ACTG2

Summary

ACTG2 (actin gamma 2, smooth muscle, HGNC:145) is a protein-coding gene on chromosome 2p13.1, encoding Actin, gamma-enteric smooth muscle (P63267). Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Actins are highly conserved proteins that are involved in various types of cell motility and in the maintenance of the cytoskeleton. Three types of actins, alpha, beta and gamma, have been identified in vertebrates. 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. This gene encodes actin gamma 2; a smooth muscle actin found in enteric tissues. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Based on similarity to peptide cleavage of related actins, the mature protein of this gene is formed by removal of two N-terminal peptides.

Source: NCBI Gene 72 — RefSeq curated summary.

At a glance

• Gene–disease (curated): visceral myopathy 1 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 122 total — 20 pathogenic, 18 likely-pathogenic
• GTEx eGene: eQTL in 3 tissues, sQTL in 22 (q < 0.05)
• Phenotypes (HPO): 54
• Constraint (gnomAD): pLI 0.28 (intermediate), LOEUF 0.63 (unconstrained)
• MANE Select transcript: NM_001615

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:145
Approved symbol	ACTG2
Name	actin gamma 2, smooth muscle
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Aliases	ACTSG
Ensembl gene	ENSG00000163017
Ensembl biotype	protein_coding
OMIM	102545
Entrez	72

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 30 protein_coding, 6 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000345517

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

ENST00000345517, ENST00000409624, ENST00000409731, ENST00000409918, ENST00000429756, ENST00000438902, ENST00000442912, ENST00000468543, ENST00000473016, ENST00000880127, ENST00000880128, ENST00000880129, ENST00000880130, ENST00000880131, ENST00000880132, ENST00000958362, ENST00000958363, ENST00000958364, ENST00000958365, ENST00000958366, ENST00000958367, ENST00000958368, ENST00000958369, ENST00000958370, ENST00000958371, ENST00000958372, ENST00000958373, ENST00001002269, ENST00001002270, ENST00001019386, ENST00001019387, ENST00001098411, ENST00001098412, ENST00001098413, ENST00001112653, ENST00001126380, ENST00001129169, ENST00001140083

RefSeq mRNA: 2 — MANE Select: NM_001615 NM_001199893, NM_001615

CCDS: CCDS1930, CCDS56124

Canonical transcript exons

ENST00000345517 — 9 exons

Exon	Start	End
ENSE00001578701	73893008	73893051
ENSE00001587209	73919432	73919865
ENSE00002534503	73902360	73902488
ENSE00003537201	73909055	73909139
ENSE00003566166	73901276	73901437
ENSE00003594003	73908673	73908783
ENSE00003603567	73916584	73916765
ENSE00003618744	73913485	73913646
ENSE00003663177	73914680	73914871

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.98.

FANTOM5 (CAGE): breadth broad, TPM avg 80.6591 / max 11080.0969, expressed in 808 samples.

Highest expression (Bgee): seminal vesicle, cauda epididymis, saphenous vein, lower esophagus, lower esophagus muscularis layer.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACTG2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 3 tissues and its splicing (sQTL) in 22 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	sqtl	6.1e-66	+0.53	2:73903430:C:G
Artery Aorta	sqtl	2.6e-46	+0.67	2:73903430:C:G
Esophagus Muscularis	sqtl	3.2e-27	+0.47	2:73903430:C:G
Lung	sqtl	2.0e-26	+0.59	2:73903542:A:G
Breast Mammary Tissue	sqtl	5.2e-26	+0.65	2:73902347:T:C
Colon Sigmoid	sqtl	1.3e-24	+0.49	2:73902347:T:C
Skin Sun Exposed Lower leg	sqtl	1.3e-21	+0.47	2:73902347:T:C
Adipose Subcutaneous	sqtl	1.3e-21	+0.51	2:73902897:C:A
Esophagus Gastroesophageal Junction	sqtl	1.3e-19	+0.67	2:73901778:G:A
Colon Transverse	sqtl	1.9e-18	+0.47	2:73903430:C:G
Esophagus Mucosa	sqtl	1.4e-14	+0.47	2:73903430:C:G
Small Intestine Terminal Ileum	sqtl	7.0e-14	+0.78	2:73902347:T:C
Stomach	sqtl	1.5e-13	+0.58	2:73902585:C:G
Nerve Tibial	sqtl	1.3e-09	+0.43	2:73910870:G:T
Uterus	sqtl	1.6e-09	+0.69	2:73902585:C:G
Prostate	sqtl	9.0e-09	+0.53	2:73902585:C:G
Skin Not Sun Exposed Suprapubic	sqtl	1.4e-07	+0.34	2:73911259:C:T
Thyroid	sqtl	3.4e-05	+0.35	2:73903679:T:C
Artery Coronary	sqtl	6.6e-05	+0.68	2:73903679:T:C
Adipose Visceral Omentum	sqtl	5.2e-04	+0.26	2:73903542:A:G

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
20964	80.1950	800
20965	0.1470	33
20968	0.1154	39
20966	0.1130	36
20967	0.0886	32

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	99.98	gold quality
cauda epididymis	UBERON:0004360	99.94	gold quality
saphenous vein	UBERON:0007318	99.94	gold quality
lower esophagus	UBERON:0013473	99.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.88	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.87	gold quality
mucosa of stomach	UBERON:0001199	99.78	gold quality
popliteal artery	UBERON:0002250	99.76	gold quality
tibial artery	UBERON:0007610	99.76	gold quality
prostate gland	UBERON:0002367	99.75	gold quality
myometrium	UBERON:0001296	99.74	gold quality
urethra	UBERON:0000057	99.73	gold quality
body of uterus	UBERON:0009853	99.72	gold quality
left uterine tube	UBERON:0001303	99.67	gold quality
blood vessel layer	UBERON:0004797	99.62	gold quality
vermiform appendix	UBERON:0001154	99.60	gold quality
right coronary artery	UBERON:0001625	99.57	gold quality
adult organism	UBERON:0007023	99.54	gold quality
urinary bladder	UBERON:0001255	99.53	gold quality
lower esophagus mucosa	UBERON:0035834	99.53	gold quality
aorta	UBERON:0000947	99.52	gold quality
vena cava	UBERON:0004087	99.51	gold quality
caecum	UBERON:0001153	99.48	gold quality
fundus of stomach	UBERON:0001160	99.46	gold quality
left coronary artery	UBERON:0001626	99.45	gold quality
gall bladder	UBERON:0002110	99.45	gold quality
coronary artery	UBERON:0001621	99.37	gold quality
nipple	UBERON:0002030	99.32	gold quality
descending thoracic aorta	UBERON:0002345	99.27	gold quality
rectum	UBERON:0001052	99.25	gold quality
thoracic aorta	UBERON:0001515	99.21	gold quality
ascending aorta	UBERON:0001496	99.18	gold quality
superficial temporal artery	UBERON:0001614	99.18	gold quality
pylorus	UBERON:0001166	99.07	gold quality
right uterine tube	UBERON:0001302	98.92	gold quality
sigmoid colon	UBERON:0001159	98.83	gold quality
body of stomach	UBERON:0001161	98.76	gold quality
stomach	UBERON:0000945	98.73	gold quality
decidua	UBERON:0002450	98.70	gold quality
esophagus	UBERON:0001043	98.64	gold quality
endocervix	UBERON:0000458	98.58	gold quality
mucosa of urinary bladder	UBERON:0001259	98.55	gold quality
penis	UBERON:0000989	98.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.28	gold quality
trachea	UBERON:0003126	97.96	gold quality
small intestine	UBERON:0002108	97.84	gold quality
transverse colon	UBERON:0001157	97.82	gold quality
intestine	UBERON:0000160	97.76	gold quality
large intestine	UBERON:0000059	97.69	gold quality
colon	UBERON:0001155	97.67	gold quality
cardia of stomach	UBERON:0001162	97.62	gold quality
esophagus mucosa	UBERON:0002469	97.47	gold quality
smooth muscle tissue	UBERON:0001135	97.27	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.69	gold quality
upper lobe of lung	UBERON:0008948	96.61	gold quality
upper lobe of left lung	UBERON:0008952	96.49	gold quality
mammary duct	UBERON:0001765	96.47	gold quality
epithelium of mammary gland	UBERON:0003244	95.86	gold quality
caput epididymis	UBERON:0004358	95.57	gold quality
corpus epididymis	UBERON:0004359	95.40	gold quality
ectocervix	UBERON:0012249	95.40	gold quality
right lung	UBERON:0002167	95.11	gold quality
parotid gland	UBERON:0001831	95.05	gold quality
duodenum	UBERON:0002114	94.80	gold quality
colonic epithelium	UBERON:0000397	94.49	gold quality
skin of leg	UBERON:0001511	94.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.46	gold quality
mammary gland	UBERON:0001911	94.14	gold quality
thoracic mammary gland	UBERON:0005200	94.13	gold quality
upper arm skin	UBERON:0004263	93.98	gold quality
pericardium	UBERON:0002407	93.93	gold quality
saliva-secreting gland	UBERON:0001044	93.91	gold quality
lung	UBERON:0002048	93.63	gold quality
minor salivary gland	UBERON:0001830	93.52	gold quality
visceral pleura	UBERON:0002401	92.99	gold quality
skin of hip	UBERON:0001554	92.88	gold quality
zone of skin	UBERON:0000014	92.83	gold quality
mucosa of transverse colon	UBERON:0004991	92.70	gold quality
placenta	UBERON:0001987	92.42	gold quality
colonic mucosa	UBERON:0000317	92.17	gold quality
lower lobe of lung	UBERON:0008949	92.07	gold quality
skin of abdomen	UBERON:0001416	91.78	gold quality
vagina	UBERON:0000996	91.77	gold quality
right ovary	UBERON:0002118	91.12	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.07	gold quality
jejunal mucosa	UBERON:0000399	90.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.80	gold quality
mouth mucosa	UBERON:0003729	89.79	gold quality
peritoneum	UBERON:0002358	88.93	gold quality
omental fat pad	UBERON:0010414	88.91	gold quality
jejunum	UBERON:0002115	88.57	gold quality
tibial nerve	UBERON:0001323	88.45	gold quality
uterine cervix	UBERON:0000002	88.29	gold quality
right atrium auricular region	UBERON:0006631	87.30	gold quality
female reproductive system	UBERON:0000474	86.90	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.60	gold quality
cardiac atrium	UBERON:0002081	86.48	gold quality
left ovary	UBERON:0002119	86.00	gold quality
ovary	UBERON:0000992	85.59	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	11366.78
E-MTAB-10287	yes	5911.12
E-HCAD-24	yes	5578.39
E-CURD-126	yes	4465.60
E-CURD-7	yes	3638.15
E-ENAD-21	yes	2819.31
E-HCAD-11	yes	2526.80
E-MTAB-8221	yes	2420.43
E-MTAB-10662	yes	1459.03
E-ANND-5	yes	840.79
E-HCAD-1	yes	38.86
E-MTAB-8410	yes	29.89
E-CURD-46	yes	9.61
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Smooth muscle	tissue	8032.7	high
Seminal vesicle	tissue	5865.9	not detected
Prostate	tissue	2037.7	not detected
Urinary bladder	tissue	1900.2	not detected
Colon	tissue	1880.9	high
Esophagus	tissue	1834.1	not detected
Rectum	tissue	1109.5	high
Endometrium 1	tissue	1024.7	not detected
Appendix	tissue	683.4	high
Vagina	tissue	590.5	not detected
Duodenum	tissue	367.7	high
Small intestine	tissue	330.6	high
Gallbladder	tissue	309.6	medium
Cervix	tissue	192.6	not detected
Adipose tissue	tissue	177.7	not detected
Fallopian tube	tissue	176.6	not detected
Breast	tissue	129.5	medium
Epididymis	tissue	117.5	medium
Stomach 1	tissue	106.0	medium
Placenta	tissue	90.4	not detected
Salivary gland	tissue	70.7	not detected
Ovary	tissue	44.8	not detected
Lung	tissue	35.3	low
Adrenal gland	tissue	35.1	not detected
Heart muscle	tissue	22.4	not detected
Substantia nigra	tissue	15.6
Spleen	tissue	10.0	not detected
Pancreas	tissue	7.7	low
Tongue	tissue	6.5
Thyroid gland	tissue	6.4	not detected
Lymph node	tissue	6.3	medium
Kidney	tissue	6.3	low
Spinal cord	tissue	6.2
Pituitary gland	tissue	5.6
Choroid plexus	tissue	4.5
Superior colliculi	tissue	4.5
Skeletal muscle	tissue	3.9	not detected
Testis	tissue	3.7	low
Liver	tissue	3.6	low
Skin 1	tissue	3.0	medium
Putamen	tissue	2.6
Thalamus	tissue	2.6
Thymus	tissue	2.6
Hippocampal formation	tissue	2.5
Pons	tissue	2.3
Septum	tissue	2.3
Midbrain	tissue	2.1
Medulla oblongata	tissue	1.6
Entorhinal cortex	tissue	1.2
Tonsil	tissue	1.1	medium
Cerebral cortex	tissue	0.9	not detected
Parathyroid gland	tissue	0.9	not detected
Basal ganglia	tissue	0.9	not detected
Retrosplenial and cingulate cortex	tissue	0.9
Temporal cortex	tissue	0.8
Ventral forebrain	tissue	0.7
Motor cortex	tissue	0.6
Somatosensory cortex	tissue	0.6
Prefrontal cortex	tissue	0.5
Hippocampus	tissue	0.5	not detected

