PRUNE1

prune exopolyphosphatase 1

Basic information

Region (hg38): 1:151008420-151035713

Previous symbols: [ "PRUNE" ]

Links

ENSG00000143363 ∙ NCBI:58497 ∙ OMIM:617413 ∙ HGNC:13420 ∙ Uniprot:Q86TP1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (Strong), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	26539891; 28211990; 28334956

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRUNE1 gene.

• not provided (2 variants)
• Inborn genetic diseases (2 variants)
• Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRUNE1 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			1	23	3	27
missense		6	33	3	5	47
nonsense	1	1	3			5
start loss						0
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2				3
splice region			3	2		5
non coding		2	2	15	2	21
Total	5	11	39	41	10

Variants in PRUNE1

This is a list of pathogenic ClinVar variants found in the PRUNE1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-151008635-G-A		Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	Likely pathogenic (-)
1-151008634-T-TGGAGG		Inborn genetic diseases	Pathogenic (May 16, 2017)
1-151008662-T-C		PRUNE1-related disorder	Likely benign (Jan 25, 2023)
1-151008666-C-T			Likely benign (Mar 19, 2022)
1-151008668-G-A			Likely benign (May 18, 2023)
1-151008672-G-T			Likely pathogenic (Apr 26, 2023)
1-151008684-T-G			Likely benign (Nov 08, 2022)
1-151017798-T-A			Likely benign (May 03, 2022)
1-151017816-C-T		PRUNE1-related disorder	Benign (Jan 09, 2024)
1-151017819-G-A			Uncertain significance (Mar 20, 2023)
1-151017820-A-AC		Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	Pathogenic (Oct 21, 2022)
1-151017828-A-G		Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	Uncertain significance (Mar 28, 2023)
1-151017843-A-G			Uncertain significance (Oct 03, 2023)
1-151017860-G-A		Abnormal brain morphology • Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	Pathogenic/Likely pathogenic (Oct 13, 2020)
1-151017887-G-C		Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	Uncertain significance (Dec 03, 2018)
1-151017906-T-C		Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	Pathogenic (Sep 21, 2023)
1-151017911-A-G			Uncertain significance (Sep 13, 2022)
1-151017911-A-T			Likely benign (Jul 11, 2022)
1-151017919-G-A			Likely benign (Dec 19, 2023)
1-151017922-G-T			Likely benign (Aug 04, 2023)
1-151018447-C-T			Likely benign (Jun 08, 2022)
1-151018454-C-T			Likely benign (Apr 24, 2023)
1-151018475-G-A			Likely benign (Oct 24, 2022)
1-151018494-C-A		Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	Pathogenic (Sep 19, 2017)
1-151018504-A-G			Uncertain significance (Mar 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRUNE1	protein_coding	protein_coding	ENST00000271620	8	27294

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00915	0.989	125722	0	25	125747	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.11	193	242	0.799	0.0000122	2933
Missense in Polyphen		54	82.829	0.65195		1009
Synonymous	1.34	82	99.0	0.828	0.00000500	935
Loss of Function	2.68	7	19.9	0.352	0.00000113	220

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000362	0.000362
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000109	0.000109
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:28334956). Involved in the regulation of microtubule polymerization (PubMed:28334956). {ECO:0000269|PubMed:10602478, ECO:0000269|PubMed:11687967, ECO:0000269|PubMed:14998490, ECO:0000269|PubMed:16428445, ECO:0000269|PubMed:17906697, ECO:0000269|PubMed:28334956}.
• Pathway: Purine metabolism - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.63

Haploinsufficiency Scores

• pHI: 0.175
• hipred: Y
• hipred_score: 0.528
• ghis: 0.489

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Prune1
• 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); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: polyphosphate catabolic process;dephosphorylation;regulation of microtubule polymerization;regulation of neurogenesis
• Cellular component: nucleus;cytoplasm;cytosol;focal adhesion
• Molecular function: exopolyphosphatase activity;inorganic diphosphatase activity;protein binding;tubulin binding;phosphatase activity;metal ion binding