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.

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.

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						0
missense			79	8		87
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	79	8	0

Variants in PIWIL2

This is a list of pathogenic ClinVar variants found in the PIWIL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-22279403-C-G		not specified	Uncertain significance (Oct 09, 2024)
8-22279415-G-A		not specified	Uncertain significance (Aug 15, 2023)
8-22279453-C-T		not specified	Uncertain significance (Oct 19, 2024)
8-22279477-G-A		not specified	Uncertain significance (Oct 12, 2021)
8-22279486-C-A		not specified	Uncertain significance (Dec 01, 2022)
8-22279529-G-C		not specified	Uncertain significance (Aug 02, 2022)
8-22279577-C-T		not specified	Uncertain significance (Dec 16, 2023)
8-22281129-G-T		not specified	Uncertain significance (Dec 30, 2023)
8-22281148-G-A		not specified	Uncertain significance (Jan 17, 2024)
8-22281195-A-G		not specified	Conflicting classifications of pathogenicity (Oct 20, 2024)
8-22281398-G-T		not specified	Uncertain significance (Mar 07, 2024)
8-22281418-C-T		not specified	Uncertain significance (Jun 30, 2022)
8-22281419-G-A		not specified	Likely benign (Feb 16, 2023)
8-22281429-G-C		not specified	Uncertain significance (Apr 26, 2023)
8-22281435-A-C		not specified	Uncertain significance (Jan 24, 2025)
8-22281457-C-T		not specified	Uncertain significance (Jul 27, 2024)
8-22281470-C-T		not specified	Uncertain significance (Apr 12, 2022)
8-22281478-G-T		not specified	Uncertain significance (Jun 09, 2022)
8-22281487-A-G		not specified	Uncertain significance (Mar 21, 2023)
8-22283036-C-T		not specified	Likely benign (Jul 14, 2021)
8-22283059-G-T		not specified	Uncertain significance (Feb 09, 2025)
8-22283060-C-T		not specified	Likely benign (Mar 01, 2023)
8-22283120-C-T		not specified	Uncertain significance (Feb 24, 2025)
8-22283134-A-G		not specified	Likely benign (Aug 02, 2023)
8-22283144-G-A		not specified	Uncertain significance (Sep 22, 2022)

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