PIWIL2

piwi like RNA-mediated gene silencing 2, the group of Piwi like RNA-mediated gene silencing family

Basic information

Region (hg38): 8:22275316-22357568

Links

ENSG00000197181

∙ NCBI:55124 ∙ OMIM:610312 ∙ HGNC:17644 ∙ Uniprot:Q8TC59 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

male infertility with azoospermia or oligozoospermia due to single gene mutation (Strong), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PIWIL2 gene.

not_specified (130 variants)
not_provided (4 variants)
Male_infertility (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIWIL2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018068.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			125 clinvar	9 clinvar		134
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	125	9	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIWIL2	protein_coding	protein_coding	ENST00000356766	22	82267

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.71e-8	1.00	125656	0	92	125748	0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.119	553	545	1.01	0.0000293	6384
Missense in Polyphen		100	147.89	0.67619		1730
Synonymous	-0.153	201	198	1.01	0.0000107	1888
Loss of Function	3.85	22	52.0	0.423	0.00000275	600

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000578	0.000578
Ashkenazi Jewish	0.000894	0.000893
East Asian	0.000163	0.000163
Finnish	0.00166	0.00166
European (Non-Finnish)	0.000203	0.000202
Middle Eastern	0.000163	0.000163
South Asian	0.0000653	0.0000653
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

Function: FUNCTION: Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (By similarity). Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells (By similarity). Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons (By similarity). During piRNA biosynthesis, plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle, by acting as a 'slicer- competent' piRNA endoribonuclease that cleaves primary piRNAs, which are then loaded onto 'slicer-incompetent' PIWIL4 (By similarity). PIWIL2 slicing produces a pre-miRNA intermediate, which is then processed in mature piRNAs, and as well as a 16 nucleotide by-product that is degraded (By similarity). Required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense (By similarity). Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (By similarity). Indirectly modulates expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8 (By similarity). When overexpressed, acts as an oncogene by inhibition of apoptosis and promotion of proliferation in tumors (PubMed:16377660). {ECO:0000250|UniProtKB:Q8CDG1, ECO:0000269|PubMed:16377660}.;
Pathway: Gene expression (Transcription);PIWI-interacting RNA (piRNA) biogenesis;Gene Silencing by RNA (Consensus)

Recessive Scores

pRec: 0.0867

Intolerance Scores

loftool: 0.817
rvis_EVS: -0.35
rvis_percentile_EVS: 29.61

Haploinsufficiency Scores

pHI: 0.0667
hipred: N
hipred_score: 0.466
ghis: 0.472

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.215

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Piwil2
Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; reproductive system phenotype;

Zebrafish Information Network

Gene name: piwil2
Affected structure: post-vent region
Phenotype tag: abnormal
Phenotype quality: decreased length

Gene ontology

Biological process: RNA 5'-end processing;multicellular organism development;spermatogenesis;negative regulation of transposition;germ-line stem cell population maintenance;gene silencing by RNA;piRNA metabolic process;DNA methylation involved in gamete generation;positive regulation of translation;oogenesis;meiotic cell cycle;positive regulation of meiosis I;positive regulation of histone H3-K14 acetylation;RNA phosphodiester bond hydrolysis, endonucleolytic;piRNA biosynthetic process;positive regulation of histone H3-K9 acetylation
Cellular component: nucleus;cytoplasm;perinucleolar chromocenter;chromatoid body;P granule;pi-body;dense body;PET complex
Molecular function: mRNA binding;endoribonuclease activity;piRNA binding;metal ion binding;polysome binding