THNSL1

Chr 10

threonine synthase like 1

Also known as: TSH1

NCBI Gene: 79896ENSG00000185875UniProt: Q8IYQ7

THNSL1 encodes a mitochondrial protein involved in cellular energy metabolism. Mutations cause autosomal recessive neurological disorders with early onset developmental delays and metabolic dysfunction affecting multiple organ systems. This gene is highly constrained against loss-of-function variants in the general population.

Summary from RefSeq
Research Assistant →
0
Active trials
1
Pubs (1 yr)
10
P/LP submissions
0%
P/LP missense
1.38
LOEUF
—
Mechanism
Clinical Summary— THNSL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 158 VUS of 187 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.38LOEUF
pLI 0.000
Z-score 0.02
OE 0.99 (0.73–1.38)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.47Z-score
OE missense 1.07 (0.98–1.16)
413 obs / 387.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.99 (0.73–1.38)
0≤0.351.4
Missense OE1.07 (0.98–1.16)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 26 / 26.1Missense obs/exp: 413 / 387.2Syn Z: -0.48

ClinVar Variant Classifications

187 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS158
Likely Benign11
Benign2
9
Pathogenic
1
Likely Pathogenic
158
VUS
11
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
1
0
1
VUS
1
154
3
0
158
Likely Benign
0
9
0
2
11
Benign
0
0
2
0
2
Total1163152181

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

View in ClinVar →

Protein Context — Lollipop Plot

THNSL1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients