PTRH2

Chr 17AR

peptidyl-tRNA hydrolase 2

Also known as: BIT1, CFAP37, CGI-147, IMNEPD, PTH 2, PTH2

The encoded mitochondrial protein functions as a peptidyl-tRNA hydrolase that releases tRNAs from ribosomes during protein synthesis and regulates cell survival and apoptosis pathways. Mutations cause infantile-onset multisystem neurologic, endocrine, and pancreatic disease characterized by intellectual disability, postnatal microcephaly, progressive cerebellar atrophy, hearing impairment, polyneuropathy, failure to thrive, and organ fibrosis with exocrine pancreatic insufficiency. This condition follows autosomal recessive inheritance with onset in infancy affecting neurologic, endocrine, and gastrointestinal systems.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.701 OMIM phenotype
Clinical SummaryPTRH2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 26 VUS of 69 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.70LOEUF
pLI 0.001
Z-score 0.28
OE 0.87 (0.451.70)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.43Z-score
OE missense 0.88 (0.731.05)
83 obs / 94.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.87 (0.451.70)
00.351.4
Missense OE0.88 (0.731.05)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 5 / 5.7Missense obs/exp: 83 / 94.7Syn Z: -0.68
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePTRH2-related neurologic, endocrine, and pancreatic disease, multisystem, infantile-onsetLOFAR

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

DN
0.6452th %ile
GOF
0.2597th %ile
LOF
0.4037th %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

69 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic11
VUS26
Likely Benign16
Benign1
13
Pathogenic
11
Likely Pathogenic
26
VUS
16
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
11
0
13
Likely Pathogenic
6
1
4
0
11
VUS
2
21
3
0
26
Likely Benign
0
2
8
6
16
Benign
0
0
1
0
1
Total92527667

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

View in ClinVar →

Protein Context — Lollipop Plot

PTRH2 · 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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Clinical Literature
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