PTRH1

Chr 9

peptidyl-tRNA hydrolase 1 homolog

Also known as: C9orf115, PTH1

The protein functions as a peptidyl-tRNA hydrolase that cleaves nascent protein chains from stalled ribosomes and acts in the ribosome-associated quality control pathway. Mutations cause autosomal recessive infantile-onset mitochondrial disorders characterized by severe neurodegeneration, developmental delay, and multi-organ dysfunction. This gene is highly intolerant to loss-of-function variants, suggesting complete loss of function is likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.66
Clinical SummaryPTRH1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.66LOEUF
pLI 0.000
Z-score 0.29
OE 0.88 (0.481.66)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.03Z-score
OE missense 1.01 (0.871.17)
125 obs / 124.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.88 (0.481.66)
00.351.4
Missense OE1.01 (0.871.17)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 6 / 6.8Missense obs/exp: 125 / 124.0Syn Z: -0.43
DN
0.7132th %ile
GOF
0.5169th %ile
LOF
0.3358th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PTRH1 · 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.

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