AGO4

Summary

AGO4 (argonaute RISC component 4, HGNC:18424) is a protein-coding gene on chromosome 1p34.3, encoding Protein argonaute-4 (Q9HCK5). Required for RNA-mediated gene silencing (RNAi).

This gene encodes a member of the Argonaute family of proteins which contain PAZ and PIWI domains and play an integral role in RNA interference and short-interfering-RNA-mediated gene silencing. This gene is located on chromosome 1 in a cluster of related family members.

Source: NCBI Gene 192670 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 102 total
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_017629

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18424
Approved symbol	AGO4
Name	argonaute RISC component 4
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	hAGO4, KIAA1567, FLJ20033
Ensembl gene	ENSG00000134698
Ensembl biotype	protein_coding
OMIM	607356
Entrez	192670

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000373210, ENST00000488778, ENST00000496257, ENST00000965193, ENST00000965194

RefSeq mRNA: 1 — MANE Select: NM_017629 NM_017629

CCDS: CCDS397

Canonical transcript exons

ENST00000373210 — 18 exons

Exon	Start	End
ENSE00000916716	35835834	35835993
ENSE00000956049	35825926	35826060
ENSE00001036943	35841616	35841750
ENSE00001036980	35841165	35841480
ENSE00001079136	35825313	35825494
ENSE00001079141	35822862	35822982
ENSE00001144275	35833990	35834174
ENSE00001144439	35816882	35817047
ENSE00001202063	35832437	35832570
ENSE00001202066	35832057	35832185
ENSE00001202069	35831427	35831574
ENSE00001459799	35808016	35808435
ENSE00001595927	35826748	35826835
ENSE00001672558	35831812	35831931
ENSE00001711140	35850854	35851053
ENSE00001806565	35825679	35825815
ENSE00001836069	35853497	35857890
ENSE00003537937	35850157	35850258

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 94.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3614 / max 535.4932, expressed in 1730 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2127	4.4241	1508
2129	1.9019	854
2128	1.1264	550
2126	0.9090	471

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	94.50	gold quality
mononuclear cell	CL:0000842	94.10	gold quality
leukocyte	CL:0000738	93.90	gold quality
cortical plate	UBERON:0005343	92.32	gold quality
upper leg skin	UBERON:0004262	92.16	gold quality
skin of hip	UBERON:0001554	91.73	gold quality
blood	UBERON:0000178	91.72	gold quality
trabecular bone tissue	UBERON:0002483	90.92	gold quality
granulocyte	CL:0000094	89.24	gold quality
stromal cell of endometrium	CL:0002255	88.12	gold quality
mucosa of stomach	UBERON:0001199	87.21	gold quality
right lung	UBERON:0002167	87.01	gold quality
body of pancreas	UBERON:0001150	86.79	gold quality
ventricular zone	UBERON:0003053	86.78	gold quality
tibia	UBERON:0000979	86.72	gold quality
bone marrow	UBERON:0002371	86.49	gold quality
body of stomach	UBERON:0001161	86.44	gold quality
ganglionic eminence	UBERON:0004023	86.40	gold quality
right coronary artery	UBERON:0001625	86.29	gold quality
seminal vesicle	UBERON:0000998	86.16	gold quality
palpebral conjunctiva	UBERON:0001812	86.15	gold quality
buccal mucosa cell	CL:0002336	85.80	gold quality
skin of abdomen	UBERON:0001416	85.62	gold quality
skin of leg	UBERON:0001511	85.56	gold quality
spleen	UBERON:0002106	85.50	gold quality
fundus of stomach	UBERON:0001160	85.41	gold quality
stomach	UBERON:0000945	85.18	gold quality
zone of skin	UBERON:0000014	85.07	gold quality
bronchial epithelial cell	CL:0002328	84.78	gold quality
lower esophagus	UBERON:0013473	84.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

244 targeting AGO4, 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-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520G-5P	99.99	66.76	658
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 6)

• The specificity of RNA interference depends on the concentration of Ago1, Ago3, and Ago4 relative to Ago2. (PMID:18771919)
• EIF2C4 protein is expressed in differentiating and terminally differentiated N-type cells more than in S- and I-type cells (PMID:19393748)
• EIF2C2-4 and PIWIL4 appear increased in advanced tumors with distant metastasis, suggesting they may promote tumor invasion (PMID:20146808)
• Chimeras with Ago4 N-terminal domains were defective in RISC activation & sometimes also in RNA loading. This highlights the pleiotropic role of the Ago N domain & emphasizes the unique position of human Ago4 within the Ago protein family. (PMID:23748378)
• The Importance of AGO 1 and 4 in Post-Transcriptional Gene Regulatory Function of tRF5-GluCTC, an Respiratory Syncytial Virus-Induced tRNA-Derived RNA Fragment. (PMID:33233493)
• AGO4 suppresses tumor growth by modulating autophagy and apoptosis via enhancing TRIM21-mediated ubiquitination of GRP78 in a p53-independent manner. (PMID:36371565)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	ago4	ENSDARG00000100854
mus_musculus	Ago4	ENSMUSG00000042500
rattus_norvegicus	Ago4	ENSRNOG00000025596
caenorhabditis_elegans	ppw-1	WBGENE00004093
caenorhabditis_elegans	ppw-2	WBGENE00004094
caenorhabditis_elegans		WBGENE00006449
caenorhabditis_elegans		WBGENE00007624
caenorhabditis_elegans		WBGENE00010263
caenorhabditis_elegans	wago-1	WBGENE00011061
caenorhabditis_elegans		WBGENE00011910
caenorhabditis_elegans	sago-2	WBGENE00018921
caenorhabditis_elegans		WBGENE00020707
caenorhabditis_elegans		WBGENE00022877

Paralogs (3): AGO1 (ENSG00000092847), AGO2 (ENSG00000123908), AGO3 (ENSG00000126070)

Protein

Protein identifiers

Protein argonaute-4 — Q9HCK5 (reviewed: Q9HCK5)

Alternative names: Argonaute RISC catalytic component 4, Eukaryotic translation initiation factor 2C 4

All UniProt accessions (1): Q9HCK5

UniProt curated annotations — full annotation on UniProt →

Function. Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for RNA-directed transcription and replication of the human hapatitis delta virus (HDV).

Subunit / interactions. Interacts with EIF4B, IMP8, PRMT5, TNRC6A and TNRC6B. Interacts with ZFP36.

Subcellular location. Cytoplasm. P-body.

Post-translational modifications. Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO4 when it is engaged with a TDMD target.

Similarity. Belongs to the argonaute family. Ago subfamily.

RefSeq proteins (1): NP_060099* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003100	PAZ_dom	Domain
IPR003165	Piwi	Domain
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR014811	ArgoL1	Domain
IPR028604	AGO4	Family
IPR032472	ArgoL2	Domain
IPR032473	Argonaute_Mid_dom	Domain
IPR032474	Argonaute_N	Domain
IPR036085	PAZ_dom_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR045246	Piwi_ago-like	Domain

Pfam: PF02170, PF02171, PF08699, PF16486, PF16487, PF16488

UniProt features (71 total): strand 35, helix 25, turn 7, domain 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6OON	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCK5-F1	91.56	0.81

Function

Pathways and Gene Ontology

Reactome pathways

65 pathways

ID	Pathway
R-HSA-165159	MTOR signalling
R-HSA-1912408	Pre-NOTCH Transcription and Translation
R-HSA-203927	MicroRNA (miRNA) biogenesis
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559585	Oncogene Induced Senescence
R-HSA-4086398	Ca2+ pathway
R-HSA-426486	Small interfering RNA (siRNA) biogenesis
R-HSA-426496	Post-transcriptional silencing by small RNAs
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-8853884	Transcriptional Regulation by VENTX
R-HSA-8934593	Regulation of RUNX1 Expression and Activity
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-8943723	Regulation of PTEN mRNA translation
R-HSA-8948700	Competing endogenous RNAs (ceRNAs) regulate PTEN translation
R-HSA-8986944	Transcriptional Regulation by MECP2
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9022692	Regulation of MECP2 expression and activity
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer
R-HSA-9759811	Regulation of CDH11 mRNA translation by microRNAs
R-HSA-9764562	Regulation of CDH1 mRNA translation by microRNAs
R-HSA-9768778	Regulation of NPAS4 mRNA translation
R-HSA-9824594	Regulation of MITF-M-dependent genes involved in apoptosis
R-HSA-9839394	TGFBR3 expression
R-HSA-9909620	Regulation of PD-L1(CD274) translation
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1266738	Developmental Biology
R-HSA-1500931	Cell-Cell communication
R-HSA-157118	Signaling by NOTCH

MSigDB gene sets: 324 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_SIGNALING_BY_NOTCH, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOMF_NUCLEASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS

GO Biological Process (14): mRNA catabolic process (GO:0006402), synaptonemal complex assembly (GO:0007130), male meiotic nuclear division (GO:0007140), male gonad development (GO:0008584), miRNA metabolic process (GO:0010586), regulation of cell morphogenesis (GO:0022604), pre-miRNA processing (GO:0031054), regulatory ncRNA-mediated post-transcriptional gene silencing (GO:0035194), miRNA processing (GO:0035196), miRNA-mediated gene silencing by inhibition of translation (GO:0035278), negative regulation of apoptotic process (GO:0043066), RISC complex assembly (GO:0070922), regulation of translation (GO:0006417), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (7): double-stranded RNA binding (GO:0003725), single-stranded RNA binding (GO:0003727), RNA endonuclease activity (GO:0004521), miRNA binding (GO:0035198), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (9): P-body (GO:0000932), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), RISC complex (GO:0016442), cytoplasmic ribonucleoprotein granule (GO:0036464), RISC-loading complex (GO:0070578), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Gene Silencing by RNA	3
Cellular Senescence	2
Generic Transcription Pathway	2
Transcriptional regulation by RUNX1	2
Signal Transduction	1
Pre-NOTCH Expression and Processing	1
Beta-catenin independent WNT signaling	1
Transcriptional Regulation by TP53	1
MAPK family signaling cascades	1
PTEN Regulation	1
Regulation of PTEN mRNA translation	1
ESR-mediated signaling	1
Transcriptional Regulation by MECP2	1
NR1H2 and NR1H3-mediated signaling	1
Signaling by ALK fusions and activated point mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
negative regulation of gene expression	2
regulatory ncRNA-mediated gene silencing	2
RNA binding	2
binding	2
cytoplasm	2
RNA catabolic process	1
mRNA metabolic process	1
homologous chromosome pairing at meiosis	1
cellular component assembly	1
chromosome organization involved in meiotic cell cycle	1
synaptonemal complex organization	1
male gamete generation	1
meiotic cell cycle	1
meiotic nuclear division	1
gonad development	1
development of primary male sexual characteristics	1
RNA metabolic process	1
cell morphogenesis	1
regulation of anatomical structure morphogenesis	1
miRNA processing	1
post-transcriptional gene silencing	1
regulatory ncRNA processing	1
negative regulation of translation	1
miRNA-mediated post-transcriptional gene silencing	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
protein-RNA complex assembly	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
endonuclease activity	1
RNA nuclease activity	1
regulatory RNA binding	1
nucleic acid binding	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
RNAi effector complex	1

Protein interactions and networks

STRING

1802 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGO4	AGO1	Q9UL18	975
AGO4	AGO2	Q9UKV8	947
AGO4	DICER1	Q9UPY3	883
AGO4	TNRC6A	Q8NDV7	881
AGO4	DNMT3A	Q9Y6K1	875
AGO4	SUPT5H	O00267	757
AGO4	TARBP2	Q15633	740
AGO4	DROSHA	Q9NRR4	730
AGO4	AGO3	Q9H9G7	693
AGO4	TNRC6B	Q9UPQ9	670
AGO4	DGCR8	Q8WYQ5	659
AGO4	HENMT1	Q5T8I9	648
AGO4	XPO5	Q9HAV4	633
AGO4	PIWIL4	Q7Z3Z4	628
AGO4	P4HA1	P13674	623

IntAct

39 interactions, top by confidence:

A	B	Type	Score
DDX6	EDC4	psi-mi:“MI:0914”(association)	0.820
TNRC6A	AGO4	psi-mi:“MI:0915”(physical association)	0.770
TNRC6A	AGO4	psi-mi:“MI:0403”(colocalization)	0.770
AGO4	TNRC6A	psi-mi:“MI:0915”(physical association)	0.770
STAMBP	PIK3C2A	psi-mi:“MI:0914”(association)	0.730
AGO3	IPO8	psi-mi:“MI:0915”(physical association)	0.640
AGO4	TNRC6C	psi-mi:“MI:0915”(physical association)	0.600
TNRC6C	AGO4	psi-mi:“MI:0403”(colocalization)	0.600
IPO8	AGO4	psi-mi:“MI:0915”(physical association)	0.580
IGFBP6	TCAF2	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530
AGO4	LIMD1	psi-mi:“MI:0915”(physical association)	0.460
AGO4	LIMD1	psi-mi:“MI:0403”(colocalization)	0.460
AGO4	TNRC6B	psi-mi:“MI:0915”(physical association)	0.460
TNRC6B	AGO4	psi-mi:“MI:0403”(colocalization)	0.460
AGO4	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
AGO4	WTIP	psi-mi:“MI:0915”(physical association)	0.400
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
ANKMY2	ADCY6	psi-mi:“MI:0914”(association)	0.350
AGO4	CDIPT	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
AGO4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PCSK1N	CLTCL1	psi-mi:“MI:0914”(association)	0.350
PITRM1	TIAL1	psi-mi:“MI:0914”(association)	0.350
ZFP42	EEF1A2	psi-mi:“MI:0914”(association)	0.350
LEPR	ANKLE2	psi-mi:“MI:0914”(association)	0.350
ECD	POLR3G	psi-mi:“MI:0914”(association)	0.350

BioGRID (145): AGO4 (Reconstituted Complex), AGO4 (Affinity Capture-MS), AGO4 (Affinity Capture-Western), AGO4 (Proximity Label-MS), AGO4 (Proximity Label-MS), AGO4 (Proximity Label-MS), AGO4 (Proximity Label-MS), AGO4 (Affinity Capture-MS), AGO4 (Affinity Capture-MS), TNRC6A (Affinity Capture-MS), ZSWIM8 (Affinity Capture-MS), CUL7 (Affinity Capture-MS), AGO4 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), AGO4 (Affinity Capture-MS)

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: A3KPK0, O04379, O48771, O74957, O77503, P34681, Q0JF58, Q10F39, Q4KLV6, Q5NBN9, Q5Z5B2, Q5ZLG4, Q5ZMW0, Q69UP6, Q69VD5, Q6DCX2, Q6DJB9, Q6EU14, Q6H6C3, Q6K972, Q6QME8, Q6T5B7, Q6YSJ5, Q6Z4F1, Q75HC2, Q7XSA2, Q7XTS3, Q7XTS4, Q7Y001, Q84VQ0, Q851R2, Q852N2, Q8CJF8, Q8CJF9, Q8CJG0, Q8CJG1, Q9C793, Q9H9G7, Q9HCK5, Q9QZ81

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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
Regulation of RUNX1 Expression and Activity	5	84.0×	1e-07
Regulation of MITF-M-dependent genes involved in apoptosis	5	79.3×	2e-07
TGFBR3 expression	5	57.1×	1e-06
Oncogene Induced Senescence	6	50.4×	1e-07
Regulation of MECP2 expression and activity	5	46.0×	3e-06
Transcriptional Regulation by MECP2	5	39.6×	6e-06
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	5	38.6×	6e-06
MTOR signalling	5	33.2×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
miRNA-mediated gene silencing by inhibition of translation	8	141.9×	1e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2815 predictions. Top by Δscore:

Variant	Effect	Δscore
1:35817043:AACAG:A	donor_loss	1.0000
1:35817045:CAGG:C	donor_loss	1.0000
1:35817046:AGGTA:A	donor_loss	1.0000
1:35817047:GGTAA:G	donor_loss	1.0000
1:35817048:G:C	donor_loss	1.0000
1:35817049:T:A	donor_loss	1.0000
1:35822855:T:A	acceptor_gain	1.0000
1:35825309:TTAG:T	acceptor_loss	1.0000
1:35825310:TAGGT:T	acceptor_loss	1.0000
1:35825924:A:AG	acceptor_gain	1.0000
1:35825925:G:GC	acceptor_gain	1.0000
1:35825925:GT:G	acceptor_gain	1.0000
1:35826836:G:GG	donor_gain	1.0000
1:35831807:GGCA:G	acceptor_loss	1.0000
1:35831808:GCA:G	acceptor_loss	1.0000
1:35831809:CA:C	acceptor_loss	1.0000
1:35831810:A:AT	acceptor_loss	1.0000
1:35831811:G:GT	acceptor_loss	1.0000
1:35831811:GGTCT:G	acceptor_gain	1.0000
1:35831914:G:GT	donor_gain	1.0000
1:35831920:A:G	donor_gain	1.0000
1:35831927:GACTG:G	donor_gain	1.0000
1:35831932:GTCA:G	donor_gain	1.0000
1:35831936:G:GG	donor_gain	1.0000
1:35835832:A:AG	acceptor_gain	1.0000
1:35835832:AGC:A	acceptor_gain	1.0000
1:35835833:G:GG	acceptor_gain	1.0000
1:35835833:GC:G	acceptor_gain	1.0000
1:35835833:GCG:G	acceptor_gain	1.0000
1:35835833:GCGGA:G	acceptor_gain	1.0000

AlphaMissense

5648 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:35816961:T:A	N33K	1.000
1:35816961:T:G	N33K	1.000
1:35822929:G:C	D85H	1.000
1:35822933:G:A	G86D	1.000
1:35822933:G:T	G86V	1.000
1:35822947:T:G	Y91D	1.000
1:35825704:T:C	F172L	1.000
1:35825706:C:A	F172L	1.000
1:35825706:C:G	F172L	1.000
1:35825804:T:C	L205P	1.000
1:35825940:T:C	F214L	1.000
1:35825942:C:A	F214L	1.000
1:35825942:C:G	F214L	1.000
1:35826757:T:A	V257D	1.000
1:35826799:T:A	V271D	1.000
1:35826808:T:A	V274E	1.000
1:35826823:C:A	A279D	1.000
1:35831428:T:C	F284L	1.000
1:35831429:T:C	F284S	1.000
1:35831430:T:A	F284L	1.000
1:35831430:T:G	F284L	1.000
1:35831479:T:G	Y301D	1.000
1:35831482:T:C	F302L	1.000
1:35831483:T:C	F302S	1.000
1:35831484:T:A	F302L	1.000
1:35831484:T:G	F302L	1.000
1:35831522:T:C	L315P	1.000
1:35831527:T:C	C317R	1.000
1:35831528:G:A	C317Y	1.000
1:35831529:T:G	C317W	1.000

dbSNP variants (sampled 300 via entrez): RS1000070288 (1:35809124 C>A,T), RS1000076412 (1:35807956 G>A,T), RS1000143431 (1:35854541 T>C), RS1000215285 (1:35850075 C>G,T), RS1000282909 (1:35839458 A>G), RS1000336762 (1:35808794 C>G), RS1000504785 (1:35827965 G>A), RS1000516737 (1:35854253 A>G), RS1000570796 (1:35826492 T>A), RS1000633886 (1:35821378 A>T), RS1000716299 (1:35820924 T>G), RS1000757919 (1:35835181 C>A,G), RS1000769219 (1:35813592 C>T), RS1000862547 (1:35807680 G>A,T), RS1000928903 (1:35814212 GATT>G)

Disease associations

OMIM: gene MIM:607356 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
entinostat	decreases expression, affects cotreatment	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
terbufos	decreases methylation	1
sodium arsenite	decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Diclofenac	affects expression	1
Doxorubicin	decreases expression	1
Fonofos	decreases methylation	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8B4	Abcam HCT 116 AGO4 KO	Cancer cell line	Male
CVCL_B9D6	Abcam A-549 AGO4 KO	Cancer cell line	Male
CVCL_D2DV	Abcam MCF-7 AGO4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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