PTRH2

peptidyl-tRNA hydrolase 2, the group of Cilia and flagella associated

Basic information

Region (hg38): 17:59674635-59707626

Links

ENSG00000141378 ∙ NCBI:51651 ∙ OMIM:608625 ∙ HGNC:24265 ∙ Uniprot:Q9Y3E5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 (Definitive), mode of inheritance: AR
• infantile multisystem neurologic-endocrine-pancreatic disease (Supportive), mode of inheritance: AR
• neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1	AR	Gastrointestinal	The condition has been described as including exocrine pancreatic insufficiency, among other manifestatons, and awareness may allow medical management	Audiologic/Otolaryngologic; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic	25558065; 25574476; 27129381; 28328138; 33092935

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PTRH2 gene.

• not provided (12 variants)
• not specified (10 variants)
• Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 (6 variants)
• Inborn genetic diseases (6 variants)
• Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset (1 variants)
• Global developmental delay;Cerebellar ataxia;Hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTRH2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense	1		8	1		10
nonsense	1	1				2
start loss						0
frameshift	1	2	2			5
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				8	1	9
Total	3	3	10	12	1

Highest pathogenic variant AF is 0.0000131

Variants in PTRH2

This is a list of pathogenic ClinVar variants found in the PTRH2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-59674679-TTC-T			Benign (Jan 25, 2024)
17-59674681-C-G			Likely benign (Aug 03, 2023)
17-59674681-C-T			Likely benign (Mar 06, 2022)
17-59674683-ACTT-A			Likely benign (Mar 14, 2023)
17-59674687-C-G			Likely benign (Sep 03, 2023)
17-59674708-C-G			Uncertain significance (Sep 07, 2022)
17-59674718-TC-T		Intellectual disability, autosomal dominant 56	Pathogenic (May 05, 2022)
17-59674753-G-T			Uncertain significance (Oct 23, 2022)
17-59674769-A-T			Likely benign (Feb 04, 2022)
17-59674784-T-C			Likely benign (Mar 09, 2023)
17-59674785-G-A		Intellectual disability, autosomal dominant 56	Uncertain significance (May 03, 2023)
17-59674799-A-G		Intellectual disability, autosomal dominant 56	Uncertain significance (Aug 16, 2023)
17-59674808-T-C			Likely benign (May 28, 2021)
17-59674822-C-T			Uncertain significance (Apr 30, 2021)
17-59674842-A-T			Likely pathogenic (Dec 28, 2017)
17-59674852-C-G			Likely benign (Aug 17, 2023)
17-59674853-C-T			Likely benign (Dec 06, 2023)
17-59676933-GT-G			Benign (Jan 07, 2024)
17-59676934-T-C			Likely benign (Feb 01, 2024)
17-59676934-T-TTTTTTTCC		CLTC-related disorder	Likely benign (Dec 14, 2023)
17-59676940-T-C			Likely benign (Jan 25, 2024)
17-59676942-C-CT		not specified	Conflicting classifications of pathogenicity (Oct 12, 2023)
17-59676943-T-G			Likely benign (Feb 09, 2023)
17-59676949-C-T		CLTC-related disorder	Likely benign (Feb 01, 2024)
17-59676953-G-C		Intellectual disability, autosomal dominant 56	Likely pathogenic (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTRH2	protein_coding	protein_coding	ENST00000470557	1	32991

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000638	0.511	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.427	83	94.7	0.876	0.00000474	1158
Missense in Polyphen		22	33.501	0.6567		404
Synonymous	-0.684	40	34.9	1.15	0.00000175	368
Loss of Function	0.280	5	5.72	0.874	3.79e-7	69

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The natural substrate for this enzyme may be peptidyl- tRNAs which drop off the ribosome during protein synthesis. {ECO:0000250}.
• Disease: DISEASE: Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset (IMNEPD) [MIM:616263]: A progressive multisystem disease characterized by a variety of neurologic, endocrine, and, in some patients, pancreatic features. Variable clinical symptoms include global developmental delay, hypotonia, hearing loss, ataxia, hyporeflexia, facial dysmorphism, hypothyroidism, and pancreatic insufficiency. {ECO:0000269|PubMed:25558065, ECO:0000269|PubMed:25574476}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Apoptosis Modulation and Signaling;Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.0903

Intolerance Scores

• loftool: 0.264
• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.28

Haploinsufficiency Scores

• pHI: 0.442
• hipred: N
• hipred_score: 0.354
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ptrh2
• Phenotype: immune system phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: apoptotic process;negative regulation of gene expression;positive regulation of anoikis;negative regulation of anoikis
• Cellular component: mitochondrion;cytosol;membrane
• Molecular function: aminoacyl-tRNA hydrolase activity;protein binding