PIWIL1

piwi like RNA-mediated gene silencing 1, the group of Piwi like RNA-mediated gene silencing family

Basic information

Region (hg38): 12:130337887-130372637

Links

ENSG00000125207 ∙ NCBI:9271 ∙ OMIM:605571 ∙ HGNC:9007 ∙ Uniprot:Q96J94 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PIWIL1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIWIL1 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				8	5	13
missense			31	2	1	34
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	2	5
non coding					1	1
Total	0	1	31	10	7

Variants in PIWIL1

This is a list of pathogenic ClinVar variants found in the PIWIL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-130342609-A-G		PIWIL1-related disorder	Benign (Dec 31, 2019)
12-130342644-C-T		not specified	Uncertain significance (Mar 31, 2024)
12-130342661-T-A		not specified	Uncertain significance (Oct 22, 2021)
12-130342661-T-C		not specified	Uncertain significance (Jun 07, 2024)
12-130342662-C-A		not specified	Uncertain significance (Jun 07, 2024)
12-130342662-C-G		not specified	Uncertain significance (Jan 26, 2022)
12-130342677-C-T		PIWIL1-related disorder	Likely benign (Jul 16, 2019)
12-130343005-T-G		PIWIL1-related disorder	Likely benign (Feb 21, 2019)
12-130343032-C-A		not specified	Uncertain significance (Sep 06, 2022)
12-130343043-G-T		PIWIL1-related disorder	Likely benign (Aug 16, 2023)
12-130343063-G-A		not specified	Uncertain significance (Jun 16, 2024)
12-130345740-A-AT		PIWIL1-related disorder	Likely benign (Mar 20, 2019)
12-130345810-G-A		not specified	Uncertain significance (Jul 26, 2022)
12-130345834-T-C		not specified	Uncertain significance (Jan 17, 2024)
12-130345841-A-G		PIWIL1-related disorder	Likely benign (Apr 24, 2019)
12-130345856-C-T		PIWIL1-related disorder	Likely benign (Aug 07, 2019)
12-130346361-C-T		PIWIL1-related disorder	Benign (Nov 11, 2019)
12-130346398-C-T		PIWIL1-related disorder	Likely benign (Sep 11, 2019)
12-130346436-C-T		not specified	Uncertain significance (Nov 17, 2023)
12-130346471-A-G		not specified	Uncertain significance (Mar 01, 2024)
12-130346477-G-T		not specified	Uncertain significance (Jan 10, 2022)
12-130346513-G-A		not specified	Uncertain significance (Feb 11, 2022)
12-130346963-C-T		not specified	Uncertain significance (Feb 21, 2024)
12-130346968-A-G		not specified	Uncertain significance (Oct 27, 2021)
12-130346990-C-T		not specified	Uncertain significance (Dec 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIWIL1	protein_coding	protein_coding	ENST00000245255	20	34751

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.28e-14	0.998	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.90	310	491	0.631	0.0000273	5631
Missense in Polyphen		99	183.43	0.53972		2138
Synonymous	-0.249	179	175	1.02	0.00000976	1631
Loss of Function	2.92	30	53.0	0.567	0.00000303	585

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000414	0.000414
Ashkenazi Jewish	0.000204	0.000198
East Asian	0.000274	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000326	0.000325
Middle Eastern	0.000274	0.000272
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Endoribonuclease that plays a central role in postnatal germ cells by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. 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 governs the methylation and subsequent repression of transposons. Directly binds methylated piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Strongly prefers a uridine in the first position of their guide (g1U preference, also named 1U-bias). Not involved in the piRNA amplification loop, also named ping-pong amplification cycle. Acts as an endoribonuclease that cleaves transposon messenger RNAs. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Probable component of some RISC complex, which mediates RNA cleavage and translational silencing. Also plays a role in the formation of chromatoid bodies and is required for some miRNAs stability. Required to sequester RNF8 in the cytoplasm until late spermatogenesis; RNF8 being released upon ubiquitination and degradation of PIWIL1. {ECO:0000250|UniProtKB:Q9JMB7}.
• Disease: DISEASE: Note=Defects in PIWIL1 may be a cause of a disorder resulting in the absence of sperm (azoospermia) in the semen, leading to male infertility. Male sterility can be caused by defects in ubiquitination and degradation during late spermatogenesis. {ECO:0000269|PubMed:28552346}.
• Pathway: Gene expression (Transcription);PIWI-interacting RNA (piRNA) biogenesis;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.0992

Intolerance Scores

• loftool: 0.822
• rvis_EVS: -0.46
• rvis_percentile_EVS: 23.57

Haploinsufficiency Scores

• pHI: 0.276
• hipred: Y
• hipred_score: 0.627
• ghis: 0.383

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.537

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Piwil1
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: piwil1
• Affected structure: germ line cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of translation;multicellular organism development;spermatogenesis;spermatid development;negative regulation of transposition;gene silencing by RNA;piRNA metabolic process;spermatogenesis, exchange of chromosomal proteins;meiotic cell cycle;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: nucleus;cytoplasm;chromatoid body;P granule;dense body
• Molecular function: single-stranded RNA binding;mRNA binding;endoribonuclease activity;protein binding;protein kinase binding;piRNA binding;metal ion binding;mRNA cap binding complex binding;polysome binding