PIWIL4

piwi like RNA-mediated gene silencing 4, the group of Piwi like RNA-mediated gene silencing family

Basic information

Region (hg38): 11:94543840-94621421

Links

ENSG00000134627 ∙ NCBI:143689 ∙ OMIM:610315 ∙ HGNC:18444 ∙ Uniprot:Q7Z3Z4 ∙ 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 PIWIL4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIWIL4 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				3	2	5
missense			41	4	2	47
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding						0
Total	0	0	41	7	4

Variants in PIWIL4

This is a list of pathogenic ClinVar variants found in the PIWIL4 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-94544173-G-T		not specified	Uncertain significance (May 30, 2023)
11-94544174-C-G		not specified	Uncertain significance (Apr 13, 2023)
11-94544177-G-C		not specified	Uncertain significance (Sep 16, 2021)
11-94544188-G-C		not specified	Uncertain significance (Jun 02, 2023)
11-94544212-G-A		not specified	Likely benign (Oct 13, 2023)
11-94544227-T-G		not specified	Uncertain significance (Jul 09, 2021)
11-94544233-C-T		not specified	Likely benign (Apr 06, 2023)
11-94544241-C-T			Likely benign (Jun 20, 2018)
11-94544295-A-C			Benign (Aug 15, 2018)
11-94544303-T-C		not specified	Uncertain significance (Jan 27, 2022)
11-94544357-G-A		not specified	Uncertain significance (Sep 01, 2021)
11-94544393-G-C		not specified	Uncertain significance (Dec 13, 2023)
11-94544398-A-T		not specified	Uncertain significance (May 31, 2023)
11-94544408-G-T		not specified	Likely benign (Nov 29, 2023)
11-94544416-C-G		not specified	Uncertain significance (Feb 23, 2023)
11-94544441-A-G		not specified	Uncertain significance (Aug 17, 2022)
11-94544446-C-G		not specified	Uncertain significance (Jun 02, 2024)
11-94544476-T-C		not specified	Likely benign (Sep 16, 2021)
11-94544494-C-G		not specified	Uncertain significance (Feb 28, 2023)
11-94544495-T-G		not specified	Uncertain significance (Feb 28, 2023)
11-94544532-G-A			Likely benign (Feb 26, 2018)
11-94544560-T-G		not specified	Uncertain significance (Jun 18, 2021)
11-94544573-G-A		not specified	Uncertain significance (May 24, 2023)
11-94544612-G-A		not specified	Uncertain significance (Jun 09, 2022)
11-94544632-A-T		not specified	Uncertain significance (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIWIL4	protein_coding	protein_coding	ENST00000299001	20	77582

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000183	1.00	125690	1	57	125748	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.49	377	468	0.806	0.0000248	5578
Missense in Polyphen		79	109.26	0.72306		1269
Synonymous	1.14	151	170	0.889	0.00000911	1587
Loss of Function	3.79	18	45.6	0.395	0.00000217	562

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.00101
Ashkenazi Jewish	0.00	0.00
East Asian	0.000383	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.000383	0.000381
South Asian	0.000610	0.000555
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (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 governs the methylation and subsequent repression of transposons (By similarity). Directly binds 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 (By similarity). Associates with secondary piRNAs antisense and PIWIL2/MILI is required for such association (By similarity). The piRNA process acts upstream of known mediators of DNA methylation (By similarity). Does not show endonuclease activity (By similarity). Plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle, by acting as a 'slicer-incompetent' component that loads cleaved piRNAs from the 'slicer-competent' component PIWIL2 and target them on genomic transposon loci in the nucleus (By similarity). May be involved in the chromatin-modifying pathway by inducing 'Lys-9' methylation of histone H3 at some loci (PubMed:17544373). {ECO:0000250|UniProtKB:Q8CGT6, ECO:0000269|PubMed:17544373}.
• Pathway: Gene expression (Transcription);PIWI-interacting RNA (piRNA) biogenesis;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.0924

Intolerance Scores

• loftool: 0.789
• rvis_EVS: 1.27
• rvis_percentile_EVS: 93.63

Haploinsufficiency Scores

• pHI: 0.0953
• hipred: N
• hipred_score: 0.322
• ghis: 0.400

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.771

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Piwil4
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: regulation of translation;multicellular organism development;spermatogenesis;negative regulation of transposition;epithelial structure maintenance;cell differentiation;gene silencing by RNA;piRNA metabolic process;DNA methylation involved in gamete generation;meiotic cell cycle;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: nucleus;cytoplasm;P granule;piP-body
• Molecular function: endoribonuclease activity;piRNA binding