SLC25A19

Chr 17AR

solute carrier family 25 member 19

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

This gene encodes a mitochondrial transporter that mediates uptake of thiamine diphosphate (thiamine pyrophosphate) into mitochondria. Mutations cause autosomal recessive disorders including microcephaly, Amish type (characterized by severe congenital microcephaly, 2-ketoglutaric aciduria, and death within the first year) and thiamine metabolism dysfunction syndrome 4 with progressive polyneuropathy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.524), reflecting its essential role in mitochondrial thiamine metabolism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
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
26 unique Pathogenic / Likely Pathogenic· 95 VUS of 231 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 OE0.17 (0.070.52)
00.351.4
Missense OE0.88 (0.781.00)
00.61.4
Synonymous OE0.92
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

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.

ClinVar Variant Classifications

231 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic4
VUS95
Likely Benign63
Benign28
Conflicting13
22
Pathogenic
4
Likely Pathogenic
95
VUS
63
Likely Benign
28
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
10
11
0
22
Likely Pathogenic
0
3
1
0
4
VUS
2
70
23
0
95
Likely Benign
0
4
29
30
63
Benign
0
0
26
2
28
Conflicting
13
Total3879032225

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC25A19 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC