PRUNE2

protein-coding

prune homolog 2 with BCH domain, the group of BCH domain containing

Gene summary

The protein encoded by this gene belongs to the B-cell CLL/lymphoma 2 and adenovirus E1B 19 kDa interacting family, whose members play roles in many cellular processes including apotosis, cell transformation, and synaptic function. Several functions for this protein have been demonstrated including suppression of Ras homolog family member A activity, which results in reduced stress fiber formation and suppression of oncogenic cellular transformation. A high molecular weight isoform of this protein has also been shown to colocalize with Adaptor protein complex 2, beta-Adaptin and endodermal markers, suggesting an involvement in post-endocytic trafficking. In prostate cancer cells, this gene acts as a tumor suppressor and its expression is regulated by prostate cancer antigen 3, a non-protein coding gene on the opposite DNA strand in an intron of this gene. Prostate cancer antigen 3 regulates levels of this gene through formation of a double-stranded RNA that undergoes adenosine deaminase actin on RNA-dependent adenosine-to-inosine RNA editing. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

Previous symbols:

C9orf65
KIAA0367

MANE transcript

NM_015225.3

Inheritance

—

ClinVar variants

U:444B:71

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr9:76,611,376-76,906,114

External References & Databases

Ensembl (ENSG00000106772)

Transcript & Mutation Effects

hg38 • Region Span ~294.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRUNE2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 463

not providedTotal: 40

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015225.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	10 clinvar	8 clinvar	20
missense			435 clinvar	45 clinvar	8 clinvar	488
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	444	55	16	515

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015225.3	RefSeq	NP_056040.2	19	MANE Select
ENST00000376718.8	Ensembl	ENSP00000365908.3	19	MANE Select
NM_001308047.2	RefSeq	NP_001294976.1	18	Standard
NM_001308048.2	RefSeq	NP_001294977.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

polyphosphate catabolic process
apoptotic process

Molecular Function

exopolyphosphatase activity
metal ion binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376718
Coding exons: 19
Length: 294712
Individuals with no LoFs: 125185
Homozygous LoFs: 1
Heterozygous LoFs: 562
Defined: 125748
p: 0.00224

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.540	1534	1.59e+3	0.962	0.0000813	20440
Missense (PolyPhen)		383	441.2	0.86809		5831
Synonymous	-0.163	619	614	1.01	0.0000352	5858
Loss of Function	4.02	62	107	0.580	0.00000527	1406

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.00062	0.00061	rare
Ashkenazi Jewish	0.0019	0.0018	notable
East Asian	0.00089	0.00087	rare
Finnish	0.0093	0.0091	notable
European (Non-Finnish)	0.0021	0.0020	notable
South Asian	0.0017	0.0016	notable
Other	0.0021	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play an important role in regulating differentiation, survival and aggressiveness of the tumor cells. {ECO:0000269|PubMed:16288218}.;

Recessive Scores

pRec: 0.0780

Intolerance Scores

LoFtool: 0.952
RVIS EVS: 2.78
RVIS percentile EVS: 99.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.334

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High