PTRH1

Summary

PTRH1 (peptidyl-tRNA hydrolase 1 homolog, HGNC:27039) is a protein-coding gene on chromosome 9q34.11, encoding Peptidyl-tRNA hydrolase (Q86Y79). Peptidyl-tRNA hydrolase that cleaves nascent chains-tRNAs that are not stably fixed in the P-site of 60S ribosome-nascent chain complexes.

Enables peptidyl-tRNA hydrolase activity. Involved in rescue of stalled ribosome. Located in mitochondrion.

Source: NCBI Gene 138428 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001002913

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27039
Approved symbol	PTRH1
Name	peptidyl-tRNA hydrolase 1 homolog
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	PTH1
Ensembl gene	ENSG00000187024
Ensembl biotype	protein_coding
OMIM	621047
Entrez	138428

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000335223, ENST00000414832, ENST00000416214, ENST00000419060, ENST00000423807, ENST00000429848, ENST00000456267, ENST00000543175, ENST00000641641, ENST00000913017, ENST00000913018

RefSeq mRNA: 5 — MANE Select: NM_001002913 NM_001002913, NM_001345977, NM_001345978, NM_001345979, NM_001345980

CCDS: CCDS35147, CCDS87693

Canonical transcript exons

ENST00000543175 — 5 exons

Exon	Start	End
ENSE00002223209	127713807	127714282
ENSE00002231805	127715544	127715663
ENSE00003531074	127714379	127714424
ENSE00003755118	127714975	127715194
ENSE00003757083	127714603	127714702

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 87.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3661 / max 55.9687, expressed in 1745 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102556	4.7133	1689
102555	2.6246	1295
102557	0.0283	8

Top tissues by expression

242 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	87.07	gold quality
apex of heart	UBERON:0002098	86.51	gold quality
left adrenal gland	UBERON:0001234	86.45	gold quality
left adrenal gland cortex	UBERON:0035825	85.82	gold quality
right adrenal gland cortex	UBERON:0035827	85.82	gold quality
skin of leg	UBERON:0001511	84.76	gold quality
right lobe of thyroid gland	UBERON:0001119	84.63	gold quality
skin of abdomen	UBERON:0001416	84.56	gold quality
left lobe of thyroid gland	UBERON:0001120	83.97	gold quality
adenohypophysis	UBERON:0002196	83.96	gold quality
gastrocnemius	UBERON:0001388	83.22	gold quality
adrenal gland	UBERON:0002369	82.98	gold quality
right uterine tube	UBERON:0001302	82.77	gold quality
anterior cingulate cortex	UBERON:0009835	82.77	gold quality
adrenal cortex	UBERON:0001235	82.66	gold quality
zone of skin	UBERON:0000014	82.65	gold quality
body of pancreas	UBERON:0001150	82.61	gold quality
thyroid gland	UBERON:0002046	82.16	gold quality
left coronary artery	UBERON:0001626	82.04	gold quality
granulocyte	CL:0000094	81.97	gold quality
body of stomach	UBERON:0001161	81.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.80	gold quality
right atrium auricular region	UBERON:0006631	81.78	gold quality
lower esophagus	UBERON:0013473	81.77	gold quality
prefrontal cortex	UBERON:0000451	81.75	gold quality
heart left ventricle	UBERON:0002084	81.45	gold quality
muscle of leg	UBERON:0001383	81.36	gold quality
omental fat pad	UBERON:0010414	81.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.18	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting PTRH1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-6888-5P	95.89	63.78	831

Literature-anchored findings (GeneRIF, showing 1)

• arrangement of secondary structure elements generates a fold not previously reported for peptidyl-trna hydrolase and intermolecular contacts in the crystal asymmetric unit cell suggest a likely surface for protein-protein interactions (PMID:14660562)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptrh1	ENSDARG00000098206
mus_musculus	Ptrh1	ENSMUSG00000053746
rattus_norvegicus	Ptrh1	ENSRNOG00000049034

Protein

Protein identifiers

Peptidyl-tRNA hydrolase — Q86Y79 (reviewed: Q86Y79)

All UniProt accessions (7): A0A096LP22, A0A096LP34, A0A096LPA3, A0A286YER0, A0A286YF52, C9J7Z1, Q86Y79

UniProt curated annotations — full annotation on UniProt →

Function. Peptidyl-tRNA hydrolase that cleaves nascent chains-tRNAs that are not stably fixed in the P-site of 60S ribosome-nascent chain complexes. Acts downstream of the ribosome-associated quality control (RQC) pathway to release non-ubiquitinated nascent chains from 60S and 80S ribosome-nascent chain complexes. Does not act on ubiquitinated nascent chains, which are cleaved by ANKZF1 for degradation.

Similarity. Belongs to the PTH family.

RefSeq proteins (5): NP_001002913, NP_001332906, NP_001332907, NP_001332908, NP_001332909 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001328	Pept_tRNA_hydro	Family
IPR018171	Pept_tRNA_hydro_CS	Conserved_site
IPR036416	Pept_tRNA_hydro_sf	Homologous_superfamily

Pfam: PF01195

Catalyzed reactions (Rhea), 1 shown:

• an N-acyl-L-alpha-aminoacyl-tRNA + H2O = an N-acyl-L-amino acid + a tRNA + H(+) (RHEA:54448)

UniProt features (7 total): binding site 2, mutagenesis site 2, chain 1, active site 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86Y79-F1	89.49	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 46 (proton acceptor); 121 (stabilizes the basic form of h active site to accept a proton)

Ligand- & substrate-binding residues (2): 96; 142

Mutagenesis-validated functional residues (2):

Position	Phenotype
46	abolished peptidyl-trna activity.
121	abolished peptidyl-trna activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_TRANSLATION, GOBP_TRANSLATIONAL_ELONGATION, GOBP_ORGANELLE_DISASSEMBLY, GOMF_TRNA_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_CARBOXYLIC_ESTER_HYDROLASE_ACTIVITY, VECCHI_GASTRIC_CANCER_EARLY_UP, GOBP_RIBOSOME_DISASSEMBLY, FORTSCHEGGER_PHF8_TARGETS_DN, AKT_UP.V1_UP, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_A_TRNA, CAHOY_ASTROGLIAL, chr9q34

GO Biological Process (1): rescue of stalled cytosolic ribosome (GO:0072344)

GO Molecular Function (5): tRNA binding (GO:0000049), RNA binding (GO:0003723), peptidyl-tRNA hydrolase activity (GO:0004045), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasmic translational elongation	1
ribosome disassembly	1
RNA binding	1
nucleic acid binding	1
carboxylic ester hydrolase activity	1
catalytic activity, acting on a tRNA	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

994 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTRH1	TOR2A	Q5JU69	520
PTRH1	PPP1R26	Q5T8A7	515
PTRH1	GRIFIN	A4D1Z8	506
PTRH1	GPR152	Q8TDT2	498
PTRH1	ANKZF1	Q9H8Y5	477
PTRH1	MRRF	Q96E11	475
PTRH1	NEMF	O60524	455
PTRH1	PTRH2	Q9Y3E5	455
PTRH1	THAP6	Q8TBB0	445
PTRH1	TMEM134	Q9H6X4	443
PTRH1	CABP4	P57796	441
PTRH1	MRPL58	Q14197	437
PTRH1	RNF170	Q96K19	407
PTRH1	LRRC37A	A6NMS7	396
PTRH1	EEF1AKMT1	Q8WVE0	395

IntAct

32 interactions, top by confidence:

A	B	Type	Score
FAM9B	PTRH1	psi-mi:“MI:0915”(physical association)	0.560
PTRH1	FAM9B	psi-mi:“MI:0915”(physical association)	0.560
ANKRD28	PTRH1	psi-mi:“MI:0915”(physical association)	0.560
PTRH1	PICK1	psi-mi:“MI:0915”(physical association)	0.560
LCN2	PTRH1	psi-mi:“MI:0915”(physical association)	0.560
RCN1	WDR45B	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
	LAMA5	psi-mi:“MI:0914”(association)	0.350
PTRH1	PDHA1	psi-mi:“MI:0914”(association)	0.350
PTRH1	AARS2	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
CASP3	NACA	psi-mi:“MI:0914”(association)	0.350
CTNNA1	KIF2A	psi-mi:“MI:0914”(association)	0.350
PTRH1	ANKRD28	psi-mi:“MI:0915”(physical association)	0.000
PTRH1	PICK1	psi-mi:“MI:0915”(physical association)	0.000
PTRH1	LCN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): FAM9B (Two-hybrid), PTRH1 (Affinity Capture-MS), PTRH1 (Affinity Capture-MS), PTRH1 (Affinity Capture-MS), PTRH1 (Two-hybrid), PTRH1 (Two-hybrid), ANKRD28 (Two-hybrid), PTRH1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), PDHA1 (Affinity Capture-MS), AARS2 (Affinity Capture-MS), PTRH1 (Affinity Capture-MS), PTRH1 (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), ZER1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNU3, A1A4L8, A2BDX3, A5GFZ6, A6NK58, A6QQ74, O19179, O43542, O60294, O95336, O95396, P19971, P85971, Q02846, Q05922, Q08DH8, Q0VFH3, Q28F19, Q29R99, Q2TBQ8, Q2V057, Q3SZ07, Q3UQ84, Q561R2, Q5ZKI2, Q68FW7, Q6PAT0, Q6QHF9, Q86U10, Q86WU2, Q86Y79, Q8BW00, Q8IVS8, Q8N8Q3, Q8R123, Q8VCZ9, Q8VDG5, Q8WV74, Q8WVB3, Q8WZ82

Diamond homologs: A0JU94, A0PW66, A0QBW3, A0R3D3, A1AM05, A1KHF2, A1R4G4, A1TEG1, A1UL23, A2CCI1, A3Q5H1, A4T6N5, A5FRL3, A5G7R5, A5U157, A5UGR0, A6TJM7, A6W6V3, A9WBS1, A9WU36, B0K466, B0KBG1, B2HDJ5, B2JA15, B2UPQ2, B3E6F9, B4R8Q8, B4U5H3, B5EHX1, B5EKJ0, B5ZY55, B6JIP3, B7J502, B8G3X3, B8GZU8, B8HFE2, B8ZJI3, B8ZU62, B9LE93, B9M5U5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

3 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4293 predictions. Top by Δscore:

Variant	Effect	Δscore
9:127707188:GCCCG:G	donor_gain	1.0000
9:127707191:CGGTG:C	donor_loss	1.0000
9:127707193:GTGC:G	donor_loss	1.0000
9:127709691:TTGG:T	donor_loss	1.0000
9:127709692:TG:T	donor_loss	1.0000
9:127709695:T:A	donor_loss	1.0000
9:127711222:T:A	acceptor_gain	1.0000
9:127711223:G:A	acceptor_gain	1.0000
9:127711224:GCCA:G	acceptor_loss	1.0000
9:127711226:CA:C	acceptor_loss	1.0000
9:127711227:A:AC	acceptor_loss	1.0000
9:127711227:A:AG	acceptor_gain	1.0000
9:127711228:G:GG	acceptor_gain	1.0000
9:127711228:GA:G	acceptor_gain	1.0000
9:127711228:GAC:G	acceptor_gain	1.0000
9:127711228:GACT:G	acceptor_gain	1.0000
9:127711392:GAGAA:G	donor_gain	1.0000
9:127711411:G:GT	donor_gain	1.0000
9:127711411:G:T	donor_gain	1.0000
9:127711509:GCC:G	donor_gain	1.0000
9:127711816:GCA:G	acceptor_loss	1.0000
9:127711817:CA:C	acceptor_loss	1.0000
9:127711818:A:AG	acceptor_gain	1.0000
9:127711818:AG:A	acceptor_loss	1.0000
9:127711819:G:GA	acceptor_gain	1.0000
9:127711819:GAT:G	acceptor_gain	1.0000
9:127711819:GATC:G	acceptor_gain	1.0000
9:127711944:C:T	donor_gain	1.0000
9:127711951:G:GG	donor_gain	1.0000
9:127712346:GCAG:G	donor_gain	1.0000

AlphaMissense

1341 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:127714657:T:A	D121V	0.995
9:127714400:G:C	C147W	0.991
9:127714656:A:C	D121E	0.989
9:127714656:A:T	D121E	0.989
9:127714401:C:T	C147Y	0.987
9:127714402:A:G	C147R	0.985
9:127714657:T:G	D121A	0.985
9:127715006:C:A	M95I	0.983
9:127715006:C:G	M95I	0.983
9:127715006:C:T	M95I	0.983
9:127714205:G:C	F180L	0.981
9:127714205:G:T	F180L	0.981
9:127714207:A:G	F180L	0.981
9:127714413:C:T	G143E	0.981
9:127715150:G:C	S47R	0.981
9:127715150:G:T	S47R	0.981
9:127715152:T:G	S47R	0.981
9:127714997:G:C	N98K	0.979
9:127714997:G:T	N98K	0.979
9:127714658:C:G	D121H	0.978
9:127714272:C:A	R158M	0.975
9:127714988:G:C	S101R	0.975
9:127714988:G:T	S101R	0.975
9:127714990:T:G	S101R	0.975
9:127714405:A:G	S146P	0.974
9:127714657:T:C	D121G	0.974
9:127714658:C:A	D121Y	0.974
9:127714995:C:T	G99E	0.974
9:127715093:C:A	W66C	0.974
9:127715093:C:G	W66C	0.974

dbSNP variants (sampled 300 via entrez): RS1000115192 (9:127712714 C>A,G,T), RS1000281861 (9:127716006 C>A,G,T), RS1000300733 (9:127699793 T>C), RS1000301801 (9:127706595 A>G), RS1000469126 (9:127701517 C>A,T), RS1000519736 (9:127701275 T>A), RS1000723301 (9:127704431 C>A), RS1000775422 (9:127704110 G>A,C), RS1000793078 (9:127710514 G>A), RS1000906121 (9:127698621 G>A), RS1001518546 (9:127705936 G>A), RS1001570668 (9:127705555 G>A), RS1001606731 (9:127714940 G>A,T), RS1001730026 (9:127702940 C>G,T), RS1001745378 (9:127699323 G>A)

Disease associations

OMIM: gene MIM:621047 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	6
Cyclosporine	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
decabromobiphenyl ether	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
jinfukang	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Gallic Acid	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.