PNPT1

polyribonucleotide nucleotidyltransferase 1

Basic information

Region (hg38): 2:55634061-55693863

Previous symbols: [ "DFNB70" ]

Links

ENSG00000138035NCBI:87178OMIM:610316HGNC:23166Uniprot:Q8TCS8AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • combined oxidative phosphorylation defect type 13 (Strong), mode of inheritance: AR
  • autosomal recessive nonsyndromic hearing loss 70 (Limited), mode of inheritance: AR
  • combined oxidative phosphorylation defect type 13 (Definitive), mode of inheritance: AR
  • combined oxidative phosphorylation defect type 13 (Strong), mode of inheritance: AR
  • hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
  • spinocerebellar ataxia type 25 (Limited), mode of inheritance: AD
  • autosomal recessive nonsyndromic hearing loss 70 (Limited), mode of inheritance: Unknown
  • combined oxidative phosphorylation defect type 13 (Strong), mode of inheritance: AR
  • Leigh syndrome (Moderate), mode of inheritance: AR
  • hearing loss disorder (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Deafness, autosomal recessive 70, with or without adult-onset neurodegenerationARAudiologic/OtolaryngologicEarly recognition and treatment of hearing impairment may improve outcomes, including speech and language developmentAudiologic/Otolaryngologic; Biochemical; Neurologic23084290; 23084291; 30244537; 35411967

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PNPT1 gene.

  • not_provided (770 variants)
  • Inborn_genetic_diseases (89 variants)
  • Combined_oxidative_phosphorylation_defect_type_13 (42 variants)
  • not_specified (40 variants)
  • PNPT1-related_disorder (32 variants)
  • Autosomal_recessive_nonsyndromic_hearing_loss_70 (27 variants)
  • Spinocerebellar_ataxia_type_25 (15 variants)
  • Neurodevelopmental_disorder (2 variants)
  • Global_developmental_delay (2 variants)
  • Hereditary_ataxia (2 variants)
  • Schizophrenia (1 variants)
  • See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PNPT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000033109.5. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
151
clinvar
4
clinvar
159
missense
7
clinvar
14
clinvar
300
clinvar
20
clinvar
341
nonsense
10
clinvar
3
clinvar
1
clinvar
14
start loss
0
frameshift
10
clinvar
8
clinvar
2
clinvar
20
splice donor/acceptor (+/-2bp)
2
clinvar
16
clinvar
2
clinvar
20
Total 30 41 308 171 4

Highest pathogenic variant AF is 0.000318397

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PNPT1protein_codingprotein_codingENST00000447944 2859646
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.0004011.001257200281257480.000111
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.4243854090.9410.00002015029
Missense in Polyphen1021310.77861622
Synonymous-1.181641461.120.000007851518
Loss of Function4.561651.20.3130.00000256638

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002850.000277
Ashkenazi Jewish0.000.00
East Asian0.0001650.000163
Finnish0.00009460.0000924
European (Non-Finnish)0.0001260.000123
Middle Eastern0.0001650.000163
South Asian0.00006650.0000653
Other0.0001640.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: RNA-binding protein implicated in numerous RNA metabolic processes. Catalyzes the phosphorolysis of single-stranded polyribonucleotides processively in the 3'-to-5' direction. Mitochondrial intermembrane factor with RNA-processing exoribonulease activity. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double- stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. Required for correct processing and polyadenylation of mitochondrial mRNAs. Plays a role as a cytoplasmic RNA import factor that mediates the translocation of small RNA components, like the 5S RNA, the RNA subunit of ribonuclease P and the mitochondrial RNA-processing (MRP) RNA, into the mitochondrial matrix. Plays a role in mitochondrial morphogenesis and respiration; regulates the expression of the electron transport chain (ETC) components at the mRNA and protein levels. In the cytoplasm, shows a 3'-to-5' exoribonuclease mediating mRNA degradation activity; degrades c-myc mRNA upon treatment with IFNB1/IFN-beta, resulting in a growth arrest in melanoma cells. Regulates the stability of specific mature miRNAs in melanoma cells; specifically and selectively degrades miR-221, preferentially. Plays also a role in RNA cell surveillance by cleaning up oxidized RNAs. Binds to the RNA subunit of ribonuclease P, MRP RNA and miR-221 microRNA. {ECO:0000269|PubMed:12473748, ECO:0000269|PubMed:12721301, ECO:0000269|PubMed:12798676, ECO:0000269|PubMed:16055741, ECO:0000269|PubMed:16410805, ECO:0000269|PubMed:16934922, ECO:0000269|PubMed:18083836, ECO:0000269|PubMed:18083837, ECO:0000269|PubMed:18501193, ECO:0000269|PubMed:19509288, ECO:0000269|PubMed:20547861, ECO:0000269|PubMed:20691904}.;
Disease
DISEASE: Combined oxidative phosphorylation deficiency 13 (COXPD13) [MIM:614932]: A mitochondrial disorder characterized by early onset severe encephalomyopathy, dystonia, choreoathetosis, bucofacial dyskinesias and combined mitochondrial respiratory chain deficiency. Nerve conductions velocities are decreased. Levels of plasma and cerebrospinal fluid lactate are increased. {ECO:0000269|PubMed:23084291}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal recessive, 70 (DFNB70) [MIM:614934]: A form of non-syndromic deafness characterized by severe, bilateral hearing impairment with prelingual onset, resulting in inability to acquire normal speech. {ECO:0000269|PubMed:23084290}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Pyrimidine metabolism - Homo sapiens (human);RNA degradation - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Pyrimidine metabolism;Purine metabolism;Pyrimidine metabolism (Consensus)

Recessive Scores

pRec
0.0952

Intolerance Scores

loftool
0.427
rvis_EVS
0.14
rvis_percentile_EVS
63.62

Haploinsufficiency Scores

pHI
0.231
hipred
Y
hipred_score
0.540
ghis
0.562

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.915

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerHighMediumHigh

Mouse Genome Informatics

Gene name
Pnpt1
Phenotype
skeleton phenotype; hematopoietic system 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); normal phenotype; cellular phenotype;

Gene ontology

Biological process
mitochondrial RNA catabolic process;mitochondrial mRNA catabolic process;positive regulation of mitochondrial RNA catabolic process;mitochondrial RNA processing;mitochondrial RNA 5'-end processing;mitochondrial RNA 3'-end processing;RNA catabolic process;mRNA catabolic process;cellular response to oxidative stress;cellular response to interferon-beta;RNA import into mitochondrion;rRNA import into mitochondrion;regulation of cellular respiration;RNA polyadenylation;negative regulation of growth;protein homooligomerization;response to cAMP;response to growth hormone;positive regulation of mRNA catabolic process;protein homotrimerization;mitochondrion morphogenesis;nuclear polyadenylation-dependent mRNA catabolic process;mitotic cell cycle arrest;RNA phosphodiester bond hydrolysis, exonucleolytic;mitochondrial mRNA polyadenylation;liver regeneration;positive regulation of miRNA catabolic process;regulation of cellular senescence
Cellular component
nucleus;cytoplasm;mitochondrion;mitochondrial intermembrane space;endoplasmic reticulum membrane;cytosol;polysomal ribosome;mitochondrial degradosome
Molecular function
3'-5'-exoribonuclease activity;RNA binding;polyribonucleotide nucleotidyltransferase activity;protein binding;poly(U) RNA binding;poly(G) binding;miRNA binding