ACTB

Summary

ACTB (actin beta, HGNC:132) is a protein-coding gene on chromosome 7p22.1, encoding Actin, cytoplasmic 1 (P60709). Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells. It is a selective cancer dependency (DepMap: 72.1% of cell lines).

This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a major constituent of the contractile apparatus and one of the two nonmuscle cytoskeletal actins that are ubiquitously expressed. Mutations in this gene cause Baraitser-Winter syndrome 1, which is characterized by intellectual disability with a distinctive facial appearance in human patients. Numerous pseudogenes of this gene have been identified throughout the human genome.

Source: NCBI Gene 60 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Baraitser-Winter cerebrofrontofacial syndrome (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 714 total — 69 pathogenic, 85 likely-pathogenic
• Phenotypes (HPO): 158
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 72.1% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001101

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:132
Approved symbol	ACTB
Name	actin beta
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000075624
Ensembl biotype	protein_coding
OMIM	102630
Entrez	60

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 35 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000414620, ENST00000417101, ENST00000425660, ENST00000432588, ENST00000443528, ENST00000462494, ENST00000464611, ENST00000473257, ENST00000477812, ENST00000480301, ENST00000484841, ENST00000493945, ENST00000642480, ENST00000645025, ENST00000645576, ENST00000646584, ENST00000646664, ENST00000647275, ENST00000674681, ENST00000675515, ENST00000676189, ENST00000676319, ENST00000676397, ENST00000899420, ENST00000899421, ENST00000899422, ENST00000899423, ENST00000899424, ENST00000899425, ENST00000899426, ENST00000899427, ENST00000899428, ENST00000899429, ENST00000919298, ENST00000919299, ENST00000919300, ENST00000919301, ENST00000919302, ENST00000919303, ENST00000919304, ENST00000919305, ENST00000919306, ENST00000950579

RefSeq mRNA: 1 — MANE Select: NM_001101 NM_001101

CCDS: CCDS5341

Canonical transcript exons

ENST00000646664 — 6 exons

Exon	Start	End
ENSE00001526557	5530524	5530601
ENSE00003465957	5528004	5528185
ENSE00003542066	5529535	5529663
ENSE00003549974	5529161	5529400
ENSE00003614573	5528281	5528719
ENSE00003821088	5527148	5527891

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 100.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4893.4285 / max 55843.0669, expressed in 1829 samples.

FANTOM5 promoters (23 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82608	4800.6647	1829
82602	22.7306	1816
82595	12.4852	1793
82585	10.3422	1765
82584	9.9612	1728
82600	7.4903	1663
82582	5.0654	1625
82589	4.0504	1618
82593	3.7775	1540
82583	3.1399	1347

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
urethra	UBERON:0000057	100.00	gold quality
postcentral gyrus	UBERON:0002581	100.00	gold quality
saphenous vein	UBERON:0007318	100.00	gold quality
ileal mucosa	UBERON:0000331	99.99	gold quality
parietal lobe	UBERON:0001872	99.99	gold quality
nipple	UBERON:0002030	99.99	gold quality
synovial joint	UBERON:0002217	99.99	gold quality
olfactory bulb	UBERON:0002264	99.99	gold quality
CA1 field of hippocampus	UBERON:0003881	99.99	gold quality
vena cava	UBERON:0004087	99.99	gold quality
orbitofrontal cortex	UBERON:0004167	99.99	gold quality
cauda epididymis	UBERON:0004360	99.99	gold quality
blood vessel layer	UBERON:0004797	99.99	gold quality
endometrium epithelium	UBERON:0004811	99.99	gold quality
inferior vagus X ganglion	UBERON:0005363	99.99	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.99	gold quality
adult organism	UBERON:0007023	99.99	gold quality
lower lobe of lung	UBERON:0008949	99.99	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.99	gold quality
buccal mucosa cell	CL:0002336	99.98	gold quality
dorsal root ganglion	UBERON:0000044	99.98	gold quality
colonic mucosa	UBERON:0000317	99.98	gold quality
renal medulla	UBERON:0000362	99.98	gold quality
seminal vesicle	UBERON:0000998	99.98	gold quality
cardia of stomach	UBERON:0001162	99.98	gold quality
pylorus	UBERON:0001166	99.98	gold quality
mucosa of urinary bladder	UBERON:0001259	99.98	gold quality
superficial temporal artery	UBERON:0001614	99.98	gold quality
right coronary artery	UBERON:0001625	99.98	gold quality
trigeminal ganglion	UBERON:0001675	99.98	gold quality

Single-cell (SCXA)

Detected in 66 experiment(s), a significant marker in 33.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	38051.11
E-MTAB-10042	yes	31024.49
E-HCAD-4	yes	26662.76
E-CURD-98	yes	18582.01
E-CURD-97	yes	17329.23
E-MTAB-10432	yes	17240.56
E-MTAB-6819	yes	11852.94
E-MTAB-6678	yes	11683.87
E-ANND-2	yes	11316.65
E-CURD-46	yes	10653.43
E-MTAB-9467	yes	10524.20
E-GEOD-135922	yes	10010.74
E-MTAB-8884	yes	9610.42
E-CURD-88	yes	9124.77
E-HCAD-11	yes	9094.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, APEX1, CNBP, CUX2, FOS, HOXA1, HOXA7, JUN, MBD1, MYC, MYOD1, MYOG, NFIC, NFKB, NFYA, NFYB, RARB, SFPQ, SP1, SRF, TBP, TP63, YBX1, ZBTB14, ZGLP1, ZHX2

miRNA regulators (miRDB)

81 targeting ACTB, 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-6870-5P	99.99	68.55	2115
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-LET-7G-3P	99.85	70.43	1929

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 72.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• region responsible for down-regulation of the gamma-actin gene during differentiation is not in the 3’ end of the gene in contrast to that for beta-actin. (PMID:11787062)
• human fibroblast cells infected by Cytomegalovirus could express immediate early mRNA and the expression of beta-actin mRNA decreased in a time- and titer-dependent manner (PMID:15101111)
• GLI oncogene is activated through fusion with the beta-actin gene (ACTB) in a group of distinctive pericytic neoplasms (PMID:15111311)
• characterization of the breakpoints of the ACTB-GLI and GLI-ACTB fusions at the genomic level in pericytoma with t(7;12) (PMID:15555571)
• beta-actin localizes to an active U6 promoter in RNA polymerase III (pol III) and is essential for basal pol III transcription. (PMID:15574586)
• Data lead to the conclusion that there is a distinct correlation between metastatic capacity of examined human colon adenocarcinoma cells, the state of actin polymerization, actin cytoskeleton organization and beta-actin expression. (PMID:15940343)
• both monomeric and oligomeric or polymeric forms of actin are at play and raising the possibility that the equilibrium between them, perhaps differentially regulated at various intranuclear sites, may be a major determinant of nuclear function. (PMID:16148048)
• beta-actin is a transcription factor stimulates eNOS expression; and the transcriptional effect appears to be 27nt-dependent (PMID:16210567)
• Actin could contribute to the initiation of apoptosis by enabling cytosolic pro-apoptotic proteins to be carried to mitochondria by the cytoskeleton-driven trafficking system. (PMID:16536728)
• These findings suggest that mutations in beta actin may be associated with a broad spectrum of developmental malformations and/or neurological abnormalities such as dystonia. (PMID:16685646)
• The results from this controlled CCT-actin folding assay are consistent with a model where CCT and Ac(I) are in a binding pre-equilibrium with a rate-limiting binding step, followed by a faster ATP-driven processing to native actin. (PMID:16762366)
• These data establish that the posttranscriptional event involving HuR-mediated beta-actin mRNA stabilization could be a part of the regulatory mechanisms responsible for maintaining cell integrity. (PMID:17548472)
• Beta-actin can be directly tyrosine-phosphorylated by Src in vitro, and in a Src-dependent manner in cells. Moreover, beta-actin dynamics are suppressed when Src is rendered kinase-inactive. (PMID:17651734)
• The specific and directed rearrangement of the beta-actin structure, seen in the natural beta-actin-TRiC system, is vital for guiding beta-actin to the native state. (PMID:17939680)
• We observed the nuclear translocation of the transcription factor Nrf2 associated with thinning of the actin stress fibers. (PMID:18261463)
• There was no significant difference in IL-4/beta-actin between the patients with AIH and the healthy controls. In contrast there was a significant difference of IFN-gamma/beta-actin between those two groups. (PMID:18533937)
• Results show overexpression or depletion of RHA could influence the interaction of Pol II with beta-actin and beta-actin-involved gene transcription regulation. (PMID:19309309)
• CTCF colocalizes with NELF on the U2 and beta-actin genes, raising the possibility that it helps the positioning and/or function of the NELF-dependent control point on these genes. (PMID:19451231)
• MARCKS regulates lamellipodia formation induced by IGF-I via association with PIP2 and beta-actin at membrane microdomains. (PMID:19475567)
• Data show that inducible Hox genes are selectively sensitive to the inhibition of actin polymerization and that actin polymerization is required for the assembly of a transcription complex on the regulatory region of the Hox genes. (PMID:19477923)
• These results reveal new aspects of beta- and gamma-actin organization that support their functional diversity. (PMID:19638415)
• Results suggest a novel mechanism by which cofilin is regulated by v-Src through tyrosine phosphorylation that triggers the degradation of cofilin through ubiquitination-proteosome pathway and reducing cellular F-actin contents and cell spreading. (PMID:19802004)
• Immunoblot analysis revealed profoundly decreased beta-actin levels during Ectromelia virus infection replicative cycle in the infected cells 24 hrs post infection. (PMID:20201613)
• The actin network plays a role in nuclear ERalpha actions in breast cancer cells. (PMID:20308691)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)
• Data suggest that the existence of a common epitope on the molecules of phosducin and beta-actin may reflect a topological similarity of a small region of their surfaces. (PMID:20804785)
• Findings indicate that activation of the cofilin-F-actin pathway contributes to tumor cell migration and metastasis enhanced by Aur-A, revealing a novel function for mitotic Aur-A kinase in tumor progression. (PMID:21045147)
• Nuclear beta-actin controls growth arrest of epithelial cells. (PMID:21172822)
• ACTB showed high expression in forensic skin and body-fluid samples, providing a suitable marker for skin identification (PMID:21221983)
• Data indicate taht candidate genes ACTB, BZW, OCM, MACC1, NXPH1, PRPS1L1, RAC1 and RPA3, which lie within the DFNB90 region, were sequenced and no potentially causal variants were identified. (PMID:21734401)
• non-muscle alpha-ACTN4, HSPA5 and cytoplasmic ACTB, should be targeted in idiopathic premature ovarian failure cases (PMID:21890413)
• Data show that ENOA, PARK7 and Beta-actin are proper reference standards in obesity studies based on omental fat. (PMID:22272336)
• Antioxidant supplementation was noted to increase G6PDH in the pentose phosphate cycle and 18S rRNA in the ribosome. There were no significant changes in the gene expression levels of beta-ACT (PMID:22285204)
• Recombinant human actin is constantly shuttled into the murine nucleus by importin 9 and out by exportin 6. Nuclear actin is required for maximal transcription. (PMID:22323606)
• identified de novo missense changes in the cytoplasmic actin-encoding genes ACTB and ACTG1 in one and two probands, respectively; suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes (PMID:22366783)
• Cofilin nuclear shuttling is critical for the cofilin-actin rod stress response. (PMID:22623727)
• Data indicate beta-cytoplasmic (beta-CYA) and gamma-cytoplasmic (gamma-CYA) actins differential localization and dynamics at epithelial junctions. (PMID:22855531)
• roles for undetected ACtB in liver cancer progression (PMID:22961449)
• These results indicate that F-actin in association with the M protein alters the interaction between the M and H proteins, thereby modulating measles virus cell-cell fusion and assembly. (PMID:23221571)
• the roles of ACTB in tumors (PMID:23266771)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Actb	ENSMUSG00000029580
rattus_norvegicus	Potef	ENSRNOG00000034254

Paralogs (26): ACTR6 (ENSG00000075089), ACTL6B (ENSG00000077080), ACTR5 (ENSG00000101442), ACTR3C (ENSG00000106526), ACTA2 (ENSG00000107796), ACTR8 (ENSG00000113812), ACTR1B (ENSG00000115073), ACTR3 (ENSG00000115091), ACTL8 (ENSG00000117148), ACTRT1 (ENSG00000123165), ACTR10 (ENSG00000131966), ACTR3B (ENSG00000133627), ACTL6A (ENSG00000136518), ACTR2 (ENSG00000138071), ACTR1A (ENSG00000138107), ACTA1 (ENSG00000143632), ACTL7B (ENSG00000148156), ACTC1 (ENSG00000159251), ACTG2 (ENSG00000163017), ACTBL2 (ENSG00000169067), ACTRT2 (ENSG00000169717), ACTL9 (ENSG00000181786), ACTG1 (ENSG00000184009), ACTRT3 (ENSG00000184378), ACTL7A (ENSG00000187003), ACTL10 (ENSG00000288649)

Protein

Protein identifiers

Actin, cytoplasmic 1 — P60709 (reviewed: P60709)

Alternative names: Beta-actin

All UniProt accessions (14): P60709, A0A2R8Y793, A0A2R8YEA7, A0A2R8YFE2, A0A2R8YGF8, A0A6Q8PFE4, A0A6Q8PGD7, A0A6Q8PH58, C9JTX5, C9JUM1, C9JZR7, E7EVS6, G5E9R0, Q1KLZ0

UniProt curated annotations — full annotation on UniProt →

Function. Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells. Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction. In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA. Plays a role in the assembly of the gamma-tubulin ring complex (gTuRC), which regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments. Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules.

Subunit / interactions. Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Component of the BAF complex, which includes at least actin (ACTB), ARID1A, ARID1B/BAF250, SMARCA2, SMARCA4/BRG1, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57 SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more of SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3. Found in a complex with XPO6, Ran, ACTB and PFN1. Interacts with PFN1. Interacts with XPO6 and EMD. Interacts with ERBB2. Interacts with GCSAM. Interacts with TBC1D21. Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain). Interacts with DHX9 (via C-terminus); this interaction is direct and mediates the attachment to nuclear ribonucleoprotein complexes. Interacts with FAM107A. Associates with the gamma-tubulin ring complex (gTuRC) consisting of TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6 and gamma-tubulin TUBG1 or TUBG2; within the complex, interacts with TUBGCP3 and TUBGCP6 to form a luminal bridge with MZT1 that stabilizes the initial structure during complex assembly. Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The filament contains 8 copies of ACTR1A and 1 ACTB. Interacts with TPRN which forms ring-like structures in the stereocilium taper region; the interaction may stabilize stereocilia in inner ear hair cells. Interacts with AMOTL2 (via N-terminus), the interaction facilitates binding of cell junction complexes to actin fibers in endothelial cells.

Subcellular location. Cytoplasm. Cytoskeleton. Nucleus.

Post-translational modifications. ISGylated. Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization. Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration. Methylated at His-73 by SETD3. Methylation at His-73 is required for smooth muscle contraction of the laboring uterus during delivery. N-terminal cleavage of acetylated methionine of immature cytoplasmic actin by ACTMAP. N-terminal acetylation by NAA80 affects actin filament depolymerization and elongation, including elongation driven by formins. In contrast, filament nucleation by the Arp2/3 complex is not affected. (Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-50 of one monomer and Glu-270 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding. The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners.

Disease relevance. Dystonia-deafness syndrome 1 (DDS1) [MIM:607371] An autosomal dominant form of dystonia with juvenile onset, associated with congenital or childhood-onset sensorineural deafness. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. Some DDS1 patients have dysmorphic features, skeletal anomalies, and/or mild developmental delay with impaired intellectual development. The disease is caused by variants affecting the gene represented in this entry. Baraitser-Winter syndrome 1 (BRWS1) [MIM:243310] A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss. The disease is caused by variants affecting the gene represented in this entry. Thrombocytopenia 8, with dysmorphic features and developmental delay (THC8) [MIM:620475] A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC8 is an autosomal dominant form characterized by early-childhood onset of thrombocytopenia with platelet anisotropy. Affected individuals also have dysmorphic facial features and variable developmental delay with speech delay and mildly impaired intellectual development. The disease is caused by variants affecting the gene represented in this entry. Becker nevus syndrome (BNS) [MIM:604919] A syndrome characterized by the association of Becker nevi with musculoskeletal abnormalities, unilateral breast hypoplasia, intellectual disability, developmental delay, and cardiomyopathy. Becker nevus is a cutaneous hamartoma that appears in childhood as a unilateral tan patch and increases in thickness, pigmentation, and hair growth during adolescence. Histologically, epidermal acanthosis is accompanied by irregularly dispersed ectopic smooth muscle bundles and increased terminal hair follicles. Most cases are sporadic. The disease is caused by variants affecting the gene represented in this entry. Congenital smooth muscle hamartoma, with or without hemihypertrophy (CSMH) [MIM:620470] A benign skin lesion that usually presents as an indurated, slightly pigmented or flesh-colored plaque with perifollicular papules or coarse hair. Histopathologically, there is excessive proliferation of ectopic smooth muscle within the dermis. Hair follicles are normal in number and hyperkeratosis, acanthosis and hyperpigmentation of the basal cell layer can sometimes be seen. Rarely, CSMH is associated with hemihypertrophy. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.

Similarity. Belongs to the actin family.

RefSeq proteins (1): NP_001092* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004000	Actin	Family
IPR004001	Actin_CS	Conserved_site
IPR020902	Actin/actin-like_CS	Conserved_site
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00022

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (92 total): helix 22, strand 21, sequence variant 19, mutagenesis site 10, turn 7, modified residue 6, chain 2, cross-link 2, sequence conflict 2, initiator methionine 1

Structure

Experimental structures (PDB)

88 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6MBK	X-RAY DIFFRACTION	1.69
6OX0	X-RAY DIFFRACTION	1.75
6WK2	X-RAY DIFFRACTION	1.76
6MBJ	X-RAY DIFFRACTION	1.78
6OX3	X-RAY DIFFRACTION	1.78
7W28	X-RAY DIFFRACTION	1.79
6WK1	X-RAY DIFFRACTION	1.89
6OX1	X-RAY DIFFRACTION	1.95
6ICT	X-RAY DIFFRACTION	1.95
6V63	X-RAY DIFFRACTION	2.02
6OX2	X-RAY DIFFRACTION	2.09
6OX5	X-RAY DIFFRACTION	2.1
6ICV	X-RAY DIFFRACTION	2.15
9QEW	ELECTRON MICROSCOPY	2.18
6MBL	X-RAY DIFFRACTION	2.2
3D2U	X-RAY DIFFRACTION	2.21
8OI8	ELECTRON MICROSCOPY	2.28
6OX4	X-RAY DIFFRACTION	2.29
8OID	ELECTRON MICROSCOPY	2.3
9QFJ	ELECTRON MICROSCOPY	2.31
6V62	X-RAY DIFFRACTION	2.36
8QR1	ELECTRON MICROSCOPY	2.4
9QF2	ELECTRON MICROSCOPY	2.42
6NBW	X-RAY DIFFRACTION	2.5
9QFD	ELECTRON MICROSCOPY	2.61
9QEY	ELECTRON MICROSCOPY	2.74
9QFB	ELECTRON MICROSCOPY	2.74
9UXC	ELECTRON MICROSCOPY	2.74
9C57	ELECTRON MICROSCOPY	2.75
9QFQ	ELECTRON MICROSCOPY	2.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60709-F1	95.31	0.93

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 270, 1, 2, 44, 47, 73, 84, 50

Mutagenesis-validated functional residues (10):

Position	Phenotype
69	decreased interaction with setd3.
71	decreased interaction with setd3.
71	impaired methylation by setd3.
73	abolished methylation by setd3.
73	weak methylation by a a-256 or v-256 setd3 mutant. high methylation by a f-256 and a-274 setd3 mutant.
74	impaired methylation by setd3.
79	does not affect methylation by setd3.
80	decreased interaction with setd3.
81	decreased interaction with setd3.
82	decreased interaction with setd3.

Function

Pathways and Gene Ontology

Reactome pathways

100 pathways

ID	Pathway
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-190873	Gap junction degradation
R-HSA-196025	Formation of annular gap junctions
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-3214847	HATs acetylate histones
R-HSA-389957	Prefoldin mediated transfer of substrate to CCT/TriC
R-HSA-390450	Folding of actin by CCT/TriC
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-3928665	EPH-ephrin mediated repulsion of cells
R-HSA-418990	Adherens junctions interactions
R-HSA-437239	Recycling pathway of L1
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-445095	Interaction between L1 and Ankyrins
R-HSA-446353	Cell-extracellular matrix interactions
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-5626467	RHO GTPases activate IQGAPs
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-5674135	MAP2K and MAPK activation
R-HSA-5689603	UCH proteinases
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9035034	RHOF GTPase cycle
R-HSA-9649948	Signaling downstream of RAS mutants
R-HSA-9656223	Signaling by RAF1 mutants
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea

MSigDB gene sets: 1028 (showing top): GOBP_APICAL_PROTEIN_LOCALIZATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, MACLACHLAN_BRCA1_TARGETS_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP

GO Biological Process (36): morphogenesis of a polarized epithelium (GO:0001738), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), cytoskeleton organization (GO:0007010), establishment or maintenance of cell polarity (GO:0007163), axonogenesis (GO:0007409), positive regulation of cell population proliferation (GO:0008284), substantia nigra development (GO:0021762), regulation of mitotic metaphase/anaphase transition (GO:0030071), adherens junction assembly (GO:0034333), maintenance of blood-brain barrier (GO:0035633), regulation of apoptotic process (GO:0042981), apical protein localization (GO:0045176), positive regulation of T cell differentiation (GO:0045582), negative regulation of cell differentiation (GO:0045596), positive regulation of cell differentiation (GO:0045597), positive regulation of myoblast differentiation (GO:0045663), positive regulation of DNA-templated transcription (GO:0045893), cell motility (GO:0048870), regulation of norepinephrine uptake (GO:0051621), positive regulation of norepinephrine uptake (GO:0051623), regulation of cell cycle (GO:0051726), regulation of G0 to G1 transition (GO:0070316), platelet aggregation (GO:0070527), protein localization to adherens junction (GO:0071896), cellular response to cytochalasin B (GO:0072749), regulation of transepithelial transport (GO:0150111), regulation of synaptic vesicle endocytosis (GO:1900242), positive regulation of stem cell population maintenance (GO:1902459), regulation of protein localization to plasma membrane (GO:1903076), positive regulation of double-strand break repair via homologous recombination (GO:1905168), regulation of G1/S transition of mitotic cell cycle (GO:2000045), regulation of double-strand break repair (GO:2000779), positive regulation of double-strand break repair (GO:2000781), regulation of nucleotide-excision repair (GO:2000819), postsynaptic actin cytoskeleton organization (GO:0098974)

GO Molecular Function (16): structural constituent of cytoskeleton (GO:0005200), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), kinesin binding (GO:0019894), protein kinase binding (GO:0019901), nitric-oxide synthase regulator activity (GO:0030235), Tat protein binding (GO:0030957), identical protein binding (GO:0042802), tau protein binding (GO:0048156), nitric-oxide synthase binding (GO:0050998), structural constituent of postsynaptic actin cytoskeleton (GO:0098973), transporter regulator activity (GO:0141108), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787), nucleosomal DNA binding (GO:0031492)

GO Cellular Component (44): kinetochore (GO:0000776), chromatin (GO:0000785), nucleosome (GO:0000786), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), actin filament (GO:0005884), plasma membrane (GO:0005886), brush border (GO:0005903), cell-cell junction (GO:0005911), adherens junction (GO:0005912), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), membrane (GO:0016020), nuclear matrix (GO:0016363), SWI/SNF complex (GO:0016514), RSC-type complex (GO:0016586), lamellipodium (GO:0030027), axon (GO:0030424), cortical cytoskeleton (GO:0030863), vesicle (GO:0031982), protein-containing complex (GO:0032991), brahma complex (GO:0035060), NuA4 histone acetyltransferase complex (GO:0035267), cytoplasmic ribonucleoprotein granule (GO:0036464), apical junction complex (GO:0043296), calyx of Held (GO:0044305), synapse (GO:0045202), extracellular exosome (GO:0070062), tight junction (GO:0070160), npBAF complex (GO:0071564), nBAF complex (GO:0071565), blood microparticle (GO:0072562), dense body (GO:0097433), Schaffer collateral - CA1 synapse (GO:0098685), presynapse (GO:0098793), postsynaptic actin cytoskeleton (GO:0098871)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
RHO GTPase Effectors	3
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	2
EPH-Ephrin signaling	2
L1CAM interactions	2
Membrane Trafficking	1
Gap junction trafficking	1
Gap junction degradation	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Chromatin modifying enzymes	1
Cell-cell junction organization	1
Signaling by VEGF	1
Cell junction organization	1
Positive epigenetic regulation of rRNA expression	1
RAF/MAP kinase cascade	1
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
regulation of DNA-templated transcription	2
cellular process	2
positive regulation of cellular process	2
cell differentiation	2
regulation of cell differentiation	2
cytoskeleton	2
cytoskeletal protein binding	2
intracellular membraneless organelle	2
nuclear lumen	2
SWI/SNF superfamily-type complex	2
morphogenesis of an epithelium	1
chromatin organization	1
transcription by RNA polymerase II	1
organelle organization	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
cell population proliferation	1
regulation of cell population proliferation	1
midbrain development	1
neural nucleus development	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of metaphase/anaphase transition of cell cycle	1
cell-cell junction assembly	1
adherens junction organization	1
tissue homeostasis	1
apoptotic process	1
regulation of programmed cell death	1
intracellular protein localization	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1
negative regulation of cellular process	1
negative regulation of developmental process	1
positive regulation of developmental process	1
myoblast differentiation	1
positive regulation of cell differentiation	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

617 interactions, top by confidence:

A	B	Type	Score
ACTG1	ACTB	psi-mi:“MI:0915”(physical association)	0.950
ACTB	ACTB	psi-mi:“MI:0915”(physical association)	0.950
ACTB	ACTG1	psi-mi:“MI:0915”(physical association)	0.950
ACTB	ACTB	psi-mi:“MI:0407”(direct interaction)	0.950
CFL1	ACTB	psi-mi:“MI:0915”(physical association)	0.930
ACTB	CFL1	psi-mi:“MI:0915”(physical association)	0.930
ACTB	CFL2	psi-mi:“MI:0915”(physical association)	0.910
DSTN	ACTB	psi-mi:“MI:0915”(physical association)	0.900
ACTB	DSTN	psi-mi:“MI:0915”(physical association)	0.900
ACTB	CAP2	psi-mi:“MI:0915”(physical association)	0.820
ACTB	NTAQ1	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (1595): ACTB (Affinity Capture-MS), ACTB (Affinity Capture-MS), ACTB (Affinity Capture-MS), ACTB (Affinity Capture-Western), ACTB (Two-hybrid), ACTG1 (Two-hybrid), CFL1 (Two-hybrid), CFL2 (Two-hybrid), EHHADH (Two-hybrid), CAP2 (Two-hybrid), DSTN (Two-hybrid), WDYHV1 (Two-hybrid), ACTB (Affinity Capture-MS), ACTB (Affinity Capture-Western), ACTB (Reconstituted Complex)

ESM2 similar proteins: A2BDB0, O18499, O18500, O18840, O42161, O93400, P04829, P10984, P10986, P15475, P41340, P48975, P53478, P53485, P53505, P53506, P60706, P60707, P60708, P60709, P60710, P60711, P60712, P60713, P63256, P63257, P63258, P63259, P63260, P63261, P68142, P68143, P83750, P83751, Q25010, Q4L0Y2, Q4R561, Q5JAK2, Q5R1X3, Q5R6G0

Diamond homologs: A2AKE7, A2BDB0, A3C6D7, O17320, O18840, O65314, O93400, P02572, P02576, P02578, P07828, P07829, P07830, P0C539, P10984, P10995, P12432, P12433, P12716, P18602, P20904, P29751, P30163, P41339, P41341, P43239, P45520, P48975, P49055, P49128, P53458, P53459, P53465, P53470, P53471, P53472, P53477, P53478, P53479, P53498

SIGNOR signaling

27 interactions.

