CAP1

Summary

CAP1 (cyclase associated actin cytoskeleton regulatory protein 1, HGNC:20040) is a protein-coding gene on chromosome 1p34.2, encoding Adenylyl cyclase-associated protein 1 (Q01518). Directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity.

The protein encoded by this gene is related to the S. cerevisiae CAP protein, which is involved in the cyclic AMP pathway. The human protein is able to interact with other molecules of the same protein, as well as with CAP2 and actin. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 10487 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 91 total
• Druggable target: yes
• MANE Select transcript: NM_006367

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20040
Approved symbol	CAP1
Name	cyclase associated actin cytoskeleton regulatory protein 1
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	CAP
Ensembl gene	ENSG00000131236
Ensembl biotype	protein_coding
OMIM	617801
Entrez	10487

Gene structure

Transcript identifiers

Ensembl transcripts: 93 — 90 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000340450, ENST00000372792, ENST00000372797, ENST00000372798, ENST00000372802, ENST00000372805, ENST00000414281, ENST00000414893, ENST00000417287, ENST00000420216, ENST00000421589, ENST00000424977, ENST00000427843, ENST00000435719, ENST00000446031, ENST00000449311, ENST00000461993, ENST00000479759, ENST00000494114, ENST00000911193, ENST00000911194, ENST00000911195, ENST00000911196, ENST00000911197, ENST00000911198, ENST00000911199, ENST00000911200, ENST00000911201, ENST00000911202, ENST00000911203, ENST00000911204, ENST00000911205, ENST00000911206, ENST00000911207, ENST00000911208, ENST00000911209, ENST00000911210, ENST00000911211, ENST00000911212, ENST00000911213, ENST00000911214, ENST00000911215, ENST00000911216, ENST00000911217, ENST00000911218, ENST00000911219, ENST00000911220, ENST00000911221, ENST00000911222, ENST00000911223, ENST00000915716, ENST00000915717, ENST00000915718, ENST00000915719, ENST00000915720, ENST00000915721, ENST00000915722, ENST00000915723, ENST00000915724, ENST00000915725, ENST00000915726, ENST00000915727, ENST00000915728, ENST00000915729, ENST00000915730, ENST00000915731, ENST00000915732, ENST00000915733, ENST00000915734, ENST00000915735, ENST00000915736, ENST00000915737, ENST00000915738, ENST00000915739, ENST00000915740, ENST00000915741, ENST00000915742, ENST00000915743, ENST00000915744, ENST00000915745, ENST00000942534, ENST00000942535, ENST00000942536, ENST00000942537, ENST00000942538, ENST00000942539, ENST00000942540, ENST00000942541, ENST00000942542, ENST00000942543, ENST00000942544, ENST00000942545, ENST00000942546

RefSeq mRNA: 14 — MANE Select: NM_006367 NM_001105530, NM_001330502, NM_001350475, NM_001350476, NM_001350477, NM_001350478, NM_001350479, NM_001350480, NM_001350481, NM_001350482, NM_001350483, NM_001350484, NM_001350485, NM_006367

CCDS: CCDS41309, CCDS81304

Canonical transcript exons

ENST00000372805 — 13 exons

Exon	Start	End
ENSE00000899727	40060067	40060170
ENSE00001192138	40066215	40066320
ENSE00001192141	40064474	40064559
ENSE00001192143	40064227	40064370
ENSE00001192144	40061735	40061812
ENSE00001192151	40040729	40040801
ENSE00001458654	40071450	40072648
ENSE00001458701	40059337	40059458
ENSE00003459410	40070159	40070282
ENSE00003477815	40070430	40070512
ENSE00003512323	40070836	40070979
ENSE00003554678	40069690	40069874
ENSE00003580138	40067540	40067717

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 163.8730 / max 4911.8392, expressed in 1827 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2335	154.2031	1827
2334	2.3363	1251
2333	1.7151	1067
2331	1.5645	777
2332	1.5000	808
2330	1.0597	543
2336	0.8583	414
2340	0.4635	240
2337	0.1725	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.54	gold quality
monocyte	CL:0000576	99.50	gold quality
leukocyte	CL:0000738	99.49	gold quality
mononuclear cell	CL:0000842	99.49	gold quality
trabecular bone tissue	UBERON:0002483	99.43	gold quality
granulocyte	CL:0000094	99.31	gold quality
smooth muscle tissue	UBERON:0001135	99.27	gold quality
vermiform appendix	UBERON:0001154	99.26	gold quality
esophagus squamous epithelium	UBERON:0006920	99.24	gold quality
colonic mucosa	UBERON:0000317	99.17	gold quality
olfactory bulb	UBERON:0002264	99.16	gold quality
popliteal artery	UBERON:0002250	99.13	gold quality
descending thoracic aorta	UBERON:0002345	99.13	gold quality
bone marrow	UBERON:0002371	99.13	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.13	gold quality
tibial artery	UBERON:0007610	99.13	gold quality
aorta	UBERON:0000947	99.11	gold quality
lymph node	UBERON:0000029	99.09	gold quality
thoracic aorta	UBERON:0001515	99.09	gold quality
right coronary artery	UBERON:0001625	99.09	gold quality
ascending aorta	UBERON:0001496	99.08	gold quality
rectum	UBERON:0001052	99.05	gold quality
mucosa of stomach	UBERON:0001199	99.05	gold quality
lower esophagus	UBERON:0013473	99.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.05	gold quality
left coronary artery	UBERON:0001626	99.04	gold quality
coronary artery	UBERON:0001621	99.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.01	gold quality
epithelium of esophagus	UBERON:0001976	99.00	gold quality
stromal cell of endometrium	CL:0002255	98.99	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	20.00
E-MTAB-10042	yes	16.67
E-HCAD-10	yes	16.05
E-MTAB-9388	yes	11.15
E-MTAB-9801	yes	8.69
E-ANND-3	yes	8.47
E-MTAB-5061	yes	4.16
E-MTAB-4850	no	2045.64
E-MTAB-7606	no	817.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

113 targeting CAP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4650-5P	99.98	64.69	999
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-1236-3P	99.94	68.04	1695

Literature-anchored findings (GeneRIF, showing 35)

• plays a key role in speeding up the turnover of actin filaments by effectively recycling cofilin and actin and through its effect on both ends of actin filament (PMID:11950878)
• Based on an analysis of 1075 beta-thalassemia alleles the CAP+1 (A–>C) mutation constituted 3.2% of north Indians. (PMID:17900295)
• The high turnover rate of CAP1 by MMP-9, comparable to that of gelatin as the natural extracellular substrate of this enzyme, may be critical to prevent pathological conditions associated with considerable cytolysis. (PMID:18671965)
• These studies suggest that CAP1 provides a direct link from the actin cytoskeleton to the mitochondria by functioning as an actin shuttle. (PMID:18716285)
• The overexpression of CAP1 in pancreatic cancers is demonstrated and the involvement of CAP1 in the aggressive behavior of pancreatic cancer cells is suggested. (PMID:19188911)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• CAP1 depletion also led to changes in cofilin phosphorylation and localization as well as activation of focal adhesion kinase (FAK) and enhanced cell spreading. (PMID:23737525)
• overexpression of CAP1 in lung cancer cells, particularly at the metastatic stage, may have significant clinical implications as a diagnostic/prognostic factor for lung cancer. (PMID:23842884)
• Findings suggest that CAP1 (cyclase-associated protein 1) is involved in the metastasis of esophageal squamous cell carcinoma, and increased expression may indicate a poor prognosis. (PMID:23904342)
• results indicate that upregulated expression of CAP1 might contribute heavily to the metastasis of hepatocellular carcinoma. (PMID:24359721)
• CAP1 might be a potential molecular targeted therapy for surgery and immune treatment. (PMID:24509166)
• Overexpression of CAP1 is associated with breast carcinoma. (PMID:24522810)
• Overexpression of CAP1 in monocytes enhanced the resistin-induced increased activity of the cAMP-dependent signaling. (PMID:24606903)
• This study demonstrated an inverse relationship between CAP1 and MMP-9 expression, high expression of MMP-9 and low expression of CAP1 in those with chronic obstructive pulmonary disease compared with the non-chronic obstructive pulmonary disease group. (PMID:25332229)
• CAP1 is involved in the brain metastasis in non-small cell lung cancer.CAP1 overexpression is associated with poor prognosis in non-small cell lung cancer patients. (PMID:25371324)
• a high expression of CAP1 is involved in the pathogenesis of EOC, and that the downregulation of CAP1 in tumor cells may be a therapeutic target for the treatment of patients with EOC. (PMID:25652936)
• our results indicated that CAP1 participated in the molecular pathological process of glioma (PMID:26810579)
• Results identify a role for CAP1 in regulating proliferative transformation of cancer cells, with ERK signaling playing pivotal roles in mediating both cell functions. (PMID:27173014)
• CAP1 expression is markedly increased in human glioma and that downregulation of CAP1 in tumors may serve as a treatment for glioma patients. (PMID:27432289)
• Significant up-regulation of PBMCs CAP1, CD36 mRNA and plasma resistin found in significant coronary artery disease, as well as in nonsignificant coronary artery disease compared to control group, indicates that resistin could be able to exert its effects stronger on cells with up-regulated CAP1 mRNA thus contributing atherosclerosis development. (PMID:28707728)
• Using multiple -omics approach, study validated key molecules, such as CAP1, SHC1 and PRCP, that might play a significant role in IgA nephropathy pathogenesis. (PMID:28831120)
• REVIEW: summarizes information available to date about the structural organization, regulation of functional activity of adenylyl cyclase-associated protein 1 (CAP1), and its participation in cellular processes (PMID:29534668)
• findings indicate that CAP1 is a geranylgeranyl-binding partner of Rap1 (PMID:29618512)
• RETN and CAP1 polymorphisms and gene expression may be potential biomarkers for breast cancer risk (PMID:29641286)
• It identified CAP1 as a negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells. (PMID:30847953)
• Phosphorylation Regulates CAP1 (Cyclase-Associated Protein 1) Functions in the Motility and Invasion of Pancreatic Cancer Cells. (PMID:30894654)
• Resistin induces breast cancer cells epithelial to mesenchymal transition (EMT) and stemness through both adenylyl cyclase-associated protein 1 (CAP1)-dependent and CAP1-independent mechanisms. (PMID:31085453)
• Serum Resistin, Adenylate Cyclase-Associated Protein 1 Gene Expression, and Carotid Intima-Media Thickness in Patients with End-Stage Renal Disease and Healthy Controls. (PMID:31722350)
• this study provides direct cellular evidence that transient phosphorylation is required for CAP1 functions in both actin filament turnover and adhesion, and the novel mechanistic insights substantially extend our knowledge of the cell signals that function in concert to regulate CAP1 by facilitating its transient phosphorylation. (PMID:31791978)
• Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer. (PMID:32560703)
• Mutual functional dependence of cyclase-associated protein 1 (CAP1) and cofilin1 in neuronal actin dynamics and growth cone function. (PMID:33845164)
• Novel role of CAP1 in regulation RNA polymerase II-mediated transcription elongation depends on its actin-depolymerization activity in nucleoplasm. (PMID:33911205)
• Relationship of intracellular proteolysis with CAP1 and cofilin1 in non-small-cell lung cancer. (PMID:34148878)
• Serum levels of cytoskeleton remodeling proteins and their mRNA expression in tumor tissue of metastatic laryngeal and hypopharyngeal cancers. (PMID:34231097)
• Phosphorylation of CAP1 regulates lung cancer proliferation, migration, and invasion. (PMID:34636991)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cap1	ENSDARG00000016350
mus_musculus	Cap1	ENSMUSG00000028656
rattus_norvegicus	Cap1	ENSRNOG00000013492
drosophila_melanogaster	capt	FBGN0261458
caenorhabditis_elegans		WBGENE00000294
caenorhabditis_elegans	cas-2	WBGENE00015975

Paralogs (1): CAP2 (ENSG00000112186)

Protein

Protein identifiers

Adenylyl cyclase-associated protein 1 — Q01518 (reviewed: Q01518)

All UniProt accessions (11): Q01518, Q5T0R1, Q5T0R2, Q5T0R3, Q5T0R4, Q5T0R5, Q5T0R6, Q5T0R7, Q5T0R8, Q5T0R9, Q5T0S3

UniProt curated annotations — full annotation on UniProt →

Function. Directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity.

Subunit / interactions. Homodimer. Binds actin monomers.

Subcellular location. Cell membrane.

Similarity. Belongs to the CAP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q01518-1	1	yes
Q01518-2	2

RefSeq proteins (14): NP_001099000, NP_001317431, NP_001337404, NP_001337405, NP_001337406, NP_001337407, NP_001337408, NP_001337409, NP_001337410, NP_001337411, NP_001337412, NP_001337413, NP_001337414, NP_006358* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001837	Adenylate_cyclase-assoc_CAP	Family
IPR006599	CARP_motif	Domain
IPR013912	Adenylate_cyclase-assoc_CAP_C	Domain
IPR013992	Adenylate_cyclase-assoc_CAP_N	Conserved_site
IPR016098	CAP/MinC_C	Homologous_superfamily
IPR017901	C-CAP_CF_C-like	Domain
IPR018106	CAP_CS_N	Conserved_site
IPR028417	CAP_CS_C	Conserved_site
IPR036222	CAP_N_sf	Homologous_superfamily
IPR036223	CAP_C_sf	Homologous_superfamily
IPR053950	CAP_N	Domain

Pfam: PF01213, PF08603, PF21938

UniProt features (41 total): strand 14, modified residue 11, sequence variant 6, region of interest 2, initiator methionine 1, chain 1, cross-link 1, splice variant 1, domain 1, sequence conflict 1, turn 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1K8F	X-RAY DIFFRACTION	2.8
9Q7O	ELECTRON MICROSCOPY	3.02
9XYE	ELECTRON MICROSCOPY	3.18
9Y52	ELECTRON MICROSCOPY	3.46
9Y9J	ELECTRON MICROSCOPY	3.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01518-F1	82.85	0.64

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 (12): 287, 290, 295, 301, 307, 308, 310, 348, 2, 31, 34, 81

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-428890	Role of ABL in ROBO-SLIT signaling
R-HSA-6798695	Neutrophil degranulation
R-HSA-109582	Hemostasis
R-HSA-1266738	Developmental Biology
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-376176	Signaling by ROBO receptors
R-HSA-422475	Axon guidance
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+
R-HSA-9675108	Nervous system development

MSigDB gene sets: 311 (showing top): DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_MSN, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, ATACCTC_MIR202, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_HDAC1, HSIAO_HOUSEKEEPING_GENES, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION

GO Biological Process (11): cell morphogenesis (GO:0000902), ameboidal-type cell migration (GO:0001667), receptor-mediated endocytosis (GO:0006898), actin filament organization (GO:0007015), establishment or maintenance of cell polarity (GO:0007163), signal transduction (GO:0007165), activation of adenylate cyclase activity (GO:0007190), obsolete cAMP-mediated signaling (GO:0019933), modification of postsynaptic actin cytoskeleton (GO:0098885), cytoskeleton organization (GO:0007010), actin cytoskeleton organization (GO:0030036)

GO Molecular Function (3): actin binding (GO:0003779), adenylate cyclase binding (GO:0008179), protein binding (GO:0005515)

GO Cellular Component (11): extracellular region (GO:0005576), cytoplasm (GO:0005737), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cortical actin cytoskeleton (GO:0030864), azurophil granule lumen (GO:0035578), extracellular exosome (GO:0070062), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Signaling by ROBO receptors	1
Innate Immune System	1
Immune System	1
Axon guidance	1
Nervous system development	1
Hemostasis	1
Platelet activation, signaling and aggregation	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
synapse	3
cellular process	2
anatomical structure morphogenesis	1
cell migration	1
endocytosis	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
positive regulation of adenylate cyclase activity	1
modification of postsynaptic structure	1
organelle organization	1
cytoskeleton organization	1
actin filament-based process	1
cytoskeletal protein binding	1
enzyme binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cell-substrate junction	1
actin cytoskeleton	1
cortical cytoskeleton	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

1144 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAP1	RETN	Q9HD89	963
CAP1	RETNLB	Q9BQ08	937
CAP1	PFN4	Q8NHR9	689
CAP1	PFN1	P07737	658
CAP1	PFN3	P60673	611
CAP1	ROR1	Q01973	568
CAP1	DCN	P07585	554
CAP1	CFL1	P23528	526
CAP1	TLR4	O00206	513
CAP1	WDR1	O75083	501
CAP1	CFL2	Q9Y281	470
CAP1	TWF2	Q6IBS0	431
CAP1	CAPZB	P47756	409
CAP1	TWF1	Q12792	359
CAP1	MYH10	P35580	353
CAP1	MYH3	P11055	353

IntAct

91 interactions, top by confidence:

A	B	Type	Score
CAP1	CFTR	psi-mi:“MI:0915”(physical association)	0.720
CFTR	CAP1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
TWF2	CAP2	psi-mi:“MI:0914”(association)	0.640
	CAP1	psi-mi:“MI:0915”(physical association)	0.610
CAP1		psi-mi:“MI:0915”(physical association)	0.560
TWF1	MYO1C	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
PLA2G4A	CAP1	psi-mi:“MI:0915”(physical association)	0.370
WLS	CAP1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (281): CAP1 (Two-hybrid), CAP1 (Affinity Capture-MS), CAP1 (Co-fractionation), CAP1 (Co-fractionation), DPH2 (Co-fractionation), DPYSL2 (Co-fractionation), NPLOC4 (Co-fractionation), RNASEH2C (Co-fractionation), TTC38 (Co-fractionation), CAP1 (Affinity Capture-MS), CAP1 (Affinity Capture-MS), CAP1 (Affinity Capture-MS), CAP1 (Affinity Capture-MS), ACTA1 (Affinity Capture-MS), CAP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A223HDI2, A2BG43, B0BLT4, B0BNM9, B0YN54, O22797, O64587, O94360, P40124, P68265, P68266, Q01518, Q08163, Q0VCQ0, Q2WBN3, Q3SYV4, Q3T1J9, Q4R4I6, Q54XJ0, Q5F495, Q5HZ92, Q5RAE0, Q5RDB1, Q5TA50, Q5XIS2, Q63ZQ3, Q66JG2, Q6DBQ8, Q6NLQ3, Q6NU44, Q6PEB6, Q6Z6S1, Q70IA6, Q7L9L4, Q8BPB0, Q8BS40, Q8GYX0, Q8VI63, Q921Y0, Q949G5

Diamond homologs: O65902, P36621, P40122, P40123, P40124, P40125, P52481, P54654, Q01518, Q08163, Q3SYV4, Q4R4I6, Q5R5X8, Q5R8B4, Q9CYT6, P17555

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
GSK3B	“up-regulates activity”	CAP1	phosphorylation
CAP1	“down-regulates activity”	PTK2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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
Signaling by high-kinase activity BRAF mutants	5	26.9×	1e-04
MAP2K and MAPK activation	5	24.2×	1e-04
Signaling by RAF1 mutants	5	23.6×	1e-04
Signaling by moderate kinase activity BRAF mutants	5	21.5×	1e-04
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	21.5×	1e-04
Signaling downstream of RAS mutants	5	21.5×	1e-04
Sensory processing of sound by outer hair cells of the cochlea	6	20.7×	1e-04
Signaling by BRAF and RAF1 fusions	6	17.3×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of axon extension	5	34.5×	1e-04
chromatin remodeling	7	6.9×	5e-03
positive regulation of gene expression	9	4.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1575 predictions. Top by Δscore:

Variant	Effect	Δscore
1:40059332:A:AG	acceptor_gain	1.0000
1:40059332:AGCAG:A	acceptor_gain	1.0000
1:40059333:G:GG	acceptor_gain	1.0000
1:40059333:GC:G	acceptor_gain	1.0000
1:40059333:GCA:G	acceptor_gain	1.0000
1:40059333:GCAGG:G	acceptor_gain	1.0000
1:40059454:AAAAG:A	donor_loss	1.0000
1:40059455:AAAGG:A	donor_loss	1.0000
1:40059456:AAGG:A	donor_loss	1.0000
1:40059457:AGGT:A	donor_loss	1.0000
1:40059459:G:GA	donor_loss	1.0000
1:40059460:T:A	donor_loss	1.0000
1:40060065:A:AG	acceptor_gain	1.0000
1:40060066:G:GG	acceptor_gain	1.0000
1:40060066:GCA:G	acceptor_gain	1.0000
1:40060167:ACAT:A	donor_gain	1.0000
1:40060168:CAT:C	donor_gain	1.0000
1:40060169:ATGT:A	donor_loss	1.0000
1:40060170:TG:T	donor_loss	1.0000
1:40060171:G:GA	donor_loss	1.0000
1:40060171:G:GG	donor_gain	1.0000
1:40060172:T:A	donor_loss	1.0000
1:40060176:G:GT	donor_gain	1.0000
1:40061733:A:AG	acceptor_gain	1.0000
1:40061734:G:GG	acceptor_gain	1.0000
1:40061808:CAGAA:C	donor_gain	1.0000
1:40061809:AGAA:A	donor_gain	1.0000
1:40061810:GAA:G	donor_gain	1.0000
1:40061810:GAAG:G	donor_gain	1.0000
1:40061811:AA:A	donor_gain	1.0000

AlphaMissense

3106 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:40064341:A:C	S137R	1.000
1:40064343:T:A	S137R	1.000
1:40064343:T:G	S137R	1.000
1:40064359:T:A	W143R	1.000
1:40064359:T:C	W143R	1.000
1:40064361:G:C	W143C	1.000
1:40064361:G:T	W143C	1.000
1:40064522:T:C	F163L	1.000
1:40064524:T:A	F163L	1.000
1:40064524:T:G	F163L	1.000
1:40066234:T:A	W182R	1.000
1:40066234:T:C	W182R	1.000
1:40066258:T:A	W190R	1.000
1:40066258:T:C	W190R	1.000
1:40069866:T:A	W329R	1.000
1:40069866:T:C	W329R	1.000
1:40060138:A:C	S62R	0.999
1:40060140:T:A	S62R	0.999
1:40060140:T:G	S62R	0.999
1:40064330:C:A	A133D	0.999
1:40064351:C:A	A140D	0.999
1:40064360:G:C	W143S	0.999
1:40064484:C:A	P150H	0.999
1:40064496:T:A	V154E	0.999
1:40064516:G:C	A161P	0.999
1:40064517:C:A	A161D	0.999
1:40064523:T:C	F163S	0.999
1:40064523:T:G	F163C	0.999
1:40064535:G:C	R167P	0.999
1:40064538:T:A	V168D	0.999

dbSNP variants (sampled 300 via entrez): RS1000144800 (1:40050062 A>G), RS1000166165 (1:40069024 A>C,G), RS1000235098 (1:40063631 T>A), RS1000245056 (1:40050507 A>G), RS1000254086 (1:40055874 G>A), RS1000295072 (1:40062150 T>C), RS1000390025 (1:40072890 C>T), RS1000572798 (1:40054455 C>T), RS1000596581 (1:40054395 C>T), RS1000603972 (1:40062551 A>G), RS1000670548 (1:40063861 G>T), RS1000739453 (1:40068373 C>G,T), RS1000808103 (1:40042064 A>G), RS1000903273 (1:40062206 C>T), RS1000913029 (1:40054871 G>C)

Disease associations

OMIM: gene MIM:617801 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_380	Refractive error	4.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067136 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases methylation, affects expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
bisphenol A	decreases expression, affects expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Ozone	increases abundance, affects cotreatment, increases oxidation	2
1-Methyl-4-phenylpyridinium	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
4-hydroxy-2-nonenal	affects binding	1
cupric oxide	decreases expression	1
JP8 aviation fuel	increases expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases 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
CHEMBL5651031	Binding	Binding affinity to human CAP1 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

Clinical trials (associated diseases)

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