PTRH1

Chr 9

peptidyl-tRNA hydrolase 1 homolog

Also known as: C9orf115, PTH1

NCBI Gene: 138428 ENSG00000187024 UniProt: Q86Y79 OMIM: 621047

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables peptidyl-tRNA hydrolase activity. Involved in rescue of stalled cytosolic ribosome. Located in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.66

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.66LOEUF

pLI 0.000

Z-score 0.29

OE 0.88 (0.48–1.66)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.03Z-score

OE missense 1.01 (0.87–1.17)

125 obs / 124.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.88 (0.48–1.66)

0≤0.351.4

Missense OE?1.01 (0.87–1.17)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 6 / 6.8Missense obs/exp: 125 / 124.0Syn Z: -0.43

Background carrier burden — how many people carry a rare variant somewhere in PTRH1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

535 rare PASS variants

Rare truncating (LoF)

1 in 760

114 rare PASS variants

Rare synonymous (reference)

1 in 350

169 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PTRH1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 940
South Asian	~43k	1 in 48	1 in 350
Remaining (unassigned)	~30k	1 in 82	1 in 750
European (Finnish)	~27k	1 in 430	1 in 580
Admixed American	~22k	1 in 99	1 in 390
African / African American	~21k	1 in 62	1 in 280
East Asian	~20k	1 in 86	1 in 850
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 91	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