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — Blood vessel (1892.1), Anterior insular cortex, dorsal (7.8), Dorsal spinal cord (6.2), Parietal operculum (4.8), Frontal operculum (2.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ARID4B, ASCL1, CEBPB, GATA6, GTF3A, HMGA2, KLF4, MEF2A, MYB, MYC, MYOCD, NKX2-5, NKX3-1, NR0B2, NR1H4, PGR, POU5F1, PPARD, PPARG, RARA, SMAD2, SMAD3, SMAD7, SP1, SRF, STAT3, TGIF1, ZEB1

Functional genomics

gnomAD constraint: pLI 0.282, LOEUF 0.626, missense Z 4.36 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000345517 — one region, missense o/e 0.48.

Literature-anchored findings (GeneRIF, showing 32)

• SMGA gene activity in prostate epithelia is due, in part, to the androgen-dependent expression of Nkx 3.1 (PMID:12450213)
• RNA polymerase II accumulates in the promoter-proximal region of the dihydrofolate reductase and gamma-actin genes. (PMID:12612070)
• It was suggested that peritubular alphaSMA-positive myofibroblastic cells, in collaboration with interstitial macrophages, contribute to the progression of interstitial fibrosis in diabetic nephropathy. (PMID:17009076)
• TNF-alpha suppresses TGF-beta1-induced myofibroblast (fibroproliferative) phenotypic genes, for example, alpha-SMA, collagen type 1A, and fibronectin at the mRNA level. (PMID:17554369)
• The insertion-deletion polymorphism in intron 1 of the gamma 2 actin gene is unlikely to play any significant role in obstetric cholestasis or preeclampsia in patients from eastern Finland. (PMID:17934296)
• MYOCD can discriminate among several juxtaposed CArG elements, presumably through its novel partnership with NKX3.1, to optimally transactivate the human ACTG2 promoter (PMID:19797053)
• NOX4 and ROS have a role in myofibroblast differentiation and collagen and alpha-actin production of TGF- beta1-induced nasal polyp-derived fibroblasts. (PMID:22722757)
• The R148S variant in ACTG2 as a cause of autosomal dominant familial visceral myopathy in one family. (PMID:22960657)
• Two novel mutations in the ACTG2 gene, p.R178L and p.R178C, have been identified in two unrelated children with congenital distended bladder, microcolon, and intestinal hypoperistalsis (MMIHS). (PMID:24337657)
• ACTG2 encodes g2 enteric actin and is the first gene to be clearly associated with Megacystis-microcolon-intestinal hypoperistalsis syndrome, suggesting an important role for contractile proteins in enteric smooth muscle disease. (PMID:24676022)
• Phenotypic spectrum of ACTG2 missense variants involved severe pathology in multiple smooth muscle-dependent organs including the biliary tract and the uterus in the family with visceral myopathy. (PMID:25782675)
• Mutations within ACTG2 are associated with fetal megacystis in microcolon intestinal hypoperistalsis syndrome. (PMID:25998219)
• gammaSMA expression in hepatocellular carcinoma is strongly correlated with the EMT process, HCC aggressiveness and the identification of cancer stem cells (PMID:26110787)
• A heterozygous missense variant in ACTG2 was identified that impaired actin polymerization in sporadic Megacystis microcolon intestinal hypoperistalsis syndrome. (PMID:26647307)
• Missense variants in ACTG2 were identified in the patients with either megacystis-microcolon-intestinal hypoperistalsis syndrome or intestinal pseudo-obstruction. (PMID:26813947)
• R257 variant in the ACTG2 appear to be more frequent in populations of Asian ancestry; mutation of this locus could cause alterations of the intestinal and bladder smooth muscle filaments. (PMID:27007401)
• ACTG2 is expressed in a fraction of small intestinal neuroendocrine tumors, can inhibit cell growth in vitro, and is positively regulated by miR-145. (PMID:27107594)
• ACTG2 boosts the metastatic potential of hepatocellular carcinoma in a Notch1-dependent manner. (PMID:28385530)
• Whole exome and Sanger sequencing revealed a pathogenic variant in the ACTG2 gene in 4 out of 28 probands with chronic intestinal pseudo-obstruction and megacystis. Moreover, a mutational hotspot in the ACTG2 gene was recognized. Genetic heterogeneity is evident. (PMID:28422808)
• fetus with intestinal pseudo-obstruction heterozygous for p.R63G pathogenic variant (NM_001615.3 c.187C>G; rs864309491) in exon 3 (PMID:29072330)
• mutations represent a significant underlying cause of primary chronic intestinal pseudo-obstruction with visceral myopathy and associated phenotypes in Australasian patients. (PMID:29781137)
• Studied Actin G2 gene variants in patients with Hirschsprung disease as a possible molecular basis for abnormal smooth muscle function. (PMID:30885557)
• Recurrent arginine substitutions in the ACTG2 gene are the primary driver of disease burden and severity in visceral myopathy. (PMID:31769566)
• Variants in the Enteric Smooth Muscle Actin gamma-2 Cause Pediatric Intestinal Pseudo-obstruction in Chinese Patients. (PMID:32810037)
• Pseudo-obstruction-inducing ACTG2R257C alters actin organization and function. (PMID:32814715)
• Novel ACTG2 variants disclose allelic heterogeneity and bi-allelic inheritance in pediatric chronic intestinal pseudo-obstruction. (PMID:33294969)
• Expanding the genotypic spectrum of ACTG2-related visceral myopathy. (PMID:33883208)
• LINC01278 Sponges miR-500b-5p to Regulate the Expression of ACTG2 to Control Phenotypic Switching in Human Vascular Smooth Muscle Cells During Aortic Dissection. (PMID:33910387)
• Intestinal Pathology in Patients With Pathogenic ACTG2-Variant Visceral Myopathy: 16 Patients From 12 Families and Review of the Literature. (PMID:35695198)
• Variant in ACTG2 Causing Megacystis Microcolon Hypoperistalsis Syndrome and Severe Familial Postpartum Bleeding. (PMID:36509086)
• Analysis of the Regulatory Effect of ACTG2 on Biological Behavior of Bladder Cancer Cells Based on Database Screening. (PMID:37213144)
• Molecular mechanisms linking missense ACTG2 mutations to visceral myopathy. (PMID:38820162)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Actg2	ENSMUSG00000059430
rattus_norvegicus	Actg2	ENSRNOG00000029401

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), ACTBL2 (ENSG00000169067), ACTRT2 (ENSG00000169717), ACTL9 (ENSG00000181786), ACTG1 (ENSG00000184009), ACTRT3 (ENSG00000184378), ACTL7A (ENSG00000187003), ACTL10 (ENSG00000288649)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104589) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal colon morphology	1
abnormal small intestine morphology	1
distended urinary bladder	1
cataract	1
abnormal vibrissa morphology	1
oliguria	1
increased circulating creatinine level	1
abnormal intestinal transit time	1
abnormal intestine physiology	1
abnormal bladder urine volume	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
Oryza sativa Indica Group	A2WKK5	100.0%	Diamond
Oryza sativa Japonica Group	A2ZP58	100.0%	Diamond
Pleurodeles waltl	P10994	100.0%	Diamond
Bos taurus	P62739	100.0%	Diamond
Oryctolagus cuniculus	P62740	100.0%	Diamond
Gallus gallus	P63270	100.0%	Diamond
Sus scrofa	P68137	100.0%	Diamond
Takifugu rubripes	P68140	100.0%	Diamond
Oreochromis mossambicus	P68264	100.0%	Diamond
Pongo abelii	Q5R9Q5	100.0%	Diamond
Xenopus tropicalis	Q6P640	100.0%	Diamond
Xenopus laevis	P04751	99.7%	Diamond
Styela clava	P26198	99.7%	Diamond
Cyprinus carpio	P53479	99.7%	Diamond
Atractaspis microlepidota microlepidota	Q90X97	99.7%	Diamond
Oryzias latipes	Q98972	99.7%	Diamond
Carassius auratus	P49055	99.5%	Diamond
Branchiostoma belcheri	Q93130	99.5%	Diamond
Branchiostoma floridae	Q93132	99.5%	Diamond
Halocynthia roretzi	P27130	99.2%	Diamond
Ciona savignyi	O15998	98.9%	Diamond
Lytechinus pictus	Q25381	98.3%	Diamond
Branchiostoma lanceolatum	O17502	98.2%	Diamond
Tetrahymena thermophila	P10992	97.3%	Diamond
Molgula oculata	Q25472	97.3%	Diamond
Styela plicata	Q00214	96.8%	Diamond
Cyanidioschyzon merolae strain 10D	P53500	85.1%	Diamond
Arabidopsis thaliana	Q8LGE3	63.2%	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
DGUOK-AS1	ncRNA	100874048
STAMBP	protein-coding	10617
DGUOK	protein-coding	1716
TET3	protein-coding	200424
BOLA3	protein-coding	388962
C2orf78	protein-coding	388960
DUSP11	protein-coding	8446

Protein

Protein identifiers

Actin, gamma-enteric smooth muscle — P63267 (reviewed: P63267)

Alternative names: Alpha-actin-3, Gamma-2-actin, Smooth muscle gamma-actin

All UniProt accessions (5): B8ZZJ2, C9JFL5, P63267, F8WB63, F8WCH0

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.

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.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. In the intestine, abundantly expressed in smooth muscle cells of muscularis mucosa and muscularis propria. Also detected in intestinal vascular smooth muscle cells.

Post-translational modifications. Oxidation of Met-45 and Met-48 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 promotes actin repolymerization. N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP. Monomethylation at Lys-85 (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-74 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-51 of one monomer and Glu-271 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. Visceral myopathy 1 (VSCM1) [MIM:155310] An autosomal dominant form of myopathic pseudo-obstruction characterized by impaired function of enteric smooth muscle cells, resulting in abnormal intestinal motility, severe abdominal pain, malnutrition, and even death. The disease shows inter- and intrafamilial variability. Most severely affected patients exhibit prenatal bladder enlargement, intestinal malrotation, neonatal functional gastrointestinal obstruction, and dependence on total parenteral nutrition and urinary catheterization. The disease is caused by variants affecting the gene represented in this entry. Megacystis-microcolon-intestinal hypoperistalsis syndrome 5 (MMIHS5) [MIM:619431] A form of megacystis-microcolon-intestinal hypoperistalsis syndrome, a congenital visceral myopathy primarily affecting females, and characterized by loss of smooth muscle contraction in the bladder and intestine. Affected individuals present at birth with functional obstruction of intestine, microcolon, dilation of bladder, and secondary hydronephrosis. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure. MMIHS5 is an autosomal dominant form with significant inter- and intrafamilial variability. 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.

Isoforms (2)

UniProt ID	Names	Canonical?
P63267-1	1	yes
P63267-2	2

RefSeq proteins (2): NP_001186822, NP_001606* (*=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 (78 total): helix 24, sequence variant 21, strand 17, modified residue 5, chain 2, mutagenesis site 2, sequence conflict 2, cross-link 2, initiator methionine 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
8V2O	Cryo-EM Structure of Wildtype Smooth Muscle Gamma Actin (ACTG2)	ELECTRON MICROSCOPY	2.45
8V30	Smooth Muscle Gamma Actin (ACTG2) Filament Mutant R40C	ELECTRON MICROSCOPY	2.54
6JAT	Crystal structure of SETD3 bound to Actin peptide and SFG	X-RAY DIFFRACTION	2.71
8V2Z	Cryo-EM Structure of Smooth Muscle Gamma Actin (ACTG2) Mutant R257C	ELECTRON MICROSCOPY	2.72

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63267-F1	95.46	0.93

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of the digestive system

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 (7)

Type	Positions
N-acetylcysteine	2
N-acetylglutamate	3
Methionine (r)-sulfoxide	45, 48
Tele-methylhistidine	74
Isoglutamyl lysine isopeptide (lys-glu) (interchain with e-271)	51
Isoglutamyl lysine isopeptide (glu-lys) (interchain with k-51)	271

Mutagenesis-validated functional residues (2)

Position	Phenotype
72	abolished methylation by setd3.
72	slightly decreased methylation by setd3.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 14; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

14 pathways:

ID	Pathway	Evidence
R-HSA-9764561	Regulation of CDH1 Function	curated
R-HSA-445355	Smooth Muscle Contraction	curated
R-HSA-9958825	Activation of STAT3 by cadherin engagement	electronic
R-HSA-418990	Adherens junctions interactions	—
R-HSA-446728	Cell junction organization	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-421270	Cell-cell junction organization	—
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-9913351	Formation of the dystrophin-glycoprotein complex (DGC)	electronic
R-HSA-397014	Muscle contraction	—
R-HSA-3000171	Non-integrin membrane-ECM interactions	—
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: 336 (showing top): GOBP_RESPONSE_TO_ETHANOL, WWTAAGGC_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_RESPONSE_TO_PEPTIDE, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, MODULE_329, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CAGCTG_AP4_Q5, SRF_Q5_01, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, SRF_01

GO Biological Process (6): positive regulation of gene expression (GO:0010628), response to ethanol (GO:0045471), cellular response to interleukin-6 (GO:0071354), mesenchyme migration (GO:0090131), cellular response to acetaldehyde (GO:1905641), cytoskeleton organization (GO:0007010)

GO Molecular Function (4): structural constituent of cytoskeleton (GO:0005200), ATP binding (GO:0005524), hydrolase activity (GO:0016787), nucleotide binding (GO:0000166)

GO Cellular Component (11): cytoplasm (GO:0005737), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), filopodium (GO:0030175), myosin filament (GO:0032982), cell body (GO:0044297), extracellular exosome (GO:0070062), cell periphery (GO:0071944), blood microparticle (GO:0072562), cytoskeleton (GO:0005856)

Reactome top-level categories

10 top-level categories:

Category	Pathways
Adherens junctions interactions	2
Muscle contraction	1
Regulation of CDH1 Expression and Function	1
Non-integrin membrane-ECM interactions	1
Extracellular matrix organization	1
Cell-cell junction organization	1
Cell junction organization	1
Cell-Cell communication	1
Regulation of Expression and Function of Type I Classical Cadherins	1
Regulation of Homotypic Cell-Cell Adhesion	1

GO top-level categories

31 GO namespaces:

Category	Terms
cellular anatomical structure	5
cytoskeleton	2
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
response to alcohol	1
response to interleukin-6	1
cellular response to cytokine stimulus	1
mesenchyme morphogenesis	1
tissue migration	1
cellular response to aldehyde	1
response to acetaldehyde	1
organelle organization	1
structural molecule activity	1
cytoskeleton organization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
catalytic activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
intracellular anatomical structure	1
cytoplasm	1
cell leading edge	1
plasma membrane bounded cell projection	1
actin-based cell projection	1
myosin complex	1
supramolecular fiber	1
extracellular vesicle	1
extracellular region	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
blood microparticle	CC	high-throughput assay
extracellular exosome	CC	high-throughput assay

Protein interactions and networks

IntAct

Human interaction partners of ACTG2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
MLH1	physical association	0.370	1
TMEM165	association	0.350	1

BioGRID (109 interactions; top human partners by supporting records): ACTB (Cross-Linking-MS (XL-MS); 8 records), ACTG1 (Cross-Linking-MS (XL-MS); 5 records), ACTA2 (Cross-Linking-MS (XL-MS); 3 records), CFL1 (Cross-Linking-MS (XL-MS); 3 records), ACTBL2 (Cross-Linking-MS (XL-MS); 2 records), ACTC1 (Cross-Linking-MS (XL-MS); 2 records), CAP1 (Cross-Linking-MS (XL-MS); 2 records), DSTN (Cross-Linking-MS (XL-MS); 2 records), EMD (Affinity Capture-Western; 2 records), LIMA1 (Cross-Linking-MS (XL-MS); 2 records), POTEE (Cross-Linking-MS (XL-MS); 2 records), TRIM6 (Affinity Capture-MS; 2 records), ACTA1 (Cross-Linking-MS (XL-MS)), ACTL6A (Cross-Linking-MS (XL-MS)), ADARB1 (Proximity Label-MS)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
NKX3-1	“up-regulates quantity by expression”	ACTG2	“transcriptional regulation”
MYOCD	“up-regulates quantity by expression”	ACTG2	“transcriptional regulation”

Protein complexes (CORUM) (1)

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

1 complexes by size:

Complex	Subunits	Members
★ Nop56p-associated pre-rRNA complex	104	LUC7L2, NCL, RPL27, RPL29, RPL39, RPL7, RPS23, RPS6, MYBBP1A, RPL21, RPL28, RPL5, RPS9, U2AF2, LYAR, RPL13, RPL23, RPL23A, RPL35A, RPL4, RPS24, HNRNPA1, EBNA1BP2, RPLP1, RPS17, U2AF1, DHX9, RPL30, SCYL2, RPL11, RPS11, NOLC1, RPL12, RPL14, RPL17, RPL19, RPL32, RPS13, RPS8, NOP58, RPL36A, RPLP2, RPS2, RPS29, SRP14, TCOF1, TUFM, ACTG2, RBM28, RPL10, RPL37A, RPS12, RPS7, TUBB1, BRIX1, DDX21, GNL3, IGF2BP1, ILF2, RPL10A, RPL15, RPLP0, EEF2, HNRNPU, NOP56, RPL26, RPL3, RPS14, RPS16, RSL1D1, ACTA2, EEF1A1, H1-3, RPL24, RPL6, RPL8, SRPK1, TOP1, FBL, HNRNPM, RPL13A, RPL31, RPL7A, RPS18, H1-10, ILF3, NPM1, RPS15A, TUBA1A, YBX1, H2BC14, PWP1, RPL18A, RPL22, RPL27A, RPS15, RPS3A, SLC25A5, NAP1L1, RPL18, RPL35, RPL36, RPL9, SNU13

Disease & clinical

Genetic variants

Variant evidence for ACTG2: 122 ClinVar records (38 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	18
Uncertain significance	55
Likely benign	7
Benign	9

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 38 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
132803	NM_001615.4(ACTG2):c.769C>T (p.Arg257Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	26
132800	NM_001615.4(ACTG2):c.532C>T (p.Arg178Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	13
132801	NM_001615.4(ACTG2):c.533G>A (p.Arg178His)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
208792	NM_001615.4(ACTG2):c.770G>A (p.Arg257His)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
132798	NM_001615.4(ACTG2):c.533G>T (p.Arg178Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
218310	NM_001615.4(ACTG2):c.187C>G (p.Arg63Gly)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
218312	NM_001615.4(ACTG2):c.593G>A (p.Gly198Asp)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
369682	NM_001615.4(ACTG2):c.613G>A (p.Ala205Thr)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1177291	NM_001615.4(ACTG2):c.442C>T (p.Arg148Cys)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1709289	NM_001615.4(ACTG2):c.188G>T (p.Arg63Leu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
132797	NM_001615.4(ACTG2):c.442C>A (p.Arg148Ser)	Pathogenic	criteria provided, single submitter	3
156554	NM_001615.4(ACTG2):c.806_807delinsAA (p.Gly269Glu)	Pathogenic	criteria provided, single submitter	2
218311	NM_001615.4(ACTG2):c.255+210C>A	Pathogenic	criteria provided, single submitter	2
694269	NM_001615.4(ACTG2):c.188G>A (p.Arg63Gln)	Pathogenic	criteria provided, single submitter	2
694268	NM_001615.4(ACTG2):c.116C>T (p.Pro39Leu)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ACTG2’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; 29 predictions of 581):

Position(s)	Effect	Δscore	Sites
2:73901267	acceptor_gain	1.0000
2:73909053	acceptor_gain	1.0000
2:73909053–73909054	acceptor_loss	1.0000	5
2:73909140–73909141	donor_loss	1.0000	4
2:73913483–73913484	acceptor_loss	1.0000	4
2:73914668	acceptor_gain	1.0000
2:73914678–73914679	acceptor_loss	1.0000	4
2:73914805	donor_gain	1.0000
2:73916766–73916767	donor_loss	1.0000	5
2:73893052–73893053	donor_loss	0.9900	3

AlphaMissense

2,123 missense substitutions predicted likely pathogenic (of 2,485 scored), across 372 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
M45	9	0.974	0.998
M120	9	0.964	0.999
M83	9	0.954	0.998
M48	9	0.946	0.992
M356	9	0.924	0.993
M124	9	0.852	0.998
D12	8	0.999	1.000
D155	8	0.998	0.999
D287	8	0.998	1.000
D289	8	0.998	0.999
D245	8	0.997	1.000
D26	8	0.994	0.999
F353	8	0.994	1.000
H89	8	0.992	0.999
D158	8	0.991	0.999
D82	8	0.989	0.998
F125	8	0.988	1.000
H162	8	0.988	0.998
H174	8	0.985	0.998
D212	8	0.985	0.997

HPA cancer prognostics

RNA cancer specificity: Group enriched (Bladder Urothelial Carcinoma, Prostate Adenocarcinoma, Stomach Adenocarcinoma)

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	1.87e-06
Bladder Urothelial Carcinoma (TCGA)	favorable	0.000714

Disease associations

OMIM: gene MIM:102545 | disease phenotypes: MIM:155310, MIM:619431, MIM:609629, MIM:249210

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
visceral myopathy 1	Strong	Autosomal dominant	2
familial visceral myopathy	Strong	Autosomal dominant	2
megacystis-microcolon-intestinal hypoperistalsis syndrome	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 9 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
CAKUT	green
Fetal anomalies	green
Gastrointestinal neuromuscular disorders	green
Paediatric disorders	green
Paediatric disorders - additional genes	green
Paediatric pseudo-obstruction syndrome	green
Unexplained kidney failure in young people	green
Unexplained young onset end-stage renal disease	green
Unexplained young onset end-stage renal disease - additional genes	green
Laterality disorders and isomerism	amber

