PTRHD1

protein-coding

peptidyl-tRNA hydrolase domain containing 1

Gene summary

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. [provided by RefSeq, May 2017]

Previous symbols:

C2orf79

MANE transcript

NM_001013663.2

Inheritance

ClinVar variants

P:5U:31B:6

Top phenotype

Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities

gnomAD constraint

pLI —, LoF o/e 1.59

Max pathogenic AF

—

Genomic locus

chr2:24,789,728-24,793,391

External References & Databases

Ensembl (ENSG00000184924)

Transcript & Mutation Effects

hg38 • Region Span ~3.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0958323

Submitter: PanelApp Australia

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalitiesAR

Manifestation: Neurologic

Intervention: Neurologic

Rationale: Individuals have been described as responding to levodopa

Refs: 27134041; 27753167; 30398675; 38346691

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTRHD1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 24

Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalitiesTotal: 8

not providedTotal: 7

PTRHD1-related disorderTotal: 6

Paediatric disordersTotal: 1

Parkinsonian disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001013663.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar		4
missense	3 clinvar		30 clinvar	1 clinvar	1 clinvar	35
nonsense		1 clinvar				1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	3	2	31	5	1	42

Highest pathogenic variant AF is 0.00016238917

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001013663.2	RefSeq	NP_001013685.1	2	MANE Select
ENST00000328379.6	Ensembl	ENSP00000330389.4	2	MANE Select
ENST00000915621.1	Ensembl	ENSP00000585680.1	2	Standard
ENST00000915621.2	Ensembl	ENSP00000585680.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

aminoacyl-tRNA hydrolase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000328379
Coding exons: 2
Length: 3649
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125747
p: 0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.192	89	84.1	1.06	0.00000407	891
Missense (PolyPhen)		28	29.07	0.96319		342
Synonymous	-1.19	47	37.7	1.25	0.00000187	300
Loss of Function	-1.22	8	5.04	1.59	2.24e-7	51

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0016	0.0015	notable
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00033	0.00033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

RVIS EVS: -0.36
RVIS percentile EVS: 28.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium