PNPT1

Summary

PNPT1 (polyribonucleotide nucleotidyltransferase 1, HGNC:23166) is a protein-coding gene on chromosome 2p16.1, encoding Polyribonucleotide nucleotidyltransferase 1, mitochondrial (Q8TCS8). RNA-binding protein implicated in numerous RNA metabolic processes. It is a selective cancer dependency (DepMap: 89.1% of cell lines).

The protein encoded by this gene belongs to the evolutionary conserved polynucleotide phosphorylase family comprised of phosphate dependent 3’-to-5’ exoribonucleases implicated in RNA processing and degradation. This enzyme is predominantly localized in the mitochondrial intermembrane space and is involved in import of RNA to mitochondria. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency-13 and autosomal recessive nonsyndromic deafness-70. Related pseudogenes are found on chromosomes 3 and 7.

Source: NCBI Gene 87178 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss disorder (Definitive, GenCC) — +5 more curated relationships
• GWAS associations: 43
• Clinical variants (ClinVar): 978 total — 37 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 80
• Cancer dependency (DepMap): dependent in 89.1% of screened cell lines
• MANE Select transcript: NM_033109

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23166
Approved symbol	PNPT1
Name	polyribonucleotide nucleotidyltransferase 1
Location	2p16.1
Locus type	gene with protein product
Status	Approved
Aliases	PNPase, OLD35, old-35
Ensembl gene	ENSG00000138035
Ensembl biotype	protein_coding
OMIM	610316
Entrez	87178

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000260604, ENST00000415374, ENST00000415489, ENST00000429805, ENST00000447944, ENST00000481066, ENST00000625249, ENST00000867132, ENST00000867134, ENST00000867135, ENST00000867136, ENST00000867137, ENST00000867138, ENST00000917022, ENST00000917023, ENST00000917024, ENST00000917025, ENST00000917026, ENST00000917027, ENST00000949800, ENST00000949801, ENST00000949802, ENST00000949803, ENST00000949804

RefSeq mRNA: 1 — MANE Select: NM_033109 NM_033109

CCDS: CCDS1856

Canonical transcript exons

ENST00000447944 — 28 exons

Exon	Start	End
ENSE00000962790	55686370	55686444
ENSE00001146479	55687645	55687705
ENSE00001929655	55693663	55693844
ENSE00001935471	55634061	55636392
ENSE00003469282	55637552	55637599
ENSE00003488570	55683785	55683834
ENSE00003503681	55647347	55647453
ENSE00003513836	55661956	55662026
ENSE00003528561	55640627	55640705
ENSE00003531549	55672893	55673079
ENSE00003531734	55644637	55644720
ENSE00003543179	55643319	55643425
ENSE00003546756	55679682	55679795
ENSE00003547884	55684943	55685048
ENSE00003562746	55654900	55654953
ENSE00003571247	55666991	55667093
ENSE00003572290	55667862	55667958
ENSE00003574252	55680712	55680759
ENSE00003576260	55671319	55671376
ENSE00003620386	55680855	55680918
ENSE00003624991	55656131	55656220
ENSE00003629820	55645349	55645432
ENSE00003632765	55646415	55646486
ENSE00003657544	55646259	55646322
ENSE00003659453	55660157	55660193
ENSE00003669107	55671995	55672046
ENSE00003676495	55643158	55643213
ENSE00003689665	55656305	55656371

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 96.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.3940 / max 1113.4826, expressed in 1810 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28482	27.3940	1810

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	96.86	gold quality
secondary oocyte	CL:0000655	96.15	gold quality
tibialis anterior	UBERON:0001385	95.65	gold quality
deltoid	UBERON:0001476	95.30	gold quality
oocyte	CL:0000023	95.06	gold quality
corpus callosum	UBERON:0002336	93.15	gold quality
myocardium	UBERON:0002349	92.77	gold quality
subthalamic nucleus	UBERON:0001906	92.52	gold quality
biceps brachii	UBERON:0001507	92.38	gold quality
quadriceps femoris	UBERON:0001377	92.30	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.08	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.03	gold quality
heart right ventricle	UBERON:0002080	91.74	gold quality
vastus lateralis	UBERON:0001379	91.72	gold quality
inferior vagus X ganglion	UBERON:0005363	91.66	gold quality
skeletal muscle tissue	UBERON:0001134	91.56	gold quality
epithelial cell of pancreas	CL:0000083	91.42	gold quality
muscle tissue	UBERON:0002385	90.92	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.81	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.75	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.63	gold quality
substantia nigra pars compacta	UBERON:0001965	90.25	gold quality
kidney epithelium	UBERON:0004819	90.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.10	gold quality
lateral globus pallidus	UBERON:0002476	89.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.69	gold quality
skeletal muscle organ	UBERON:0014892	89.64	gold quality
spinal cord	UBERON:0002240	89.56	gold quality
sperm	CL:0000019	89.53	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	3286.33
E-MTAB-9435	yes	2702.85
E-MTAB-6701	yes	2114.29
E-CURD-79	yes	1899.69
E-MTAB-6308	yes	1793.98
E-HCAD-9	yes	1227.43
E-MTAB-8142	yes	109.65
E-HCAD-1	yes	39.04
E-GEOD-137537	yes	17.12
E-HCAD-10	yes	8.78
E-MTAB-8410	yes	8.19
E-MTAB-7316	no	1259.63
E-HCAD-8	no	1205.97
E-MTAB-7037	no	470.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF331

miRNA regulators (miRDB)

89 targeting PNPT1, 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-656-3P	100.00	72.15	2788
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4753-3P	99.90	71.03	3786

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring (PMID:12419256)
• an important role for hPNPase(old-35)in growth control associated with terminal differentiation and cellular senescence. (PMID:12473748)
• the molecular mechanism of the growth-arresting property of hPNPaseold-35 (PMID:12721301)
• demonstrate that the hPNPase is localized in mitochondria; finding suggests the involvement of mitochondrial RNA metabolism in cellular senescence (PMID:12798676)
• analysis of domains of human polynucleotide phosphorylase (hPNPaseOLD-35) mediating cellular senescence (PMID:16055741)
• Targeted overexpression of hPNPase(old-35) might be a novel therapeutic strategy for c-myc-overexpressing and IFN-resistant tumors, such as melanomas. (PMID:16410805)
• human PNPase mRNA upregulation by beta-interferon has no effect on protein level in melanoma cell lines (PMID:16505900)
• PNPase localization to the mitochondrial intermembrane space suggests a unique role distinct from its highly conserved function in RNA processing in chloroplasts and bacteria. (PMID:16966379)
• Combined, the data demonstrate an unexpected IMS localization and a key role for PNPase in maintaining mitochondrial homeostasis. (PMID:16966381)
• A novel pathway by which an evolutionary conserved RNA-metabolizing enzyme, hPNPase(old-35), regulates cell growth and viability. (PMID:17804700)
• recent advances in understanding the various roles of hPNPase both within and potentially outside of the mitochondria [review] (PMID:17983748)
• In this work, the degradation, polymerization, and RNA-binding properties of the human PNPase were analyzed and compared to its bacterial and organellar counterparts. (PMID:18083836)
• Involvement of human polynucleotide phosphorylase in mtRNA degradation was studied. (PMID:18083837)
• The complex of hSUV3-hPNPase is an integral entity for efficient degradation of structured RNA and may be the long sought RNA-degrading complex in the mammalian mitochondria. (PMID:19509288)
• maintained expression and even up-regulation of some (PNPT1, PMPCB, HMMR/RHAMM, BSG and ERCC1) tumor associated antigens in CD40-activated leukemic cells. (PMID:19580345)
• Inhibition of PNPase by shRNA or stable overexpression of miR-221 protected melanoma cells from IFN-beta-mediated growth inhibition, accentuating the importance of PNPase induction and miR-221 down-regulation in mediating IFN-beta action. (PMID:20547861)
• The data support an unanticipated role for PNPASE in mediating the translocation of RNAs into mitochondria. (PMID:20691904)
• targeted overexpression of hPNPase(old-35) represents a novel strategy to selectively downregulate RNA expression and consequently intervene in a variety of pathophysiological conditions (PMID:21151174)
• The study provides structural and functional insights into hPNPase, which uses a KH pore to trap a long RNA 3’ tail that is further delivered into an RNase PH channel for the degradation process. (PMID:22210891)
• a novel role of nEGFR in radioresistance, and that is, upon ionizing radiation, nEGFR inactivates the ribonuclease activity of PNPase toward c-MYC mRNA through DNAPK-mediated Ser-776 phosphorylation (PMID:22815474)
• A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss. (PMID:23084290)
• Mutation in PNPT1, which encodes a polyribonucleotide nucleotidyltransferase, impairs RNA import into mitochondria and causes respiratory-chain deficiency. (PMID:23084291)
• Interaction between PNPase and hSuv3 is essential for efficient mitochondrial RNA degradation. (PMID:23221631)
• fresh insight into cellular pathways regulated by PNPT1 (PMID:24143183)
• this study provides further evidence that hPNPase(old-35) is associated with global changes in cell cycle-associated genes and identifies potential gene targets for future investigation (PMID:24729470)
• In vitro rescue experiments, using exogenous expression of wild-type PNPT1 in patient fibroblasts, ameliorated the deficiencies in the OXPHOS complex protein expression, supporting the likely pathogenicity of these variants and the importance of Whole-exome sequencingin efficiently identifying rare genetic disease genes (PMID:27759031)
• Inhibition of homologous PNPase by citrate may represent an evolutionarily conserved communicative link between RNA degradation and central metabolism. (PMID:28334892)
• Our cases expand the phenotypic spectrum of PNPT1 mutations that can cause delayed myelination. (PMID:28594066)
• The PNPT1 p.Arg136His and p.Pro140Leu variants in our subject showed 1) the mutated amino acids are highly conserved and our structural analysis supported them to be functionally deleterious; 2) The carrier frequencies of the variants are very low in populations (1:60.000), with no homozygous carriers found; 3) The RC complex amounts in the subject’s myoblasts were functionally rescued by expression of wild-type PNPT1. (PMID:28645153)
• The disease-linked human PNPase mutants, Q387R and E475G, form dimers, not trimers, and have significantly lower RNA binding and degradation activities compared to wild-type. The S1 domain is responsible for binding structured RNAs. The RNA-binding K homology and S1 domains are inaccessible in the dimeric assembly. Mutations at the trimeric PNPase interface produce a dimeric protein with destructsive RNA-binding surfaces. (PMID:30020492)
• PNPT1-related disorders may constitute a spectrum rather than distinct phenotypes. (PMID:30244537)
• PNPT1 and PCGF3 variants associated with angiotensin-converting enzyme inhibitor-induced cough: a nested case-control genome-wide study. (PMID:32397904)
• Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both? (PMID:33199448)
• Crystallographic modeling of the PNPT1:c.1453A>G variant as a cause of mitochondrial dysfunction and autosomal recessive deafness; expanding the neuroimaging and clinical features. (PMID:33812062)
• PNPT1, MYO15A, PTPRQ, and SLC12A2-associated genetic and phenotypic heterogeneity among hearing impaired assortative mating families in Southern India. (PMID:34374074)
• Ocular Manifestations of PNPT1-Related Neuropathy. (PMID:34415280)
• Activity and Function in Human Cells of the Evolutionary Conserved Exonuclease Polynucleotide Phosphorylase. (PMID:35163574)
• Heterozygous PNPT1 Variants Cause Spinocerebellar Ataxia Type 25. (PMID:35411967)
• SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer. (PMID:36232701)
• Human PNPase causes RNA stabilization and accumulation of R-loops in the Escherichia coli model system. (PMID:37479726)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pnpt1	ENSMUSG00000020464
rattus_norvegicus	Pnpt1	ENSRNOG00000003600
drosophila_melanogaster	PNPase	FBGN0039846
caenorhabditis_elegans		WBGENE00015266

Protein

Protein identifiers

Polyribonucleotide nucleotidyltransferase 1, mitochondrial — Q8TCS8 (reviewed: Q8TCS8)

Alternative names: 3’-5’ RNA exonuclease OLD35, PNPase old-35, Polynucleotide phosphorylase 1, Polynucleotide phosphorylase-like protein

All UniProt accessions (4): Q8TCS8, F8WBI3, H7BXF6, H7C3C5

UniProt curated annotations — full annotation on UniProt →

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. Involved in the degradation of non-coding mitochondrial transcripts (MT-ncRNA) and tRNA-like molecules. 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. Also plays 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.

Subunit / interactions. Homotrimer; in free form. Homooligomer. Component of the mitochondrial degradosome (mtEXO) complex which is a heteropentamer containing 2 copies of SUPV3L1 and 3 copies of PNPT1. As part of the mitochondrial degradosome complex, interacts with GRSF1 in an RNA-dependent manner; the interaction enhances the activity of the complex. Interacts with TCL1A; the interaction has no effect on PNPT1 exonuclease activity.

Subcellular location. Cytoplasm. Mitochondrion matrix. Mitochondrion intermembrane space.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal recessive, 70, with or without adult-onset neurodegeneration (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. Affected individuals may develop a neurodegenerative disease in adulthood, including ataxia with loss of ambulation, optic atrophy, dystonia or spasticity, and cognitive decline with psychiatric features. The disease is caused by variants affecting the gene represented in this entry. Spinocerebellar ataxia 25 (SCA25) [MIM:608703] An autosomal dominant form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA25 is characterized by the onset of lower limb ataxia and gait difficulties in the first few decades of life, although later onset has been reported. There is incomplete penetrance and variable expressivity, even within families. The disease is caused by variants affecting the gene represented in this entry. Both genetic variants associated so far with this disease are affecting splicing.

Induction. Up-regulated in cells upon senescence and terminal differentiation. Up-regulated after treatment with IFNB1/IFN-beta.

