.2(SLC25A19):c.76G>A (p.Gly26Arg)	Pathogenic
30590	NM_001126121.2(SLC25A19):c.373G>A (p.Gly125Ser)	Pathogenic
4269	NM_001126121.2(SLC25A19):c.530G>C (p.Gly177Ala)	Pathogenic
438730	NM_001126121.2(SLC25A19):c.194C>T (p.Ala65Val)	Pathogenic
438731	NM_001126121.2(SLC25A19):c.454C>A (p.Pro152Thr)	Pathogenic
438733	NM_001126121.2(SLC25A19):c.550G>C (p.Ala184Pro)	Pathogenic
191086	NM_001126121.2(SLC25A19):c.505G>A (p.Glu169Lys)	Likely pathogenic
488598	NM_001126121.2(SLC25A19):c.240A>C (p.Lys80Asn)	Likely pathogenic
692004	NM_001126121.2(SLC25A19):c.470C>T (p.Thr157Met)	Likely pathogenic

SpliceAI

1379 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75273638:ACC:A	acceptor_loss	1.0000
17:75273639:CCT:C	acceptor_loss	1.0000
17:75273641:T:A	acceptor_loss	1.0000
17:75283419:TCACC:T	donor_loss	1.0000
17:75283421:A:AG	donor_loss	1.0000
17:75283422:C:A	donor_loss	1.0000
17:75283589:AAGAA:A	acceptor_gain	1.0000
17:75283590:AGAA:A	acceptor_gain	1.0000
17:75286302:A:AC	donor_gain	1.0000
17:75286303:C:CC	donor_gain	1.0000
17:75286354:T:A	donor_gain	1.0000
17:75286798:TCAAG:T	acceptor_gain	1.0000
17:75286799:CAAG:C	acceptor_gain	1.0000
17:75286799:CAAGC:C	acceptor_gain	1.0000
17:75289353:CA:C	donor_gain	1.0000
17:75289353:CACGG:C	donor_gain	1.0000
17:75277347:GCTCA:G	donor_loss	0.9900
17:75277349:TCA:T	donor_loss	0.9900
17:75277350:CACC:C	donor_loss	0.9900
17:75277351:A:T	donor_loss	0.9900
17:75277352:C:T	donor_loss	0.9900
17:75277484:C:CC	acceptor_gain	0.9900
17:75277490:C:CT	acceptor_gain	0.9900
17:75277491:A:T	acceptor_gain	0.9900
17:75277503:T:TC	acceptor_gain	0.9900
17:75283416:CACTC:C	donor_loss	0.9900
17:75283417:ACTCA:A	donor_loss	0.9900
17:75283591:GAA:G	acceptor_gain	0.9900
17:75283592:AA:A	acceptor_gain	0.9900
17:75283593:ACT:A	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000013377 (17:75289701 C>A,G,T), RS1000524023 (17:75284998 G>C), RS1000559661 (17:75279550 T>C), RS1000560987 (17:75289543 A>T), RS1000576481 (17:75284724 C>T), RS1000691256 (17:75273487 G>A,T), RS1000889408 (17:75273788 T>C), RS1001375413 (17:75288929 T>C), RS1001603175 (17:75280798 G>A), RS1001656710 (17:75289245 G>A), RS1001688432 (17:75278037 C>G), RS1001756937 (17:75283071 G>A,C,T), RS1001897303 (17:75284089 C>T), RS1001988574 (17:75290367 G>A), RS1001989469 (17:75275310 A>G)

Disease associations

OMIM: gene MIM:606521 | disease phenotypes: MIM:607196, MIM:613710

GenCC curated gene-disease

Disease	Classification	Inheritance
Amish lethal microcephaly	Strong	Autosomal recessive
progressive demyelinating neuropathy with bilateral striatal necrosis	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Leigh syndrome	Limited	AR

Mondo (2): Amish lethal microcephaly (MONDO:0011790), progressive demyelinating neuropathy with bilateral striatal necrosis (MONDO:0013382)

Orphanet (2): Progressive polyneuropathy with bilateral striatal necrosis (Orphanet:217396), Amish lethal microcephaly (Orphanet:99742)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000185	Cleft soft palate
HP:0000237	Small anterior fontanelle
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000648	Optic atrophy
HP:0000737	Irritability
HP:0000939	Osteoporosis
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001265	Hyporeflexia
HP:0001274	Agenesis of corpus callosum
HP:0001288	Gait disturbance
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001324	Muscle weakness
HP:0001336	Myoclonus
HP:0001338	Partial agenesis of the corpus callosum
HP:0001339	Lissencephaly
HP:0001371	Flexion contracture
HP:0001376	Limitation of joint mobility
HP:0001508	Failure to thrive
HP:0001522	Death in infancy
HP:0001558	Decreased fetal movement
HP:0001762	Talipes equinovarus
HP:0001942	Metabolic acidosis
HP:0001992	Organic aciduria
HP:0002033	Poor suck
HP:0002069	Bilateral tonic-clonic seizure

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002385_319	High light scatter reticulocyte count	2.000000e-10
GCST90002386_193	High light scatter reticulocyte percentage of red cells	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538247	Amish lethal microcephaly (supp.)

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 — SLC25 mitochondrial vitamin and co-factor carriers subfamily

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Estradiol	affects expression, affects binding, increases expression, affects cotreatment, decreases expression	4
Leflunomide	decreases expression	2
Acetaminophen	increases expression	2
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment	2
Benzo(a)pyrene	increases expression	2
Nickel	increases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol A	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	increases expression	1
monomethylpropion	increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
Temozolomide	increases expression	1
Artesunate	decreases response to substance	1
Atrazine	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Dexamethasone	increases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Oxygen	decreases expression	1
Silver	decreases expression	1
Smoke	decreases expression	1
Streptozocin	decreases expression, decreases reaction	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4JI	HCT116-SLC25A19-KO-c11	Cancer cell line	Male
CVCL_D4JJ	HCT116-SLC25A19-KO-c2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening