PRUNE1 (prune exopolyphosphatase 1)

Gene

• Entrez ID: 58497
• Gene name: Prune exopolyphosphatase 1
• Gene symbol: PRUNE1
• Synonyms (NCBI Gene): DRES-17, DRES17, H-PRUNE, HTCD37, NMIHBA, PRUNE
• Chromosome: 1
• Chromosome location: 1q21.3
• Summary: This gene encodes a member of the DHH protein superfamily of phosphoesterases. This protein has been found to function as both a nucleotide phosphodiesterase and an exopolyphosphatase. This protein is believed to stimulate cancer progression and metastase

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137929776	C>T	Pathogenic	5 prime UTR variant, intron variant, stop gained, coding sequence variant
rs200618384	G>C,T	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained, intron variant, 5 prime UTR variant, missense variant
rs752599948	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, intron variant, missense variant
rs767769359	G>A,C,T	Pathogenic, likely-pathogenic	Intron variant, missense variant, coding sequence variant, 5 prime UTR variant
rs773618224	G>A	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant, intron variant, synonymous variant
rs886039608	A>G	Pathogenic, likely-pathogenic	Splice acceptor variant, intron variant
rs1057521927	G>A	Likely-pathogenic, pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant, intron variant, non coding transcript variant
rs1085308033	C>A	Pathogenic	5 prime UTR variant, missense variant, intron variant, coding sequence variant
rs1553253812	G>-	Pathogenic	Intron variant, frameshift variant, coding sequence variant, non coding transcript variant
rs1553254265	T>C	Likely-pathogenic	Intron variant, coding sequence variant, missense variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT439887	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT439887	hsa-miR-218-5p	HITS-CLIP	23212916

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004309	Function	Exopolyphosphatase activity	IBA
GO:0004427	Function	Inorganic diphosphate phosphatase activity	IEA
GO:0005515	Function	Protein binding	IPI	10602478, 17906697, 33961781
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005925	Component	Focal adhesion	IEA
GO:0015631	Function	Tubulin binding	IDA	28334956
GO:0016462	Function	Pyrophosphatase activity	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016791	Function	Phosphatase activity	IDA	28334956
GO:0031113	Process	Regulation of microtubule polymerization	IMP	28334956
GO:0046872	Function	Metal ion binding	IEA
GO:0050767	Process	Regulation of neurogenesis	IMP	28334956
GO:0070161	Component	Anchoring junction	IEA

Other IDs

• MIM: 617413
• HGNC: 13420
• e!Ensembl: ENSG00000143363

Protein

• UniProt ID: Q86TP1
• Protein name: Exopolyphosphatase PRUNE1 (EC 3.6.1.1) (Drosophila-related expressed sequence 17) (DRES-17) (DRES17) (HTcD37) (Protein prune homolog 1) (hPrune)
• Protein function: Phosphodiesterase (PDE) that has higher activity toward cAMP than cGMP, as substrate. Plays a role in cell proliferation, migration and differentiation, and acts as a negative regulator of NME1. Plays a role in the regulation of neurogenesis (Pu
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01368	DHH	19 → 176	DHH family	Family
  PF02833	DHHA2	216 → 358	DHHA2 domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed. Seems to be overexpressed in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas. {ECO:0000269|PubMed:10602478, ECO:000026
• Sequence:

  MEDYLQGCRAALQESRPLHVVLGNEACDLDSTVSALALAFYLAKTTEAEEVFVPVLNIKR
  SELPLRGDIVFFLQKVHIPESILIFRDEIDLHALYQAGQLTLILVDHHILSKSDTALEEA
  VAEVLDHRPIEPKHCPPCHVSVELVGSCATLVTERILQGAPEILDRQTAALLHGTIILDC
  VNMDLKIGKATPKDSKYVEKLEALFPDLPKRNDIFDSLQKAKFDVSGLTTEQMLRKDQKT
  IYRQGVKVAISAIYMDLEAFLQRSNLLADLHAFCQAHSYDVLVAMTIFFNTHNEPVRQLA
  IFCPHVALQTTICEVLERSHSPPLKLTPASSTHPNLHAYLQGNTQVSRKKLLPLLQEALS
  AYFDSMKIPSGQPETADVSREQVDKELDRASNSLISGLSQDEEDPPLPPTPMNSLVDECP
  LDQGLPKLSAEAVFEKCSQISLSQSTTASLSKK

• Sequence length: 453

Pathways

KEGG:

Purine metabolism
Metabolic pathways

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormal brain morphology	Likely pathogenic; Pathogenic	rs1057521927, rs767769359, rs773618224, rs200618384	RCV000454192 RCV000454286 RCV000454333 RCV000454323	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	Likely pathogenic; Pathogenic	rs1232331611, rs2102908451, rs1456845940, rs2528381693, rs886039608, rs1057521927, rs767769359, rs773618224, rs200618384, rs1085308033, rs752599948, rs137929776, rs1674200670	RCV001542543 RCV002293291 RCV002293292 RCV002293293 RCV000490536 RCV000490538 RCV000490541 RCV000490535 RCV000490537 RCV000490539 RCV000490542 RCV004689765 RCV001200669	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
PRUNE1-related disorder	Likely pathogenic	rs886039608, rs587684563	RCV003897593 RCV003899192	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Squamous cell lung carcinoma	Likely pathogenic	rs886039608	RCV005895450	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
GESTATIONAL DIABETES	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adult Medulloblastoma	Medulloblastoma	BEFREE	29490009		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic lateral sclerosis	Pubtator	32134588	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	32134588, 35379233	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	11687967, 15671547, 17906697		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	14998490, 20735841	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	30665854	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	35379233	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral cortical atrophy	Cerebral cortical atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral Palsy	Cerebral palsy	Pubtator	35379233	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Palsy Spastic Quadriplegic 2	Cerebral palsy	Pubtator	35379233	Associate	★☆☆☆☆ Found in Text Mining only
Childhood Medulloblastoma	Medulloblastoma	BEFREE	29490009		★☆☆☆☆ Found in Text Mining only
Congenital anomaly of brain	Brain malformation	BEFREE	28211990, 30556349		★☆☆☆☆ Found in Text Mining only
Congenital clubfoot	Congenital Clubfoot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	29307700		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	32134588, 35379233	Associate	★☆☆☆☆ Found in Text Mining only
Exophthalmos	Proptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
leiomyosarcoma	Leiomyosarcoma	BEFREE	11687967		★☆☆☆☆ Found in Text Mining only
liposarcoma	Liposarcoma	BEFREE	11687967		★☆☆☆☆ Found in Text Mining only
Macrotia	Macrotia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant Fibrous Histiocytoma	Malignant Histiocytoma	BEFREE	11687967		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	15671547, 17906697		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	17952613		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	29449633		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	15671547		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	BEFREE	29490009		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	28334956, 30556349		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	28334956, 32134588, 35379233	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Muscular Atrophy Spinal	Spinal muscular atrophy	Pubtator	32134588	Associate	★☆☆☆☆ Found in Text Mining only
Nervous System Diseases	Nervous system disease	Pubtator	28334956	Associate	★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	11687967, 23448979		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	32134588	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	29307700, 30556349		★☆☆☆☆ Found in Text Mining only
NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, HYPOTONIA, AND VARIABLE BRAIN ANOMALIES	Neurodevelopmental Disorder With Microcephaly, Hypotonia, And Variable Brain Anomalies	UNIPROT_DG	26539891, 28211990, 28334956		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, HYPOTONIA, AND VARIABLE BRAIN ANOMALIES	Neurodevelopmental Disorder With Microcephaly, Hypotonia, And Variable Brain Anomalies	GENOMICS_ENGLAND_DG	28334956		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, HYPOTONIA, AND VARIABLE BRAIN ANOMALIES	Neurodevelopmental Disorder With Microcephaly, Hypotonia, And Variable Brain Anomalies	BEFREE	29797509		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, HYPOTONIA, AND VARIABLE BRAIN ANOMALIES	Neurodevelopmental Disorder With Microcephaly, Hypotonia, And Variable Brain Anomalies	ORPHANET_DG	30556349		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, HYPOTONIA, AND VARIABLE BRAIN ANOMALIES	Neurodevelopmental Disorder With Microcephaly, Hypotonia, And Variable Brain Anomalies	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	30556349		★☆☆☆☆ Found in Text Mining only
Plagiocephaly	Plagiocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Profound global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
PRUNE1-related neurological syndrome	Neurological Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Sarcoma	Sarcoma	BEFREE	11687967		★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	32134588	Associate	★☆☆☆☆ Found in Text Mining only
Spastic tetraparesis	Spastic tetraparesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	17532757	Associate	★☆☆☆☆ Found in Text Mining only