Similarity. Belongs to the polyribonucleotide nucleotidyltransferase family.

RefSeq proteins (1): NP_149100* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001247	ExoRNase_PH_dom1	Domain
IPR003029	S1_domain	Domain
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR012162	PNPase	Family
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR015847	ExoRNase_PH_dom2	Domain
IPR015848	PNPase_PH_RNA-bd_bac/org-type	Domain
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR027408	PNPase/RNase_PH_dom_sf	Homologous_superfamily
IPR036345	ExoRNase_PH_dom2_sf	Homologous_superfamily
IPR036456	PNPase_PH_RNA-bd_sf	Homologous_superfamily
IPR036612	KH_dom_type_1_sf	Homologous_superfamily

Pfam: PF00013, PF00575, PF01138, PF03725, PF03726

Enzyme classification (BRENDA):

• EC 2.7.7.8 — polyribonucleotide nucleotidyltransferase (BRENDA: 59 organisms, 216 substrates, 43 inhibitors, 23 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ADP	0.0536–25	6
UDP	0.4–1	2
2’,3’-CYCLIC RNAN	0.042	1
3’-PHOSPHORYLATED RNA(N)	0.156	1
CDP	1	1
GLOBIN MRNA	0.0002	1
HEPTAURIDYLATE	0.05	1
MG2+	0.05	1
NONAADENYLATE	0.033	1
PHOSPHATE	0.25	1
POLY(A)	0.32	1
RNA(N)	0.022	1
TETRAURIDYLATE	0.25	1
TRIADENYLATE	2.5	1
POLY(A)N	—	0

Catalyzed reactions (Rhea), 1 shown:

• RNA(n+1) + phosphate = RNA(n) + a ribonucleoside 5’-diphosphate (RHEA:22096)

UniProt features (71 total): strand 27, helix 21, modified residue 7, sequence variant 5, mutagenesis site 4, domain 2, turn 2, transit peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
9NO0	ELECTRON MICROSCOPY	2.08
3U1K	X-RAY DIFFRACTION	2.13
9NJB	ELECTRON MICROSCOPY	2.15
9NJC	ELECTRON MICROSCOPY	2.36
9NJD	ELECTRON MICROSCOPY	2.44
9NJE	ELECTRON MICROSCOPY	2.44
9XYI	ELECTRON MICROSCOPY	2.46
9XZF	ELECTRON MICROSCOPY	2.65
5ZF6	X-RAY DIFFRACTION	2.8
9KJT	ELECTRON MICROSCOPY	3.84
9KJR	ELECTRON MICROSCOPY	3.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCS8-F1	87.46	0.71

Functional residue map

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

Post-translational modifications (7): 782, 250, 264, 285, 289, 552, 754

Mutagenesis-validated functional residues (4):

Position	Phenotype
135	inhibits poly(a) polymerase and rna degradation activities. inhibits the import or stabilization of rnase p rna into the
445–446	stimulates in vitro poly(a) polymerase activity. inhibits rna degradation activity. does not inhibit the import or stabi
484	inhibits poly(a) polymerase and rna degradation activities. does not inhibit the import or stabilization of rnase p rna
544	stimulates in vitro poly(a) polymerase activity. inhibits rna degradation activity. inhibits the import or stabilization

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9836573	Mitochondrial RNA degradation

MSigDB gene sets: 432 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOMF_RNA_NUCLEASE_ACTIVITY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, GOMF_NUCLEASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGENERATION, GOBP_CELLULAR_SENESCENCE, GOBP_RESPONSE_TO_INTERFERON_BETA, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY

GO Biological Process (25): mitochondrial RNA catabolic process (GO:0000957), mitochondrial mRNA catabolic process (GO:0000958), positive regulation of mitochondrial RNA catabolic process (GO:0000962), mitochondrial RNA 5’-end processing (GO:0000964), mitochondrial RNA 3’-end processing (GO:0000965), mRNA processing (GO:0006397), RNA catabolic process (GO:0006401), mRNA catabolic process (GO:0006402), mitochondrion organization (GO:0007005), cellular response to oxidative stress (GO:0034599), cellular response to interferon-beta (GO:0035458), RNA import into mitochondrion (GO:0035927), rRNA import into mitochondrion (GO:0035928), regulation of cellular respiration (GO:0043457), protein homooligomerization (GO:0051260), response to cAMP (GO:0051591), response to growth hormone (GO:0060416), positive regulation of mRNA catabolic process (GO:0061014), protein homotrimerization (GO:0070207), nuclear polyadenylation-dependent mRNA catabolic process (GO:0071042), mitochondrial mRNA polyadenylation (GO:0097222), liver regeneration (GO:0097421), positive regulation of miRNA catabolic process (GO:2000627), regulation of cellular senescence (GO:2000772), RNA processing (GO:0006396)

GO Molecular Function (14): 3’-5’-RNA exonuclease activity (GO:0000175), RNA binding (GO:0003723), polyribonucleotide nucleotidyltransferase activity (GO:0004654), poly(U) RNA binding (GO:0008266), poly(G) binding (GO:0034046), miRNA binding (GO:0035198), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), hydrolase activity (GO:0016787)

GO Cellular Component (10): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), ribosome (GO:0005840), mitochondrial degradosome (GO:0045025), membrane (GO:0016020), exoribonuclease complex (GO:1905354)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	5
cellular anatomical structure	3
RNA catabolic process	2
mitochondrial RNA catabolic process	2
mRNA catabolic process	2
positive regulation of catabolic process	2
mitochondrial RNA processing	2
mRNA metabolic process	2
binding	2
catalytic activity	2
cytoplasm	2
mitochondrial RNA metabolic process	1
regulation of mitochondrial RNA catabolic process	1
positive regulation of RNA metabolic process	1
RNA 5’-end processing	1
RNA 3’-end processing	1
RNA processing	1
RNA metabolic process	1
nucleic acid catabolic process	1
negative regulation of gene expression	1
organelle organization	1
response to oxidative stress	1
cellular response to chemical stress	1
response to interferon-beta	1
cellular response to cytokine stimulus	1
intercellular transport	1
RNA transport	1
transmembrane transport	1
RNA import into mitochondrion	1
rRNA transport	1
regulation of generation of precursor metabolites and energy	1
cellular respiration	1
protein complex oligomerization	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
response to peptide hormone	1
regulation of mRNA catabolic process	1
positive regulation of mRNA metabolic process	1
protein homooligomerization	1

Protein interactions and networks

STRING

3438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PNPT1	SUPV3L1	Q8IYB8	997
PNPT1	PPP1R8	Q12972	952
PNPT1	REXO2	Q9Y3B8	743
PNPT1	YBEY	P58557	713
PNPT1	MTPAP	Q9NVV4	709
PNPT1	EXOSC4	Q9NPD3	688
PNPT1	IRF9	Q00978	675
PNPT1	EXOSC10	Q01780	664
PNPT1	DIS3	Q9Y2L1	645
PNPT1	SLIRP	Q9GZT3	628
PNPT1	FASTKD3	Q14CZ7	621
PNPT1	ELAC2	Q9BQ52	608
PNPT1	LRPPRC	P42704	601
PNPT1	PAPOLA	P51003	586
PNPT1	EXOSC7	Q15024	586

IntAct

104 interactions, top by confidence:

A	B	Type	Score
SUPV3L1	PNPT1	psi-mi:“MI:0407”(direct interaction)	0.860
PNPT1	SUPV3L1	psi-mi:“MI:0407”(direct interaction)	0.860
PNPT1	SUPV3L1	psi-mi:“MI:0915”(physical association)	0.860
TMED2	ATP9A	psi-mi:“MI:0914”(association)	0.640
TBRG4	PNPT1	psi-mi:“MI:0914”(association)	0.640
ADARB1	PNPT1	psi-mi:“MI:0915”(physical association)	0.560
PNPT1	PNPT1	psi-mi:“MI:0407”(direct interaction)	0.560
HSCB	PNPT1	psi-mi:“MI:0915”(physical association)	0.550
SERPINA12	TSPAN6	psi-mi:“MI:0914”(association)	0.530
ATP5F1D	NDUFB5	psi-mi:“MI:0914”(association)	0.530
ACAD9	PPL	psi-mi:“MI:0914”(association)	0.530
FAHD1	CLUH	psi-mi:“MI:0914”(association)	0.530
AURKB	SMCHD1	psi-mi:“MI:0914”(association)	0.530
UQCRFS1	NDUFAB1	psi-mi:“MI:0914”(association)	0.530
SUPV3L1	HNRNPDL	psi-mi:“MI:0914”(association)	0.480
TRMT61B	GLS	psi-mi:“MI:0914”(association)	0.480
	PNPT1	psi-mi:“MI:0902”(rna cleavage)	0.440
XIRP2	PNPT1	psi-mi:“MI:0915”(physical association)	0.400
GBP4	PNPT1	psi-mi:“MI:0915”(physical association)	0.400
HSPB1	PNPT1	psi-mi:“MI:0915”(physical association)	0.370
LTN1	KIF2A	psi-mi:“MI:0914”(association)	0.350
FASTKD3	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (199): PNPT1 (Affinity Capture-RNA), PNPT1 (Affinity Capture-MS), PNPT1 (Affinity Capture-MS), PNPT1 (Affinity Capture-MS), PNPT1 (Two-hybrid), CLTB (Co-fractionation), EIF4A1 (Co-fractionation), PMPCA (Co-fractionation), PNPT1 (Co-fractionation), PNPT1 (Affinity Capture-MS), PNPT1 (Affinity Capture-MS), PNPT1 (Affinity Capture-MS), PNPT1 (Affinity Capture-MS), PNPT1 (Affinity Capture-MS), PNPT1 (Affinity Capture-MS)

ESM2 similar proteins: A2RVK7, A2X0Q3, A6QLJ3, O00442, O23617, O81147, O81852, P0CT46, P31754, P37142, P48605, P49080, P49368, P80318, Q01415, Q06265, Q14181, Q2HJ88, Q2KHU3, Q3SWZ4, Q3T0K2, Q4QR75, Q4R3J0, Q4R963, Q5NVF9, Q5R6J8, Q5R7P3, Q5RCW2, Q5RGJ5, Q5XJQ5, Q69LE7, Q6P502, Q6STH5, Q6YXZ7, Q7YRA3, Q84T68, Q8C3X4, Q8GZQ3, Q8K1R3, Q8N442

Diamond homologs: A0LHM4, A0Q0Q1, A1AMM6, A1B5P9, A1U5Z6, A1VG88, A4IME3, A4XL64, A5E870, A5GF91, A5ISF8, A5URV5, A5VCY9, A6QGH3, A6TRK1, A6U193, A6UF34, A7H9F8, A7IC03, A7MZI2, A7X1Q8, A8Z3V4, A9WEJ7, B0K1D0, B0K9P4, B0S1D9, B0SH22, B0SQH8, B0THS2, B1ZS98, B2UNA9, B3DZ86, B3PIA0, B3QAB0, B3QY14, B4S5G5, B5EMD4, B6J6S7, B7J4D8, B8DN07

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKDC	“up-regulates activity”	PNPT1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial ribosome-associated quality control	8	12.9×	8e-05
Mitochondrial protein import	5	11.1×	8e-03
Mitochondrial translation initiation	6	10.0×	5e-03
Mitochondrial translation elongation	6	10.0×	5e-03
Mitochondrial translation termination	6	8.7×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial large ribosomal subunit assembly	7	64.8×	5e-09
mitochondrial translation	8	13.0×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	31
Uncertain significance	343
Likely benign	401
Benign	81

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1034189	NM_033109.5(PNPT1):c.298-2A>T	Pathogenic
1034190	NM_033109.5(PNPT1):c.918del (p.Val307fs)	Pathogenic
1455027	NM_033109.5(PNPT1):c.1748dup (p.Glu584fs)	Pathogenic
1460256	NC_000002.11:g.(?55910900)(55920958_?)del	Pathogenic
1695428	NM_033109.5(PNPT1):c.2069+3A>G	Pathogenic
1700630	NM_033109.5(PNPT1):c.1579_1580insGAT (p.Tyr527Ter)	Pathogenic
1705644	NM_033109.5(PNPT1):c.574C>T (p.Arg192Ter)	Pathogenic
1805654	NM_033109.5(PNPT1):c.406C>T (p.Arg136Cys)	Pathogenic
1938148	NM_033109.5(PNPT1):c.885_886del (p.Tyr296fs)	Pathogenic
2063935	NM_033109.5(PNPT1):c.1789C>T (p.Arg597Ter)	Pathogenic
2095601	NM_033109.5(PNPT1):c.1920_1923del (p.Ser640fs)	Pathogenic
2109038	NM_033109.5(PNPT1):c.1336A>T (p.Arg446Ter)	Pathogenic
2113226	NM_033109.5(PNPT1):c.2014C>T (p.Gln672Ter)	Pathogenic
218175	NM_033109.5(PNPT1):c.404-1G>A	Pathogenic
2312554	NM_033109.5(PNPT1):c.887_888del (p.Tyr296fs)	Pathogenic
2427121	NC_000002.11:g.(?55894977)(55913599_?)del	Pathogenic
253225	NM_033109.5(PNPT1):c.760C>A (p.Gln254Lys)	Pathogenic
2581355	NC_000002.11:g.(?_55861197)_55874535del	Pathogenic
2805003	NM_033109.5(PNPT1):c.1180del (p.Leu394fs)	Pathogenic
2826377	NM_033109.5(PNPT1):c.2131C>T (p.Gln711Ter)	Pathogenic
2836084	NM_033109.5(PNPT1):c.1012G>T (p.Glu338Ter)	Pathogenic
3233882	NM_033109.5(PNPT1):c.1002T>G (p.Tyr334Ter)	Pathogenic
3247575	NC_000002.11:g.(?55870273)(55883526_?)del	Pathogenic
3649678	NM_033109.5(PNPT1):c.195del (p.Arg65fs)	Pathogenic
3722315	NM_033109.5(PNPT1):c.1841T>G (p.Leu614Ter)	Pathogenic
3724544	NM_033109.5(PNPT1):c.600dup (p.Val201fs)	Pathogenic
39801	NM_033109.5(PNPT1):c.1160A>G (p.Gln387Arg)	Pathogenic
419024	NM_033109.5(PNPT1):c.1174_1175del (p.Gln392fs)	Pathogenic
4540450	NM_033109.5(PNPT1):c.1258del (p.Asp420fs)	Pathogenic
4731230	NM_033109.5(PNPT1):c.828dup (p.Phe277fs)	Pathogenic

SpliceAI

3258 predictions. Top by Δscore:

Variant	Effect	Δscore
2:55636390:CAC:C	acceptor_gain	1.0000
2:55636391:ACCT:A	acceptor_loss	1.0000
2:55636392:CC:C	acceptor_loss	1.0000
2:55636392:CCTG:C	acceptor_gain	1.0000
2:55636393:C:CC	acceptor_gain	1.0000
2:55636394:T:C	acceptor_loss	1.0000
2:55636395:G:C	acceptor_gain	1.0000
2:55636395:G:GC	acceptor_gain	1.0000
2:55637547:AATAC:A	donor_loss	1.0000
2:55637548:ATACC:A	donor_loss	1.0000
2:55637549:TA:T	donor_loss	1.0000
2:55637550:ACCT:A	donor_loss	1.0000
2:55637551:C:CA	donor_loss	1.0000
2:55637596:TAAT:T	acceptor_gain	1.0000
2:55637596:TAATC:T	acceptor_loss	1.0000
2:55637597:AATC:A	acceptor_loss	1.0000
2:55637598:ATCTG:A	acceptor_loss	1.0000
2:55637599:TCTGG:T	acceptor_loss	1.0000
2:55637600:C:CA	acceptor_loss	1.0000
2:55637600:C:CC	acceptor_gain	1.0000
2:55637601:T:C	acceptor_loss	1.0000
2:55640621:TTTTA:T	donor_loss	1.0000
2:55640622:TTTA:T	donor_loss	1.0000
2:55640623:TTACC:T	donor_loss	1.0000
2:55640624:TACCT:T	donor_loss	1.0000
2:55640626:C:A	donor_loss	1.0000
2:55640701:TATCT:T	acceptor_gain	1.0000
2:55640704:CT:C	acceptor_gain	1.0000
2:55640705:TCTAC:T	acceptor_loss	1.0000
2:55640706:C:A	acceptor_loss	1.0000

AlphaMissense

5065 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:55636386:A:C	Y735D	0.999
2:55640640:A:G	L712P	0.999
2:55646457:G:C	D544E	0.999
2:55646457:G:T	D544E	0.999
2:55646458:T:G	D544A	0.999
2:55646459:C:G	D544H	0.999
2:55646475:A:C	D538E	0.999
2:55646475:A:T	D538E	0.999
2:55646476:T:A	D538V	0.999
2:55646476:T:C	D538G	0.999
2:55646476:T:G	D538A	0.999
2:55646477:C:G	D538H	0.999
2:55647354:T:A	D532V	0.999
2:55647355:C:G	D532H	0.999
2:55647414:C:T	G512E	0.999
2:55654947:G:A	S483F	0.999
2:55654947:G:T	S483Y	0.999
2:55654953:C:T	G481E	0.999
2:55656131:C:A	G481W	0.999
2:55656306:A:C	H450Q	0.999
2:55656306:A:T	H450Q	0.999
2:55656318:T:A	R446S	0.999
2:55656318:T:G	R446S	0.999
2:55656369:A:C	F429L	0.999
2:55656369:A:T	F429L	0.999
2:55656371:A:G	F429L	0.999
2:55667022:C:T	G382E	0.999
2:55667064:C:A	R368M	0.999
2:55667064:C:G	R368T	0.999
2:55667082:C:G	R362P	0.999

dbSNP variants (sampled 300 via entrez): RS1000029307 (2:55682137 C>T), RS1000079124 (2:55673871 A>T), RS1000109181 (2:55640529 T>C), RS1000191519 (2:55690052 A>G), RS1000244236 (2:55684418 C>T), RS1000283117 (2:55650018 T>C), RS1000320975 (2:55642513 G>A), RS1000337743 (2:55693570 G>C), RS1000374762 (2:55642873 T>G), RS1000380727 (2:55668634 T>C), RS1000403182 (2:55693404 C>A,G,T), RS1000423887 (2:55679644 T>A), RS1000557587 (2:55634993 G>GACCT), RS1000571214 (2:55689322 A>C), RS1000574938 (2:55651645 C>T)

Disease associations

OMIM: gene MIM:610316 | disease phenotypes: MIM:608703, MIM:614932, MIM:614934, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation defect type 13	Definitive	Autosomal recessive
hearing loss disorder	Definitive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 70	Strong	Autosomal dominant
spinocerebellar ataxia type 25	Moderate	Autosomal dominant
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Leigh syndrome	Moderate	AR

Mondo (8): spinocerebellar ataxia type 25 (MONDO:0012103), combined oxidative phosphorylation defect type 13 (MONDO:0013977), autosomal recessive nonsyndromic hearing loss 70 (MONDO:0013978), hereditary ataxia (MONDO:0100309), schizophrenia (MONDO:0005090), neurodevelopmental disorder (MONDO:0700092), hearing loss, autosomal recessive (MONDO:0019588), hearing loss disorder (MONDO:0005365)

Orphanet (5): Spinocerebellar ataxia type 25 (Orphanet:101111), Combined oxidative phosphorylation defect type 13 (Orphanet:319514), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Hereditary ataxia (Orphanet:183518), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000317	Facial myokymia
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000496	Abnormality of eye movement
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000639	Nystagmus
HP:0000657	Oculomotor apraxia
HP:0000762	Decreased nerve conduction velocity
HP:0000763	Sensory neuropathy
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001273	Abnormal corpus callosum morphology
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001751	Abnormal vestibular function

GWAS associations

43 associations (top):

Study	Trait	p-value
GCST000175_37	Height	6.000000e-11
GCST002702_33	Height	1.000000e-25
GCST004137_47	Optic cup area	8.000000e-07
GCST004137_7	Optic cup area	5.000000e-08
GCST004278_86	Pulse pressure	8.000000e-06
GCST005580_236	Intraocular pressure	6.000000e-17
GCST005580_239	Intraocular pressure	8.000000e-17
GCST006065_13	Glaucoma (primary open-angle)	6.000000e-10
GCST006258_26	Diastolic blood pressure	2.000000e-09
GCST006259_34	Systolic blood pressure	3.000000e-06
GCST006291_60	Spherical equivalent or myopia (age of diagnosis)	1.000000e-10
GCST007096_44	Pulse pressure	2.000000e-11
GCST007097_4	Pulse pressure	7.000000e-06
GCST007932_56	Medication use (thyroid preparations)	3.000000e-08
GCST007944_14	Medication use (antiglaucoma preparations and miotics)	5.000000e-08
GCST008161_28	Waist circumference adjusted for body mass index	1.000000e-06
GCST008163_123	Height	7.000000e-06
GCST009724_92	Vertical cup-disc ratio (multi-trait analysis)	1.000000e-19
GCST009725_58	Intraocular pressure	2.000000e-09
GCST009726_18	Glaucoma	6.000000e-06
GCST010002_365	Refractive error	3.000000e-34
GCST010571_11	Autoimmune thyroid disease	4.000000e-09
GCST011946_17	White matter hyperintensity volume	2.000000e-07
GCST011947_19	White matter hyperintensity volume	1.000000e-06
GCST011949_33	White matter hyperintensity volume (adjusted for hypertension)	8.000000e-07
GCST011950_24	White matter hyperintensity volume (adjusted for hypertension)	7.000000e-06
GCST011952_12	White matter hyperintensity volume x hypertension interaction (2df)	3.000000e-06
GCST012226_162	Waist circumference adjusted for body mass index	1.000000e-14
GCST012226_166	Waist circumference adjusted for body mass index	3.000000e-10
GCST012226_167	Waist circumference adjusted for body mass index	6.000000e-16

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004695	intraocular pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0004847	age at onset
EFO:0009933	Thyroid preparation use measurement
EFO:0009944	Antiglaucoma preparations and miotics use measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0006939	cup-to-disc ratio measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D065886	Neurodevelopmental Disorders	F03.625
C564609	Deafness, Autosomal Recessive (supp.)
C531684	Hereditary spinal ataxia (supp.)
C537202	Spinocerebellar ataxia 25 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs13009649	PNPT1		0.00	0
rs13015243	PNPT1		0.00	0

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Acetaminophen	decreases expression, increases expression	3
Arsenic	increases expression, decreases expression, affects cotreatment, increases abundance	2
Estradiol	increases expression	2
Hydrogen Peroxide	affects expression	2
Lipopolysaccharides	increases expression, affects response to substance	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression	2
Particulate Matter	decreases expression, increases expression	2
afuresertib	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F1MB	HyCyte A-549 KO-hPNPT1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
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