PIWIL4

Summary

PIWIL4 (piwi like RNA-mediated gene silencing 4, HGNC:18444) is a protein-coding gene on chromosome 11q21, encoding Piwi-like protein 4 (Q7Z3Z4). Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity.

PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).

Source: NCBI Gene 143689 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 138 total
• MANE Select transcript: NM_152431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18444
Approved symbol	PIWIL4
Name	piwi like RNA-mediated gene silencing 4
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36156, HIWI2, Miwi2
Ensembl gene	ENSG00000134627
Ensembl biotype	protein_coding
OMIM	610315
Entrez	143689

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 nonsense_mediated_decay

ENST00000299001, ENST00000446230, ENST00000537419, ENST00000543336, ENST00000545603

RefSeq mRNA: 1 — MANE Select: NM_152431 NM_152431

CCDS: CCDS31656

Canonical transcript exons

ENST00000299001 — 20 exons

Exon	Start	End
ENSE00000915750	94583448	94583569
ENSE00000915754	94593518	94593641
ENSE00000915755	94595309	94595426
ENSE00001099044	94577278	94577492
ENSE00001195411	94589121	94589232
ENSE00001195418	94587050	94587247
ENSE00001195421	94585445	94585525
ENSE00001262088	94597804	94597915
ENSE00001335558	94567368	94567605
ENSE00001718590	94603984	94604056
ENSE00001785165	94608583	94608686
ENSE00002317659	94601795	94601979
ENSE00003458792	94617954	94618107
ENSE00003466022	94568730	94568808
ENSE00003525117	94619997	94620144
ENSE00003547350	94619760	94619885
ENSE00003555840	94620876	94621421
ENSE00003563525	94574999	94575130
ENSE00003607961	94616493	94616563
ENSE00003619193	94607439	94607639

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 93.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1990 / max 23.2282, expressed in 52 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116264	0.1853	47
206418	0.0137	5

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.06	gold quality
bone marrow	UBERON:0002371	86.11	gold quality
body of pancreas	UBERON:0001150	84.03	gold quality
bone marrow cell	CL:0002092	83.59	gold quality
trabecular bone tissue	UBERON:0002483	82.83	gold quality
tibia	UBERON:0000979	82.28	gold quality
calcaneal tendon	UBERON:0003701	81.36	gold quality
mucosa of transverse colon	UBERON:0004991	81.32	gold quality
ascending aorta	UBERON:0001496	80.98	gold quality
thoracic aorta	UBERON:0001515	80.86	gold quality
jejunal mucosa	UBERON:0000399	80.10	gold quality
transverse colon	UBERON:0001157	79.92	gold quality
aorta	UBERON:0000947	79.65	gold quality
descending thoracic aorta	UBERON:0002345	79.60	gold quality
pancreas	UBERON:0001264	79.46	gold quality
testis	UBERON:0000473	79.31	gold quality
monocyte	CL:0000576	79.12	gold quality
mucosa of stomach	UBERON:0001199	79.08	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.04	gold quality
tibial artery	UBERON:0007610	78.96	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.95	gold quality
popliteal artery	UBERON:0002250	78.94	gold quality
right testis	UBERON:0004534	78.78	gold quality
leukocyte	CL:0000738	78.72	gold quality
colonic mucosa	UBERON:0000317	78.68	gold quality
duodenum	UBERON:0002114	78.59	gold quality
ileal mucosa	UBERON:0000331	78.19	gold quality
small intestine	UBERON:0002108	78.03	gold quality
body of stomach	UBERON:0001161	78.00	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	4.14
E-ANND-3	no	5.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting PIWIL4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-12113	99.32	67.54	1072

Literature-anchored findings (GeneRIF, showing 21)

• PIWIL4 plays important roles in the chromatin-modifying pathway in human somatic cells (PMID:17544373)
• EIF2C2-4 and PIWIL4 appear increased in advanced tumors with distant metastasis, suggesting they may promote tumor invasion (PMID:20146808)
• An SNP in the 3’untranslated region of HIWI2 and a non-synonymous SNP in HIWI3 were significantly associated with an altered risk of oligozoospermia. (PMID:20940137)
• PIWIL4 might play an oncogenic role in cervical cancer (PMID:22483988)
• we identified a significant association between the expression of Piwi-like 2 and 4 mRNAs and the tumor-specific survival of soft tissue sarcoma patients. (PMID:22748119)
• Data suggest that MIWI2 and MIWI2-associated piRNAs have functions beyond TE suppression. (PMID:24464225)
• associations were determined between the Piwi-like family member expression levels and clinicopathological parameters of ccRCC, suggesting a potential role for these genes/proteins in ccRCC diagnostics and tumorigenesis (PMID:24509249)
• study to evaluate frequency of PIWIL4 genetic variants in order to better define the relationship between PIWIL4 SNPs and defective spermatogenesis and specific spermatogenic disorders; results suggest genetic and epigenetic alterations that affect the PIWI pathway contribute to unsuccessful sperm production (PMID:24969058)
• Immunoprecipitation of Hiwi2 from MDAMB231 cancer cells enriches for piRNAs that are predominantly derived from processed tRNAs and expressed genes. (PMID:25038252)
• Results show that three CpG loci within FYN were hypermethylated in obese individuals, while obesity was associated with lower methylation of CpG loci within PIWIL4 and TAOK3. (PMID:26646899)
• PIWIL4 is highly expressed in both breast cancer tissues and the cytoplasm of MDA-MB-231 cells derived from breast cancer. Reducing PIWIL4 expression drastically impairs the migration ability of MDA-MB-231 cells, significantly increases their apoptosis, and mildly affects their proliferation. (PMID:26957540)
• PIWIL2 and PIWIL4 genes expression in synovial fibroblasts of the rheumatoid arthritis patients.PIWIL4 does not regulate methylation or expression of LINE-1. (PMID:27893851)
• Results revealed that Piwil4 exhibits lower expression in the cell nucleus than in the cytoplasm. Along with nuclear location of PIWIL2, PIWIL4 expression is associated with worse prognosis of hepatocellular carcinoma. (PMID:27894076)
• study demonstrates the presence of PIWI-like proteins in somatic cells and the possible role of HIWI2 in preserving the functional integrity of epithelial cells probably by modulating the phosphorylation status of Akt. (PMID:28025795)
• HIWI2 is aberrantly expressed in cells of the Retinoblastoma (RB) line (Y79) and silencing of HIWI2 downregulates OTX2, suggesting that HIWI2 might affects cell cycle and plays a role in the progression of RB. (PMID:28861107)
• data delineate MIWI2-dependent functions outside of the germline and demonstrate the presence of distinct subsets of airway multiciliated cells that can be discriminated by MIWI2 expression. (PMID:28920925)
• these findings revealed that Piwil4 is a novel regulator of ER signaling that could be targeted to inhibit breast cancer growth and migration. (PMID:30226541)
• PIWIL4 Maintains HIV-1 Latency by Enforcing Epigenetically Suppressive Modifications on the 5’ Long Terminal Repeat. (PMID:32161174)
• Role of PIWI-like 4 in modulating neuronal differentiation from human embryonal carcinoma cells. (PMID:32372724)
• HIWI2 induces G2/M cell cycle arrest and apoptosis in human fibrosarcoma via the ROS/DNA damage/p53 axis. (PMID:35074406)
• A noncanonical enzymatic function of PIWIL4 maintains genomic integrity and leukemic growth in AML. (PMID:37146239)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Piwil4	ENSMUSG00000036912
rattus_norvegicus	Piwil4	ENSRNOG00000009043
drosophila_melanogaster	aub	FBGN0000146
drosophila_melanogaster	piwi	FBGN0004872
caenorhabditis_elegans	prg-1	WBGENE00004178

Paralogs (3): PIWIL1 (ENSG00000125207), PIWIL3 (ENSG00000184571), PIWIL2 (ENSG00000197181)

Protein

Protein identifiers

Piwi-like protein 4 — Q7Z3Z4 (reviewed: Q7Z3Z4)

All UniProt accessions (4): A0A140VKG8, Q7Z3Z4, F5GX26, F5H116

UniProt curated annotations — full annotation on UniProt →

Function. Plays a central role during spermatogenesis 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. The PIWIL4-piRNA pathway acts in the nucleus and mediates silencing of active transposons: engages with nascent transposable element transcripts and governs the piRNA-directed DNA methylation and subsequent repression of transposons. In contrast to PIWIL1 and PIWIL2, does not show endonuclease activity. 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. Associates with secondary piRNAs antisense and PIWIL2/MILI is required for such association. The piRNA process acts upstream of known mediators of DNA methylation. 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. May be involved in the chromatin-modifying pathway by inducing ‘Lys-9’ methylation of histone H3 at some loci. In addition to its role in germline, PIWIL4 also plays a role in the regulation of somatic cells activities. Plays a role in pancreatic beta cell function and insulin secretion. Involved in maintaining cell morphology and functional integrity of retinal epithelial through Akt/GSK3alpha/beta signaling pathway. When overexpressed, acts as an oncogene by inhibition of apoptosis and promotion of cells proliferation in tumors.

Subunit / interactions. Interacts with PRMT5 and WDR77. Interacts (when methylated on arginine residues) with TDRD1, TDRKH/TDRD2 and TDRD9. Interacts with MOV10L1. Interacts with TEX15 and SPOCD1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitously expressed. Detected in retina, retinal pigment epithelia cells (RPE) (at protein level).

Post-translational modifications. Arginine methylation by PRMT5 is required for the interaction with Tudor domain-containing protein (TDRD1, TDRKH/TDRD2 and TDRD9) and subsequent localization to the meiotic nuage, also named P granule.

Induction. Up-regulated in vitreous aspirates of patients with proliferative diabetic retinopathies (at protein level). Up-regulated after exposure to oxidative stress and VEGF in adult retinal pigment epithelial cell line (ARPE19 cells). Up-regulated in cervical cancer tissues.

Similarity. Belongs to the argonaute family. Piwi subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z3Z4-1	1	yes
Q7Z3Z4-2	2
Q7Z3Z4-3	3

RefSeq proteins (1): NP_689644* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003100	PAZ_dom	Domain
IPR003165	Piwi	Domain
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR036085	PAZ_dom_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily

Pfam: PF02170, PF02171, PF23278

UniProt features (19 total): sequence conflict 5, sequence variant 4, splice variant 4, domain 2, compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z3Z4-F1	85.84	0.66

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5601884	PIWI-interacting RNA (piRNA) biogenesis
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)

MSigDB gene sets: 116 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, TTTGTAG_MIR520D, KEGG_DORSO_VENTRAL_AXIS_FORMATION, GOBP_MALE_GAMETE_GENERATION, BOYLAN_MULTIPLE_MYELOMA_D_DN, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, GOMF_RNA_ENDONUCLEASE_ACTIVITY, GOBP_PIRNA_PROCESSING, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION

GO Biological Process (10): regulation of translation (GO:0006417), spermatogenesis (GO:0007283), epithelial structure maintenance (GO:0010669), cell differentiation (GO:0030154), regulatory ncRNA-mediated gene silencing (GO:0031047), piRNA processing (GO:0034587), meiotic cell cycle (GO:0051321), secondary piRNA processing (GO:0140965), transposable element silencing by heterochromatin formation (GO:0141005), transposable element silencing by piRNA-mediated DNA methylation (GO:0141196)

GO Molecular Function (5): RNA endonuclease activity (GO:0004521), piRNA binding (GO:0034584), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), P granule (GO:0043186), piP-body (GO:0071547)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gene Silencing by RNA	1
Regulation of endogenous retroelements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
tissue homeostasis	1
cellular developmental process	1
negative regulation of gene expression	1
regulatory ncRNA processing	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
piRNA processing	1
transposable element silencing	1
constitutive heterochromatin formation	1
transposable element silencing by heterochromatin formation	1
gene silencing by piRNA-directed DNA methylation	1
endonuclease activity	1
RNA nuclease activity	1
regulatory RNA binding	1
nucleic acid binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
germ plasm	1
P granule	1

Protein interactions and networks

STRING

2054 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIWIL4	PIR	O00625	981
PIWIL4	TDRD9	Q8NDG6	972
PIWIL4	TNRC6A	Q8NDV7	932
PIWIL4	DICER1	Q9UPY3	916
PIWIL4	TDRKH	Q9Y2W6	875
PIWIL4	DROSHA	Q9NRR4	847
PIWIL4	PIWIL1	Q96J94	845
PIWIL4	TDRD1	Q9BXT4	843
PIWIL4	GTSF1	Q8WW33	836
PIWIL4	HENMT1	Q5T8I9	813
PIWIL4	PLD6	Q8N2A8	797
PIWIL4	HSP90AB1	P08238	790
PIWIL4	HSP90AA1	P07900	789
PIWIL4	MAEL	Q96JY0	785
PIWIL4	TARBP2	Q15633	768

IntAct

21 interactions, top by confidence:

A	B	Type	Score
PIWIL4	H1-5	psi-mi:“MI:0915”(physical association)	0.400
AGO2	HSP90AA1	psi-mi:“MI:0915”(physical association)	0.400
FKBP5	PIWIL4	psi-mi:“MI:0915”(physical association)	0.400
PIWIL4	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
NUDC	PIWIL4	psi-mi:“MI:0915”(physical association)	0.400
NUDCD3	PIWIL4	psi-mi:“MI:0915”(physical association)	0.400
	PIWIL4	psi-mi:“MI:0915”(physical association)	0.400
HSP90AA1	PIWIL4	psi-mi:“MI:0915”(physical association)	0.400
FKBP6	PIWIL4	psi-mi:“MI:0915”(physical association)	0.400
PIWIL4	CACYBP	psi-mi:“MI:0915”(physical association)	0.400
PTGES3	PIWIL4	psi-mi:“MI:0915”(physical association)	0.400
PIWIL4	AARSD1	psi-mi:“MI:0915”(physical association)	0.400
PIWIL4	PPP5C	psi-mi:“MI:0915”(physical association)	0.400
DICER1	PIWIL4	psi-mi:“MI:0915”(physical association)	0.370
PIWIL4	DICER1	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
PIWIL4	CSTA	psi-mi:“MI:0914”(association)	0.350
PIWIL4	FCHO1	psi-mi:“MI:0914”(association)	0.350
PIWIL4	MIA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): PIWIL4 (Affinity Capture-MS), PIWIL4 (Affinity Capture-Western), PIWIL4 (Proximity Label-MS), PIWIL4 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), CSTA (Affinity Capture-MS), PIWIL4 (Affinity Capture-MS), PIWIL4 (Affinity Capture-MS), KPRP (Affinity Capture-MS), PIWIL4 (Affinity Capture-RNA), BEND3 (Affinity Capture-MS), TDRKH (Affinity Capture-MS), FCHO1 (Affinity Capture-MS), PCDHGA9 (Affinity Capture-MS), PIWIL4 (Two-hybrid)

ESM2 similar proteins: A2CEI6, A3KPK0, A6P7L8, A8D8P8, A8KBF3, A9ZSZ2, O04379, O48771, O76922, O77503, O89040, Q0JF58, Q4G033, Q4KLV6, Q5NBN9, Q5Z5B2, Q5ZLG4, Q5ZMW0, Q69VD5, Q6DCX2, Q6DJB9, Q6EU14, Q6K972, Q6QME8, Q6T5B7, Q6YSJ5, Q6Z4F1, Q7PLK0, Q7XSA2, Q7Y001, Q7Z3Z3, Q7Z3Z4, Q84VQ0, Q851R2, Q8CDG1, Q8CGT6, Q8CJF8, Q8CJF9, Q8CJG0, Q8CJG1

Diamond homologs: A2CEI6, A6N7Y9, A6P7L8, A8D8P8, A8KBF3, A9ZSZ2, O76922, Q4G033, Q7PLK0, Q7Z3Z3, Q7Z3Z4, Q8CDG1, Q8CGT6, Q8TC59, Q8UVX0, Q96J94, Q9JMB7, Q9VKM1, O61931, Q2PC95, Q09249, Q21770, P34681, Q7XTS3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
ESR-mediated signaling	6	55.0×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	7	40.2×	3e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

138 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	16
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3250 predictions. Top by Δscore:

Variant	Effect	Δscore
11:94568728:A:AG	acceptor_gain	1.0000
11:94568729:G:GG	acceptor_gain	1.0000
11:94568729:GCCT:G	acceptor_gain	1.0000
11:94568729:GCCTA:G	acceptor_gain	1.0000
11:94577276:A:AG	acceptor_gain	1.0000
11:94577276:A:G	acceptor_loss	1.0000
11:94577277:G:GC	acceptor_loss	1.0000
11:94577277:G:GG	acceptor_gain	1.0000
11:94577488:AAAAG:A	donor_loss	1.0000
11:94577489:AAAG:A	donor_loss	1.0000
11:94577490:AAG:A	donor_loss	1.0000
11:94577491:AG:A	donor_loss	1.0000
11:94577492:GG:G	donor_loss	1.0000
11:94577493:G:GC	donor_loss	1.0000
11:94577494:T:G	donor_loss	1.0000
11:94583566:GAAA:G	donor_gain	1.0000
11:94583567:A:T	donor_gain	1.0000
11:94583570:G:GG	donor_gain	1.0000
11:94585524:AAG:A	donor_loss	1.0000
11:94585525:AG:A	donor_loss	1.0000
11:94585526:G:GG	donor_gain	1.0000
11:94585526:GTAG:G	donor_loss	1.0000
11:94589116:GGCA:G	acceptor_loss	1.0000
11:94589117:GCA:G	acceptor_loss	1.0000
11:94589118:CA:C	acceptor_loss	1.0000
11:94589119:A:AG	acceptor_gain	1.0000
11:94589119:A:C	acceptor_loss	1.0000
11:94589120:G:GA	acceptor_gain	1.0000
11:94589120:G:GT	acceptor_loss	1.0000
11:94589120:GAT:G	acceptor_gain	1.0000

AlphaMissense

5623 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:94608664:A:C	S641R	0.996
11:94608666:T:A	S641R	0.996
11:94608666:T:G	S641R	0.996
11:94607520:A:C	S574R	0.995
11:94607522:C:A	S574R	0.995
11:94607522:C:G	S574R	0.995
11:94607489:A:C	K563N	0.994
11:94607489:A:T	K563N	0.994
11:94607622:T:A	W608R	0.992
11:94607622:T:C	W608R	0.992
11:94618010:T:G	Y691D	0.992
11:94597875:G:C	R447P	0.991
11:94618014:G:C	R692P	0.990
11:94620107:T:C	L802P	0.990
11:94607606:G:C	K602N	0.989
11:94607606:G:T	K602N	0.989
11:94616494:T:A	W649R	0.989
11:94616494:T:C	W649R	0.989
11:94601873:T:A	W487R	0.988
11:94601873:T:C	W487R	0.988
11:94608653:G:A	G637E	0.988
11:94608661:G:C	A640P	0.988
11:94620004:T:C	F768L	0.988
11:94620006:T:A	F768L	0.988
11:94620006:T:G	F768L	0.988
11:94620910:C:A	A826D	0.988
11:94587238:T:A	V302D	0.986
11:94607445:T:C	C549R	0.986
11:94620110:C:A	T803K	0.985
11:94620919:T:C	L829P	0.984

dbSNP variants (sampled 300 via entrez): RS1000027234 (11:94583094 C>CT), RS1000111310 (11:94570389 A>G,T), RS1000123885 (11:94610384 T>C), RS1000158830 (11:94620347 TAAC>T), RS1000210174 (11:94579442 A>T), RS1000283690 (11:94566174 C>T), RS1000308929 (11:94588827 G>C), RS1000327582 (11:94606198 G>A,C), RS1000370487 (11:94616503 C>T), RS1000380167 (11:94573238 A>G), RS1000440367 (11:94566541 G>T), RS1000443791 (11:94606474 T>C), RS1000508061 (11:94600026 T>A,G), RS1000681842 (11:94576575 A>T), RS1000748945 (11:94587685 G>A,T)

Disease associations

OMIM: gene MIM:610315 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000247_2	Attention deficit hyperactivity disorder symptoms (maternal expressed emotions interaction)	9.000000e-07
GCST002862_2	Mood disorder and prion disease	4.000000e-06
GCST002864_3	Mood disorder in prion disease	8.000000e-06
GCST002929_11	Chromium levels	5.000000e-06
GCST004746_25	Small cell lung carcinoma	8.000000e-06
GCST005150_1	Colorectal cancer	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008342	parental emotion expression measurmement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	5
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	increases expression	2
butyraldehyde	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
NSC 689534	affects binding, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases mutagenesis	1
Copper	affects binding, increases expression	1
Rotenone	increases expression	1
Silicon Dioxide	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8MM	Abcam HCT 116 PIWIL4 KO	Cancer cell line	Male
CVCL_B9PV	Abcam A-549 PIWIL4 KO	Cancer cell line	Male
CVCL_D2GX	Abcam MCF-7 PIWIL4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.