A	Effect	B	Mechanism
FKBP15	“up-regulates activity”	ACTB	binding
ACTB	up-regulates	Endocytosis
ACTB	up-regulates	“Early Endosome”
ACTB	“up-regulates quantity”	F-actin_assembly	binding
CD2AP	“up-regulates activity”	ACTB	binding
CKB	“up-regulates quantity”	ACTB	relocalization
SYN2	“up-regulates activity”	ACTB	binding
SYN3	“up-regulates activity”	ACTB	binding
SYN1	“up-regulates activity”	ACTB	binding
GFAP	“up-regulates quantity”	ACTB	binding
MYO5A	“up-regulates activity”	ACTB	binding
ACTB	“form complex”	“NuA4 complex”	binding
ACTB	“form complex”	GBAF	binding
ACTB	“form complex”	“SWI/SNF ACTL6A-ARID1A-SMARCA2 variant”	binding
ACTB	“form complex”	“SWI/SNF ACTL6B varian”	binding
ACTB	“form complex”	“Neural progenitor-specific SWI/SNF”	binding
ACTB	“form complex”	“Muscle cell-specific SWI/SNF ARID1A variant”	binding
ACTB	“form complex”	“Muscle cell-specific SWI/SNF ARID1B variant”	binding
ACTB	“form complex”	“Muscle cell-specific SWI/SNF SMARCA4 variant”	binding
ACTB	“form complex”	“Brain-specific SWI/SNF SMARCA2 variant”	binding
ACTB	“form complex”	“Brain-specific SWI/SNF SMARCA4 variant”	binding
FHOD1	“up-regulates quantity by stabilization”	ACTB	binding
ACTB	“form complex”	“Embryonic stem cell-specific SWI/SNF”	binding
IGF2BP1	“up-regulates quantity”	ACTB	“post transcriptional regulation”
TAGLN2	“down-regulates activity”	ACTB	binding
“IPP complex”	“up-regulates activity”	ACTB	relocalization
NTN1	“up-regulates quantity”	ACTB	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 182 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
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	5	19.2×	2e-03
Striated Muscle Contraction	6	15.6×	1e-03
Regulation of MITF-M-dependent genes involved in pigmentation	5	11.2×	6e-03
Oncogenic MAPK signaling	5	10.4×	6e-03
Extra-nuclear estrogen signaling	6	8.6×	5e-03
Signaling by ALK fusions and activated point mutants	6	7.6×	7e-03
ESR-mediated signaling	7	7.5×	5e-03
Cargo recognition for clathrin-mediated endocytosis	7	6.2×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	5	21.1×	8e-04
regulation of nucleotide-excision repair	5	18.8×	9e-04
regulation of mitotic metaphase/anaphase transition	5	15.5×	2e-03
sarcomere organization	6	14.4×	8e-04
regulation of G1/S transition of mitotic cell cycle	6	11.5×	2e-03
intrinsic apoptotic signaling pathway	5	11.2×	6e-03
positive regulation of double-strand break repair	5	10.8×	6e-03
cerebral cortex development	6	7.7×	8e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	69
Likely pathogenic	85
Uncertain significance	168
Likely benign	287
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1193058	NM_001101.5(ACTB):c.586C>G (p.Arg196Gly)	Pathogenic
1202044	NM_001101.5(ACTB):c.484A>G (p.Thr162Ala)	Pathogenic
1253973	NM_001101.5(ACTB):c.353_356delinsTGAC (p.Lys118_Met119delinsMetThr)	Pathogenic
127166	NM_001101.5(ACTB):c.34A>C (p.Asn12His)	Pathogenic
127167	NM_001101.5(ACTB):c.356T>C (p.Met119Thr)	Pathogenic
127168	NM_001101.5(ACTB):c.359C>T (p.Thr120Ile)	Pathogenic
127169	NM_001101.5(ACTB):c.446C>T (p.Thr149Ile)	Pathogenic
127170	NM_001101.5(ACTB):c.586C>A (p.Arg196Ser)	Pathogenic
127171	NM_001101.5(ACTB):c.611C>G (p.Ala204Gly)	Pathogenic
1319337	NM_001101.5(ACTB):c.474_475dup (p.Val159fs)	Pathogenic
1334712	NM_001101.5(ACTB):c.439C>T (p.Arg147Cys)	Pathogenic
1344710	NM_001101.5(ACTB):c.439C>A (p.Arg147Ser)	Pathogenic
147563	GRCh38/hg38 7p22.3-22.1(chr7:54185-6638027)x3	Pathogenic
148450	GRCh38/hg38 7p22.3-21.3(chr7:45130-7252065)x3	Pathogenic
1685500	NM_001101.5(ACTB):c.141G>A (p.Met47Ile)	Pathogenic
1711132	GRCh37/hg19 7p22.3-21.3(chr7:43360-9649794)x3	Pathogenic
1809374	GRCh37/hg19 7p22.1(chr7:4655928-5990874)x1	Pathogenic
18275	NM_001101.5(ACTB):c.547C>T (p.Arg183Trp)	Pathogenic
203375	NM_001101.5(ACTB):c.123+1G>A	Pathogenic
2445203	NM_001101.5(ACTB):c.220G>T (p.Gly74Cys)	Pathogenic
2574241	NM_001101.5(ACTB):c.905G>C (p.Gly302Ala)	Pathogenic
2575112	NM_001101.5(ACTB):c.437G>T (p.Gly146Val)	Pathogenic
2575113	NM_001101.5(ACTB):c.437G>A (p.Gly146Asp)	Pathogenic
2577405	NM_001101.5(ACTB):c.992_1008del (p.Ala331fs)	Pathogenic
2577406	NM_001101.5(ACTB):c.1012_1023del (p.Ser338_Ile341del)	Pathogenic
2577407	NM_001101.5(ACTB):c.1101dup (p.Ser368fs)	Pathogenic
264642	NM_001101.5(ACTB):c.802G>C (p.Gly268Arg)	Pathogenic
2684469	GRCh37/hg19 7p22.3-21.3(chr7:43361-8890475)x3	Pathogenic
2684470	GRCh37/hg19 7p22.3-22.1(chr7:43361-5965440)x3	Pathogenic
279939	NM_001101.5(ACTB):c.127G>A (p.Val43Met)	Pathogenic

SpliceAI

540 predictions. Top by Δscore:

Variant	Effect	Δscore
7:5527887:ATGAT:A	acceptor_gain	1.0000
7:5527888:TGAT:T	acceptor_gain	1.0000
7:5527889:GAT:G	acceptor_gain	1.0000
7:5527890:AT:A	acceptor_gain	1.0000
7:5527892:C:CC	acceptor_gain	1.0000
7:5527892:CTGAG:C	acceptor_loss	1.0000
7:5527893:T:G	acceptor_loss	1.0000
7:5528000:CCAC:C	donor_loss	1.0000
7:5528000:CCACC:C	donor_gain	1.0000
7:5528001:CACC:C	donor_loss	1.0000
7:5528002:A:AC	donor_gain	1.0000
7:5528002:AC:A	donor_gain	1.0000
7:5528003:C:CC	donor_gain	1.0000
7:5528003:CC:C	donor_gain	1.0000
7:5528003:CCTTG:C	donor_gain	1.0000
7:5528181:CATGC:C	acceptor_gain	1.0000
7:5528182:ATGC:A	acceptor_gain	1.0000
7:5528183:TGC:T	acceptor_gain	1.0000
7:5528183:TGCCT:T	acceptor_loss	1.0000
7:5528184:GC:G	acceptor_gain	1.0000
7:5528184:GCCTG:G	acceptor_loss	1.0000
7:5528185:CC:C	acceptor_gain	1.0000
7:5528186:C:CC	acceptor_gain	1.0000
7:5528186:CTGA:C	acceptor_loss	1.0000
7:5528187:T:G	acceptor_loss	1.0000
7:5528276:CTCA:C	donor_loss	1.0000
7:5528277:TCA:T	donor_loss	1.0000
7:5528278:CA:C	donor_loss	1.0000
7:5528279:A:AC	donor_gain	1.0000
7:5528279:A:AT	donor_loss	1.0000

AlphaMissense

2483 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:5527754:G:C	C374W	1.000
7:5527767:A:T	V370D	1.000
7:5527779:C:T	G366D	1.000
7:5527780:C:G	G366R	1.000
7:5527810:A:G	W356R	1.000
7:5527810:A:T	W356R	1.000
7:5527820:G:C	F352L	1.000
7:5527820:G:T	F352L	1.000
7:5527822:A:G	F352L	1.000
7:5527830:A:G	L349P	1.000
7:5527830:A:T	L349Q	1.000
7:5527834:A:G	S348P	1.000
7:5527836:G:T	A347D	1.000
7:5527837:C:G	A347P	1.000
7:5527839:A:G	L346P	1.000
7:5527842:A:T	I345N	1.000
7:5527845:G:A	S344F	1.000
7:5527845:G:T	S344Y	1.000
7:5527846:A:G	S344P	1.000
7:5527848:C:A	G343V	1.000
7:5527848:C:T	G343D	1.000
7:5527849:C:A	G343C	1.000
7:5527849:C:G	G343R	1.000
7:5527851:C:A	G342V	1.000
7:5527851:C:T	G342D	1.000
7:5527852:C:A	G342C	1.000
7:5527852:C:G	G342R	1.000
7:5527852:C:T	G342S	1.000
7:5527856:C:A	W340C	1.000
7:5527856:C:G	W340C	1.000

dbSNP variants (sampled 300 via entrez): RS1000706434 (7:5532384 G>C), RS1001036176 (7:5527107 G>T), RS1001089924 (7:5526982 C>T), RS1001528164 (7:5531577 C>A), RS1001654212 (7:5528918 C>A,G,T), RS1001913807 (7:5530749 C>G,T), RS1001972616 (7:5531451 C>G), RS1002137247 (7:5528782 G>A), RS1002321926 (7:5531624 C>A,T), RS1002532746 (7:5532537 C>T), RS1002736649 (7:5529500 C>T), RS1003588455 (7:5530314 C>G,T), RS1004201338 (7:5530336 G>A,T), RS1004901723 (7:5531514 C>T), RS1004931101 (7:5531389 A>G)

Disease associations

OMIM: gene MIM:102630 | disease phenotypes: MIM:243310, MIM:607371, MIM:609924, MIM:620475, MIM:604919, MIM:620453, MIM:620470

GenCC curated gene-disease

Disease	Classification	Inheritance
Baraitser-Winter cerebrofrontofacial syndrome	Definitive	Autosomal dominant
Baraitser-Winter syndrome 1	Definitive	Autosomal dominant
ACTB-associated syndromic thrombocytopenia	Strong	Autosomal dominant
developmental malformations-deafness-dystonia syndrome	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
ACTB-associated syndromic thrombocytopenia	Moderate	AD
Baraitser-Winter cerebrofrontofacial syndrome	Definitive	AD

Mondo (15): Baraitser-Winter syndrome 1 (MONDO:0009470), neurodevelopmental disorder (MONDO:0700092), developmental malformations-deafness-dystonia syndrome (MONDO:0011823), aminoacylase 1 deficiency (MONDO:0012368), intellectual disability (MONDO:0001071), Baraitser-Winter cerebrofrontofacial syndrome (MONDO:0017579), ACTB-associated syndromic thrombocytopenia (MONDO:0100433), thrombocytopenia (MONDO:0002049), Becker nevus syndrome (MONDO:0011500), congenital smooth muscle hamartoma (MONDO:0016986), dystonia 22, juvenile-onset (MONDO:0957539), congenital smooth muscle hamartoma, with or without hemihypertrophy (MONDO:0957564), dystonic disorder (MONDO:0003441), cleft palate (MONDO:0016064), microcephaly (MONDO:0001149)

Orphanet (9): Short stature-intellectual disability-eye anomalies-cleft lip/palate syndrome (Orphanet:2649), Baraitser-Winter cerebrofrontofacial syndrome (Orphanet:2995), Developmental malformations-deafness-dystonia syndrome (Orphanet:79107), Aminoacylase 1 deficiency (Orphanet:137754), Actinomyopathy-associated syndromic thrombocytopenia (Orphanet:674653), Becker nevus syndrome (Orphanet:64755), Congenital smooth muscle hamartoma (Orphanet:263435), Cleft palate (Orphanet:2014), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

158 total (30 of 158 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000045	Abnormal scrotum morphology
HP:0000054	Micropenis
HP:0000064	Hypoplastic labia minora
HP:0000072	Hydroureter
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000233	Thin vermilion border
HP:0000239	Large fontanelles
HP:0000243	Trigonocephaly
HP:0000252	Microcephaly
HP:0000270	Delayed cranial suture closure
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002183_6	Relative hand skill in reading disability	4.000000e-06
GCST005905_15	Global electrical heterogeneity phenotypes	8.000000e-09
GCST010244_420	Triglyceride levels	9.000000e-10
GCST90002386_124	High light scatter reticulocyte percentage of red cells	1.000000e-12
GCST90002388_17	Lymphocyte count	1.000000e-09
GCST90002390_237	Mean corpuscular hemoglobin	3.000000e-12
GCST90002391_216	Mean corpuscular hemoglobin concentration	4.000000e-12
GCST90002405_217	Reticulocyte count	3.000000e-09
GCST90002406_236	Reticulocyte fraction of red cells	1.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0009902	handedness
EFO:0004327	electrocardiography
EFO:0004530	triglyceride measurement
EFO:0004587	lymphocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007986	reticulocyte count

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D020821	Dystonic Disorders	C10.228.662.300
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C538246	Aminoacylase 1 deficiency (supp.)
C565735	Becker Nevus Syndrome (supp.)
C537704	Juvenile-onset dystonia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2062353 (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

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.33	Kd	4698	nM	MOLIBRESIB
5.05	IC50	8840	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 22 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179248: Binding affinity against ACTB (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	4.6980	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, affects cotreatment	7
bisphenol A	affects expression, decreases expression, decreases reaction, increases abundance	5
Cadmium Chloride	affects expression, decreases expression, increases expression, decreases methylation	5
sodium arsenite	affects cotreatment, increases expression, decreases expression	4
Arsenic Trioxide	decreases expression, increases expression	3
Air Pollutants	increases expression, affects cotreatment, increases abundance, increases oxidation, decreases expression	3
Valproic Acid	increases expression, increases methylation	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
mono-(2-ethylhexyl)phthalate	affects cotreatment, increases expression	2
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment, increases expression	2
dibenzo(a,l)pyrene	decreases expression, increases expression	2
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Caffeine	affects phosphorylation, decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Dinitrochlorobenzene	affects binding, increases metabolic processing	2
Doxorubicin	affects expression	2
Endosulfan	decreases expression	2
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Quercetin	affects binding, decreases expression	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases metabolic processing	2
Tretinoin	affects cotreatment, increases expression	2
Metribolone	affects binding, increases reaction, increases expression	2
Copper Sulfate	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
9-hydroxyoctadecadienoic acid	increases expression	1
napabucasin	decreases expression	1

ChEMBL screening assays

21 unique, capped per target: 21 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2065201	Binding	Binding affinity to ACTB in human Jurkat cells at 150 uM followed by UV irradiation for 30 mins with Wood’s glass filtered medium pressure mercury arc light after cell lysis measured after denaturing wash by SDS-PAGE based pull down assay	Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. — Bioorg Med Chem

Cellosaurus cell lines

11 cell lines: 5 induced pluripotent stem cell, 2 cancer cell line, 2 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6ML	IUFi004-A-1	Induced pluripotent stem cell	Female
CVCL_D6MM	IUFi004-A-2	Induced pluripotent stem cell	Female
CVCL_D6RH	WTSIi018-B-19	Induced pluripotent stem cell	Male
CVCL_D6RI	WTSIi018-B-20	Induced pluripotent stem cell	Male
CVCL_E4DB	HEBHMUi018-A	Induced pluripotent stem cell	Male
CVCL_SB27	HAP1 ACTB (-) 1	Cancer cell line	Male
CVCL_SB28	HAP1 ACTB (-) 2	Cancer cell line	Male
CVCL_ZV86	HEK293 cpstFRET-Actin	Transformed cell line	Female
CVCL_ZV87	HEK293 Actin-cpstFRET-Actin	Transformed cell line	Female
CVCL_ZV90	MDCK cpstFRET-Actin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays