ACTN4
geneOn this page
Summary
ACTN4 (actinin alpha 4, HGNC:166) is a protein-coding gene on chromosome 19q13.2, encoding Alpha-actinin-4 (O43707). F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a nonmuscle, alpha actinin isoform which is concentrated in the cytoplasm, and thought to be involved in metastatic processes. Mutations in this gene have been associated with focal and segmental glomerulosclerosis.
Source: NCBI Gene 81 — RefSeq curated summary.
At a glance
- Gene–disease (curated): focal segmental glomerulosclerosis 1 (Strong, GenCC) — +1 more curated relationship
- GWAS associations: 9
- Clinical variants (ClinVar): 596 total — 6 pathogenic, 11 likely-pathogenic
- Phenotypes (HPO): 27
- Druggable target: yes — 1 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_004924
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:166 |
| Approved symbol | ACTN4 |
| Name | actinin alpha 4 |
| Location | 19q13.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000130402 |
| Ensembl biotype | protein_coding |
| OMIM | 604638 |
| Entrez | 81 |
Gene structure
Transcript identifiers
Ensembl transcripts: 29 — 24 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined
ENST00000252699, ENST00000390009, ENST00000424234, ENST00000440400, ENST00000477174, ENST00000489451, ENST00000495553, ENST00000497637, ENST00000588618, ENST00000589528, ENST00000697712, ENST00000871324, ENST00000871325, ENST00000871326, ENST00000871327, ENST00000871328, ENST00000871329, ENST00000871330, ENST00000871331, ENST00000871332, ENST00000871333, ENST00000871334, ENST00000871335, ENST00000871336, ENST00000871337, ENST00000924368, ENST00000924369, ENST00000924370, ENST00000924371
RefSeq mRNA: 3 — MANE Select: NM_004924
NM_001322033, NM_001411143, NM_004924
CCDS: CCDS12518, CCDS92610, CCDS92611
Canonical transcript exons
ENST00000252699 — 21 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000895774 | 38727946 | 38728026 |
| ENSE00000895777 | 38724431 | 38724565 |
| ENSE00000895778 | 38724157 | 38724339 |
| ENSE00000895779 | 38723937 | 38724077 |
| ENSE00000895780 | 38723614 | 38723722 |
| ENSE00000895781 | 38721538 | 38721688 |
| ENSE00001909908 | 38647649 | 38647907 |
| ENSE00002256794 | 38725724 | 38725903 |
| ENSE00002529868 | 38726957 | 38727103 |
| ENSE00003478716 | 38708117 | 38708195 |
| ENSE00003521050 | 38717927 | 38718074 |
| ENSE00003542253 | 38701002 | 38701121 |
| ENSE00003563841 | 38709395 | 38709476 |
| ENSE00003590443 | 38706044 | 38706131 |
| ENSE00003605223 | 38700600 | 38700714 |
| ENSE00003612741 | 38710257 | 38710342 |
| ENSE00003616079 | 38728996 | 38729154 |
| ENSE00003622921 | 38714469 | 38714561 |
| ENSE00003628896 | 38704934 | 38705020 |
| ENSE00003790855 | 38717086 | 38717316 |
| ENSE00003842835 | 38729274 | 38731589 |
Expression profiles
Bgee: expression breadth ubiquitous, 145 present calls, max score 99.48.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 97.8361 / max 1000.0509, expressed in 1827 samples.
FANTOM5 promoters (4 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 175645 | 59.6754 | 1824 |
| 175646 | 37.4462 | 1803 |
| 175650 | 0.6088 | 365 |
| 175654 | 0.1057 | 47 |
Top tissues by expression
145 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| popliteal artery | UBERON:0002250 | 99.48 | gold quality |
| tibial artery | UBERON:0007610 | 99.48 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 99.43 | gold quality |
| right coronary artery | UBERON:0001625 | 99.43 | gold quality |
| artery | UBERON:0001637 | 99.43 | gold quality |
| aorta | UBERON:0000947 | 99.41 | gold quality |
| stromal cell of endometrium | CL:0002255 | 99.39 | gold quality |
| ascending aorta | UBERON:0001496 | 99.33 | gold quality |
| thoracic aorta | UBERON:0001515 | 99.32 | gold quality |
| placenta | UBERON:0001987 | 99.30 | gold quality |
| body of uterus | UBERON:0009853 | 99.27 | gold quality |
| islet of Langerhans | UBERON:0000006 | 99.26 | gold quality |
| myometrium | UBERON:0001296 | 99.18 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 99.11 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 99.07 | gold quality |
| left coronary artery | UBERON:0001626 | 99.04 | gold quality |
| duodenum | UBERON:0002114 | 99.04 | gold quality |
| fallopian tube | UBERON:0003889 | 98.99 | gold quality |
| vermiform appendix | UBERON:0001154 | 98.96 | gold quality |
| esophagus mucosa | UBERON:0002469 | 98.96 | gold quality |
| metanephros cortex | UBERON:0010533 | 98.95 | gold quality |
| vagina | UBERON:0000996 | 98.94 | gold quality |
| left uterine tube | UBERON:0001303 | 98.94 | gold quality |
| ectocervix | UBERON:0012249 | 98.94 | gold quality |
| right lung | UBERON:0002167 | 98.91 | gold quality |
| skin of leg | UBERON:0001511 | 98.90 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 98.90 | gold quality |
| esophagus | UBERON:0001043 | 98.88 | gold quality |
| transverse colon | UBERON:0001157 | 98.88 | gold quality |
| rectum | UBERON:0001052 | 98.86 | gold quality |
Single-cell (SCXA)
Detected in 6 experiment(s), a significant marker in 5.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-HCAD-11 | yes | 18.97 |
| E-HCAD-10 | yes | 18.91 |
| E-HCAD-13 | yes | 7.47 |
| E-GEOD-137537 | yes | 6.11 |
| E-CURD-112 | no | 2.51 |
| E-ANND-3 | no | 0.00 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): HDAC7
miRNA regulators (miRDB)
125 targeting ACTN4, 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-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-5011-5P | 100.00 | 83.46 | 5820 |
| HSA-MIR-190A-3P | 100.00 | 80.35 | 5520 |
| HSA-MIR-4692 | 100.00 | 67.32 | 2066 |
| HSA-MIR-5692B | 100.00 | 71.32 | 2622 |
| HSA-MIR-5692C | 100.00 | 71.32 | 2622 |
| HSA-MIR-6758-5P | 100.00 | 66.21 | 1470 |
| HSA-MIR-6856-5P | 100.00 | 65.47 | 1298 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-548C-3P | 99.99 | 74.01 | 7587 |
| HSA-MIR-4514 | 99.99 | 67.10 | 1870 |
| HSA-MIR-373-5P | 99.98 | 75.36 | 4753 |
| HSA-MIR-616-5P | 99.98 | 75.58 | 4775 |
| HSA-MIR-6825-5P | 99.96 | 69.81 | 3431 |
| HSA-MIR-559 | 99.95 | 72.28 | 3609 |
| HSA-MIR-548AB | 99.95 | 71.31 | 3488 |
| HSA-MIR-185-3P | 99.95 | 67.01 | 1743 |
| HSA-MIR-548A-5P | 99.94 | 71.27 | 3482 |
| HSA-MIR-548AD-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548AE-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548AK | 99.94 | 71.24 | 3488 |
| HSA-MIR-548AM-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548AP-5P | 99.94 | 71.14 | 3489 |
| HSA-MIR-548AQ-5P | 99.94 | 71.34 | 3426 |
| HSA-MIR-548AR-5P | 99.94 | 71.28 | 3515 |
| HSA-MIR-548AS-5P | 99.94 | 71.22 | 3482 |
| HSA-MIR-548AU-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548AY-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548B-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548BB-5P | 99.94 | 71.27 | 3509 |
Literature-anchored findings (GeneRIF, showing 40)
- interaction with tight junction protein MAGI-1 (PMID:12042308)
- isolated two anti-alpha-actinin-4 T cell clones from the same patient TIL and from his peripheral blood lymphocytes (PBLs) by using tetramers of soluble HLA-A2 molecules loaded with the mutated peptide (PMID:12093915)
- Sporadic FSGS is a heterogeneous disease, since ACTN4 and podocin genes are not found in our patients with sporadic FSGS. (PMID:12617336)
- ACTN4 has a role promoting tumorigenicity and regulating cell motility (PMID:15048094)
- Actinin alpha-4 is mainly present intracellularly and is involved in cellular motility via interaction with the actin cytoskeleton, thus probably affecting the metastatic potential of tumor cells. (PMID:15493875)
- Results suggest that humanin is a novel binding partner of the alpha-actinin-4 R1-R4 domain in podocytes. (PMID:15619032)
- the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation (PMID:15772161)
- No mutations detected in Japanese congenital nephrotic synddrome patients. (PMID:15780077)
- ACTN4 mutations accounts for about 3.5% of familial focal glomerulosclerosis. (PMID:16251236)
- Interaction of alpha 4 actinin with ICAM-1 is required for leukocyte extravasation. (PMID:16951376)
- The role of ACTN4 in MEF2A transcription via HDAC7 antagonism is reported. (PMID:16980305)
- A critical regulator of AKT1 localization and function. (PMID:17018644)
- Cytokine activation of MAPK14 and apoptosis is opposed by ACTN4 targeting of protein phosphatase 2A for site-specific dephosphorylation of MEK3. (PMID:17438131)
- actinin-4…could be a novel prognostic indicator for patients with ovarian carcinomas. (PMID:17873890)
- exposure of a buried actin-binding site 1 in mutant alpha-actinin-4 causes an increase in its actin-binding affinity (PMID:17901210)
- common variants in LRRC7, KIRREL, NPHS2 and ACTN4 do not appeear to contribute to susceptibility to diabetic nephropathy in Finnish patients with type 1 diabetes (PMID:17968527)
- Crystal structure of the actin-binding domain of alpha-actininin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis. (PMID:18164029)
- eNOS activity in vascular endothelial cells is tonically and dynamically regulated by competitive interaction with alpha-actinin-4 and calmodulin. (PMID:18180332)
- alpha-actinin-4 is important for the NF-kappaB nuclear translocation and its functions inside the nucleus. (PMID:18215660)
- Motility-related ACTN4 is associated with advanced and metastatic ovarian carcinoma. (PMID:18362906)
- A novel ACTN4 mutation, p.Ser262Phe, was detected in the patients, and their father was found to have a germline mosaicism for the mutation in these patients with familial focal segmental glomerulosclerosis (PMID:18436095)
- low expression levels of alpha-actinin-4 mRNA and protein are linked to the progression of glomerulopathy and proteinuria in human diabetic nephropathy (PMID:18552466)
- Actinin-4 contributes to the invasive growth of pancreatic ductal carcinoma, and ACTN4 is one of the candidate oncogenes in this chromosome locus. (PMID:18765526)
- Mutations and single nucleotide polymorphisms of the ACTN4 gene may be associated with Chinese idiopathic focal segmental glomerulosclerosis. (PMID:19142020)
- The actinin-4 gene may serve as a predictor of poor outcome and tumor chemoresistance in patients with advanced-stage ovarian cancers. (PMID:19151661)
- Mutations in ACTN4, the gene encoding the actin-binding protein alpha-actinin-4, are a cause of focal segmental glomerulosclerosis. (PMID:19357256)
- Heterozygous mutations in the promoters of the ACTN4 and SYNPO genes are found in patients with idiopathic focal segmental glomerulosclerosis. (PMID:19666657)
- Data show that actinin-4 expression levels significantly correlate with worse survival after PDAC resection. (PMID:19672209)
- expression of alpha-actinin-4 was significantly associated with invasion potential defined by the Matrigel invasion assay. Cancer cell lines with higher alpha-actinin-4 expression had greater invasive potential. (PMID:19913389)
- EGF regulates the actin binding activity of ACTN4 by inducing tyrosyl-directed phosphorylation (PMID:19920151)
- The absence of mutations of ACTN4 in this study suggests that there are other genetic causes of steroid-resistant nephrotic syndrome (PMID:19956976)
- Both alpha-actinin-1 and alpha-actinin-4 make critical and distinct contributions to cytoskeletal organization, rigidity-sensing, and motility of glioma cells. (PMID:20037648)
- Alpha-actinin 1 and 4 are differentially regulated during the development and progression of astrocytomas because each of these isoforms uniquely contributes to distinct malignant properties of astrocytoma cells. (PMID:20156433)
- The association of ACTN4 with different ribonucleoproteins suggests that a major function of nuclear ACTN4 may be regulation of mRNA metabolism and signaling. (PMID:20519146)
- Levels of eEF1A2 and alpha-actinin-4 mRNA appeared to be unrelated to breast tumour size, except for a significant down-regulation of alpha-actinin-4 mRNA in T3 cases. (PMID:20819441)
- The actin-binding protein, actinin alpha 4 (ACTN4), is a nuclear receptor coactivator that promotes proliferation of MCF-7 breast cancer cells. (PMID:21078666)
- Epothilone B antagonizes glioma cell motility associated with reorganization of the actin-binding protein alpha-actinin 4. (PMID:21234524)
- The results suggest that the interaction between HAMLET and alpha-actinins promotes tumor cell detachment. (PMID:21408150)
- The urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, alpha-actin4, and podocin were found to increase with the progression of diabetic nephropathy. (PMID:21655212)
- Alpha-actinin-4 and CLP36 protein deficiencies contribute to podocyte defects in multiple human glomerulopathies (PMID:21680739)
Cross-species orthologs
2 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| mus_musculus | Actn4 | ENSMUSG00000054808 |
| rattus_norvegicus | Actn4 | ENSRNOG00000020433 |
Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), SYNE1 (ENSG00000131018), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), FLNB (ENSG00000136068), SPTBN5 (ENSG00000137877), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)
Protein
Protein identifiers
Alpha-actinin-4 — O43707 (reviewed: O43707)
Alternative names: Non-muscle alpha-actinin 4
All UniProt accessions (6): O43707, A0A0S2Z3G9, A0A8V8TL71, F5GXS2, H7C144, K7EP19
UniProt curated annotations — full annotation on UniProt →
Function. F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation. Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions. May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA. Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation.
Subunit / interactions. Homodimer; antiparallel. Binds TRIM3 at the N-terminus. Interacts with MICALL2 (preferentially in opened conformation); stimulated by RAB13 activation. Identified in a complex with CASK, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3. Interacts with MAGI1. Interacts with PDLIM2. Interacts with PPARG and RARA. Binds to VCL; this interaction triggers VCL conformational changes. Interacts with SEPTIN14. Interacts with IGSF8.
Subcellular location. Nucleus. Cytoplasm. Cell junction. Cytoskeleton. Stress fiber. Perinuclear region.
Tissue specificity. Widely expressed.
Disease relevance. Focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278] A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. The disease is caused by variants affecting the gene represented in this entry.
Domain organisation. Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that mediates interaction with nuclear receptors.
Miscellaneous. Does not colocalize with actin cytoskeleton structures.
Similarity. Belongs to the alpha-actinin family.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| O43707-1 | 1 | yes |
| O43707-2 | ACTN4ISO | |
| O43707-3 | 3 |
RefSeq proteins (3): NP_001308962, NP_001398072, NP_004915* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001589 | Actinin_actin-bd_CS | Conserved_site |
| IPR001715 | CH_dom | Domain |
| IPR002017 | Spectrin_repeat | Repeat |
| IPR002048 | EF_hand_dom | Domain |
| IPR011992 | EF-hand-dom_pair | Homologous_superfamily |
| IPR014837 | EF-hand_Ca_insen | Domain |
| IPR018159 | Spectrin/alpha-actinin | Repeat |
| IPR018247 | EF_Hand_1_Ca_BS | Binding_site |
| IPR036872 | CH_dom_sf | Homologous_superfamily |
Pfam: PF00307, PF00435, PF08726
UniProt features (85 total): helix 18, sequence variant 17, sequence conflict 13, modified residue 10, region of interest 6, domain 4, repeat 4, binding site 3, strand 3, splice variant 2, turn 2, chain 1, short sequence motif 1, mutagenesis site 1
Structure
Experimental structures (PDB)
5 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 6OA6 | X-RAY DIFFRACTION | 1.37 |
| 6O31 | X-RAY DIFFRACTION | 1.51 |
| 1YDI | X-RAY DIFFRACTION | 1.8 |
| 2R0O | X-RAY DIFFRACTION | 2.2 |
| 1WLX | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-O43707-F1 | 84.66 | 0.48 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Ligand- & substrate-binding residues (3): 778; 780; 789
Post-translational modifications (10): 31, 114, 214, 249, 592, 625, 696, 779, 859, 909
Mutagenesis-validated functional residues (1):
| Position | Phenotype |
|---|---|
| 87–88 | reduced interaction with rara. loss of the transcriptional coac tivator activity toward rara. |
Function
Pathways and Gene Ontology
Reactome pathways
6 pathways
| ID | Pathway |
|---|---|
| R-HSA-114608 | Platelet degranulation |
| R-HSA-373753 | Nephrin family interactions |
| R-HSA-109582 | Hemostasis |
| R-HSA-1500931 | Cell-Cell communication |
| R-HSA-76002 | Platelet activation, signaling and aggregation |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ |
MSigDB gene sets: 437 (showing top):
TSENG_IRS1_TARGETS_UP, GOBP_VESICLE_LOCALIZATION, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, TATTATA_MIR374, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, KYNG_DNA_DAMAGE_DN, KEGG_TIGHT_JUNCTION, GHO_ATF5_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, CTATGCA_MIR153
GO Biological Process (13): protein transport (GO:0015031), actin cytoskeleton organization (GO:0030036), vesicle transport along actin filament (GO:0030050), positive regulation of cell migration (GO:0030335), positive regulation of sodium:proton antiporter activity (GO:0032417), tumor necrosis factor-mediated signaling pathway (GO:0033209), peroxisome proliferator activated receptor signaling pathway (GO:0035357), regulation of apoptotic process (GO:0042981), positive regulation of transcription by RNA polymerase II (GO:0045944), retinoic acid receptor signaling pathway (GO:0048384), muscle cell development (GO:0055001), negative regulation of substrate adhesion-dependent cell spreading (GO:1900025), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224)
GO Molecular Function (16): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), nucleoside binding (GO:0001882), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), actin binding (GO:0003779), integrin binding (GO:0005178), calcium ion binding (GO:0005509), nuclear receptor binding (GO:0016922), chromatin DNA binding (GO:0031490), protein homodimerization activity (GO:0042803), nuclear retinoic acid receptor binding (GO:0042974), transmembrane transporter binding (GO:0044325), actin filament binding (GO:0051015), protein binding (GO:0005515), identical protein binding (GO:0042802), metal ion binding (GO:0046872)
GO Cellular Component (21): stress fiber (GO:0001725), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), Z disc (GO:0030018), cell junction (GO:0030054), cortical actin cytoskeleton (GO:0030864), platelet alpha granule lumen (GO:0031093), pseudopodium (GO:0031143), protein-containing complex (GO:0032991), cell projection (GO:0042995), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), postsynaptic actin cytoskeleton (GO:0098871), ribonucleoprotein complex (GO:1990904), cytoskeleton (GO:0005856), anchoring junction (GO:0070161)
Reactome top-level categories
Rollup of top-4 pathways:
| Category | Pathways |
|---|---|
| Response to elevated platelet cytosolic Ca2+ | 1 |
| Cell-Cell communication | 1 |
| Hemostasis | 1 |
| Platelet activation, signaling and aggregation | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 6 |
| nuclear receptor-mediated signaling pathway | 2 |
| positive regulation of DNA-templated transcription | 2 |
| protein-containing complex binding | 2 |
| protein binding | 2 |
| actin cytoskeleton | 2 |
| transport | 1 |
| intracellular protein localization | 1 |
| establishment of protein localization | 1 |
| cytoskeleton organization | 1 |
| actin filament-based process | 1 |
| actin filament-based movement | 1 |
| actin filament-based transport | 1 |
| vesicle cytoskeletal trafficking | 1 |
| cell migration | 1 |
| regulation of cell migration | 1 |
| positive regulation of cell motility | 1 |
| sodium:proton antiporter activity | 1 |
| positive regulation of sodium ion transmembrane transporter activity | 1 |
| cytokine-mediated signaling pathway | 1 |
| cellular response to tumor necrosis factor | 1 |
| apoptotic process | 1 |
| regulation of programmed cell death | 1 |
| regulation of transcription by RNA polymerase II | 1 |
| transcription by RNA polymerase II | 1 |
| hormone-mediated signaling pathway | 1 |
| muscle cell differentiation | 1 |
| cell development | 1 |
| negative regulation of cell-substrate adhesion | 1 |
| substrate adhesion-dependent cell spreading | 1 |
| regulation of substrate adhesion-dependent cell spreading | 1 |
| non-canonical NF-kappaB signal transduction | 1 |
| regulation of non-canonical NF-kappaB signal transduction | 1 |
| positive regulation of intracellular signal transduction | 1 |
| transcription cis-regulatory region binding | 1 |
| carbohydrate derivative binding | 1 |
| heterocyclic compound binding | 1 |
| transcription coregulator activity | 1 |
| nucleic acid binding | 1 |
| cytoskeletal protein binding | 1 |
Protein interactions and networks
STRING
2468 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| ACTN4 | NPHS1 | O60500 | 988 |
| ACTN4 | SYNPO | Q8N3V7 | 979 |
| ACTN4 | NPHS2 | Q9NP85 | 971 |
| ACTN4 | VCL | P18206 | 965 |
| ACTN4 | CD2AP | Q9Y5K6 | 939 |
| ACTN4 | INF2 | Q27J81 | 929 |
| ACTN4 | MAGI1 | Q96QZ7 | 922 |
| ACTN4 | TRPC6 | Q9Y210 | 904 |
| ACTN4 | TRIM3 | O75382 | 879 |
| ACTN4 | TJP1 | Q07157 | 873 |
| ACTN4 | TLN1 | Q9Y490 | 859 |
| ACTN4 | MYH9 | P35579 | 840 |
| ACTN4 | PLCE1 | Q9P212 | 824 |
| ACTN4 | PDLIM1 | O00151 | 821 |
| ACTN4 | PDLIM2 | Q96JY6 | 794 |
IntAct
283 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| ACTN4 | MYOZ2 | psi-mi:“MI:0915”(physical association) | 0.930 |
| MYOZ2 | ACTN4 | psi-mi:“MI:0915”(physical association) | 0.930 |
| PDLIM1 | ACTN4 | psi-mi:“MI:0914”(association) | 0.800 |
| ACTN4 | PDLIM1 | psi-mi:“MI:0915”(physical association) | 0.800 |
| CFTR | ESYT2 | psi-mi:“MI:0914”(association) | 0.710 |
| CTNNB1 | ACTN4 | psi-mi:“MI:0914”(association) | 0.680 |
| ACTN4 | CTNNB1 | psi-mi:“MI:0915”(physical association) | 0.680 |
| ACTN4 | CTNNB1 | psi-mi:“MI:0403”(colocalization) | 0.680 |
BioGRID (552): ACTN4 (Affinity Capture-MS), ACTN3 (Two-hybrid), BMP7 (Two-hybrid), MYOZ2 (Two-hybrid), ACTN4 (Affinity Capture-MS), ACTN4 (Affinity Capture-MS), ACTN4 (Affinity Capture-MS), ACTN4 (Affinity Capture-MS), ACTN4 (Two-hybrid), ACTN4 (Affinity Capture-MS), ACTN4 (Affinity Capture-Western), RARA (Reconstituted Complex), ACTN4 (Affinity Capture-MS), MYOZ2 (Two-hybrid), MYOZ1 (Two-hybrid)
ESM2 similar proteins: A5D7D1, L7UZ85, O43707, O88990, P05094, P11277, P12814, P15508, P18091, P20111, P26232, P30997, P35609, P46940, P57780, Q00078, Q00963, Q01082, Q08043, Q0E908, Q0III9, Q13576, Q2PFV7, Q3B7N2, Q3UQ44, Q3ZC55, Q4QR29, Q4WVG0, Q5M7J9, Q5R416, Q5RCS6, Q61301, Q62018, Q62261, Q6DEU9, Q6INS3, Q6NXC0, Q6PD62, Q7G188, Q7PKQ5
Diamond homologs: A5D7D1, D3ZEN0, D3ZHA0, D3ZHV2, D3ZQL6, E1BBG2, F1MF74, F1RA39, F6QZ15, G3MWR8, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O75369, O76329, O88990, O94851, O97592, P05094, P05095, P07751, P11277, P11530, P11531, P11532, P11533, P12814, P13395, P13466, P15508, P16086, P16546, P18091, P20111, P21333, P30427, P35609
SIGNOR signaling
3 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| PTK2 | up-regulates | ACTN4 | phosphorylation |
| PTK2 | down-regulates | ACTN4 | phosphorylation |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 141 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 |
|---|---|---|---|
| FCGR3A-mediated phagocytosis | 5 | 11.0× | 1e-02 |
| RHOQ GTPase cycle | 5 | 10.7× | 1e-02 |
| Regulation of PLK1 Activity at G2/M Transition | 6 | 9.0× | 7e-03 |
| RHO GTPase Effectors | 8 | 6.4× | 7e-03 |
| Signaling by Rho GTPases, Miro GTPases and RHOBTB3 | 12 | 4.7× | 5e-03 |
| Signaling by Rho GTPases | 11 | 4.4× | 7e-03 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| epidermal growth factor receptor signaling pathway | 5 | 10.9× | 1e-02 |
| actin cytoskeleton organization | 13 | 9.0× | 3e-06 |
| protein phosphorylation | 9 | 5.4× | 5e-03 |
| negative regulation of apoptotic process | 13 | 4.0× | 5e-03 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
596 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 6 |
| Likely pathogenic | 11 |
| Uncertain significance | 255 |
| Likely benign | 169 |
| Benign | 59 |
Top pathogenic / likely-pathogenic (17)
| Variant ID | HGVS | Classification |
|---|---|---|
| 235864 | NM_004924.6(ACTN4):c.584G>A (p.Gly195Asp) | Pathogenic |
| 2500724 | NM_004924.6(ACTN4):c.584G>T (p.Gly195Val) | Pathogenic |
| 2736886 | NM_004924.6(ACTN4):c.445ATC[1] (p.Ile150del) | Pathogenic |
| 5420 | NM_004924.6(ACTN4):c.763A>G (p.Lys255Glu) | Pathogenic |
| 5421 | NM_004924.6(ACTN4):c.776C>T (p.Thr259Ile) | Pathogenic |
| 5422 | NM_004924.6(ACTN4):c.784T>C (p.Ser262Pro) | Pathogenic |
| 1028308 | NM_004924.6(ACTN4):c.175T>C (p.Trp59Arg) | Likely pathogenic |
| 2572429 | NM_004924.6(ACTN4):c.493G>A (p.Ala165Thr) | Likely pathogenic |
| 3035302 | NM_004924.6(ACTN4):c.608A>C (p.His203Pro) | Likely pathogenic |
| 3061635 | NM_004924.6(ACTN4):c.506T>G (p.Leu169Arg) | Likely pathogenic |
| 3068392 | NM_004924.6(ACTN4):c.517T>C (p.Cys173Arg) | Likely pathogenic |
| 3236342 | NM_004924.6(ACTN4):c.718A>G (p.Met240Val) | Likely pathogenic |
| 3900730 | NM_004924.6(ACTN4):c.757G>A (p.Asp253Asn) | Likely pathogenic |
| 4084962 | NM_004924.6(ACTN4):c.214G>C (p.Glu72Gln) | Likely pathogenic |
| 4796795 | NM_004924.6(ACTN4):c.773T>C (p.Met258Thr) | Likely pathogenic |
| 599063 | NM_004924.6(ACTN4):c.510_512del (p.Leu171del) | Likely pathogenic |
| 599130 | NM_004924.6(ACTN4):c.458T>C (p.Phe153Ser) | Likely pathogenic |
SpliceAI
4101 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 19:38647905:AAGGT:A | donor_loss | 1.0000 |
| 19:38647906:AGGTG:A | donor_loss | 1.0000 |
| 19:38647907:GGTG:G | donor_loss | 1.0000 |
| 19:38647908:G:GG | donor_gain | 1.0000 |
| 19:38647908:GT:G | donor_loss | 1.0000 |
| 19:38700589:T:TA | acceptor_gain | 1.0000 |
| 19:38700594:CCCCA:C | acceptor_loss | 1.0000 |
| 19:38700596:CCA:C | acceptor_loss | 1.0000 |
| 19:38700598:A:AG | acceptor_gain | 1.0000 |
| 19:38700598:A:C | acceptor_loss | 1.0000 |
| 19:38700599:G:GA | acceptor_gain | 1.0000 |
| 19:38700599:GA:G | acceptor_gain | 1.0000 |
| 19:38700599:GAC:G | acceptor_gain | 1.0000 |
| 19:38700599:GACC:G | acceptor_gain | 1.0000 |
| 19:38700599:GACCT:G | acceptor_gain | 1.0000 |
| 19:38700711:TCAG:T | donor_loss | 1.0000 |
| 19:38700715:G:T | donor_loss | 1.0000 |
| 19:38700988:T:TA | acceptor_gain | 1.0000 |
| 19:38700990:T:TA | acceptor_gain | 1.0000 |
| 19:38700993:A:AG | acceptor_gain | 1.0000 |
| 19:38700994:C:G | acceptor_gain | 1.0000 |
| 19:38701000:A:AG | acceptor_gain | 1.0000 |
| 19:38701000:AG:A | acceptor_gain | 1.0000 |
| 19:38701000:AGG:A | acceptor_gain | 1.0000 |
| 19:38701000:AGGG:A | acceptor_gain | 1.0000 |
| 19:38701001:G:GA | acceptor_gain | 1.0000 |
| 19:38701001:GG:G | acceptor_gain | 1.0000 |
| 19:38701001:GGG:G | acceptor_gain | 1.0000 |
| 19:38701001:GGGG:G | acceptor_gain | 1.0000 |
| 19:38701001:GGGGA:G | acceptor_gain | 1.0000 |
AlphaMissense
6111 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 19:38647887:T:A | W48R | 1.000 |
| 19:38647887:T:C | W48R | 1.000 |
| 19:38647889:G:C | W48C | 1.000 |
| 19:38647889:G:T | W48C | 1.000 |
| 19:38647900:A:C | Q52P | 1.000 |
| 19:38647901:G:C | Q52H | 1.000 |
| 19:38647901:G:T | Q52H | 1.000 |
| 19:38647903:G:C | R53P | 1.000 |
| 19:38700603:T:A | F56I | 1.000 |
| 19:38700603:T:C | F56L | 1.000 |
| 19:38700604:T:C | F56S | 1.000 |
| 19:38700604:T:G | F56C | 1.000 |
| 19:38700605:C:A | F56L | 1.000 |
| 19:38700605:C:G | F56L | 1.000 |
| 19:38700612:T:A | W59R | 1.000 |
| 19:38700612:T:C | W59R | 1.000 |
| 19:38700613:G:C | W59S | 1.000 |
| 19:38700614:G:C | W59C | 1.000 |
| 19:38700614:G:T | W59C | 1.000 |
| 19:38700615:T:C | C60R | 1.000 |
| 19:38700616:G:A | C60Y | 1.000 |
| 19:38700617:C:G | C60W | 1.000 |
| 19:38700621:T:C | S62P | 1.000 |
| 19:38700624:C:G | H63D | 1.000 |
| 19:38700628:T:A | L64Q | 1.000 |
| 19:38700628:T:C | L64P | 1.000 |
| 19:38700678:G:A | G81R | 1.000 |
| 19:38700678:G:C | G81R | 1.000 |
| 19:38700678:G:T | G81W | 1.000 |
| 19:38700679:G:A | G81E | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000043704 (19:38699663 G>A,T), RS1000116175 (19:38672359 G>T), RS1000140544 (19:38689761 C>T), RS1000150687 (19:38699181 T>C), RS1000201936 (19:38654067 A>C), RS1000215632 (19:38658727 G>A,C), RS1000254141 (19:38654328 G>A), RS1000348394 (19:38682020 G>A), RS1000372966 (19:38719783 A>C), RS1000395227 (19:38647598 G>A,T), RS1000524619 (19:38693504 C>G,T), RS1000526476 (19:38678162 G>A), RS1000538274 (19:38715314 T>A), RS1000561245 (19:38655301 C>T), RS1000597214 (19:38698431 G>T)
Disease associations
OMIM: gene MIM:604638 | disease phenotypes: MIM:603278, MIM:614607
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| focal segmental glomerulosclerosis 1 | Strong | Autosomal dominant |
| familial idiopathic steroid-resistant nephrotic syndrome | Supportive | Autosomal dominant |
Mondo (7): focal segmental glomerulosclerosis 1 (MONDO:0011303), focal segmental glomerulosclerosis (MONDO:0100313), kidney disorder (MONDO:0005240), intellectual disability, autosomal dominant 14 (MONDO:0013819), chronic kidney disease (MONDO:0005300), nephrotic syndrome (MONDO:0005377), familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006)
Orphanet (3): Hereditary steroid-resistant nephrotic syndrome (Orphanet:656), Coffin-Siris syndrome (Orphanet:1465), OBSOLETE: Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis (Orphanet:93213)
HPO phenotypes
27 total (27 of 27 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0000093 | Proteinuria |
| HP:0000097 | Focal segmental glomerulosclerosis |
| HP:0000707 | Abnormality of the nervous system |
| HP:0000737 | Irritability |
| HP:0000822 | Hypertension |
| HP:0000969 | Edema |
| HP:0001541 | Ascites |
| HP:0001903 | Anemia |
| HP:0001945 | Fever |
| HP:0001967 | Diffuse mesangial sclerosis |
| HP:0002027 | Abdominal pain |
| HP:0002202 | Pleural effusion |
| HP:0002315 | Headache |
| HP:0002586 | Peritonitis |
| HP:0003073 | Hypoalbuminemia |
| HP:0003077 | Hyperlipidemia |
| HP:0003677 | Slowly progressive |
| HP:0003774 | Stage 5 chronic kidney disease |
| HP:0003829 | Typified by incomplete penetrance |
| HP:0004719 | Hyperechogenic kidneys |
| HP:0005565 | Reduced renal corticomedullary differentiation |
| HP:0011947 | Respiratory tract infection |
| HP:0012579 | Minimal change glomerulonephritis |
| HP:0012622 | Chronic kidney disease |
| HP:0031504 | Foamy urine |
| HP:0100539 | Periorbital edema |
GWAS associations
9 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST001969_30 | Heart rate | 2.000000e-06 |
| GCST006999_4 | Logical memory (immediate recall) in mild cognitive impairment | 4.000000e-07 |
| GCST008151_16 | Waist circumference | 7.000000e-06 |
| GCST008160_61 | Waist circumference | 7.000000e-06 |
| GCST009422_1 | Retinal venular tortuosity | 2.000000e-13 |
| GCST010703_256 | Brain morphology (MOSTest) | 8.000000e-14 |
| GCST012047_17 | Fasting glucose | 7.000000e-07 |
| GCST90002387_53 | Immature fraction of reticulocytes | 1.000000e-09 |
| GCST90002395_411 | Mean platelet volume | 1.000000e-14 |
EFO canonical traits (3, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004874 | memory performance |
| EFO:0010554 | retinal vasculature measurement |
| EFO:0004346 | neuroimaging measurement |
MeSH disease descriptors (5)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D005923 | Glomerulosclerosis, Focal Segmental | C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640 |
| D007674 | Kidney Diseases | C12.050.351.968.419; C12.200.777.419; C12.950.419 |
| D007676 | Kidney Failure, Chronic | C12.050.351.968.419.780.750.500; C12.200.777.419.780.750.500; C12.950.419.780.750.500; C23.550.291.500.906.500 |
| D009404 | Nephrotic Syndrome | C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643 |
| C538457 | Segmental glomerulosclerosis (supp.) |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL5724737 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL1232461 | MOLIBRESIB | 2 | 1,538 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
ChEMBL bioactivities
5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 6.92 | Kd | 120.3 | nM | CHEMBL5653589 |
| 6.92 | ED50 | 120.3 | nM | CHEMBL5653589 |
| 6.28 | IC50 | 530 | nM | MOLIBRESIB |
| 5.40 | Kd | 4006 | nM | CHEMBL3752910 |
| 5.40 | ED50 | 4006 | nM | CHEMBL3752910 |
PubChem BioAssay actives
3 with measured affinity, of 10 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2147797: Binding affinity to human ACTN4 incubated for 45 mins by Kinobead based pull down assay | kd | 0.1203 | uM |
| 2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide | 2178896: Inhibition of ACTN4 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis | ic50 | 0.5300 | uM |
| 4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2147797: Binding affinity to human ACTN4 incubated for 45 mins by Kinobead based pull down assay | kd | 4.0058 | uM |
CTD chemical–gene interactions
59 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| bisphenol A | affects cotreatment, increases methylation, decreases methylation, increases expression, affects expression | 4 |
| Tobacco Smoke Pollution | affects expression, decreases expression, increases expression | 3 |
| Aflatoxin B1 | decreases expression, increases methylation, affects cotreatment | 3 |
| Air Pollutants | decreases expression, increases abundance, increases expression | 2 |
| Particulate Matter | decreases expression, increases abundance, affects cotreatment, increases expression | 2 |
| aristolochic acid I | increases expression | 1 |
| FR900359 | increases phosphorylation | 1 |
| triphenyl phosphate | affects expression | 1 |
| sodium arsenate | decreases expression | 1 |
| pyrogallol 1,3-dimethyl ether | decreases expression, affects localization, increases expression, affects cotreatment | 1 |
| quercitrin | affects expression | 1 |
| beta-lapachone | increases expression | 1 |
| arsenite | affects binding, increases reaction | 1 |
| sodium arsenite | decreases expression | 1 |
| cobaltous chloride | decreases expression | 1 |
| 4-hydroxy-2-nonenal | affects binding | 1 |
| aflatoxin B2 | increases methylation | 1 |
| cupric oxide | increases expression | 1 |
| beta-methylcholine | affects expression | 1 |
| perfluorooctane sulfonic acid | decreases expression | 1 |
| 2,3,5-(triglutathion-S-yl)hydroquinone | increases ADP-ribosylation | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| chloropicrin | increases expression | 1 |
| K 7174 | decreases expression | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | affects cotreatment, decreases expression | 1 |
| bisphenol B | increases expression | 1 |
| bromovanin | increases expression | 1 |
| bisphenol S | increases expression | 1 |
| LDN 193189 | affects cotreatment, decreases expression | 1 |
| (+)-JQ1 compound | increases expression | 1 |
ChEMBL screening assays
7 unique, capped per target: 7 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL5650839 | Binding | Binding affinity to human ACTN4 incubated for 45 mins by Kinobead based pull down assay | NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem |
Cellosaurus cell lines
2 cell lines: 2 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_SB30 | HAP1 ACTN4 (-) 1 | Cancer cell line | Male |
| CVCL_XL02 | HAP1 ACTN4 (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
300 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT01129557 | PHASE4 | TERMINATED | Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease |
| NCT02399462 | PHASE4 | WITHDRAWN | Acthar for Treatment of Post-transplant FSGS |
| NCT02585804 | PHASE4 | COMPLETED | Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects |
| NCT02633046 | PHASE4 | COMPLETED | Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria |
| NCT07219121 | PHASE4 | RECRUITING | Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis |
| NCT00067990 | PHASE4 | COMPLETED | Angiotensin II Blockade for Chronic Allograft Nephropathy |
| NCT00117078 | PHASE4 | COMPLETED | Aranesp® Monthly Preference Study - 2 |
| NCT00117130 | PHASE4 | COMPLETED | Study to Evaluate Effectiveness of Aranesp® |
| NCT00132431 | PHASE4 | COMPLETED | START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism |
| NCT00140985 | PHASE4 | COMPLETED | Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213) |
| NCT00246129 | PHASE4 | COMPLETED | CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation |
| NCT00275535 | PHASE4 | COMPLETED | The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients |
| NCT00282217 | PHASE4 | COMPLETED | Study Evaluating Sirolimus in the Treatment of Kidney Transplant |
| NCT00289614 | PHASE4 | COMPLETED | Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT) |
| NCT00290069 | PHASE4 | UNKNOWN | Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA) |
| NCT00338468 | PHASE4 | TERMINATED | A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa) |
| NCT00368901 | PHASE4 | COMPLETED | STAAR-2 Clinical Study |
| NCT00369733 | PHASE4 | COMPLETED | STAAR-3 Clinical Study |
| NCT00369772 | PHASE4 | COMPLETED | STAAR-1 Clinical Study |
| NCT00379899 | PHASE4 | COMPLETED | ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis |
| NCT00443508 | PHASE4 | UNKNOWN | Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion |
| NCT00452478 | PHASE4 | TERMINATED | Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5 |
| NCT00492518 | PHASE4 | COMPLETED | Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy |
| NCT00505102 | PHASE4 | UNKNOWN | Safe Renal Function In Long Term Heart Transplanted Patients |
| NCT00526331 | PHASE4 | COMPLETED | Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy |
| NCT00688480 | PHASE4 | COMPLETED | Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction? |
| NCT00863707 | PHASE4 | COMPLETED | A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment |
| NCT01101698 | PHASE4 | UNKNOWN | Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients |
| NCT01150201 | PHASE4 | COMPLETED | Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease |
| NCT01155141 | PHASE4 | COMPLETED | Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH |
| NCT01228279 | PHASE4 | COMPLETED | Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis |
| NCT01334333 | PHASE4 | COMPLETED | Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients |
| NCT01437943 | PHASE4 | TERMINATED | Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients |
| NCT01545479 | PHASE4 | COMPLETED | Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition |
| NCT01614431 | PHASE4 | COMPLETED | N Acetyl Cysteine for Cystinosis Patients |
| NCT01631149 | PHASE4 | COMPLETED | Effect of Deep BLock on Intraoperative Surgical Conditions |
| NCT01722513 | PHASE4 | UNKNOWN | Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy |
| NCT01985360 | PHASE4 | COMPLETED | ISCHEMIA-Chronic Kidney Disease Trial |
| NCT02311010 | PHASE4 | UNKNOWN | Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism |
| NCT02413073 | PHASE4 | COMPLETED | Whole Body Vibration in Kidney Disease |
Related Atlas pages
- Associated diseases: focal segmental glomerulosclerosis 1, familial idiopathic steroid-resistant nephrotic syndrome
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): chronic kidney disease, familial idiopathic steroid-resistant nephrotic syndrome, focal segmental glomerulosclerosis, focal segmental glomerulosclerosis 1, intellectual disability, autosomal dominant 14, kidney disorder, nephrotic syndrome