SLC25A19

Chr 17AR

solute carrier family 25 member 19

Also known as: DNC, MCPHA, MTPPT, MUP1, THMD3, THMD4, TPC

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. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…
MultiplemechanismARLOEUF 0.522 OMIM phenotypes
Clinical SummarySLC25A19
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.65) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 80 VUS of 204 total submissions
📖
GeneReview available — SLC25A19
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.52LOEUF
pLI 0.649
Z-score 2.68
OE 0.17 (0.070.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.59Z-score
OE missense 0.88 (0.781.00)
171 obs / 194.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.17 (0.070.52)
00.351.4
Missense OE?0.88 (0.781.00)
00.61.4
Synonymous OE?0.92
01.21.6
LoF obs/exp: 2 / 12.0Missense obs/exp: 171 / 194.0Syn Z: 0.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSLC25A19-related Amish lethal microcephalyOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7033th %ile
GOF
0.6541th %ile
LOF
0.4038th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

204 submitted variants in ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic3
VUS80
Likely Benign63
Benign28
Conflicting13
11
Pathogenic
3
Likely Pathogenic
80
VUS
63
Likely Benign
28
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
10
0
0
11
Likely Pathogenic
0
3
0
0
3
VUS
2
70
8
0
80
Likely Benign
0
4
29
30
63
Benign
0
0
26
2
28
Conflicting
13
Total3876332198

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

12 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap SLC25A19 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

SLC25A19 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →