PTRHD1

Summary

PTRHD1 (peptidyl-tRNA hydrolase domain containing 1, HGNC:33782) is a protein-coding gene on chromosome 2p23.3, encoding Putative peptidyl-tRNA hydrolase PTRHD1 (Q6GMV3). As a putative peptidyl-tRNA hydrolase, it might be involved in releasing tRNAs from the ribosome during protein synthesis.

This gene encodes the enzyme peptidyl-tRNA hydrolase. Peptidyl-tRNA hydrolases perform the essential function of recycling peptidyl-tRNAs. Mutations in this gene are associated with autosomal-recessive intellectual disability and parkinsonism.

Source: NCBI Gene 391356 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 18 total — 1 pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_001013663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33782
Approved symbol	PTRHD1
Name	peptidyl-tRNA hydrolase domain containing 1
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	LOC391356
Ensembl gene	ENSG00000184924
Ensembl biotype	protein_coding
OMIM	617342
Entrez	391356

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000328379, ENST00000467797, ENST00000474668, ENST00000480190, ENST00000487316, ENST00000492046, ENST00000915621, ENST00000915622

RefSeq mRNA: 1 — MANE Select: NM_001013663 NM_001013663

CCDS: CCDS33156

Canonical transcript exons

ENST00000328379 — 2 exons

Exon	Start	End
ENSE00001319378	24793126	24793391
ENSE00001927225	24789728	24790581

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 96.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.9721 / max 50.9726, expressed in 1541 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27337	2.6262	1466
27335	0.2849	99
27334	0.0610	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	96.03	gold quality
left testis	UBERON:0004533	95.44	gold quality
right testis	UBERON:0004534	95.36	gold quality
upper arm skin	UBERON:0004263	95.34	gold quality
oocyte	CL:0000023	94.95	gold quality
right adrenal gland cortex	UBERON:0035827	94.91	gold quality
testis	UBERON:0000473	94.87	gold quality
right adrenal gland	UBERON:0001233	94.85	gold quality
quadriceps femoris	UBERON:0001377	94.83	gold quality
pancreatic ductal cell	CL:0002079	94.73	gold quality
adult organism	UBERON:0007023	94.71	gold quality
vastus lateralis	UBERON:0001379	94.62	gold quality
left adrenal gland cortex	UBERON:0035825	94.54	gold quality
adrenal cortex	UBERON:0001235	94.41	gold quality
left adrenal gland	UBERON:0001234	94.39	gold quality
mucosa of transverse colon	UBERON:0004991	94.23	gold quality
biceps brachii	UBERON:0001507	94.14	gold quality
left ventricle myocardium	UBERON:0006566	94.05	gold quality
colonic mucosa	UBERON:0000317	93.78	gold quality
kidney epithelium	UBERON:0004819	93.78	gold quality
myocardium	UBERON:0002349	93.71	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.62	gold quality
sperm	CL:0000019	93.56	silver quality
apex of heart	UBERON:0002098	93.50	gold quality
oral cavity	UBERON:0000167	93.46	gold quality
tibialis anterior	UBERON:0001385	93.31	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.13	gold quality
bronchial epithelial cell	CL:0002328	93.06	gold quality
epithelium of nasopharynx	UBERON:0001951	93.04	gold quality
deltoid	UBERON:0001476	93.03	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.29
E-GEOD-100618	no	353.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting PTRHD1, 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-4517	99.76	69.19	1867
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-3193	92.99	64.93	116

Literature-anchored findings (GeneRIF, showing 4)

• PTRHD1 mutation leads to intellectual disability and parkinsonism in a consanguineous family. (PMID:27753167)
• Lack of PTRHD1 mutation in patients with young-onset and familial Parkinson’s disease in a Taiwanese population. (PMID:33004232)
• Analysis of PTRHD1 common and rare variants in European patients with Parkinson’s disease. (PMID:34246528)
• Rare Variant Analysis of PTRHD1 in Parkinson’s Disease in the Chinese Population. (PMID:35848037)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptrhd1	ENSDARG00000016122
mus_musculus	Ptrhd1	ENSMUSG00000096199
rattus_norvegicus	Ptrhd1	ENSRNOG00000004059
drosophila_melanogaster	CG14903	FBGN0038446
caenorhabditis_elegans		WBGENE00050885

Paralogs (1): ACP1 (ENSG00000143727)

Protein

Protein identifiers

Putative peptidyl-tRNA hydrolase PTRHD1 — Q6GMV3 (reviewed: Q6GMV3)

Alternative names: Peptidyl-tRNA hydrolase domain-containing protein 1

All UniProt accessions (1): Q6GMV3

UniProt curated annotations — full annotation on UniProt →

Function. As a putative peptidyl-tRNA hydrolase, it might be involved in releasing tRNAs from the ribosome during protein synthesis. Some evidence, however, suggests that it lacks peptidyl-tRNA hydrolase activity.

Disease relevance. Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities (NEDPBA) [MIM:620747] An autosomal recessive disorder manifesting in late infancy or early childhood. It is characterized by developmental delay, intellectual disability, learning difficulties, behavioral abnormalities, and parkinsonism and spasticity usually developing in the third or fourth decades. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the PTH2 family. PTRHD1 subfamily.

RefSeq proteins (1): NP_001013685* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002833	PTH2	Family
IPR023476	Pep_tRNA_hydro_II_dom_sf	Homologous_superfamily
IPR042237	PTRHD1	Family

Pfam: PF01981

Enzyme classification (BRENDA):

• EC 3.1.1.29 — peptidyl-tRNA hydrolase (BRENDA: 24 organisms, 89 substrates, 19 inhibitors, 50 Km, 45 kcat entries)

Substrate kinetics (BRENDA)

22 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DIACETYL-LYSYL-TRNALYS	—	14
DIACETYL-LYS-TRNALYS	—	9
DIACETYL-LYSINE-TRNA	—	5
N-ACETYL-ALA-TRNA(ALA)	0.0047–0.0269	4
FORMYL-METHIONYL-TRNAFMET	—	2
ACETYL-HIS-TRNAHIS	—	1
ACETYL-HISTIDYL-TRNA	—	1
ACETYL-HISTIDYL-TRNAHIS	—	1
BULK PEPTIDYL-TRNA	0.008	1
DEPHOSPHORYLATED DIACYL-LYSINE-TRNA	—	1
DEPHOSPHORYLATED FORMYL-MET-TRNAFMET	—	1
DEPHOSPHORYLATED FORMYL-METHIONINYL-TRNA	—	1
FORMYL-MET-TRNAFMET	—	1
FORMYL-METHIONYL-TRNA	—	1
N-ACETYL-MET-TRNA	0.0022	1

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 (5 total): sequence variant 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6GMV3-F1	91.29	0.85

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 135 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_CARBOXYLIC_ESTER_HYDROLASE_ACTIVITY, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_A_TRNA, ATF6_TARGET_GENES, CIITA_TARGET_GENES, CREB3L4_TARGET_GENES, E2F5_TARGET_GENES, HHEX_TARGET_GENES, HOXC6_TARGET_GENES, HSD17B8_TARGET_GENES, KLF7_TARGET_GENES, NFE2L1_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (3): 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
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

902 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTRHD1	DNAJC6	O75061	620
PTRHD1	TMEM230	Q96A57	609
PTRHD1	VPS13C	Q709C8	597
PTRHD1	RAB39B	Q96DA2	592
PTRHD1	DNAJC13	O75165	575
PTRHD1	FBXO7	Q9Y3I1	573
PTRHD1	RIC3	Q7Z5B4	572
PTRHD1	CHCHD2	Q9Y6H1	571
PTRHD1	SYNJ1	O43426	527
PTRHD1	GIGYF2	Q6Y7W6	506
PTRHD1	ATP13A2	Q9NQ11	489
PTRHD1	PLA2G6	O60733	479
PTRHD1	C6orf120	Q7Z4R8	419
PTRHD1	VPS35	Q96QK1	410
PTRHD1	WDR27	A2RRH5	408

IntAct

20 interactions, top by confidence:

A	B	Type	Score
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
PTRHD1	TSR2	psi-mi:“MI:0915”(physical association)	0.560
RPA4	PTRHD1	psi-mi:“MI:0915”(physical association)	0.560
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
FAHD1	CLUH	psi-mi:“MI:0914”(association)	0.530
C6orf89	PTRHD1	psi-mi:“MI:0915”(physical association)	0.400
P2RY12	GPR89A	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
SUMO1P1	GAPDHS	psi-mi:“MI:0914”(association)	0.350
GSX1	YKT6	psi-mi:“MI:0914”(association)	0.350
IL2RG	BBOX1	psi-mi:“MI:0914”(association)	0.350
LGALS9	CYB5A	psi-mi:“MI:0914”(association)	0.350
MARS2	DDX39A	psi-mi:“MI:0914”(association)	0.350
PTRHD1	RPA4	psi-mi:“MI:0915”(physical association)	0.000
TSR2	PTRHD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): PTRHD1 (Affinity Capture-RNA), PTRHD1 (Affinity Capture-RNA), PTRHD1 (Affinity Capture-MS), PTRHD1 (Co-fractionation), UBE2L3 (Co-fractionation), PTRHD1 (Affinity Capture-MS), PTRHD1 (Affinity Capture-MS), PTRHD1 (Affinity Capture-MS), PTRHD1 (Co-fractionation), PTRHD1 (Co-fractionation), FAHD1 (Co-fractionation), CARS2 (Co-fractionation), PTRHD1 (Co-fractionation), TXN2 (Co-fractionation), PTRHD1 (Co-fractionation)

ESM2 similar proteins: A6QR40, A8MPP1, B0S8I0, D3Z4S3, O55171, O75414, O88425, O88426, O95363, P47823, P49753, Q05B89, Q08DJ7, Q13144, Q14166, Q28DV7, Q2TBP8, Q3SYU1, Q3SZ85, Q3U2U7, Q499U2, Q4V7D6, Q64350, Q66LN0, Q68FL6, Q6AYQ3, Q6GMV3, Q7TMC8, Q8BWM0, Q8BYZ7, Q8CHW4, Q8N0W3, Q8N159, Q8NFF5, Q8R123, Q8R3H9, Q92771, Q96BJ8, Q99M01, Q9EQ80

Diamond homologs: D3Z4S3, Q3SZ85, Q6GMV3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	13
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3061965	NM_001013663.2(PTRHD1):c.364C>T (p.Arg122Trp)	Pathogenic

SpliceAI

350 predictions. Top by Δscore:

Variant	Effect	Δscore
2:24790577:GGGGC:G	acceptor_gain	1.0000
2:24790578:GGGC:G	acceptor_gain	1.0000
2:24790578:GGGCC:G	acceptor_gain	1.0000
2:24790579:GGC:G	acceptor_gain	1.0000
2:24790579:GGCCT:G	acceptor_gain	1.0000
2:24790580:GC:G	acceptor_gain	1.0000
2:24790580:GCC:G	acceptor_gain	1.0000
2:24790581:CC:C	acceptor_gain	1.0000
2:24790581:CCT:C	acceptor_gain	1.0000
2:24790582:C:CC	acceptor_gain	1.0000
2:24790582:C:T	acceptor_gain	1.0000
2:24790582:CTAAA:C	acceptor_gain	1.0000
2:24793122:TCA:T	donor_loss	1.0000
2:24793123:CA:C	donor_loss	1.0000
2:24793125:C:A	donor_loss	1.0000
2:24790583:T:G	acceptor_gain	0.9900
2:24793124:A:AC	donor_gain	0.9800
2:24793125:C:CC	donor_gain	0.9800
2:24793125:CCT:C	donor_gain	0.9800
2:24791578:A:C	donor_gain	0.9600
2:24793134:C:CT	donor_gain	0.9600
2:24793135:C:CT	donor_gain	0.9200
2:24791643:A:T	acceptor_gain	0.8600
2:24790596:C:CT	acceptor_gain	0.8400
2:24792781:A:AC	donor_gain	0.8300
2:24791754:CCTT:C	acceptor_gain	0.8200
2:24792782:G:C	donor_gain	0.8100
2:24793124:AC:A	donor_gain	0.7900
2:24793125:CC:C	donor_gain	0.7900
2:24793233:C:CT	donor_gain	0.7600

AlphaMissense

894 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:24790480:A:C	C118W	0.984
2:24793224:A:G	C52R	0.984
2:24793133:A:T	V82D	0.982
2:24793222:A:C	C52W	0.982
2:24793209:C:G	A57P	0.981
2:24790466:G:T	P123H	0.979
2:24790475:G:T	A120D	0.978
2:24790482:A:G	C118R	0.975
2:24790472:A:T	L121H	0.974
2:24793223:C:T	C52Y	0.973
2:24790512:A:G	W108R	0.972
2:24790512:A:T	W108R	0.972
2:24793215:C:G	A55P	0.972
2:24793217:G:T	A54E	0.971
2:24790481:C:T	C118Y	0.970
2:24790504:C:A	E110D	0.970
2:24790504:C:G	E110D	0.970
2:24793289:A:T	V30E	0.970
2:24793254:A:G	W42R	0.966
2:24793254:A:T	W42R	0.966
2:24793221:G:C	H53D	0.965
2:24793226:G:T	A51D	0.965
2:24790466:G:C	P123R	0.964
2:24790505:T:A	E110V	0.963
2:24793167:A:C	Y71D	0.963
2:24793244:C:T	G45D	0.962
2:24790472:A:C	L121R	0.961
2:24790510:C:A	W108C	0.961
2:24790510:C:G	W108C	0.961
2:24790541:A:G	L98P	0.961

dbSNP variants (sampled 300 via entrez): RS1000734371 (2:24792291 A>G), RS1000825715 (2:24792292 T>C), RS1001105893 (2:24792454 T>C), RS1001467337 (2:24789637 C>G), RS1002945512 (2:24792743 T>C), RS1003279112 (2:24793840 T>C), RS1003655610 (2:24794218 A>G), RS1004331271 (2:24794292 G>A), RS1004726572 (2:24789930 C>G), RS1004835996 (2:24793018 C>T), RS1005175035 (2:24791433 G>C), RS1005647681 (2:24793235 A>C,G), RS1006280294 (2:24793076 A>C,T), RS1006953576 (2:24790264 T>C), RS1007696490 (2:24791639 C>A)

Disease associations

OMIM: gene MIM:617342 | disease phenotypes: MIM:620747

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities	Strong	Autosomal recessive
complex neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (2): neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities (MONDO:0958323), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000298	Mask-like facies
HP:0000514	Slow saccadic eye movements
HP:0000711	Restlessness
HP:0000716	Depression
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001262	Excessive daytime somnolence
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001347	Hyperreflexia
HP:0002015	Dysphagia
HP:0002067	Bradykinesia
HP:0002172	Postural instability
HP:0002174	Postural tremor
HP:0002322	Resting tremor
HP:0002362	Shuffling gait
HP:0002396	Cogwheel rigidity
HP:0003390	Sensory axonal neuropathy
HP:0003487	Babinski sign
HP:0003763	Bruxism
HP:0008944	Distal lower limb amyotrophy
HP:0009027	Foot dorsiflexor weakness
HP:0011463	Childhood onset
HP:0031825	Freezing of gait

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001255_1	Type 1 diabetes	4.000000e-09
GCST005950_4	Body mass index x sex x age interaction (4df test)	5.000000e-26
GCST005951_195	Body mass index	3.000000e-24
GCST005952_4	Body mass index (age>50)	5.000000e-09
GCST005953_10	Body mass index (age <50)	6.000000e-20
GCST007293_13	Body fat distribution (arm fat ratio)	2.000000e-39
GCST007293_41	Body fat distribution (arm fat ratio)	5.000000e-22
GCST007293_5	Body fat distribution (arm fat ratio)	2.000000e-21
GCST007294_128	Body fat distribution (trunk fat ratio)	7.000000e-06
GCST007294_94	Body fat distribution (trunk fat ratio)	9.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004341	body fat distribution

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
triphenyl phosphate	affects expression	1
sodium arsenite	increases abundance, increases expression	1
ICG 001	decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Diuron	decreases expression	1
Ivermectin	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder