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): 748 total — 68 pathogenic, 94 likely-pathogenic (top 4% of genes corpus-wide)
• Regional missense constraint (gnomAD): 4 of 5 regions constrained (≈97% of expected missense variation)
• GTEx eGene: eQTL in 10 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 158
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 72.1% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.19 (highly constrained)
• 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: 64 — 44 protein_coding, 14 nonsense_mediated_decay, 4 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000646664

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 1, TSL 4: 4, TSL 5: 4

ENST00000646664, ENST00000414620, ENST00000417101, ENST00000425660, ENST00000432588, ENST00000443528, ENST00000462494, ENST00000464611, ENST00000473257, ENST00000477812, ENST00000480301, ENST00000484841, ENST00000493945, ENST00000642480, ENST00000645025, ENST00000645576, ENST00000646584, 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, ENST00000986666, ENST00001051011, ENST00001051014, ENST00001051023, ENST00001051029, ENST00001051031, ENST00001073015, ENST00001073017, ENST00001073018, ENST00001073020, ENST00001099860, ENST00001099861, ENST00001099862, ENST00001099863, ENST00001099864, ENST00001099865, ENST00001099866, ENST00001099867, ENST00001099868, ENST00001099869, ENST00001141547

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.

Highest expression (Bgee): urethra, postcentral gyrus, saphenous vein, ileal mucosa, parietal lobe.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACTB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	1.1e-05	-0.14	7:5532595:A:G
Cells EBV-transformed lymphocytes	sqtl	6.1e-04	-1.47	7:4785995:C:T
Brain Cerebellar Hemisphere	eqtl	1.2e-03	-1.37	7:5994589:A:C
Testis	sqtl	4.2e-03	-0.38	7:4749255:A:G
Nerve Tibial	sqtl	8.1e-03	-0.31	7:6445565:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.1e-02	-0.11	7:5532595:A:G
Artery Tibial	eqtl	1.4e-02	-0.06	7:5531457:A:C
Vagina	eqtl	2.4e-02	-2.34	7:4940908:C:G
Cells Cultured fibroblasts	eqtl	2.4e-02	-0.32	7:5107194:G:C
Brain Cortex	eqtl	3.0e-02	+0.34	7:5178455:G:A
Brain Cerebellum	eqtl	3.1e-02	+0.42	7:4732330:A:G
Kidney Cortex	eqtl	4.1e-02	+3.47	7:6311388:A:C
Brain Frontal Cortex BA9	sqtl	4.2e-02	-0.49	7:4990248:T:TC
Brain Anterior cingulate cortex BA24	eqtl	4.3e-02	-1.63	7:4607269:T:C

FANTOM5 promoters

showing 10 of 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

showing 100 of 295 tissues 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
globus pallidus	UBERON:0001875	99.98	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.98	gold quality
subthalamic nucleus	UBERON:0001906	99.98	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.98	gold quality
popliteal artery	UBERON:0002250	99.98	gold quality
thymus	UBERON:0002370	99.98	gold quality
pericardium	UBERON:0002407	99.98	gold quality
decidua	UBERON:0002450	99.98	gold quality
medial globus pallidus	UBERON:0002477	99.98	gold quality
ventricular zone	UBERON:0003053	99.98	gold quality
upper arm skin	UBERON:0004263	99.98	gold quality
tibial artery	UBERON:0007610	99.98	gold quality
layer of synovial tissue	UBERON:0007616	99.98	gold quality
stromal cell of endometrium	CL:0002255	99.97	gold quality
embryo	UBERON:0000922	99.97	gold quality
aorta	UBERON:0000947	99.97	gold quality
smooth muscle tissue	UBERON:0001135	99.97	gold quality
caecum	UBERON:0001153	99.97	gold quality
sigmoid colon	UBERON:0001159	99.97	gold quality
myometrium	UBERON:0001296	99.97	gold quality
ascending aorta	UBERON:0001496	99.97	gold quality
thoracic aorta	UBERON:0001515	99.97	gold quality
coronary artery	UBERON:0001621	99.97	gold quality
left coronary artery	UBERON:0001626	99.97	gold quality
medulla oblongata	UBERON:0001896	99.97	gold quality
substantia nigra pars compacta	UBERON:0001965	99.97	gold quality
lateral globus pallidus	UBERON:0002476	99.97	gold quality
ventral tegmental area	UBERON:0002691	99.97	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.97	gold quality
frontal pole	UBERON:0002795	99.97	gold quality
cerebellar vermis	UBERON:0004720	99.97	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.97	gold quality
paraflocculus	UBERON:0005351	99.97	gold quality
nasal cavity epithelium	UBERON:0005384	99.97	gold quality
lower esophagus	UBERON:0013473	99.97	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.97	gold quality
blood	UBERON:0000178	99.96	gold quality
pharyngeal mucosa	UBERON:0000355	99.96	gold quality
jejunal mucosa	UBERON:0000399	99.96	gold quality
pons	UBERON:0000988	99.96	gold quality
vermiform appendix	UBERON:0001154	99.96	gold quality
mucosa of stomach	UBERON:0001199	99.96	gold quality
left uterine tube	UBERON:0001303	99.96	gold quality
mammary duct	UBERON:0001765	99.96	gold quality
inferior olivary complex	UBERON:0002127	99.96	gold quality
trabecular bone tissue	UBERON:0002483	99.96	gold quality
middle frontal gyrus	UBERON:0002702	99.96	gold quality
trachea	UBERON:0003126	99.96	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.96	gold quality
ganglionic eminence	UBERON:0004023	99.96	gold quality
superior vestibular nucleus	UBERON:0007227	99.96	gold quality
body of uterus	UBERON:0009853	99.96	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.96	gold quality
granulocyte	CL:0000094	99.95	gold quality
lymph node	UBERON:0000029	99.95	gold quality
penis	UBERON:0000989	99.95	gold quality
descending thoracic aorta	UBERON:0002345	99.95	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.95	gold quality
epithelium of mammary gland	UBERON:0003244	99.95	gold quality
cortical plate	UBERON:0005343	99.95	gold quality
tendon of biceps brachii	UBERON:0008188	99.95	gold quality
upper lobe of lung	UBERON:0008948	99.95	gold quality
lower esophagus mucosa	UBERON:0035834	99.95	gold quality
monocyte	CL:0000576	99.94	gold quality
leukocyte	CL:0000738	99.94	gold quality
mononuclear cell	CL:0000842	99.94	gold quality
large intestine	UBERON:0000059	99.94	gold quality
oral cavity	UBERON:0000167	99.94	gold quality
prefrontal cortex	UBERON:0000451	99.94	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Smooth muscle	tissue	5355.5	high
Tonsil	tissue	4310.4	high
Lymph node	tissue	4107.2	high
Appendix	tissue	4010.6	high
Bone marrow	tissue	3397.8	medium
Urinary bladder	tissue	3291.7	not detected
Spinal cord	tissue	3277.1
Thymus	tissue	3055.1
Spleen	tissue	2835.2	high
Seminal vesicle	tissue	2771.3	not detected
Esophagus	tissue	2750.8	not detected
Corpus callosum	tissue	2707.2
Midbrain	tissue	2633.2
Medulla oblongata	tissue	2601.6
Endometrium 1	tissue	2536.5	medium
Vagina	tissue	2531.9	not detected
Substantia nigra	tissue	2528.8
Thalamus	tissue	2470.1
Colon	tissue	2465.1	high
Adipose tissue	tissue	2395.8	low
Superior colliculi	tissue	2379.4
Pons	tissue	2349.9
Hippocampal formation	tissue	2327.8
Hypothalamus	tissue	2196.5
Rectum	tissue	2196.3	high
Lung	tissue	2088.5	low
Putamen	tissue	2077.9
Periaqueductal gray	tissue	1985.3
Septum	tissue	1967.4
Small intestine	tissue	1924.7	high
Hippocampus	tissue	1917.3	not detected
Nucleus accumbens	tissue	1905.2
Choroid plexus	tissue	1862.8
Cerebral cortex	tissue	1814.2	low
Somatosensory cortex	tissue	1814.2
Ventral forebrain	tissue	1799.9
Postcentral gyrus	tissue	1735.5
Basal ganglia	tissue	1715.6	not detected
Placenta	tissue	1707.6	high
Locus coeruleus	tissue	1694.2
Motor cortex	tissue	1672.3
Gallbladder	tissue	1660.9	high
Liver	tissue	1643.3	not detected
Prostate	tissue	1633.9	not detected
Occipital cortex	tissue	1603.0
Duodenum	tissue	1560.3	high
Temporal cortex	tissue	1558.8
Epididymis	tissue	1538.8	high
Prefrontal cortex	tissue	1527.9
Entorhinal cortex	tissue	1519.0
Retrosplenial and cingulate cortex	tissue	1466.7
Retrosplenial cortex	tissue	1466.4
Amygdala	tissue	1411.8
Insular cortex	tissue	1390.4
Fallopian tube	tissue	1390.3	not detected
Ovary	tissue	1379.8	not detected
Stomach 1	tissue	1374.5	high
Cervix	tissue	1259.5	not detected
Thyroid gland	tissue	1233.6	not detected
Olfactory bulb	tissue	1223.6

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (8352.8), Lateral funiculus (white matter) (3694.5), Ventral spinal cord (3277.1), Dorsal funiculus (white matter) (3272.7), Anterior funiculus (white matter) (3001.9).

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)

Targeting ACTB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 81 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.193, missense Z 7.69 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000646664 splits into 5 regions with different missense tolerance; 4 are missense-constrained (≈97% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:5,527,751–5,527,883	4 / 61.9	0.06	yes (p 1.9e-13)
7:5,527,884–5,528,036	10 / 17.6	0.57	no
7:5,528,037–5,529,186	32 / 288.4	0.11	yes (p 1.6e-51)
7:5,529,187–5,529,367	0 / 81.9	0.00	yes (p 1.4e-19)
7:5,529,368–5,529,657	10 / 80.2	0.12	yes (p 4.5e-15)
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.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): COV644 (-3.511), CAMA-1 (-2.982), KMRC-3 (-2.832), EPLC-272H (-2.689), SW1116 (-2.45), SK-BR-3 (-2.371), SNU-761 (-2.364), PA-TU-8988S (-2.267), PC-14 (-2.25), NCI-H1836 (-2.209), KYSE-410 (-2.18), AU565 (-1.994), SNU-738 (-1.979), NCI-H838 (-1.884), SCC-4 (-1.867).

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

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	actb1	ENSDARG00000037746
danio_rerio	actb2	ENSDARG00000037870
mus_musculus	Actb	ENSMUSG00000029580
rattus_norvegicus	Actb	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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87904) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 15 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased susceptibility to age-related hearing loss	2
embryonic lethality during organogenesis, complete penetrance	2
decreased body weight	1
decreased body size	1
embryonic growth retardation	1
abnormal cochlear hair cell stereociliary bundle morphology	1
short cochlear hair cell stereocilia	1
abnormal outer hair cell stereociliary bundle morphology	1
decreased outer hair cell stereocilia number	1
short outer hair cell stereocilia	1
impaired hearing	1
postnatal lethality, incomplete penetrance	1
prenatal lethality, complete penetrance	1
embryonic lethality at implantation, complete penetrance	1
increased or absent threshold for auditory brainstem response	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus laevis	A2BDB0	100.0%	Diamond
Oryza sativa Indica Group	A2WNB0	100.0%	Diamond
Oryza sativa Japonica Group	A3ANB5	100.0%	Diamond
Bos taurus	A7MB62	100.0%	Diamond
Canis lupus familiaris	O18840	100.0%	Diamond
Arabidopsis thaliana	P0CJ46	100.0%	Diamond
Caenorhabditis elegans	P0DM41	100.0%	Diamond
Drosophila melanogaster	P10987	100.0%	Diamond
Pleurodeles waltl	P10994	100.0%	Diamond
Solanum tuberosum	P30170	100.0%	Diamond
Nakaseomyces glabratus CBS 138	P60009	100.0%	Diamond
Saccharomyces cerevisiae S288C	P60010	100.0%	Diamond
Saccharomyces x bayanus	P60011	100.0%	Diamond
Gallus gallus	P60706	100.0%	Diamond
Trichosurus vulpecula	P60707	100.0%	Diamond
Equus caballus	P60708	100.0%	Diamond
Ovis aries	P60713	100.0%	Diamond
Salmo salar	O42161	99.7%	Diamond
Bombyx mori	P04829	99.7%	Diamond
Dictyostelium discoideum	P07830	99.7%	Diamond
Sterkiella nova	P12715	99.7%	Diamond
Candida albicans	P14235	99.7%	Diamond
Plasmodium falciparum NF54	P14883	99.7%	Diamond
Xenopus tropicalis	P20399	99.7%	Diamond
Styela clava	P26198	99.7%	Diamond
Oryctolagus cuniculus	P29751	99.7%	Diamond
Costaria costata	P30161	99.7%	Diamond
Cricetulus griseus	P48975	99.7%	Diamond
Dibothriocephalus dendriticus	P53456	99.7%	Diamond
Heliocidaris erythrogramma	P53463	99.7%	Diamond
Heliocidaris tuberculata	P53464	99.7%	Diamond
Strongylocentrotus purpuratus	P53472	99.7%	Diamond
Cyprinus carpio	P53479	99.7%	Diamond
Takifugu rubripes	P53480	99.7%	Diamond
Botrytis cinerea	O13419	99.5%	Diamond
Mesocentrotus franciscanus	P10990	99.5%	Diamond
Xenopus borealis	P15475	99.5%	Diamond
Aspergillus nidulans FGSC A4	P20359	99.5%	Diamond
Lathyrus oleraceus	P30164	99.5%	Diamond
Bactrocera dorsalis	P45885	99.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RNF216-IT1	ncRNA	100874342
RNF216	protein-coding	54476
FSCN1	protein-coding	6624
MIR589	ncRNA	693174
FBXL18	protein-coding	80028
MIR6874	ncRNA	102466203
LINC02983	ncRNA	100129484
LINC03073	ncRNA	128071541
TNRC18-AS1	ncRNA	139281652
TNRC18	protein-coding	84629

Protein

Protein identifiers

Actin, cytoplasmic 1 — P60709 (reviewed: P60709)

Alternative names: Beta-actin

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

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

UniProt features (93 total): helix 23, strand 22, sequence variant 19, mutagenesis site 10, modified residue 6, turn 6, chain 2, cross-link 2, sequence conflict 2, initiator methionine 1

Structure

Experimental structures (PDB)

showing 30 of 93 structures by resolution:

PDB	Title	Method	Resolution (Å)
6MBK	SETD3, a Histidine Methyltransferase, in Complex with an Actin Peptide and SAH, First …	X-RAY DIFFRACTION	1.69
6OX0	SETD3 in Complex with an Actin Peptide with Sinefungin Replacing SAH as Cofactor	X-RAY DIFFRACTION	1.75
6WK2	SETD3 mutant (N255V) in Complex with an Actin Peptide with His73 Replaced with Methionine	X-RAY DIFFRACTION	1.76
6MBJ	SETD3, a Histidine Methyltransferase, in Complex with an Actin Peptide and SAH, P21 …	X-RAY DIFFRACTION	1.78
6OX3	SETD3 in Complex with an Actin Peptide with His73 Replaced with Lysine	X-RAY DIFFRACTION	1.78
7W28	Crystal Structure of SETD3-SAH in complex with betaA-4PyrAla73 peptide	X-RAY DIFFRACTION	1.79
6WK1	SETD3 in Complex with an Actin Peptide with His73 Replaced with Methionine	X-RAY DIFFRACTION	1.89
6OX1	SETD3 in Complex with an Actin Peptide with Target Histidine Partially Methylated	X-RAY DIFFRACTION	1.95
6ICT	Structure of SETD3 bound to SAH and methylated actin	X-RAY DIFFRACTION	1.95
6V63	SETD3 WT in Complex with an Actin Peptide with His73 Replaced with Glutamine	X-RAY DIFFRACTION	2.02
6OX2	SETD3in Complex with an Actin Peptide with the Target Histidine Fully Methylated	X-RAY DIFFRACTION	2.09
6OX5	A SETD3 Mutant (N255A) in Complex with an Actin Peptide with His73 Replaced with Lysine	X-RAY DIFFRACTION	2.1
6ICV	Structure of SETD3 bound to SAH and unmodified actin	X-RAY DIFFRACTION	2.15
9QEW	Cryo-EM structure of the undecorated actin filament in the ADP-Pi state.	ELECTRON MICROSCOPY	2.18
6MBL	SETD3, a Histidine Methyltransferase, in Complex with an Actin Peptide and SAH, Second …	X-RAY DIFFRACTION	2.2
3D2U	Structure of UL18, a Peptide-Binding Viral MHC Mimic, Bound to a Host Inhibitory Receptor	X-RAY DIFFRACTION	2.21
8OI8	Cryo-EM structure of ADP-bound, filamentous beta-actin harboring the R183W mutation	ELECTRON MICROSCOPY	2.28
6OX4	A SETD3 Mutant (N255A) in Complex with an Actin Peptide	X-RAY DIFFRACTION	2.29
8OID	Cryo-EM structure of ADP-bound, filamentous beta-actin harboring the N111S mutation	ELECTRON MICROSCOPY	2.3
9QFJ	Cryo-EM structure of the cofilactin filament core at 2.3 Angstrom resolution.	ELECTRON MICROSCOPY	2.31
6V62	SETD3 double mutant (N255F/W273A) in Complex with an Actin Peptide with His73 Replaced …	X-RAY DIFFRACTION	2.36
8QR1	Cryo-EM structure of the human Tip60 complex	ELECTRON MICROSCOPY	2.4
9QF2	Cryo-EM structure of the fully Coronin-1B-decorated actin filament in the ADP state.	ELECTRON MICROSCOPY	2.42
6NBW	Ternary Complex of Beta/Gamma-Actin with Profilin and AnCoA-NAA80	X-RAY DIFFRACTION	2.5
9QFD	Cryo-EM structure of the fully cofilin-1-decorated actin filament (cofilactin)	ELECTRON MICROSCOPY	2.61
9QEY	Cryo-EM structure of the actin filament bound by a single Coronin-1B molecule.	ELECTRON MICROSCOPY	2.74
9QFB	Cryo-EM structure of the fully Coronin-1B-decorated actin filament in the ADP state.	ELECTRON MICROSCOPY	2.74
9UXC	The ADP-bound structure of BCL7B-containing ARP module of the human SWI/SNF complex	ELECTRON MICROSCOPY	2.74
9C57	Reconstituted P400 Subcomplex of the human TIP60 complex	ELECTRON MICROSCOPY	2.75
9QFQ	Cryo-EM structure of the cofilactin barbed end bound by AIP1	ELECTRON MICROSCOPY	2.76

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations, Essential proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH supported

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)

Type	Positions
(microbial infection) isoglutamyl lysine isopeptide (glu-lys) (interchain with k-50)	270
N-acetylmethionine	1
N-acetylaspartate	2
Methionine (r)-sulfoxide	44, 47
Tele-methylhistidine	73
N6-methyllysine	84
(microbial infection) isoglutamyl lysine isopeptide (lys-glu) (interchain with e-270)	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

26 curated (TAS) of 106; 16 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 106 pathways:

ID	Pathway	Evidence
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF ⚕	curated
R-HSA-6802952	Signaling by BRAF and RAF1 fusions ⚕	curated
R-HSA-9656223	Signaling by RAF1 mutants ⚕	curated
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants ⚕	curated
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants ⚕	curated
R-HSA-9649948	Signaling downstream of RAS mutants ⚕	curated
R-HSA-5250924	B-WICH complex positively regulates rRNA expression	curated
R-HSA-446353	Cell-extracellular matrix interactions	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-5696394	DNA Damage Recognition in GG-NER	curated
R-HSA-3928665	EPH-ephrin mediated repulsion of cells	curated
R-HSA-3928662	EPHB-mediated forward signaling	curated
R-HSA-196025	Formation of annular gap junctions	curated
R-HSA-9933937	Formation of the canonical BAF (cBAF) complex	curated
R-HSA-9933946	Formation of the embryonic stem cell BAF (esBAF) complex	curated
R-HSA-9933947	Formation of the non-canonical BAF (ncBAF) complex	curated
R-HSA-9933939	Formation of the polybromo-BAF (pBAF) complex	curated
R-HSA-9953170	GBP-mediated host defense	curated
R-HSA-190873	Gap junction degradation	curated
R-HSA-5674135	MAP2K and MAPK activation	curated
R-HSA-5626467	RHO GTPases activate IQGAPs	curated
R-HSA-9035034	RHOF GTPase cycle	curated
R-HSA-9764561	Regulation of CDH1 Function	curated
R-HSA-9932451	SWI/SNF chromatin remodelers	curated
R-HSA-5689603	UCH proteinases	curated
R-HSA-4420097	VEGFA-VEGFR2 Pathway	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9664422	FCGR3A-mediated phagocytosis ⚕	electronic
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9658195	Leishmania infection ⚕	—
R-HSA-9664417	Leishmania phagocytosis ⚕	—
R-HSA-6802957	Oncogenic MAPK signaling ⚕	—
R-HSA-9664407	Parasite infection ⚕	—
R-HSA-9824443	Parasitic Infection Pathways ⚕	—
R-HSA-6802949	Signaling by RAS mutants ⚕	—
R-HSA-9932444	ATP-dependent chromatin remodelers	—
R-HSA-9958825	Activation of STAT3 by cadherin engagement	electronic
R-HSA-418990	Adherens junctions interactions	electronic
R-HSA-422475	Axon guidance	—
R-HSA-446728	Cell junction organization	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-421270	Cell-cell junction organization	—
R-HSA-390466	Chaperonin-mediated protein folding	—
R-HSA-3247509	Chromatin modifying enzymes	—
R-HSA-4839726	Chromatin organization	—
R-HSA-389958	Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	—
R-HSA-73894	DNA Repair	—
R-HSA-5688426	Deubiquitination	—
R-HSA-1266738	Developmental Biology	—
R-HSA-2682334	EPH-Ephrin signaling	—
R-HSA-212165	Epigenetic regulation of gene expression	—
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-983231	Factors involved in megakaryocyte development and platelet production	electronic
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	—
R-HSA-390450	Folding of actin by CCT/TriC	electronic
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	electronic
R-HSA-9913351	Formation of the dystrophin-glycoprotein complex (DGC)	electronic
R-HSA-190828	Gap junction trafficking	—
R-HSA-157858	Gap junction trafficking and regulation	—

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 (37): morphogenesis of a polarized epithelium (GO:0001738), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), cytoskeleton organization (GO:0007010), microtubule nucleation (GO:0007020), 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 (35): kinetochore (GO:0000776), chromatin (GO:0000785), 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), lamellipodium (GO:0030027), axon (GO:0030424), cortical cytoskeleton (GO:0030863), vesicle (GO:0031982), protein-containing complex (GO:0032991), 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), blood microparticle (GO:0072562), dense body (GO:0097433), Schaffer collateral - CA1 synapse (GO:0098685), presynapse (GO:0098793), postsynaptic actin cytoskeleton (GO:0098871), glutamatergic synapse (GO:0098978), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

15 top-level categories:

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

showing 60 of 91 GO namespaces:

Category	Terms
cellular anatomical structure	6
cytoskeleton	3
regulation of DNA-templated transcription	2
cellular process	2
positive regulation of cellular process	2
cell differentiation	2
regulation of cell differentiation	2
cytoskeletal protein binding	2
intracellular membraneless organelle	2
nuclear lumen	2
morphogenesis of an epithelium	1
chromatin organization	1
transcription by RNA polymerase II	1
organelle organization	1
microtubule cytoskeleton organization	1
microtubule polymerization	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
regulation of myoblast differentiation	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
structural molecule activity	1
cytoskeleton organization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
kinase binding	1
nitric-oxide synthase activity	1
enzyme regulator activity	1
nitric-oxide synthase binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
protein binding	1
enzyme binding	1
structural constituent of cytoskeleton	1
postsynaptic actin cytoskeleton	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 44 of 89 annotations. The rest are phylogenetic / computational / electronic (IEA).

44 experimentally-supported GO terms:

GO term	NS	Evidence
adherens junction assembly	BP	mutant phenotype
apical protein localization	BP	mutant phenotype
cell motility	BP	mutant phenotype
cellular response to cytochalasin B	BP	mutant phenotype
chromatin remodeling	BP	high-throughput assay
establishment or maintenance of cell polarity	BP	mutant phenotype
morphogenesis of a polarized epithelium	BP	mutant phenotype
positive regulation of double-strand break repair via homologous recombination	BP	direct assay
protein localization to adherens junction	BP	mutant phenotype
regulation of cell cycle	BP	mutant phenotype
regulation of norepinephrine uptake	BP	genetic interaction
regulation of protein localization to plasma membrane	BP	mutant phenotype
regulation of transepithelial transport	BP	mutant phenotype
substantia nigra development	BP	high-throughput mutant
NuA4 histone acetyltransferase complex	CC	direct assay
actin cytoskeleton	CC	direct assay
adherens junction	CC	direct assay
apical junction complex	CC	direct assay
blood microparticle	CC	high-throughput assay
cell-cell junction	CC	mutant phenotype
chromatin	CC	high-throughput assay
cytoplasm	CC	direct assay
cytoplasmic ribonucleoprotein granule	CC	direct assay
cytoskeleton	CC	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
glutamatergic synapse	CC	direct assay
lamellipodium	CC	direct assay
membrane	CC	high-throughput assay
nucleus	CC	direct assay
postsynaptic actin cytoskeleton	CC	direct assay
protein-containing complex	CC	direct assay
ribonucleoprotein complex	CC	direct assay
tight junction	CC	direct assay
vesicle	CC	high-throughput assay
ATP hydrolysis activity	MF	direct assay
Tat protein binding	MF	physical interaction
identical protein binding	MF	physical interaction
kinesin binding	MF	physical interaction
nitric-oxide synthase binding	MF	physical interaction
nitric-oxide synthase regulator activity	MF	direct assay
protein kinase binding	MF	physical interaction
structural constituent of postsynaptic actin cytoskeleton	MF	direct assay
transporter regulator activity	MF	genetic interaction

Protein interactions and networks

IntAct

Human interaction partners of ACTB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 126 partners by confidence:

Partner	Interaction type	MIscore	Records
ACTG1	physical association	0.950	16
CFL1	physical association	0.930	9
CFL2	physical association	0.910	14
DSTN	physical association	0.900	10
CAP2	physical association	0.820	4
NTAQ1	physical association	0.740	6
CFTR	physical association	0.730	2
PFN1	direct interaction	0.690	2
APP	physical association	0.670	6
EHHADH	physical association	0.670	4
DUSP19	physical association	0.670	3
ERBB2	physical association	0.650	9
TPT1	physical association	0.570	2
HSPA8	physical association	0.570	1
ACT1	physical association	0.560	3
AIP1	physical association	0.560	3
CDC37	physical association	0.560	3
HTT	physical association	0.560	3
NCF1	direct interaction	0.560	3
RNF4	physical association	0.560	3
SRP1	physical association	0.560	3
TAE1	physical association	0.560	3
UBE2I	physical association	0.560	3
VPS29	physical association	0.560	3
BAIAP2	physical association	0.560	1
WDR1	physical association	0.560	1
YWHAZ	physical association	0.560	1
HTRA3	physical association	0.540	4
MYL12B	physical association	0.540	3
ACP1	association	0.530	2

BioGRID (1,622 interactions; top human partners by supporting records in a sample of 600 records): ACTG1 (Two-hybrid; 6 records), CFL2 (Two-hybrid; 6 records), CFL1 (Two-hybrid; 5 records), PDIA2 (Affinity Capture-Western; 5 records), CAP2 (Two-hybrid; 4 records), DSTN (Two-hybrid; 4 records), ACTC1 (Affinity Capture-MS; 3 records), CORO1C (Co-fractionation; 3 records), DUSP19 (Affinity Capture-MS; 3 records), LMX1B (Affinity Capture-MS; 3 records), PRSS23 (Affinity Capture-MS; 3 records), RNF4 (Affinity Capture-MS; 3 records), TMOD3 (Affinity Capture-MS; 3 records), AGR2 (Proximity Label-MS; 2 records), CAP1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

27 signaling 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”

Protein complexes (CORUM) (28)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

28 complexes by size:

Complex	Subunits	Members
★ Emerin complex 52	23	DDX39A, ILF3, LEMD3, RBL2, H1-1, HNRNPK, HNRNPU, IQGAP1, NMI, PDCD4, SNRPD1, THRA, API5, CKB, EMD, HDGF, LSM8, YWHAQ, ACTB, C1QBP, HNRNPL, LMNB1, YWHAE
★ Emerin complex 32	22	HDAC1, RBL2, SMARCC1, SMARCC2, TBL1Y, BANF2, DPY30, HDAC3, H3C1, LMNB1, MED4, RBL1, SAP18, TRIM28, ACTB, CHD4, EMD, NMI, RCOR1, SMARCB1, SPTAN1, TBL1XR1
★ LARC complex (LCR-associated remodeling complex)	19	SMARCC1, SMARCC2, SMARCD2, SMARCE1, ACTL6A, CHD4, MBD3, RBBP4, ACTB, MTA2, SMARCA4, HDAC1, HDAC2, HNRNPC, MBD2, ARID1A, DPF2, GATAD2B, SMARCB1
Emerin complex 25	16	EMD, G3BP1, SAP130, SSB, BCCIP, LMNB1, LSM8, SNRPD1, YWHAE, BANF1, CDC37, LSM2, ACTB, HNRNPK, YWHAB, ZRANB2
cBAF complex	14	ARID1A, ARID1B, BCL7A, BCL7C, SMARCA4, SMARCB1, SMARCC1, SMARCD2, ACTB, ACTL6A, DPF2, SMARCC2, SMARCD1, SMARCE1
PBAF complex	14	SMARCC1, SMARCC2, SMARCD1, SMARCE1, ACTB, ACTL6A, BCL7A, BRD7, PBRM1, PHF10, SMARCA4, SMARCB1, ARID2, BCL7C
cBAF complex	14	SMARCD1, SMARCD2, ACTB, ACTL6A, ARID1A, BCL7C, SMARCB1, SMARCE1, ARID1B, BCL7A, DPF2, SMARCA2, SMARCC1, SMARCC2
PBAF complex	14	SMARCB1, SMARCC1, SMARCC2, SMARCD1, ACTL6A, BCL7A, PBRM1, PHF10, SMARCA2, SMARCE1, ACTB, ARID2, BCL7C, BRD7
BAF complex	13	ARID1A, ARID1B, SMARCA4, SMARCC1, SMARCE1, ACTL6A, ACTL6B, SMARCA2, SMARCB1, SMARCC2, SMARCD1, ACTB, ACTG1
★ P2X7 receptor signalling complex	12	ACTB, ACTN4, HSP90AB1, HSPA1A, PI4KA, PTPRB, SVIL, HSPA8, ITGB2, LAMA3, MPP3, P2RX7
PBAF complex (Polybromo- and BAF containing complex)	10	ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, ACTB, ACTL6A, PBRM1, SMARCC1, SMARCD1
★ TLE1 corepressor complex	10	HSPA4, NCL, NPM1, RAD50, TOP2B, ACTB, MYH10, NONO, PARP1, TLE1
ncBAF complex	10	ACTB, BCL7A, BICRAL, SMARCA2, SMARCC1, SMARCD1, SS18, ACTL6A, BCL7C, BRD9
ncBAF complex	10	ACTB, ACTL6A, BCL7A, BRD9, SMARCA4, SMARCD1, SS18, BCL7C, BICRAL, SMARCC1
NUMAC complex (nucleosomal methylation activator complex)	10	SMARCC1, SMARCD1, ACTB, SMARCC2, SMARCE1, ARID1A, CARM1, SCYL1, SMARCA4, SMARCB1
★ Emerin regulatory complex	9	BANF1, EMD, H3C1, LMO7, ACTB, H1-1, HDAC1, HDAC3, RBL1
BAF complex	9	SMARCA4, SMARCC1, ACTB, ACTL6A, ARID1A, SMARCB1, SMARCC2, SMARCD1, SMARCE1
Emerin complex 1	8	ACTB, CNN3, EMD, LMO7, MYH9, MYO1E, SIKE1, SPTAN1
p400-associated complex	6	EP400, RUVBL1, RUVBL2, TRRAP, ACTB, ACTL6A
Emerin architectural complex	6	ACTB, EMD, LMNA, LMNB1, NMI, SPTAN1
★ ACTB-ANP32A-C1QBP-PSMA1-PTMA-PSMA1 complex	6	C1QBP, PSMA1, PTMA, SLC25A3, ACTB, ANP32A
Emerin-actin-NMI-(alphaII)spectrin complex	4	ACTB, EMD, NMI, SPTAN1
ProTalpha C2 complex	4	ACTB, MARCKSL1, PTMA, SET
Alpha-dystrobrevin-ZO-1-actin complex	3	DTNA, TJP1, ACTB
CTGF/Hcs24-actin(beta/gamma) complex	3	ACTB, ACTG1, CCN2
ACTB-CAP1-CFL1 complex	3	ACTB, CAP1, CFL1
Emerin-actin-NMI complex	3	ACTB, EMD, NMI
Pre-initiation complex (ACTB, POLR2A, TBP)	3	ACTB, POLR2A, TBP

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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
Removal of the Flap Intermediate from the C-strand	6	41.4×	3e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	36.5×	7e-05
Signaling by VEGF	5	11.9×	4e-03
Extra-nuclear estrogen signaling	5	9.3×	6e-03
VEGFA-VEGFR2 Pathway	6	9.1×	4e-03
DNA Damage/Telomere Stress Induced Senescence	5	8.9×	6e-03
MAPK1/MAPK3 signaling	6	8.6×	4e-03
Platelet activation, signaling and aggregation	7	8.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
sarcomere organization	5	16.5×	2e-03
cellular response to epidermal growth factor stimulus	5	13.7×	5e-03
epidermal growth factor receptor signaling pathway	6	12.8×	2e-03
telomere maintenance	5	11.5×	8e-03
actin filament organization	7	7.2×	7e-03

Disease & clinical

Genetic variants

Variant evidence for ACTB: 748 ClinVar records (162 pathogenic / likely pathogenic); 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	68
Likely pathogenic	94
Uncertain significance	179
Likely benign	298
Benign	29

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 162 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
18275	NM_001101.5(ACTB):c.547C>T (p.Arg183Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	16
29599	NM_001101.5(ACTB):c.587G>A (p.Arg196His)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
29600	NM_001101.5(ACTB):c.586C>T (p.Arg196Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
1334712	NM_001101.5(ACTB):c.439C>T (p.Arg147Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
860924	NM_001101.5(ACTB):c.616C>T (p.Arg206Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
545067	NM_001101.5(ACTB):c.773C>T (p.Pro258Leu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
577358	NM_001101.5(ACTB):c.19G>A (p.Ala7Thr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
127163	NM_001101.5(ACTB):c.220G>A (p.Gly74Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1177326	NM_001101.5(ACTB):c.587G>T (p.Arg196Leu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1251980	NM_001101.5(ACTB):c.478A>G (p.Thr160Ala)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
4681736	NM_001101.5(ACTB):c.434C>G (p.Ser145Cys)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
128262	NM_001101.5(ACTB):c.64G>A (p.Ala22Thr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
372914	NM_001101.5(ACTB):c.616C>G (p.Arg206Gly)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
372917	NM_001101.5(ACTB):c.479C>T (p.Thr160Ile)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
432794	NM_001101.5(ACTB):c.890_891del (p.Thr297fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore ACTB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 271):

Position(s)	Effect	Δscore	Sites
7:5527892–5527893	acceptor_loss	1.0000	3
7:5528002–5528003	donor_loss	1.0000	4
7:5528186–5528187	acceptor_loss	1.0000	3
7:5528279–5528280	donor_loss	1.0000	5
7:5528720–5528721	acceptor_loss	1.0000	6
7:5529160	donor_loss	1.0000
7:5529401	acceptor_gain	1.0000
7:5529402	acceptor_loss	1.0000	2
7:5529533–5529534	donor_loss	1.0000	3
7:5530522–5530523	donor_loss	1.0000	3

AlphaMissense

2,155 missense substitutions predicted likely pathogenic (of 2,483 scored), across 373 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M44	9	0.975	0.999
M119	9	0.969	0.999
M355	9	0.957	0.997
M82	9	0.937	0.999
M47	9	0.926	0.990
M123	9	0.828	0.998
D11	8	0.999	1.000
D154	8	0.999	1.000
D288	8	0.998	1.000
D25	8	0.997	1.000
D244	8	0.997	1.000
D286	8	0.996	0.999
F352	8	0.996	1.000
H88	8	0.995	1.000
H161	8	0.994	0.999
D157	8	0.993	0.999
F124	8	0.990	1.000
D81	8	0.989	0.998
N111	8	0.989	1.000
H371	8	0.989	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (validation)	unfavorable	4.83e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	8.22e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000361
Lung Adenocarcinoma (TCGA)	unfavorable	0.000774

Disease associations

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

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
Baraitser-Winter cerebrofrontofacial syndrome	Definitive	Autosomal dominant	2
Baraitser-Winter syndrome 1	Definitive	Autosomal dominant	4
ACTB-associated syndromic thrombocytopenia	Strong	Autosomal dominant	2
developmental malformations-deafness-dystonia syndrome	Strong	Autosomal dominant	4

ClinGen Gene-Disease Validity

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

2 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (20 panels, 20 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

20 panels:

Panel	Rating
Adult-onset neurological disorders	green
Bleeding and platelet disorders	green
COVID-19 research	green
Cerebral malformation	green
Clefting	green
DDG2P	green
Dystonia, chorea or related movement disorder, adult onset	green
Dystonia, chorea or related movement disorder, childhood onset	green
Early onset dystonia	green
Fetal anomalies	green
Hypotonic infant	green
Inherited bleeding disorders	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Malformations of cortical development	green
Mosaic skin disorders - Deep sequencing	green
Ocular coloboma	green
Paediatric disorders	green
Rare syndromic craniosynostosis or isolated multisuture synostosis	green
Structural eye disease	green

Mondo (11): neurodevelopmental disorder (MONDO:0700092), Baraitser-Winter syndrome 1 (MONDO:0009470), aminoacylase 1 deficiency (MONDO:0012368), developmental malformations-deafness-dystonia syndrome (MONDO:0011823), Baraitser-Winter cerebrofrontofacial syndrome (MONDO:0017579), ACTB-associated syndromic thrombocytopenia (MONDO:0100433), Becker nevus syndrome (MONDO:0011500), congenital smooth muscle hamartoma (MONDO:0016986), intellectual disability (MONDO:0001071), 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), Aminoacylase 1 deficiency (Orphanet:137754), Developmental malformations-deafness-dystonia syndrome (Orphanet:79107), 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

showing 60 of 158 phenotypes (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
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000396	Overfolded helix
HP:0000407	Sensorineural hearing impairment
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000437	Depressed nasal tip
HP:0000445	Wide nose
HP:0000448	Prominent nose
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000482	Microcornea
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000527	Long eyelashes
HP:0000567	Chorioretinal coloboma
HP:0000568	Microphthalmia
HP:0000582	Upslanted palpebral fissure
HP:0000588	Optic disc coloboma
HP:0000612	Iris coloboma
HP:0000618	Blindness
HP:0000637	Long palpebral fissure
HP:0000664	Synophrys
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum

GWAS associations

9 associations:

Study	Trait	p-value
GCST90002386_581	High light scatter reticulocyte percentage of red cells	1e-12
GCST90002390_668	Mean corpuscular hemoglobin	3e-12
GCST90002391_98	Mean corpuscular hemoglobin concentration	4e-12
GCST90002406_315	Reticulocyte fraction of red cells	1e-10
GCST010244_224	Triglyceride levels	9e-10
GCST90002388_53	Lymphocyte count	1e-9
GCST90002405_465	Reticulocyte count	3e-9
GCST005905_15	Global electrical heterogeneity phenotypes	8e-9
GCST002183_6	Relative hand skill in reading disability	4e-6

EFO canonical traits (from GWAS)

7 canonical traits:

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

7 disease descriptors:

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
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
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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

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
Particulate Matter	affects cotreatment, increases expression, affects expression, decreases expression, increases abundance	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
mono-(2-ethylhexyl)phthalate	affects cotreatment, increases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	2
dibenzo(a,l)pyrene	increases expression, decreases 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	decreases expression, affects binding	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 299 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	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	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	Phase 3	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	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	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	COMPLETED	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
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03577756	Not specified	COMPLETED	Neurodevelopmental Assessment of Infants With Cystic Fibrosis
NCT03654248	Not specified	COMPLETED	Let’s Get Organized in Adult Psychiatric/habilitation Care

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ACTB across ~30M SureChEMBL compounds — explore on Sugi Predict.