Mondo (9): chronic intestinal pseudoobstruction (MONDO:0017574), intestinal obstruction (MONDO:0004565), visceral myopathy 1 (MONDO:0020754), megacystis-microcolon-intestinal hypoperistalsis syndrome 5 (MONDO:0030329), constipation disorder (MONDO:0002203), visceral neuropathy, familial, 3, autosomal dominant (MONDO:0012317), megacystis-microcolon-intestinal hypoperistalsis syndrome (MONDO:0025986), (MONDO:0007960), familial visceral myopathy (MONDO:0016829)

Orphanet (3): Chronic intestinal pseudoobstruction syndrome (Orphanet:2978), Familial visceral myopathy (Orphanet:2604), Megacystis-microcolon-intestinal hypoperistalsis syndrome (Orphanet:2241)

HPO phenotypes

54 phenotypes (HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000016	Urinary retention
HP:0000021	Megacystis
HP:0000028	Cryptorchidism
HP:0000072	Hydroureter
HP:0000076	Vesicoureteral reflux
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000311	Round face
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000774	Narrow chest
HP:0000843	Hyperparathyroidism
HP:0001166	Arachnodactyly
HP:0001387	Joint stiffness
HP:0001399	Hepatic failure
HP:0001409	Portal hypertension
HP:0001522	Death in infancy
HP:0001537	Umbilical hernia
HP:0001539	Omphalocele
HP:0001561	Polyhydramnios
HP:0001562	Oligohydramnios
HP:0001733	Pancreatitis
HP:0001798	Anonychia
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002015	Dysphagia
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002251	Aganglionic megacolon
HP:0002566	Intestinal malrotation
HP:0002578	Gastroparesis
HP:0003270	Abdominal distention
HP:0003363	Abdominal situs inversus
HP:0003577	Congenital onset
HP:0004388	Microcolon
HP:0004389	Intestinal pseudo-obstruction
HP:0004395	Malnutrition
HP:0010318	Aplasia/Hypoplasia of the abdominal wall musculature
HP:0011024	Abnormality of the gastrointestinal tract
HP:0011461	Fetal onset
HP:0030680	Abnormal cardiovascular system morphology
HP:0030996	Megaduodenum
HP:0100490	Camptodactyly of finger
HP:0100544	Neoplasm of the heart
HP:0100771	Hypoperistalsis
HP:0100806	Sepsis
HP:6000072	Thinning of outer muscular layer of small bowel

GWAS associations

1 associations:

Study	Trait	p-value
GCST010605_2	Parent of origin effect on receptive language ability (paternal)	5e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0005686	receptive language perception
EFO:0005939	parental genotype effect measurement

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D003248	Constipation	C23.888.821.150
D007415	Intestinal Obstruction	C06.405.469.531

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
Cadmium	decreases expression, increases abundance, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tretinoin	affects cotreatment, increases expression	2
methylmercuric chloride	decreases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
bisphenol A	decreases expression	1
methylselenic acid	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
trimellitic anhydride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, increases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
cadmium acetate	decreases expression	1
nickel sulfate	increases expression	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
mercuric bromide	affects cotreatment, increases expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	increases expression	1
Dasatinib	increases expression	1
Temozolomide	increases expression	1
Zoledronic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C6SS	CHOPi012-A	Induced pluripotent stem cell	Female
CVCL_C9EC	CHOPe003-A	Embryonic stem cell	Female

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT01507220	Phase 4	TERMINATED	A Health Economic Trial in Adult Patients Undergoing Open Colectomy MA402S23B301
NCT01507233	Phase 4	TERMINATED	A Health Economic Trial in Adult Patients Undergoing Open Colectomy MA402S23B302
NCT01507246	Phase 4	COMPLETED	Adult Patients Undergoing Open Colectomy MA402S23B303
NCT02058290	Phase 4	TERMINATED	A Health Economic Trial in Adult Patients Undergoing Laparoscopic Colectomy
NCT02812186	Phase 4	COMPLETED	Deep Versus Moderate Neuromuscular Blockade During Laparoscopic Surgery
NCT03334578	Phase 4	WITHDRAWN	The Use of Gastrografin to Help Alleviate Bowel Obstruction in Gastroschisis Patients.
NCT06089551	Phase 4	UNKNOWN	Early vs Postponed Parenteral Nutrition After Emergency Abdominal Surgery
NCT00149877	Phase 4	COMPLETED	Efficacy, Safety and Tolerability of Tegaserod in Patients With Chronic Constipation
NCT00153114	Phase 4	COMPLETED	PolyethyleneGlycol3350 Laxative vs Placebo in Constipated Children
NCT00153127	Phase 4	COMPLETED	Comparison of PolyethyleneGlycol and Placebo for Relief of Constipation From Constipating Medications
NCT00153140	Phase 4	COMPLETED	Polyethyleneglycol3350 vs Tegaserod in Treatment of Patients With Chronic Constipation
NCT00153153	Phase 4	COMPLETED	Extended Use of Polyethyleneglycol3350 Laxative in Constipated Patients
NCT00157638	Phase 4	COMPLETED	Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics
NCT00164125	Phase 4	COMPLETED	An Open Label Study of Chronic Polyethyleneglycol3350 Use in Constipated Patients
NCT00171522	Phase 4	COMPLETED	Preference of Tegaserod vs. PEG 3350 in Patients With Constipation
NCT00256984	Phase 4	COMPLETED	Study of Stapled Transanal Rectal Resection (STARR) Surgery in Refractory Constipation Associated With Obstructive Defecation Syndrome (ODS)
NCT00276354	Phase 4	COMPLETED	Study of Long-term Use of Forlax® in Elderly Patients With Chronic Constipation
NCT00286520	Phase 4	COMPLETED	Treatment of Fecal Incontinence and Constipation in Patients With Spinal Cord Injury
NCT00319670	Phase 4	COMPLETED	A Pilot Study of a New MiraLax® Dose Formulation For Use in Constipated Children
NCT00348634	Phase 4	TERMINATED	Effect of Tegaserod on Orocecal Transit in Elderly Chronic Constipation Patients
NCT00452335	Phase 4	COMPLETED	Safety and Efficacy of Lubiprostone in Pediatric Patients With Constipation
NCT00521872	Phase 4	COMPLETED	Stapled Trans Anal Rectal Resection (STARR) for Outlet Obstruction: Functional and Morphological Outcome
NCT00583609	Phase 4	COMPLETED	A Pilot Study of a New PEG3350 Dose Formulation For Use in Constipated Children
NCT00603681	Phase 4	COMPLETED	Comparison of PEG Solutions With and Without Electrolytes in the Treatment of Constipation
NCT00712543	Phase 4	COMPLETED	A Preference Study Comparing Kristalose® and Liquid Lactulose
NCT00763399	Phase 4	COMPLETED	Effect of Probiotics on Intestinal Bacterial Population and Immune Modulation
NCT00770432	Phase 4	COMPLETED	Study Comparing PEG 3350 Laxative to Placebo in the Treatment of Occasional Constipation (Study CL2007-12)(P08216)
NCT00799201	Phase 4	TERMINATED	Enteral Naloxone Versus a Traditional Bowel Regimen for the Prevention of Opioid Induced Constipation in Trauma Patients
NCT00844831	Phase 4	COMPLETED	Effects of Lubiprostone on Small Bowel and Colonic Bacteria: A Correlation Study With Segmental and Whole Gut Transit
NCT00949377	Phase 4	WITHDRAWN	Can Methylnaltrexone Safely Treat Opioid Related Constipation in the Emergency Department?
NCT01003249	Phase 4	TERMINATED	Dysfunctional Voiding and Lower Urinary Tract Symptoms With Baclofen
NCT01096290	Phase 4	TERMINATED	Comparison of Lubiprostone and Placebo for the Relief of Constipation From Constipating Medications
NCT01114997	Phase 4	TERMINATED	Effect of Lidocaine and Esmolol to Improve the Quality of Recovery
NCT01170039	Phase 4	COMPLETED	The Effectiveness of Lubiprostone in Constipated Diabetics
NCT01180725	Phase 4	COMPLETED	Investigation of Dried Plums in the Treatment of Adults With Constipation
NCT01189409	Phase 4	TERMINATED	Polyethylene Glycol (PEG) Versus Sennosides Study in Opioid-Induced Constipation in Cancer Patients
NCT01230840	Phase 4	COMPLETED	Effect of Wheat Dextrin on Calcium and Magnesium Absorption
NCT01236534	Phase 4	COMPLETED	Lubiprostone in Patients With Multiple Sclerosis Associated Constipation
NCT01267370	Phase 4	COMPLETED	Soy Polysaccharide Fiber for the Treatment of Chronic Constipation in Children: a Randomized, Double-blind Trial
NCT01333787	Phase 4	COMPLETED	Dietary Fiber Mixture in Constipated Pediatric Patients
NCT01424228	Phase 4	COMPLETED	Evaluation of Long-term Prucalopride Treatment With Chronic Constipation in Subjects Aged ≥ 18 Years
NCT01592734	Phase 4	COMPLETED	Efficacy and Tolerability of PEG-only Laxative for Fecal Impaction and Chronic Constipation in Children
NCT01707667	Phase 4	COMPLETED	Study to Investigate Prucalopride vs. Polyethylene Glycol 3350 on Colon Activity
NCT01773096	Phase 4	COMPLETED	Methylnaltrexone Use for Opioid-induced Postoperative Constipation
NCT01810653	Phase 4	COMPLETED	A Study to Compare the Effect of Transipeg 2.95 g or Forlax Junior 4 g in Children With Constipation
NCT01875744	Phase 4	COMPLETED	Polyethylene Glycol for Childhood Constipation
NCT01879605	Phase 4	COMPLETED	Study About Effect of Preoperative Bowel Preparation Versus no Bowel Preparation Before Spinal Surgery
NCT01917773	Phase 4	COMPLETED	Effect of Octreotide on the Colonic Motility in Pediatric Patients
NCT02110719	Phase 4	COMPLETED	Decreasing Narcotics in Advanced Pelvic Surgery
NCT02136693	Phase 4	COMPLETED	Psyllium Fiber Versus Placebo in Early Treatment After STARR for Obstructed Defecation: a Double-blind RCT
NCT02147574	Phase 4	COMPLETED	Anti-peristaltic Ileo-sigmoid Anastomosis for the Treatment of Slow-transit Constipation:Therapeutic Evaluation
NCT02228616	Phase 4	COMPLETED	Efficacy and Safety of Prucalopride in Combination With Polyethylene Glycol or Lactulose in Women With Chronic Constipation
NCT02433847	Phase 4	UNKNOWN	Effect of Mosapride on Gut Transit in Patients With Chronic Constipation or Constipated Irritable Bowel Syndrome and Healthy Subjects
NCT02571881	Phase 4	UNKNOWN	Opioid Induced Bowel Dysfunction in Patients Undergoing Cesarean Section
NCT02573922	Phase 4	COMPLETED	Opioid Induced Bowel Dysfunction in Patients Undergoing Spinal Surgery
NCT02726295	Phase 4	COMPLETED	The Efficacy of Mutaflor(E. Coli Nissle 1917, Mutaflor®) for Chronic Constipation:Multicenter Study
NCT02789111	Phase 4	COMPLETED	Trial of Alvimopan in Major Spine Surgery
NCT02839889	Phase 4	TERMINATED	Tolerability, Safety, and Feasibility of Naloxegol in Patients With Cancer and OIC (Opioid Induced Constipation)
NCT02946580	Phase 4	TERMINATED	Naloxegol for the Prevention of Constipation in Postoperative Spinal Surgery Patients
NCT02949882	Phase 4	UNKNOWN	Improving Bowel Habits of Elderly With Probiotics and Non-probiotics