ACTG1

Summary

ACTG1 (actin gamma 1, HGNC:144) is a protein-coding gene on chromosome 17q25.3, encoding Actin, cytoplasmic 2 (P63261). Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. It is a selective cancer dependency (DepMap: 83.3% of cell lines).

Actins are highly conserved proteins that are involved in various types of cell motility and in maintenance of the cytoskeleton. Three main groups of actin isoforms have been identified in vertebrate animals: alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. Actin gamma 1, encoded by this gene, is a cytoplasmic actin found in all cell types. Mutations in this gene are associated with DFNA20/26, a subtype of autosomal dominant non-syndromic sensorineural progressive hearing loss and also with Baraitser-Winter syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 71 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Baraitser-winter syndrome 2 (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 757 total — 14 pathogenic, 38 likely-pathogenic (top 4% of genes corpus-wide)
• Regional missense constraint (gnomAD): 4 of 8 regions constrained (≈51% of expected missense variation)
• GTEx eGene: eQTL in 25 tissues, sQTL in 12 (q < 0.05)
• Phenotypes (HPO): 76
• Cancer dependency (DepMap): dependent in 83.3% of screened cell lines
• Constraint (gnomAD): pLI 0.46 (intermediate), LOEUF 0.62 (unconstrained)
• MANE Select transcript: NM_001614

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:144
Approved symbol	ACTG1
Name	actin gamma 1
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000184009
Ensembl biotype	protein_coding
OMIM	102560
Entrez	71

Gene structure

Transcript identifiers

Ensembl transcripts: 57 — 34 protein_coding, 17 nonsense_mediated_decay, 6 retained_intron

MANE Select: ENST00000573283

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 3: 3, TSL 4: 1, TSL 5: 7

ENST00000573283, ENST00000570382, ENST00000571691, ENST00000571721, ENST00000572105, ENST00000574671, ENST00000575087, ENST00000575659, ENST00000575842, ENST00000575994, ENST00000576209, ENST00000576214, ENST00000576544, ENST00000576917, ENST00000615544, ENST00000644774, ENST00000679410, ENST00000679480, ENST00000679535, ENST00000679778, ENST00000680227, ENST00000680727, ENST00000681052, ENST00000681092, ENST00000681842, ENST00000863045, ENST00000863046, ENST00000915961, ENST00000915962, ENST00000915963, ENST00000915964, ENST00000915965, ENST00000915966, ENST00000915967, ENST00000915968, ENST00000915969, ENST00000915970, ENST00000915971, ENST00000915972, ENST00000915973, ENST00000915974, ENST00000915975, ENST00000915976, ENST00000954444, ENST00001028843, ENST00001028844, ENST00001028846, ENST00001028848, ENST00001028858, ENST00001070208, ENST00001070214, ENST00001070219, ENST00001070230, ENST00001070233, ENST00001103500, ENST00001103501, ENST00001103502

RefSeq mRNA: 2 — MANE Select: NM_001614 NM_001199954, NM_001614

CCDS: CCDS11782

Canonical transcript exons

ENST00000573283 — 6 exons

Exon	Start	End
ENSE00002660192	81509971	81510833
ENSE00002665639	81512734	81512799
ENSE00003550950	81511188	81511626
ENSE00003591451	81511903	81512142
ENSE00003635001	81512232	81512360
ENSE00003653583	81510927	81511108

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4927.9052 / max 26726.1625, expressed in 1828 samples.

Highest expression (Bgee): ileal mucosa, ventricular zone, amniotic fluid, embryo, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACTG1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 12 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 37 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.9e-38	-0.34	17:81510872:GC:G
Artery Tibial	eqtl	8.3e-23	-0.29	17:81499819:G:A
Esophagus Muscularis	sqtl	1.4e-15	+0.32	17:81511845:C:T
Esophagus Muscularis	eqtl	1.2e-14	-0.28	17:81502092:T:A
Liver	eqtl	3.6e-14	+0.43	17:81513660:T:C
Muscle Skeletal	sqtl	6.8e-14	+0.40	17:81511845:C:T
Esophagus Gastroesophageal Junction	eqtl	9.1e-14	-0.32	17:81508673:C:T
Artery Tibial	sqtl	1.8e-13	-0.42	17:81510872:GC:G
Colon Sigmoid	eqtl	6.7e-12	-0.30	17:81510872:GC:G
Colon Sigmoid	sqtl	3.4e-11	-0.29	17:81489511:T:C
Artery Aorta	sqtl	1.3e-09	+0.47	17:81522407:G:A
Esophagus Gastroesophageal Junction	sqtl	1.2e-08	-0.32	17:81499819:G:A
Artery Aorta	eqtl	4.1e-08	-0.24	17:81511844:C:A
Heart Left Ventricle	sqtl	2.8e-05	-0.53	17:81499763:G:A
Adipose Subcutaneous	sqtl	1.3e-04	+0.19	17:81487336:C:T
Artery Coronary	eqtl	1.6e-04	-0.28	17:81499819:G:A
Heart Left Ventricle	eqtl	3.6e-04	-0.11	17:81496298:G:A
Brain Putamen basal ganglia	eqtl	4.0e-04	+0.91	17:81037577:T:C
Artery Coronary	sqtl	1.1e-03	+0.39	17:81499819:G:A
Cells EBV-transformed lymphocytes	eqtl	1.1e-03	+0.50	17:81525144:G:A

FANTOM5 promoters

showing 10 of 22 alternative TSS:

Promoter ID	TPM avg	Samples expressed
168753	4832.8779	1828
168747	41.8485	1793
168746	9.9495	1704
168740	8.0135	1615
168734	6.9481	1552
168735	6.3556	1517
168745	5.5632	1580
168741	3.6143	1327
168736	2.7801	1247
168737	2.4367	1086

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.98	gold quality
ventricular zone	UBERON:0003053	99.98	gold quality
amniotic fluid	UBERON:0000173	99.96	gold quality
embryo	UBERON:0000922	99.96	gold quality
ganglionic eminence	UBERON:0004023	99.96	gold quality
cortical plate	UBERON:0005343	99.96	gold quality
dorsal root ganglion	UBERON:0000044	99.95	gold quality
pleura	UBERON:0000977	99.95	gold quality
epithelium of nasopharynx	UBERON:0001951	99.95	gold quality
parietal pleura	UBERON:0002400	99.95	gold quality
visceral pleura	UBERON:0002401	99.95	gold quality
mucosa of urinary bladder	UBERON:0001259	99.94	gold quality
pericardium	UBERON:0002407	99.94	gold quality
lower lobe of lung	UBERON:0008949	99.94	gold quality
epithelial cell of pancreas	CL:0000083	99.93	gold quality
stromal cell of endometrium	CL:0002255	99.93	gold quality
cardia of stomach	UBERON:0001162	99.93	gold quality
pylorus	UBERON:0001166	99.93	gold quality
germinal epithelium of ovary	UBERON:0001304	99.93	gold quality
trigeminal ganglion	UBERON:0001675	99.93	gold quality
thymus	UBERON:0002370	99.93	gold quality
adult organism	UBERON:0007023	99.93	gold quality
type B pancreatic cell	CL:0000169	99.92	gold quality
mammary duct	UBERON:0001765	99.92	gold quality
epithelium of mammary gland	UBERON:0003244	99.92	gold quality
vena cava	UBERON:0004087	99.92	gold quality
nasal cavity epithelium	UBERON:0005384	99.92	gold quality
layer of synovial tissue	UBERON:0007616	99.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.91	gold quality
colonic mucosa	UBERON:0000317	99.91	gold quality
renal medulla	UBERON:0000362	99.91	gold quality
gall bladder	UBERON:0002110	99.91	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.91	gold quality
pancreatic ductal cell	CL:0002079	99.90	gold quality
pharyngeal mucosa	UBERON:0000355	99.90	gold quality
parotid gland	UBERON:0001831	99.90	gold quality
nipple	UBERON:0002030	99.90	gold quality
synovial joint	UBERON:0002217	99.90	gold quality
lower esophagus mucosa	UBERON:0035834	99.90	gold quality
urethra	UBERON:0000057	99.89	gold quality
seminal vesicle	UBERON:0000998	99.89	gold quality
trachea	UBERON:0003126	99.89	gold quality
choroid plexus epithelium	UBERON:0003911	99.89	gold quality
buccal mucosa cell	CL:0002336	99.88	gold quality
right coronary artery	UBERON:0001625	99.88	gold quality
upper leg skin	UBERON:0004262	99.88	gold quality
cervix squamous epithelium	UBERON:0006922	99.88	gold quality
superior vestibular nucleus	UBERON:0007227	99.88	gold quality
saphenous vein	UBERON:0007318	99.88	gold quality
penis	UBERON:0000989	99.87	gold quality
mammalian vulva	UBERON:0000997	99.87	gold quality
caecum	UBERON:0001153	99.87	gold quality
skin of hip	UBERON:0001554	99.87	gold quality
mammary gland	UBERON:0001911	99.87	gold quality
epithelium of esophagus	UBERON:0001976	99.87	gold quality
upper arm skin	UBERON:0004263	99.87	gold quality
caput epididymis	UBERON:0004358	99.87	gold quality
corpus epididymis	UBERON:0004359	99.87	gold quality
mucosa of transverse colon	UBERON:0004991	99.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.87	gold quality
thoracic mammary gland	UBERON:0005200	99.87	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.87	gold quality
squamous epithelium	UBERON:0006914	99.87	gold quality
esophagus squamous epithelium	UBERON:0006920	99.87	gold quality
endothelial cell	CL:0000115	99.86	gold quality
metanephros	UBERON:0000081	99.86	gold quality
tibia	UBERON:0000979	99.86	gold quality
vermiform appendix	UBERON:0001154	99.86	gold quality
bronchus	UBERON:0002185	99.86	gold quality
descending thoracic aorta	UBERON:0002345	99.86	gold quality
middle temporal gyrus	UBERON:0002771	99.86	gold quality
cervix epithelium	UBERON:0004801	99.86	gold quality
oviduct epithelium	UBERON:0004804	99.86	gold quality
upper lobe of lung	UBERON:0008948	99.86	gold quality
upper lobe of left lung	UBERON:0008952	99.86	gold quality
oral cavity	UBERON:0000167	99.85	gold quality
jejunal mucosa	UBERON:0000399	99.85	gold quality
thoracic aorta	UBERON:0001515	99.85	gold quality
palpebral conjunctiva	UBERON:0001812	99.85	gold quality
medulla oblongata	UBERON:0001896	99.85	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.85	gold quality
epithelium of bronchus	UBERON:0002031	99.85	gold quality
lung	UBERON:0002048	99.85	gold quality
hair follicle	UBERON:0002073	99.85	gold quality
postcentral gyrus	UBERON:0002581	99.85	gold quality
superior frontal gyrus	UBERON:0002661	99.85	gold quality
orbitofrontal cortex	UBERON:0004167	99.85	gold quality
cauda epididymis	UBERON:0004360	99.85	gold quality
bronchial epithelial cell	CL:0002328	99.84	gold quality
ascending aorta	UBERON:0001496	99.84	gold quality
superficial temporal artery	UBERON:0001614	99.84	gold quality
parietal lobe	UBERON:0001872	99.84	gold quality
gingival epithelium	UBERON:0001949	99.84	gold quality
substantia nigra pars compacta	UBERON:0001965	99.84	gold quality
placenta	UBERON:0001987	99.84	gold quality
esophagus mucosa	UBERON:0002469	99.84	gold quality
metanephric glomerulus	UBERON:0004736	99.84	gold quality
periodontal ligament	UBERON:0008266	99.84	gold quality
renal glomerulus	UBERON:0000074	99.83	gold quality
aorta	UBERON:0000947	99.83	gold quality

Single-cell (SCXA)

Detected in 43 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	13973.79
E-MTAB-10042	yes	7259.49
E-CURD-77	yes	6772.60
E-CURD-122	yes	6605.15
E-MTAB-9221	yes	5469.24
E-CURD-46	yes	4384.63
E-CURD-98	yes	3864.90
E-MTAB-9467	yes	3429.30
E-CURD-119	yes	1317.83
E-GEOD-131882	yes	1285.13
E-HCAD-4	yes	68.51
E-GEOD-137537	yes	45.44
E-CURD-88	yes	32.60
E-MTAB-7316	yes	27.31
E-GEOD-135922	yes	25.64

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	1767.8
Caudate putamen	tissue	1699.1
Ovary	tissue	1655.1	low
Esophagus	tissue	1597.9	low
Lymph node	tissue	1586.8	high
Vagina	tissue	1501.6	low
Frontal cortex	tissue	1496.8
Urinary bladder	tissue	1438.5	low
Midbrain	tissue	1381.0
Putamen	tissue	1343.4
Substantia nigra	tissue	1332.6
Medulla oblongata	tissue	1316.9
Thalamus	tissue	1299.6
Pons	tissue	1296.9
Hippocampal formation	tissue	1287.0
Superior colliculi	tissue	1260.9
Thymus	tissue	1256.0
Appendix	tissue	1250.9	high
Tonsil	tissue	1212.8	high
Basal ganglia	tissue	1211.1	low
Thyroid gland	tissue	1171.9	low
Corpus callosum	tissue	1150.0
Ventral forebrain	tissue	1147.3
Cerebral cortex	tissue	1145.7	medium
Somatosensory cortex	tissue	1145.7
Motor cortex	tissue	1139.7
Septum	tissue	1126.2
Prefrontal cortex	tissue	1109.7
Gallbladder	tissue	1105.8	high
Hypothalamus	tissue	1086.7
Bone marrow	tissue	1067.2	medium
Occipital cortex	tissue	1048.9
Temporal cortex	tissue	1046.4
Entorhinal cortex	tissue	1041.8
Stomach 1	tissue	1009.9	high
Colon	tissue	1004.3	high
Retrosplenial and cingulate cortex	tissue	1002.2
Retrosplenial cortex	tissue	990.7
Skin 1	tissue	973.1	medium
Small intestine	tissue	966.5	high
Insular cortex	tissue	957.2
Locus coeruleus	tissue	941.7
Periaqueductal gray	tissue	940.5
Duodenum	tissue	935.3	high
Olfactory bulb	tissue	932.0
Amygdala	tissue	907.5
Placenta	tissue	867.2	low
Spleen	tissue	857.2	high
Lung	tissue	842.8	low
Endometrium 1	tissue	831.5	low
Pituitary gland	tissue	828.7
Pancreas	tissue	826.9	low
Fallopian tube	tissue	824.4	low
Cervix	tissue	817.4	low
Adipose tissue	tissue	791.2	low
Salivary gland	tissue	768.1	low
Adrenal gland	tissue	746.5	low
Cerebellum	tissue	726.8	low
Nucleus accumbens	tissue	717.0
Smooth muscle	tissue	690.3	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (1791.6), Ventral spinal cord (1767.8), Dorsal spinal cord (1526.1), Dorsal hippocampus (1287.0), White matter (1150.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, JUN, MYC, SRF

miRNA regulators (miRDB)

Targeting ACTG1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 32 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-203B-3P	97.82	66.27	979
HSA-MIR-144-5P	97.66	69.90	531
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-3194-5P	96.80	64.90	1027

Functional genomics

gnomAD constraint: pLI 0.459, LOEUF 0.617, missense Z 4.89 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000573283 splits into 8 regions with different missense tolerance; 4 are missense-constrained (≈51% 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
17:81,510,693–81,511,090	49 / 146.5	0.33	yes (p 8.0e-16)
17:81,511,091–81,511,356	63 / 85.1	0.74	no
17:81,511,357–81,511,386	1 / 18.7	0.05	yes (p 4.2e-05)
17:81,511,387–81,511,427	12 / 16.3	0.74	no
17:81,511,428–81,511,592	7 / 79.4	0.09	yes (p 4.4e-16)
17:81,511,593–81,511,927	21 / 26.6	0.79	no
17:81,511,928–81,511,986	4 / 26.9	0.15	yes (p 1.0e-05)
17:81,511,987–81,512,354	76 / 129.9	0.58	no
DepMap (CRISPR cell-line fitness): dependent in 83.3% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SNU-840 (-2.106), HCC-95 (-1.836), OV-90 (-1.745), BHT-101 (-1.702), D283 Med (-1.595), HCC1143 (-1.58), Caki-1 (-1.556), A-375 (-1.457), LN-319 (-1.444), VCaP (-1.413), CAL-29 (-1.403), HUP-T4 (-1.381), SF767 (-1.378), Caov-4 (-1.364), SW1116 (-1.362).

Literature-anchored findings (GeneRIF, showing 40)

• RNA polymerase II accumulates in the promoter-proximal region of the dihydrofolate reductase and gamma-actin genes. (PMID:12612070)
• the first description of a mutation in cytoskeletal, or nonmuscle, actin; with an autosomal dominant, progressive, sensorineural hearing loss phenotype (PMID:13680526)
• A missense mutation in the gamma actin 1 gene causes autosomal dominant hearing loss. (PMID:14684684)
• Our data are consistent with the idea that DP assembles into nascent junctions from both diffusible and particulate pools in a temporally overlapping series of events triggered by cell-cell contact and regulated by actin and DP-IF interactions. (PMID:16365169)
• Espins do not activate the Arp2/3 complex in vitro, and bundle assembly is not indicative of in-vitro nucleation activity.Our results suggest a novel way to build actin bundles at specific sites in cells. (PMID:16569662)
• A major factor in the deafness caused by gamma-actin mutations is an altered ability of the actin filaments to be properly regulated by actin-binding proteins rather than an inability to polymerize. (PMID:16690605)
• the present results do not indicate that mutations in ACTG1 are a frequent cause of autosomal-dominant postlingual sensorineural hearing impairment in Norway nor Denmark. (PMID:16773128)
• actin and vimentin filaments can interact directly through the tail domain of vimentin (PMID:16901892)
• During cell membrane blebbing actin recruitment is involved in cortex assembly. (PMID:17088428)
• In both AA and AL renal amyloidosis groups there were significant positive correlations between immunostaining of TGFbeta-1 and alpha-SMA. (PMID:17285762)
• IQGAP1 regulates Salmonella invasion through interactions with actin, Rac1, and Cdc42 (PMID:17693642)
• In this report we have used mutagenesis of the Talin1 I/LWEQ module to show that the amino acids responsible for dimerization are necessary for F-actin binding, stabilization and cross-linking of actin filaments, and focal adhesion targeting. (PMID:17722883)
• analysis of the structural basis of profilin-actin complexes during filament elongation by Ena/VASP (PMID:17914456)
• In this study, a novel missense mutation (c.364A>G; p.I122V) co-segregated with the affected individuals in the family and did not exist in the unaffected family members and 150 unrelated normal controls. (PMID:18804074)
• Both RPEL peptides of the MAL protein bind to the G-actin hydrophobic cleft and to subdomain 3. (PMID:19008859)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• Two novel ACTG1 missense mutations are associated with DFNA20/26 hearing impairment. (PMID:19477959)
• audiometric phenotype of the Dutch DFNA20/26 family with a novel mutation in ACTG1 was largely consistent with previous reports on DFNA20/26. All suffered from hearing loss.This is the first known DFNA20/26 family that has experienced tinnitus. (PMID:19548389)
• These results reveal new aspects of beta- and gamma-actin organization that support their functional diversity. (PMID:19638415)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)
• actin participates in transcription elongation by recruiting Cdk9,a catalytic subunit of P-TEFb, for phosphorylation of the Pol II C-terminal domain, and the actin-Cdk9 interaction promotes chromatin remodeling (PMID:21378166)
• Cytoplasmic G-actin concentration is a critical parameter for determining the extent of stimulus-induced G-actin assembly and cell extension. (PMID:21502360)
• knockdown of gamma-actin significantly reduced speed of motility and severely affected the cell’s ability to explore, which was, in part, due to a loss of cell polarity (PMID:21908715)
• 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)
• These results showed the biphasic F-actin dynamics in herpes simplex virus 1 neuronal infection and confirmed the association of F-actin with the changes in the expression and activity of cofilin 1. (PMID:22623803)
• Data indicate beta-cytoplasmic (beta-CYA) and gamma-cytoplasmic (gamma-CYA) actins differential localization and dynamics at epithelial junctions. (PMID:22855531)
• the novel variant p.M305T in ACTG1 (DFNA20/26) was selected as a disease-causing variant. (PMID:23506231)
• Mutations in ACTB cause a distinctly more severe phenotype than ACTG1 mutations in Baraitser-Winter syndrome. (PMID:23756437)
• The data, for the first time, link ASAP3 with ACTG1 in the regulation of cytoskeletal maintenance and cell motility (PMID:24284654)
• The actin/MKL1 signalling pathway influences cell growth and gene expression through large-scale chromatin reorganization and histone post-translational modifications. (PMID:24762104)
• In this study we sought to clarify the detailed mutational spectrum, clinical features, and genotype-phenotype correlations for ACTG1 gene associated autosomal dominant sensorineural hearing loss (PMID:25792668)
• Three unrelated cases of rare ACTG1 variants in fetal microlissencephaly have been described. (PMID:26188271)
• Data indicate that F-actin is significantly elevated in septic shock, and F-actin and the F:G-actin ratio are potential biomarkers for the diagnosis of septic shock. (PMID:26754286)
• a novel mutation in ACTG1 was found to be co-segregated with hearing loss and the genetic cause of autosomal dominant nonsyndromic hearing impairment in a Chinese family (PMID:26832775)
• We have identified a three-generation pedigree segregating a novel mutation in the ACTG1 gene that causes Baraitser-Winter Syndrome with extremely variable expressivity, leading to an initial diagnosis of isolated AD hearing loss in two members. (PMID:27096712)
• we expand the clinical spectrum of the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome demonstrating the mild end of the facial and brain manifestations. (PMID:27240540)
• Baraitser-Winter cerebrofrontofacial syndrome is caused by missense mutations in the cytoplasmic beta- and gamma-actin genes ACTB and ACTG1. We provide an overview of the clinical characteristics (including some novel findings in four recently diagnosed patients), diagnosis, management, mutation spectrum and genetic counselling. (PMID:27625340)
• Data reports a recurrent de novo mutation in ACTG1 causes isolated ocular coloboma (PMID:28493397)
• Results identified ACTG1 with significant high expression in skin cancer tissue and suggested that ACTG1 can regulate the cell proliferation and migration through ROCK signaling pathway. (PMID:28727228)
• A novel actin gamma 1 (ACTG1) de novo mutation is identified in two sporadic, juvenile, Chinese non-syndromic hearing loss (NSHL) cases using targeted high-throughput sequencing. (PMID:29357087)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Actg1	ENSMUSG00000062825
rattus_norvegicus		ENSRNOG00000064444

Paralogs (26): ACTR6 (ENSG00000075089), ACTB (ENSG00000075624), 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), ACTRT3 (ENSG00000184378), ACTL7A (ENSG00000187003), ACTL10 (ENSG00000288649)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87906) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 24 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased or absent threshold for auditory brainstem response	2
abnormal craniofacial morphology	1
decreased body weight	1
microphthalmia	1
decreased locomotor activity	1
limb grasping	1
edema	1
hemorrhage	1
deafness	1
premature death	1
impaired skeletal muscle contractility	1
spina bifida	1
abnormal skeletal muscle fiber morphology	1
pallor	1
embryonic growth retardation	1
abnormal Z line morphology	1
abnormal cochlear hair cell stereociliary bundle morphology	1
decreased outer hair cell stereocilia number	1
increased susceptibility to age-related hearing loss	1
impaired hearing	1
increased variability of skeletal muscle fiber size	1
centrally nucleated skeletal muscle fibers	1
perinatal lethality, incomplete penetrance	1
preweaning lethality, incomplete penetrance	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
Oryctolagus cuniculus	P62740	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
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
Cyprinus carpio	P53479	99.7%	Diamond
Takifugu rubripes	P53480	99.7%	Diamond
Botrytis cinerea	O13419	99.5%	Diamond
Xenopus borealis	P15475	99.5%	Diamond
Aspergillus nidulans FGSC A4	P20359	99.5%	Diamond
Bactrocera dorsalis	P45885	99.5%	Diamond
Carassius auratus	P49055	99.5%	Diamond
Manduca sexta	P49871	99.5%	Diamond
Anser anser anser	P63256	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
MIR3186	ncRNA	100422944
FSCN2	protein-coding	25794
BAHCC1	protein-coding	57597
LINC01971	ncRNA	105371927
MIR4740	ncRNA	100616294
PDE6G	protein-coding	5148
NPLOC4	protein-coding	55666
FAAP100	protein-coding	80233
TSPAN10	protein-coding	83882
LINC03048	ncRNA	100130370

Protein

Protein identifiers

Actin, cytoplasmic 2 — P63261 (reviewed: P63261)

Alternative names: Gamma-actin

All UniProt accessions (9): A0A7P0TBL1, A0A804GS07, I3L1U9, I3L3I0, I3L3R2, I3L4N8, J3KT65, K7EM38, P63261

UniProt curated annotations — full annotation on UniProt →

Function. Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. May play a role in the repair of noise-induced stereocilia gaps thereby maintains hearing sensitivity following loud noise damage.

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. Interacts with TWF1, CAPZB, cofilin and profilin.

Subcellular location. Cytoplasm. Cytoskeleton.

Post-translational modifications. 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. 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. Methylated at His-73 by SETD3. (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. Deafness, autosomal dominant, 20 (DFNA20) [MIM:604717] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. Baraitser-Winter syndrome 2 (BRWS2) [MIM:614583] 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. Defects in ACTG1 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea.

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 (2): NP_001186883, NP_001605* (*=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 (73 total): helix 21, sequence variant 19, strand 17, modified residue 6, turn 4, chain 2, cross-link 2, initiator methionine 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures by resolution:

PDB	Title	Method	Resolution (Å)
6WK2	SETD3 mutant (N255V) in Complex with an Actin Peptide with His73 Replaced with Methionine	X-RAY DIFFRACTION	1.76
6WK1	SETD3 in Complex with an Actin Peptide with His73 Replaced with Methionine	X-RAY DIFFRACTION	1.89
6V63	SETD3 WT in Complex with an Actin Peptide with His73 Replaced with Glutamine	X-RAY DIFFRACTION	2.02
6V62	SETD3 double mutant (N255F/W273A) in Complex with an Actin Peptide with His73 Replaced …	X-RAY DIFFRACTION	2.36
7NVM	Human TRiC complex in closed state with nanobody Nb18, actin and PhLP2A bound	ELECTRON MICROSCOPY	3.1
8DNF	Cryo-EM structure of nonmuscle gamma-actin	ELECTRON MICROSCOPY	3.38
9SMX	CM1-activated gTuRC in complex with nascent alpha-E254D mutant microtubules	ELECTRON MICROSCOPY	3.67
5JLH	Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution	ELECTRON MICROSCOPY	3.9
6G2T	human cardiac myosin binding protein C C1 Ig-domain bound to native cardiac thin filament	ELECTRON MICROSCOPY	9
6CXI	Cardiac thin filament decorated with C0C1 fragment of cardiac myosin binding protein C …	ELECTRON MICROSCOPY	11
6CXJ	Cardiac thin filament decorated with C0C1 fragment of cardiac myosin binding protein C …	ELECTRON MICROSCOPY	11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63261-F1	95.44	0.93

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 7NVM

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

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-acetylglutamate	2
Methionine (r)-sulfoxide	44, 47
Tele-methylhistidine	73
N6-methyllysine	84
(microbial infection) isoglutamyl lysine isopeptide (lys-glu) (interchain with e-270)	50

Function

Pathways and Gene Ontology

Reactome pathways

18 curated (TAS) of 72; 16 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 72 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-446353	Cell-extracellular matrix interactions	curated
R-HSA-8856828	Clathrin-mediated endocytosis	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-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-9013418	RHOBTB2 GTPase cycle	curated
R-HSA-9764561	Regulation of CDH1 Function	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-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-1266738	Developmental Biology	—
R-HSA-2682334	EPH-Ephrin signaling	—
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	—
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	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-445095	Interaction between L1 and Ankyrins	electronic
R-HSA-373760	L1CAM interactions	—
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-5684996	MAPK1/MAPK3 signaling	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-9675108	Nervous system development	—
R-HSA-3000171	Non-integrin membrane-ECM interactions	—
R-HSA-5673001	RAF/MAP kinase cascade	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-5663220	RHO GTPases Activate Formins	electronic
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs	electronic
R-HSA-9706574	RHOBTB GTPase Cycle	—
R-HSA-437239	Recycling pathway of L1	electronic
R-HSA-9764265	Regulation of CDH1 Expression and Function	—
R-HSA-9764274	Regulation of Expression and Function of Type I Classical Cadherins	—
R-HSA-9759476	Regulation of Homotypic Cell-Cell Adhesion	—

MSigDB gene sets: 670 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_WOUND_HEALING, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_PLATELET_ACTIVATION, GCM_NPM1, MORF_UBE2I, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, HSIAO_HOUSEKEEPING_GENES, GOBP_NEUROGENESIS

GO Biological Process (17): angiogenesis (GO:0001525), morphogenesis of a polarized epithelium (GO:0001738), axonogenesis (GO:0007409), positive regulation of gene expression (GO:0010628), positive regulation of cell migration (GO:0030335), maintenance of blood-brain barrier (GO:0035633), cell motility (GO:0048870), regulation of stress fiber assembly (GO:0051492), regulation of focal adhesion assembly (GO:0051893), platelet aggregation (GO:0070527), positive regulation of wound healing (GO:0090303), tight junction assembly (GO:0120192), regulation of transepithelial transport (GO:0150111), regulation of synaptic vesicle endocytosis (GO:1900242), protein localization to bicellular tight junction (GO:1902396), cytoskeleton organization (GO:0007010), postsynaptic actin cytoskeleton organization (GO:0098974)

GO Molecular Function (10): structural constituent of cytoskeleton (GO:0005200), profilin binding (GO:0005522), ATP binding (GO:0005524), hydrolase activity (GO:0016787), protein kinase binding (GO:0019901), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), structural constituent of postsynaptic actin cytoskeleton (GO:0098973), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (24): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), actin filament (GO:0005884), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), membrane (GO:0016020), myofibril (GO:0030016), axon (GO:0030424), filamentous actin (GO:0031941), NuA4 histone acetyltransferase complex (GO:0035267), apical junction complex (GO:0043296), calyx of Held (GO:0044305), synapse (GO:0045202), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), dense body (GO:0097433), Schaffer collateral - CA1 synapse (GO:0098685), basal body patch (GO:0120220), apical part of cell (GO:0045177)

Reactome top-level categories

12 top-level categories:

Category	Pathways
Oncogenic MAPK signaling	4
RHO GTPase Effectors	3
Membrane Trafficking	2
EPH-Ephrin signaling	2
L1CAM interactions	2
Gap junction trafficking	1
Gap junction degradation	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Cell-cell junction organization	1
Signaling by VEGF	1
Cell junction organization	1
RAF/MAP kinase cascade	1

GO top-level categories

showing 60 of 75 GO namespaces:

Category	Terms
cellular anatomical structure	4
cytoskeleton	2
protein binding	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
morphogenesis of an epithelium	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
tissue homeostasis	1
cellular process	1
regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of actomyosin structure organization	1
regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of cell-substrate junction assembly	1
platelet activation	1
homotypic cell-cell adhesion	1
wound healing	1
regulation of wound healing	1
positive regulation of response to wounding	1
cell-cell junction assembly	1
tight junction organization	1
regulation of transport	1
transepithelial transport	1
regulation of endocytosis	1
synaptic vesicle endocytosis	1
regulation of synaptic vesicle recycling	1
protein localization to cell-cell junction	1
organelle organization	1
actin cytoskeleton organization	1
postsynaptic cytoskeleton organization	1
structural molecule activity	1
cytoskeleton organization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
catalytic activity	1
kinase binding	1
ubiquitin-like protein ligase binding	1
structural constituent of cytoskeleton	1
postsynaptic actin cytoskeleton	1
postsynaptic actin cytoskeleton organization	1
structural constituent of postsynapse	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 20 of 52 annotations. The rest are phylogenetic / computational / electronic (IEA).

20 experimentally-supported GO terms:

GO term	NS	Evidence
angiogenesis	BP	mutant phenotype
morphogenesis of a polarized epithelium	BP	mutant phenotype
positive regulation of cell migration	BP	mutant phenotype
positive regulation of gene expression	BP	mutant phenotype
positive regulation of wound healing	BP	mutant phenotype
protein localization to bicellular tight junction	BP	mutant phenotype
regulation of focal adhesion assembly	BP	mutant phenotype
regulation of stress fiber assembly	BP	mutant phenotype
regulation of transepithelial transport	BP	mutant phenotype
tight junction assembly	BP	mutant phenotype
actin filament	CC	direct assay
apical junction complex	CC	direct assay
blood microparticle	CC	high-throughput assay
cell-cell junction	CC	direct assay
extracellular exosome	CC	direct assay
membrane	CC	high-throughput assay
nucleus	CC	high-throughput assay
identical protein binding	MF	physical interaction
profilin binding	MF	direct assay
ubiquitin protein ligase binding	MF	physical interaction

Protein interactions and networks

IntAct

Human interaction partners of ACTG1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 59 partners by confidence:

Partner	Interaction type	MIscore	Records
ACTB	physical association	0.950	16
CAP2	physical association	0.860	12
CFL2	physical association	0.850	15
CFL1	physical association	0.830	9
DSTN	physical association	0.790	9
NTAQ1	physical association	0.780	7
HTT	physical association	0.670	15
EHHADH	physical association	0.670	4
TRAF2	proximity	0.650	2
MLH1	physical association	0.600	6
ACT1	physical association	0.560	3
AIP1	physical association	0.560	3
CCDC22	physical association	0.560	3
CDC37	physical association	0.560	3
PS1TP5BP1	physical association	0.560	3
SRP1	physical association	0.560	3
TAE1	physical association	0.560	3
VASP	proximity	0.480	1
NDRG1	physical association	0.400	1
ATF7IP	physical association	0.370	1
CTBP2	physical association	0.370	1
FXR1	physical association	0.370	1
GIT2	physical association	0.370	1
HSPB2	physical association	0.370	1
MAPK6	physical association	0.370	1
RPS6KA5	physical association	0.370	1
TXN2	physical association	0.370	1
ENAH	association	0.350	1
DISC1	physical association	0.000	2
CHUK	physical association	0.000	1

BioGRID (730 interactions; top human partners by supporting records in a sample of 600 records): ACTB (Two-hybrid; 13 records), CFL1 (Two-hybrid; 8 records), CFL2 (Two-hybrid; 7 records), CAP1 (Two-hybrid; 6 records), CAP2 (Two-hybrid; 6 records), ACTC1 (Affinity Capture-MS; 5 records), CAPZB (Affinity Capture-MS; 5 records), ACTL6A (Affinity Capture-MS; 4 records), ACTR3 (Cross-Linking-MS (XL-MS); 4 records), DSTN (Two-hybrid; 4 records), LIMA1 (Affinity Capture-MS; 4 records), PFN1 (Affinity Capture-MS; 4 records), WDR1 (Affinity Capture-MS; 4 records), ACTA1 (Co-fractionation; 3 records), MYO10 (Cross-Linking-MS (XL-MS); 3 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
ACTG1	“up-regulates quantity”	F-actin_assembly	binding
PTPN6	down-regulates	ACTG1	dephosphorylation

Protein complexes (CORUM) (4)

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

4 complexes by size:

Complex	Subunits	Members
BAF complex	13	ARID1A, ARID1B, SMARCA4, SMARCC1, SMARCE1, ACTL6A, ACTL6B, SMARCA2, SMARCB1, SMARCC2, SMARCD1, ACTB, ACTG1
CTGF/Hcs24-actin(beta/gamma) complex	3	ACTB, ACTG1, CCN2
DISC-FEZ1-F-actin complex	3	FEZ1, ACTG1, DISC1
★ ACTG1-HDAC6 complex	2	ACTG1, HDAC6

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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
RIP-mediated NFkB activation via ZBP1	9	120.9×	9e-16
TRAF6 mediated NF-kB activation	10	91.4×	8e-16
TICAM1, RIP1-mediated IKK complex recruitment	6	72.1×	5e-09
TNFR1-induced NF-kappa-B signaling pathway	10	67.2×	1e-14
TAK1-dependent IKK and NF-kappa-B activation	11	66.1×	8e-16
Regulation of NF-kappa B signaling	5	63.4×	2e-07
IKK complex recruitment mediated by RIP1	6	59.6×	1e-08
TNF signaling	7	59.2×	9e-10

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	11	171.6×	6e-21
canonical NF-kappaB signal transduction	15	101.8×	1e-24
interleukin-1-mediated signaling pathway	6	89.2×	4e-09
tumor necrosis factor-mediated signaling pathway	11	67.3×	1e-15
toll-like receptor 4 signaling pathway	6	58.5×	5e-08
cellular response to tumor necrosis factor	8	24.2×	8e-08
negative regulation of canonical NF-kappaB signal transduction	7	22.3×	2e-06
positive regulation of canonical NF-kappaB signal transduction	16	21.5×	2e-15

Disease & clinical

Genetic variants

Variant evidence for ACTG1: 757 ClinVar records (52 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 7 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	38
Uncertain significance	201
Likely benign	338
Benign	49

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 52 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
29585	NM_001614.5(ACTG1):c.464C>T (p.Ser155Phe)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
18318	NM_001614.5(ACTG1):c.791C>T (p.Pro264Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
813525	NM_001614.5(ACTG1):c.628C>T (p.Arg210Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1065444	NM_001614.5(ACTG1):c.209C>T (p.Pro70Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
374385	NM_001614.5(ACTG1):c.118C>T (p.His40Tyr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
452404	NM_001614.5(ACTG1):c.611C>G (p.Ala204Gly)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
546156	NM_001614.5(ACTG1):c.847A>G (p.Met283Val)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
807363	NM_001614.5(ACTG1):c.728C>T (p.Pro243Leu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1526065	NM_001614.5(ACTG1):c.848T>C (p.Met283Thr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1810558	NM_001614.5(ACTG1):c.998C>G (p.Pro333Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
29590	NM_001614.5(ACTG1):c.766C>T (p.Arg256Trp)	Pathogenic	criteria provided, single submitter	5
444419	NM_001614.5(ACTG1):c.767G>A (p.Arg256Gln)	Pathogenic	criteria provided, single submitter	1
561398	NM_001614.5(ACTG1):c.277G>A (p.Glu93Lys)	Pathogenic	criteria provided, single submitter	1
871523	NM_001614.5(ACTG1):c.354G>T (p.Lys118Asn)	Pathogenic	criteria provided, single submitter	1
1483014	NM_001614.5(ACTG1):c.1013C>G (p.Ser338Trp)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ACTG1’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; 32 predictions of 288):

Position(s)	Effect	Δscore	Sites
17:81510926	donor_loss	1.0000
17:81511109–81511110	acceptor_loss	1.0000	3
17:81511186–81511187	donor_loss	1.0000	3
17:81511627–81511628	acceptor_loss	1.0000	5
17:81511901–81511902	donor_loss	1.0000	4
17:81512143	acceptor_loss	1.0000
17:81512231	donor_loss	1.0000	2
17:81512361–81512362	acceptor_loss	1.0000	6
17:81512366	acceptor_gain	1.0000
17:81510834–81510835	acceptor_loss	0.9900	6

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
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	9.19e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000188
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000404
Colon Adenocarcinoma (TCGA)	favorable	0.000495

Disease associations

OMIM: gene MIM:102560 | disease phenotypes: MIM:604717, MIM:614583, MIM:610805, MIM:607432, MIM:243310

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
Baraitser-winter syndrome 2	Definitive	Autosomal dominant	4
nonsyndromic genetic hearing loss	Definitive	Autosomal dominant
autosomal dominant nonsyndromic hearing loss 20	Strong	Autosomal dominant	2
Baraitser-Winter cerebrofrontofacial syndrome	Supportive	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

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

2 validity classifications:

Disease	Classification	Inheritance
Baraitser-winter syndrome 2	Definitive	AD
nonsyndromic genetic hearing loss	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (13 panels, 13 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

13 panels:

Panel	Rating
Cerebral malformation	green
Clefting	green
DDG2P	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Malformations of cortical development	green
Monogenic hearing loss	green
Ocular coloboma	green
Paediatric disorders	green
Rare syndromic craniosynostosis or isolated multisuture synostosis	green
Structural eye disease	green

Mondo (9): autosomal dominant nonsyndromic hearing loss 20 (MONDO:0011480), Baraitser-winter syndrome 2 (MONDO:0013812), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss disorder (MONDO:0005365), congenital anomaly of kidney and urinary tract (MONDO:0019719), lissencephaly spectrum disorders (MONDO:0018838), Baraitser-Winter cerebrofrontofacial syndrome (MONDO:0017579), microcephaly (MONDO:0001149), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (6): Baraitser-Winter cerebrofrontofacial syndrome (Orphanet:2995), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare non-syndromic genetic deafness (Orphanet:87884), Rare genetic deafness (Orphanet:96210), Renal or urinary tract malformation (Orphanet:93545), Lissencephaly (Orphanet:48471)

HPO phenotypes

showing 60 of 76 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000072	Hydroureter
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000202	Orofacial cleft
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:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000408	Progressive sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000437	Depressed nasal tip
HP:0000445	Wide nose
HP:0000448	Prominent nose
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000482	Microcornea
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000568	Microphthalmia
HP:0000588	Optic disc coloboma
HP:0000589	Coloboma
HP:0000612	Iris coloboma
HP:0000637	Long palpebral fissure
HP:0001100	Heterochromia iridis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001302	Pachygyria
HP:0001328	Specific learning disability
HP:0001339	Lissencephaly
HP:0001387	Joint stiffness
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0002000	Short columella
HP:0002119	Ventriculomegaly
HP:0002120	Cerebral cortical atrophy
HP:0002126	Polymicrogyria
HP:0002162	Low posterior hairline
HP:0002300	Mutism
HP:0002326	Transient ischemic attack
HP:0002381	Aphasia
HP:0002553	Highly arched eyebrow
HP:0002650	Scoliosis
HP:0002652	Skeletal dysplasia
HP:0003189	Long nose

GWAS associations

7 associations:

Study	Trait	p-value
GCST90013407_167	Liver enzyme levels (gamma-glutamyl transferase)	5e-83
GCST010002_360	Refractive error	2e-50
GCST90013405_58	Liver enzyme levels (alanine transaminase)	1e-32
GCST90011898_143	Alanine aminotransferase levels	7e-25
GCST011349_45	Gamma glutamyl transferase levels	2e-10
GCST011352_7	Alanine aminotransferase levels	4e-10
GCST005235_15	Hand grip strength	1e-8

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0006941	grip strength measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors

6 disease descriptors:

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D054082	Lissencephaly	C10.500.507.450.499; C16.131.666.507.450.499
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C566906	Cakut *(supp.)*
C565754	Deafness, Autosomal Dominant 20 *(supp.)*
C580334	Nonsyndromic Deafness *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs1135989	Toxicity	3	vincristine	Neurotoxicity Syndromes

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1135989	ACTG1	3	3.00	1	vincristine

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1135989	vincristine	Toxicity	Allele A is associated with increased risk of Neurotoxicity Syndromes when treated with vincristine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G.	PMID:25084203

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, affects binding, increases reaction, decreases expression (+1 more)	4
bisphenol A	increases expression, affects expression, decreases expression	3
Tobacco Smoke Pollution	increases expression, increases metabolic processing	3
Particulate Matter	affects expression, increases expression, decreases expression, increases abundance	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Copper	decreases expression, affects binding	2
Tretinoin	affects cotreatment, increases expression, decreases expression	2
9-hydroxyoctadecadienoic acid	increases expression	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
salinomycin	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	decreases expression, increases abundance	1
3,3’-diindolylmethane	decreases expression, increases reaction	1
bufalin	increases expression	1
zinc chromate	decreases expression, increases abundance	1
artenimol	affects binding	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
diallyl trisulfide	decreases expression	1
beta-methylcholine	affects expression	1
evodiamine	increases expression	1
jasplakinolide	decreases reaction, affects binding	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
thrombin receptor-activating peptide SFLLRNPNDKY	increases secretion	1
ICG 001	decreases expression	1
ON 01910	increases expression	1

Clinical trials (associated diseases)

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

showing 60 of 301 trials:

NCT	Phase	Status	Title
NCT00205881	Phase 4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	Phase 4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	Phase 4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	Phase 4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	Phase 4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	Phase 3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	Phase 3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	Phase 3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	Phase 3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	Phase 2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	Phase 2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	Phase 2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	Phase 2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	Phase 2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	Phase 2	WITHDRAWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	Phase 2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	Phase 2	UNKNOWN	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	Phase 2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	Phase 2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	Phase 2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	Phase 2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	Phase 1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	Phase 1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	Phase 1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	Phase 1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	Phase 1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	Phase 1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	Phase 1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	Phase 1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	Phase 1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT00486577	Phase 2/3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	Phase 2/3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	Phase 2/3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	Phase 2/3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	Phase 1/2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	Phase 1/2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	Phase 1/2	ACTIVE_NOT_RECRUITING	A Phase I/II Clinical Trial With SENS-501 in Children Suffering From Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	Phase 1/2	ACTIVE_NOT_RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	Phase 1/2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	Early Phase 1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss
NCT03300687	Early Phase 1	COMPLETED	First in Human Safety Study of FX-322 in Adults Undergoing Cochlear Implantation
NCT04777669	Early Phase 1	UNKNOWN	Removing Background Talker Noise for Cochlear Implant Users
NCT06025032	Early Phase 1	WITHDRAWN	a Study in Subjects With Otoferlin Mutation-related Hearing Loss Using RNA Base-eDiting Therapy(SOUND)
NCT00001668	Not specified	COMPLETED	Endolymphatic Sac Tumors in a Population of Patients With Von Hippel-Lindau Disease:The Natural History and Pathobiology, and a Prospective Non-Randomized Clinical Trial of Hearing Preservation Surgery in Patients With Early Stage Endolymphatic Sac Tumors
NCT00001782	Not specified	COMPLETED	Areas of Brain Responsible for Understanding American Sign Language
NCT00013468	Not specified	COMPLETED	Early Diagnosis of Steroid-Responsive & No-Responsive Hearing Loss
NCT00016471	Not specified	COMPLETED	A Genetic Analysis of Usher Syndrome in Ashkenazi Jews
NCT00018486	Not specified	COMPLETED	Epidemiology of Hearing Loss in Diabetic and Non-Diabetic Veterans
NCT00106743	Not specified	COMPLETED	Natural History and Genetic Studies of Usher Syndrome
NCT00110604	Not specified	COMPLETED	The Effect of Folic Acid on Atherosclerosis, Cognitive Performance and Hearing
NCT00126113	Not specified	COMPLETED	The Performance-Perceptual Test as a Counseling Tool
NCT00260663	Not specified	COMPLETED	The Hearing Aid Effectiveness After Aural Rehabilitation (HEAR) Trial
NCT00371436	Not specified	COMPLETED	Progressive Intervention Program for Tinnitus Management
NCT00371449	Not specified	COMPLETED	Predicting Success With Hearing Aids
NCT00371839	Not specified	COMPLETED	Clinical Applications for Time-Compressed Speech Tests
NCT00400413	Not specified	COMPLETED	Neuroanatomy of Reading in Congenital Deafness.
NCT00438334	Not specified	COMPLETED	Real-World Benefit From Directional Hearing Aids
NCT00451503	Not specified	COMPLETED	Evaluation of Middle Ear Implantation
NCT00484224	Not specified	UNKNOWN	Audiological Disturbances in Vitiligo