CAPG

Summary

CAPG (capping actin protein, gelsolin like, HGNC:1474) is a protein-coding gene on chromosome 2p11.2, encoding Macrophage-capping protein (P40121). Calcium-sensitive protein which reversibly blocks the barbed ends of actin filaments but does not sever preformed actin filaments.

This gene encodes a member of the gelsolin/villin family of actin-regulatory proteins. The encoded protein reversibly blocks the barbed ends of F-actin filaments in a Ca2+ and phosphoinositide-regulated manner, but does not sever preformed actin filaments. By capping the barbed ends of actin filaments, the encoded protein contributes to the control of actin-based motility in non-muscle cells. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 822 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 72 total
• GTEx eGene: eQTL in 46 tissues, sQTL in 22 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.95 (unconstrained)
• MANE Select transcript: NM_001747
• Notable: 72 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1474
Approved symbol	CAPG
Name	capping actin protein, gelsolin like
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	MCP
Ensembl gene	ENSG00000042493
Ensembl biotype	protein_coding
OMIM	153615
Entrez	822

Gene structure

Transcript identifiers

Ensembl transcripts: 67 — 51 protein_coding, 10 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 3 retained_intron

MANE Select: ENST00000263867

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

ENST00000263867, ENST00000409275, ENST00000409670, ENST00000409724, ENST00000409921, ENST00000415012, ENST00000439385, ENST00000447219, ENST00000449030, ENST00000453973, ENST00000459793, ENST00000471064, ENST00000479651, ENST00000483659, ENST00000491267, ENST00000880826, ENST00000880827, ENST00000880828, ENST00000880829, ENST00000880830, ENST00000880831, ENST00000880832, ENST00000880833, ENST00000880834, ENST00000880835, ENST00000880836, ENST00000880837, ENST00000880838, ENST00000880839, ENST00000880840, ENST00000880841, ENST00000880842, ENST00000880843, ENST00000880844, ENST00000918269, ENST00000918270, ENST00000918271, ENST00000918272, ENST00000918273, ENST00000918274, ENST00000918275, ENST00000918276, ENST00000918277, ENST00000951332, ENST00000951333, ENST00000951334, ENST00000951335, ENST00000951336, ENST00000951337, ENST00000951338, ENST00000951339, ENST00000951340, ENST00000951341, ENST00000999561, ENST00000999562, ENST00000999563, ENST00000999564, ENST00000999565, ENST00001008906, ENST00001008908, ENST00001008910, ENST00001008912, ENST00001089654, ENST00001089655, ENST00001089658, ENST00001096533, ENST00001139874

RefSeq mRNA: 6 — MANE Select: NM_001747 NM_001256139, NM_001256140, NM_001320732, NM_001320733, NM_001320734, NM_001747

CCDS: CCDS1974, CCDS58715

Canonical transcript exons

ENST00000263867 — 10 exons

Exon	Start	End
ENSE00001516724	85410317	85410366
ENSE00001713657	85394753	85394958
ENSE00003464947	85399136	85399285
ENSE00003473983	85395538	85395626
ENSE00003474428	85401785	85401957
ENSE00003486018	85402123	85402158
ENSE00003511275	85398020	85398152
ENSE00003583273	85401529	85401683
ENSE00003693166	85401165	85401329
ENSE00003785536	85398690	85398782

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.1535 / max 1148.8970, expressed in 1642 samples.

Highest expression (Bgee): monocyte, lower esophagus mucosa, mononuclear cell, leukocyte, esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CAPG is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 46 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 68 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	2.2e-79	-1.75	2:85393806:C:T
Skin Sun Exposed Lower leg	eqtl	1.7e-65	+0.32	2:85394936:T:C
Testis	eqtl	2.3e-64	+0.90	2:85418422:A:C
Skin Not Sun Exposed Suprapubic	sqtl	5.2e-55	-1.84	2:85401622:C:T
Artery Tibial	eqtl	7.0e-55	+0.79	2:85393065:T:C
Adipose Subcutaneous	sqtl	3.2e-50	-1.59	2:85393806:C:T
Skin Not Sun Exposed Suprapubic	eqtl	7.7e-50	+0.32	2:85394936:T:C
Esophagus Muscularis	eqtl	2.9e-30	+0.41	2:85410714:G:T
Artery Aorta	eqtl	7.9e-30	+0.76	2:85379188:A:G
Cells Cultured fibroblasts	sqtl	7.7e-29	-1.33	2:85397774:C:G
Thyroid	eqtl	1.9e-28	+0.28	2:85402694:A:G
Thyroid	sqtl	3.8e-28	-0.61	2:85394936:T:C
Esophagus Mucosa	eqtl	8.6e-28	+0.32	2:85394936:T:C
Testis	sqtl	1.2e-27	-0.98	2:85416026:C:T
Muscle Skeletal	eqtl	1.9e-27	+0.35	2:85410714:G:T
Colon Sigmoid	eqtl	1.5e-26	-0.67	2:85414064:C:T
Adipose Subcutaneous	eqtl	2.8e-26	-0.42	2:85414064:C:T
Cells Cultured fibroblasts	eqtl	2.0e-24	+0.27	2:85409072:T:C
Heart Atrial Appendage	eqtl	6.3e-21	-0.67	2:85414064:C:T
Whole Blood	eqtl	3.3e-20	+0.18	2:85407215:G:A

FANTOM5 promoters

showing 10 of 13 alternative TSS:

Promoter ID	TPM avg	Samples expressed
29408	26.5233	983
29410	21.0126	1369
29407	2.6010	211
29409	1.1855	298
29411	0.9325	640
29399	0.5631	226
29404	0.3044	125
29412	0.3029	155
29403	0.2430	104
29405	0.1854	88

Top tissues by expression

showing 100 of 290 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.76	gold quality
lower esophagus mucosa	UBERON:0035834	98.60	gold quality
mononuclear cell	CL:0000842	98.42	gold quality
leukocyte	CL:0000738	98.39	gold quality
esophagus mucosa	UBERON:0002469	98.20	gold quality
skin of abdomen	UBERON:0001416	98.09	gold quality
left lobe of thyroid gland	UBERON:0001120	98.04	gold quality
granulocyte	CL:0000094	97.94	gold quality
right lobe of thyroid gland	UBERON:0001119	97.92	gold quality
skin of leg	UBERON:0001511	97.76	gold quality
metanephros cortex	UBERON:0010533	97.74	gold quality
upper lobe of left lung	UBERON:0008952	97.72	gold quality
right lung	UBERON:0002167	97.46	gold quality
upper lobe of lung	UBERON:0008948	97.42	gold quality
thyroid gland	UBERON:0002046	97.32	gold quality
zone of skin	UBERON:0000014	96.66	gold quality
ectocervix	UBERON:0012249	96.20	gold quality
gingiva	UBERON:0001828	96.03	gold quality
bone marrow	UBERON:0002371	95.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.82	gold quality
mouth mucosa	UBERON:0003729	95.59	gold quality
endocervix	UBERON:0000458	95.58	gold quality
gingival epithelium	UBERON:0001949	95.56	gold quality
minor salivary gland	UBERON:0001830	95.51	gold quality
mucosa of transverse colon	UBERON:0004991	95.48	gold quality
vagina	UBERON:0000996	95.38	gold quality
blood	UBERON:0000178	95.19	gold quality
ventricular zone	UBERON:0003053	95.16	gold quality
rectum	UBERON:0001052	94.95	gold quality
calcaneal tendon	UBERON:0003701	94.85	gold quality
gall bladder	UBERON:0002110	94.81	gold quality
bone marrow cell	CL:0002092	94.54	gold quality
vermiform appendix	UBERON:0001154	94.46	gold quality
lymph node	UBERON:0000029	94.45	gold quality
descending thoracic aorta	UBERON:0002345	94.44	gold quality
tongue squamous epithelium	UBERON:0006919	94.41	gold quality
palpebral conjunctiva	UBERON:0001812	94.29	gold quality
popliteal artery	UBERON:0002250	94.25	gold quality
tibial artery	UBERON:0007610	94.24	gold quality
mucosa of stomach	UBERON:0001199	93.95	gold quality
lung	UBERON:0002048	93.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.89	gold quality
ganglionic eminence	UBERON:0004023	93.81	gold quality
adult mammalian kidney	UBERON:0000082	93.69	gold quality
epithelium of esophagus	UBERON:0001976	93.60	gold quality
esophagus squamous epithelium	UBERON:0006920	93.60	gold quality
body of stomach	UBERON:0001161	93.50	gold quality
aorta	UBERON:0000947	93.19	gold quality
right coronary artery	UBERON:0001625	93.17	gold quality
mammalian vulva	UBERON:0000997	93.16	gold quality
esophagus	UBERON:0001043	93.16	gold quality
oral cavity	UBERON:0000167	92.93	gold quality
tendon of biceps brachii	UBERON:0008188	92.89	gold quality
lower lobe of lung	UBERON:0008949	92.87	gold quality
urinary bladder	UBERON:0001255	92.71	gold quality
omental fat pad	UBERON:0010414	92.67	gold quality
peritoneum	UBERON:0002358	92.63	gold quality
nipple	UBERON:0002030	92.61	gold quality
transverse colon	UBERON:0001157	92.49	gold quality
spinal cord	UBERON:0002240	92.22	gold quality
thoracic aorta	UBERON:0001515	92.07	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.01	gold quality
stomach	UBERON:0000945	91.97	gold quality
body of uterus	UBERON:0009853	91.95	gold quality
upper leg skin	UBERON:0004262	91.89	gold quality
tonsil	UBERON:0002372	91.82	gold quality
pharyngeal mucosa	UBERON:0000355	91.81	gold quality
skin of hip	UBERON:0001554	91.75	gold quality
ascending aorta	UBERON:0001496	91.73	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.62	gold quality
left uterine tube	UBERON:0001303	91.59	gold quality
penis	UBERON:0000989	91.50	gold quality
left coronary artery	UBERON:0001626	91.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.45	gold quality
stromal cell of endometrium	CL:0002255	91.45	gold quality
periodontal ligament	UBERON:0008266	91.37	gold quality
saliva-secreting gland	UBERON:0001044	91.34	gold quality
right uterine tube	UBERON:0001302	91.12	gold quality
prostate gland	UBERON:0002367	91.06	gold quality
uterine cervix	UBERON:0000002	90.97	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.84	gold quality
upper arm skin	UBERON:0004263	90.76	gold quality
tendon	UBERON:0000043	90.75	gold quality
coronary artery	UBERON:0001621	90.63	gold quality
caecum	UBERON:0001153	90.55	gold quality
amniotic fluid	UBERON:0000173	90.51	gold quality
mucosa of urinary bladder	UBERON:0001259	90.10	gold quality
spleen	UBERON:0002106	89.95	gold quality
adipose tissue	UBERON:0001013	89.88	gold quality
connective tissue	UBERON:0002384	89.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.87	gold quality
body of pancreas	UBERON:0001150	89.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.59	gold quality
squamous epithelium	UBERON:0006914	89.59	gold quality
colonic epithelium	UBERON:0000397	89.50	gold quality
small intestine	UBERON:0002108	89.48	gold quality
layer of synovial tissue	UBERON:0007616	89.33	gold quality
smooth muscle tissue	UBERON:0001135	89.08	gold quality
large intestine	UBERON:0000059	88.83	gold quality
intestine	UBERON:0000160	88.83	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 21.

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	1598.66
E-MTAB-5061	yes	843.52
E-MTAB-6701	yes	112.77
E-HCAD-1	yes	81.67
E-HCAD-4	yes	80.31
E-CURD-122	yes	72.45
E-CURD-88	yes	43.65
E-HCAD-6	yes	43.04
E-MTAB-10287	yes	29.27
E-GEOD-134144	yes	27.67
E-CURD-112	yes	27.48
E-HCAD-10	yes	25.71
E-MTAB-8410	yes	19.41
E-MTAB-10042	yes	17.13
E-MTAB-8142	yes	14.98

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	150.5	low
Parathyroid gland	tissue	142.6	medium
Vagina	tissue	138.5	not detected
Skin 1	tissue	133.7	medium
Esophagus	tissue	131.5	medium
Lung	tissue	116.6	high
Lymph node	tissue	110.4	medium
Tonsil	tissue	102.7	medium
Stomach 1	tissue	89.0	low
Urinary bladder	tissue	79.6	medium
Thyroid gland	tissue	78.8	medium
Appendix	tissue	77.8	low
Kidney	tissue	56.9	high
Thymus	tissue	54.1
Colon	tissue	47.6	low
Fallopian tube	tissue	45.8	not detected
Epididymis	tissue	43.6	not detected
Gallbladder	tissue	41.7	low
Breast	tissue	40.6	not detected
Rectum	tissue	40.3	low
Small intestine	tissue	39.2	medium
Cervix	tissue	36.1	not detected
Seminal vesicle	tissue	35.9	not detected
Prostate	tissue	32.8	not detected
Salivary gland	tissue	31.5	not detected
Duodenum	tissue	28.5	not detected
Placenta	tissue	24.5	not detected
Adipose tissue	tissue	24.3	not detected
Pancreas	tissue	24.0	not detected
Hippocampus	tissue	23.4	not detected
Spleen	tissue	22.9	medium
Smooth muscle	tissue	22.8	not detected
Locus coeruleus	tissue	22.4
Endometrium 1	tissue	21.2	not detected
Pituitary gland	tissue	21.0
Nucleus accumbens	tissue	17.6
Adrenal gland	tissue	15.0	not detected
Choroid plexus	tissue	14.8
Testis	tissue	13.7	not detected
Spinal cord	tissue	11.3
Ovary	tissue	9.4	not detected
Liver	tissue	7.9	not detected
Postcentral gyrus	tissue	6.9
Superior colliculi	tissue	6.1
Tongue	tissue	5.6
Skeletal muscle	tissue	5.5	not detected
Heart muscle	tissue	5.2	not detected
Medulla oblongata	tissue	5.2
Substantia nigra	tissue	5.1
Hypothalamus	tissue	4.3
Retina	tissue	3.9
Pons	tissue	3.9
Septum	tissue	3.8
Basal ganglia	tissue	3.7	not detected
Thalamus	tissue	3.7
Cerebellum	tissue	3.7	not detected
Midbrain	tissue	3.5
Olfactory bulb	tissue	3.4
Amygdala	tissue	3.2
Hippocampal formation	tissue	3.2

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Lateral funiculus (white matter) (104.7), Anterior thalamic nucleus, ventral (80.3), Blood vessel (69.3), Corpus callosum, splenium (white matter) (65.3), Nucleus gracilis (62.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

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

8 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506

Functional genomics

gnomAD constraint: pLI 5.54e-08, LOEUF 0.947, missense Z 0.632 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000263867 — one region, missense o/e 0.94.

Literature-anchored findings (GeneRIF, showing 36)

• CapG lacks a nuclear export sequence present in structurally related proteins (PMID:12637565)
• importin-beta-dependent nuclear import of the actin modulating protein CapG promotes cell invasion (PMID:15454578)
• CapG is a new tumor suppressor gene involved in the tumorigenic progression of certain cancers (PMID:16767159)
• Comprehension of the mobility and compartmentalization of the CapG protein in normal and in cancer cells in vivo could constitute a new basis to characterize the invasiveness and metastasizing potential of breast cancer. (PMID:18059028)
• Dysregulated expression of gelsolin-like actin capping protein(CapG) was found in premalignant and malignant oral carcinogenesis. (PMID:18237446)
• Results report that NTF2 and Ran control nuclear import of the filamentous actin capping protein CapG. (PMID:18266911)
• CapG mobility in cell nuclei of live breast cancer cells (PMID:18461482)
• the 4 biomarkers CLU, ITGB3, PRAME and CAPG may be used as prognostic factors for patients with stage III serous ovarian adenocarcinomas. (PMID:18709641)
• These results suggest that filamentous actin in the nucleolus might be regulated by actin binding proteins such as CapG. (PMID:18938132)
• several genes that are known to be regulated by DNA methylation were up-regulated dramatically by integrin alpha6beta4 expression, including S100A4, FST, PDLIM4, CAPG, and Nkx2.2. (PMID:19011242)
• A role for the actin-binding protein CapG as a mediator of cross-talk between the actin cytoskeleton and microtubule-based organelles that regulate cell division was proposed. (PMID:19166812)
• Hypoxia-inducible factor 1alpha up-regulated CapG protein expression under normoxia. Knockdown of HIF-1alpha expression in hPASMCs also inhibited hypoxia-induced CapG up-regulation. (PMID:19188659)
• CapG was upregulated in the stroma cells of nasopharyngeal carcinoma (NPC) compared with normal nasopharyngeal epithelial tissues. CapG possibly plays a role in the complex interaction between NPC cells and the surrounding host tissue. (PMID:19242827)
• Proteomic study of macrophages exposed to oxLDL identifies a CAPG polymorphism associated with carotid atherosclerosis. (PMID:19439302)
• strong down-regulation of MCK activity contributes to F-actin instability and induces post-translational modification of alphaB-crystallin and desmin (PMID:21768101)
• These results suggest that overexpression of CapG may be associated with progression of lung adenocarcinoma. (PMID:21908955)
• CapG was identified as a novel candidate biomarker to predict response to gemcitabine treatment and survival in cholangiocarcinoma. (PMID:22155129)
• Expression of CapG, gelsolin, and P-gp was found to be associated with an increased risk of death from non-small cell lung cancer. (PMID:22190510)
• CapG is involved in the process of metastasis by promoting the invasiveness of tumor cells. (PMID:23085225)
• CapG was up-regulated in the tumor tissues of patients with lymph node metastasis (LNM), whereas it showed an equivalent expression level between non-tumor and tumor tissues of patients without LNM. (PMID:23782053)
• A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. (PMID:24804218)
• On the basis of these results, we propose a model in which dynamic vimentin filaments target CARMIL2 to critical membrane-associated locations, where CARMIL2 regulates CP, and thus actin assembly, to create cell protrusions (PMID:26466680)
• Overexpression of CAPG is associated with glioma. (PMID:26663173)
• The composite biomarker, CAPG and GIPC1 in primary breast tumors, predicted disease outcomes and benefit from zoledronate and may facilitate patient selection for adjuvant bisphosphonate treatment. (PMID:26757732)
• The combination of CTNB1, XPO2, and CAPG achieved 95% sensitivity and 96% specificity for the discrimination of these subtypes. We developed two uterine aspirate-based signatures to diagnose Endometrial cancer and classify tumors in the most prevalent histologic subtypes. This will improve diagnosis and assist in the prediction of the optimal surgical treatment (PMID:28790116)
• Results revealed that CapG is a novel independent prognostic predictor for glioma patients and highlight a key role of CapG in proliferation and metastasis of glioma. (PMID:29399702)
• CAPG competes with the transcriptional repressor arginine methyltransferase 5 (PRMT5) for binding to the STC-1 promoter. (PMID:29721098)
• it is demonstrated that CapG is expressed in the cytoplasm and could be used as a prognostic or diagnostic biomarker for mHCC in clinical specimens (PMID:29970516)
• Study suggested that CapG could be used as a biomarker for metastatic CRC in the clinical specimens. Moreover, our in vitro study demonstrated that CapG might contribute on tumor metastasis in human CRCs. (PMID:30155403)
• CapG promotes resistance to paclitaxel in breast cancer through transactivation of PIK3R1/P50. (PMID:31660072)
• The Association Between Gelsolin-like Actin-capping Protein (CapG) Overexpression and Bladder Cancer Prognosis. (PMID:32309867)
• The role of CAPG in molecular communication between the embryo and the uterine endometrium: Is its function conserved in species with different implantation strategies? (PMID:32619075)
• Oncogenic potential of macrophagecapping protein in clear cell renal cell carcinoma. (PMID:33236143)
• The migration behavior of human glioblastoma cells is influenced by the redox-sensitive human macrophage capping protein CAPG. (PMID:33711419)
• CAPG facilitates diffuse large B-cell lymphoma cell progression through PI3K/AKT signaling pathway. (PMID:36244872)
• CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway. (PMID:37468079)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	capga	ENSDARG00000035560
danio_rerio	capgb	ENSDARG00000099672
mus_musculus	Capg	ENSMUSG00000056737
rattus_norvegicus	Capg	ENSRNOG00000013668
drosophila_melanogaster	Gel	FBGN0010225
caenorhabditis_elegans		WBGENE00010593

Paralogs (7): SCIN (ENSG00000006747), VIL1 (ENSG00000127831), AVIL (ENSG00000135407), VILL (ENSG00000136059), GSN (ENSG00000148180), FLII (ENSG00000177731), SVIL (ENSG00000197321)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1098259) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
impaired macrophage phagocytosis	2
abnormal dendritic cell physiology	1
increased susceptibility to bacterial infection	1
abnormal macrophage physiology	1
impaired neutrophil chemotaxis	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	B8ATT7	99.8%	Diamond
Oryza sativa Japonica Group	Q0JAD9	99.8%	Diamond
Bos taurus	Q3SX14	96.7%	Diamond
Sus scrofa	P20305	96.3%	Diamond
Equus caballus	Q28372	94.8%	Diamond
Caenorhabditis briggsae	A8XV95	89.1%	Diamond
Gallus gallus	Q5ZIV9	85.4%	Diamond
Arabidopsis thaliana	O81644	80.9%	Diamond
Lumbricus terrestris	Q7JQD3	61.0%	Diamond
Platymeris rhadamanthus	A0A6B9KZ40	51.0%	Diamond
Homarus americanus	Q27319	47.9%	Diamond
Halocynthia roretzi	O61270	47.0%	Diamond
Dictyostelium discoideum	P10733	44.7%	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
SH2D6	protein-coding	284948
ELMOD3	protein-coding	84173
RETSAT	protein-coding	54884
PARTICL	ncRNA	100630918

Protein

Protein identifiers

Macrophage-capping protein — P40121 (reviewed: P40121)

Alternative names: Actin regulatory protein CAP-G

All UniProt accessions (7): A0A979HLS1, A0A979HLS2, B8ZZL6, E7ENU9, H7C0X8, P40121, V9HW69

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-sensitive protein which reversibly blocks the barbed ends of actin filaments but does not sever preformed actin filaments. May play an important role in macrophage function. May play a role in regulating cytoplasmic and/or nuclear structures through potential interactions with actin. May bind DNA.

Subunit / interactions. Interacts with NUP62. Interacts with NUTF2 and RAN; involved in CAPG nuclear import.

Subcellular location. Nucleus. Cytoplasm. Melanosome. Cell projection. Lamellipodium. Ruffle.

Tissue specificity. Macrophages and macrophage-like cells.

Post-translational modifications. The N-terminus is blocked.

Similarity. Belongs to the villin/gelsolin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P40121-1	1	yes
P40121-2	2

RefSeq proteins (6): NP_001243068, NP_001243069, NP_001307661, NP_001307662, NP_001307663, NP_001738* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007122	Villin/Gelsolin	Family
IPR007123	Gelsolin-like_dom	Domain
IPR029006	ADF-H/Gelsolin-like_dom_sf	Homologous_superfamily

Pfam: PF00626

UniProt features (45 total): strand 22, helix 8, turn 4, repeat 3, sequence variant 3, modified residue 2, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
1J72	Crystal Structure of Mutant Macrophage Capping Protein (Cap G) with Actin-severing …	X-RAY DIFFRACTION	2.5
1JHW	Ca2+-binding Mimicry in the Crystal Structure of the Eu3+-Bound Mutant Human Macrophage …	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40121-F1	86.89	0.56

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; mitotic chromosome

Antibody reliability (HPA): IH enhanced · IF 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 (2)

Type	Positions
N-acetylmethionine	1
Phosphoserine	337

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 409 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, MCLACHLAN_DENTAL_CARIES_UP, PAL_PRMT5_TARGETS_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, MORI_IMMATURE_B_LYMPHOCYTE_UP, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, GOCC_RUFFLE

GO Biological Process (7): central nervous system development (GO:0007417), actin polymerization or depolymerization (GO:0008154), cell projection assembly (GO:0030031), actin filament severing (GO:0051014), barbed-end actin filament capping (GO:0051016), protein-containing complex assembly (GO:0065003), actin filament capping (GO:0051693)

GO Molecular Function (7): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), protein domain specific binding (GO:0019904), protein-containing complex binding (GO:0044877), cadherin binding (GO:0045296), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (13): ruffle (GO:0001726), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), centriole (GO:0005814), F-actin capping protein complex (GO:0008290), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), melanosome (GO:0042470), extracellular exosome (GO:0070062), mitotic spindle (GO:0072686), Flemming body (GO:0090543)

GO top-level categories

34 GO namespaces:

Category	Terms
cellular anatomical structure	3
cellular component assembly	2
binding	2
cell leading edge	2
plasma membrane bounded cell projection	2
nuclear lumen	2
intracellular membraneless organelle	2
nervous system development	1
system development	1
animal gross anatomical part developmental process	1
actin filament organization	1
cell projection organization	1
actin filament-based process	1
actin filament capping	1
protein-containing complex organization	1
negative regulation of actin filament depolymerization	1
negative regulation of actin filament polymerization	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
protein binding	1
cell adhesion molecule binding	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
microtubule organizing center	1
actin cytoskeleton	1
protein-containing complex	1
cytoskeleton	1
pigment granule	1
extracellular vesicle	1
spindle	1
midbody	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
Flemming body	CC	direct assay
centriole	CC	direct assay
cytoplasm	CC	direct assay
extracellular exosome	CC	high-throughput assay
mitotic spindle	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
cadherin binding	MF	high-throughput assay
protein domain specific binding	MF	physical interaction
protein-containing complex binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 924 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPG	LCP1	P13796	414
CAPG	GIPC1	O14908	411
CAPG	ANXA2	P07355	411
CAPG	GPNMB	Q14956	407
CAPG	HLA-DPB1	P01916	370
CAPG	SERPINF1	P36955	367
CAPG	SYK	P43405	365
CAPG	TGFBI	Q15582	364
CAPG	PDC	P20941	360
CAPG	NRN1	Q9NPD7	360
CAPG	CFL1	P23528	357
CAPG	CAPS	Q13938	353
CAPG	APLP2	Q06481	338
CAPG	GHSR	Q92847	335
CAPG	RIMBP3	Q9UFD9	334

IntAct

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

9 partners by confidence:

Partner	Interaction type	MIscore	Records
SIAH1	physical association	0.560	3
SPRED1	physical association	0.560	3
TSC1	physical association	0.560	3
HSPA8	association	0.530	2
TRUB1	association	0.500	2
ACTA1	direct interaction	0.440	1
HMGN2	physical association	0.400	1
RPF1	association	0.350	1
SLC2A2	association	0.350	1

BioGRID (105 interactions; top human partners by supporting records): ZSCAN20 (Affinity Capture-MS; 3 records), CCNYL1 (Affinity Capture-MS; 2 records), CDK15 (Affinity Capture-MS; 2 records), DDX19B (Affinity Capture-MS; 2 records), HSPA8 (Affinity Capture-MS; 2 records), KHDRBS2 (Affinity Capture-MS; 2 records), STK38 (Affinity Capture-MS; 2 records), TBC1D22B (Affinity Capture-MS; 2 records), ACTG1 (Cross-Linking-MS (XL-MS)), ADK (Co-fractionation), APEX1 (Affinity Capture-RNA), ATP5A1 (Affinity Capture-MS), BID (Proximity Label-MS), BMI1 (Affinity Capture-MS), BRD2 (Cross-Linking-MS (XL-MS))

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
CAPG-PRMT5 complex	2	CAPG, PRMT5

Disease & clinical

Genetic variants

Variant evidence for CAPG: 72 ClinVar records (0 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	4
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 758):

Position(s)	Effect	Δscore	Sites
2:85395536–85395537	donor_loss	1.0000	5
2:85395627	acceptor_loss	1.0000
2:85398018	donor_loss	1.0000	2
2:85398153–85398154	acceptor_loss	1.0000	5
2:85399159–85399160	donor_gain	1.0000	2
2:85399286–85399287	acceptor_loss	1.0000	4
2:85401163–85401164	donor_loss	1.0000	5
2:85401783–85401784	donor_loss	1.0000	4
2:85401958–85401959	acceptor_loss	1.0000	6
2:85402121–85402122	donor_loss	1.0000	4

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	4.65e-05

Disease associations

OMIM: gene MIM:153615 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST006585_780	Blood protein levels	1e-48

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066906 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

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

Variant	Association	Level	Drugs	Phenotypes
rs3770102	Toxicity	3	vincristine	Drug Toxicity;Neurotoxicity Syndromes

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3770102	CAPG	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
rs3770102	vincristine	Toxicity	Allele T is associated with decreased risk of Neurotoxicity Syndromes when treated with vincristine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma.	PMID:25084203

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression	4
sodium arsenite	increases abundance, increases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
bisphenol S	affects expression, increases expression	2
(+)-JQ1 compound	affects binding, decreases expression	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Arsenic	decreases response to substance, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases expression, affects cotreatment	2
Cisplatin	affects cotreatment, increases expression	2
Ozone	increases abundance, affects cotreatment, increases oxidation	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Tretinoin	increases expression	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
beta-lapachone	increases expression	1
sodium bichromate	decreases expression	1
sulforaphane	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
benazol P	affects expression	1
pentanal	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651032	Binding	Binding affinity to human CAPG incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1M3	Abcam HeLa CAPG KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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