CAP2

Summary

CAP2 (cyclase associated actin cytoskeleton regulatory protein 2, HGNC:20039) is a protein-coding gene on chromosome 6p22.3, encoding Adenylyl cyclase-associated protein 2 (P40123). Involved in the regulation of actin polymerization.

This gene was identified by its similarity to the gene for human adenylyl cyclase-associated protein. The function of the protein encoded by this gene is unknown. However, the protein appears to be able to interact with adenylyl cyclase-associated protein and actin.

Source: NCBI Gene 10486 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardiomyopathy, dilated, 2I (Moderate, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 90 total — 3 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 18 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.76 (unconstrained)
• MANE Select transcript: NM_006366
• Notable: 90 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20039
Approved symbol	CAP2
Name	cyclase associated actin cytoskeleton regulatory protein 2
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000112186
Ensembl biotype	protein_coding
OMIM	618385
Entrez	10486

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 30 protein_coding, 11 nonsense_mediated_decay

MANE Select: ENST00000229922

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

ENST00000229922, ENST00000378990, ENST00000465994, ENST00000476263, ENST00000479291, ENST00000489374, ENST00000493172, ENST00000857692, ENST00000857693, ENST00000857694, ENST00000857695, ENST00000857696, ENST00000857697, ENST00000857698, ENST00000857699, ENST00000857700, ENST00000857701, ENST00000857702, ENST00000857703, ENST00000940429, ENST00000940430, ENST00000940431, ENST00000940432, ENST00000950865, ENST00000950866, ENST00000950867, ENST00000950868, ENST00000950869, ENST00000993372, ENST00001019685, ENST00001019687, ENST00001019688, ENST00001019689, ENST00001019692, ENST00001019695, ENST00001101063, ENST00001101064, ENST00001109932, ENST00001128401, ENST00001128402, ENST00001135266

RefSeq mRNA: 3 — MANE Select: NM_006366 NM_001363533, NM_001363534, NM_006366

CCDS: CCDS4539, CCDS87368, CCDS87369

Canonical transcript exons

ENST00000229922 — 13 exons

Exon	Start	End
ENSE00000686699	17426590	17426690
ENSE00000686701	17462996	17463073
ENSE00000848098	17421555	17421676
ENSE00000848103	17551464	17551604
ENSE00001825170	17556359	17557780
ENSE00003461779	17513849	17513954
ENSE00003481786	17540973	17541148
ENSE00003483910	17543061	17543143
ENSE00003487575	17542837	17542960
ENSE00003533357	17539269	17539458
ENSE00003638289	17507641	17507726
ENSE00003690217	17507169	17507312
ENSE00003746630	17393595	17393746

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.4061 / max 480.9291, expressed in 1309 samples.

Highest expression (Bgee): skeletal muscle tissue of biceps brachii, biceps brachii, Brodmann (1909) area 23, skeletal muscle tissue of rectus abdominis, vastus lateralis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CAP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	6.8e-98	-0.73	6:17394210:C:G
Muscle Skeletal	sqtl	5.2e-50	+1.16	6:17508782:A:G
Adrenal Gland	eqtl	5.7e-10	-0.34	6:17391808:C:A
Heart Atrial Appendage	eqtl	2.9e-08	-0.15	6:17391554:A:C
Adipose Subcutaneous	eqtl	3.4e-06	-0.13	6:17391554:A:C
Pancreas	eqtl	1.1e-05	+0.34	6:17405857:C:T
Artery Aorta	eqtl	2.3e-05	-0.15	6:17393872:T:G
Brain Cerebellum	eqtl	3.2e-05	+0.23	6:17405120:C:T
Nerve Tibial	eqtl	3.3e-05	-0.12	6:17361042:T:C
Skin Sun Exposed Lower leg	eqtl	1.7e-04	+0.29	6:17467815:A:C
Artery Tibial	eqtl	2.8e-04	+0.07	6:17542073:T:G
Thyroid	eqtl	3.0e-03	+0.13	6:17432604:C:T
Esophagus Muscularis	eqtl	5.6e-03	+0.08	6:17386807:T:G
Heart Left Ventricle	eqtl	8.0e-03	+0.49	6:17549409:G:A
Brain Cerebellar Hemisphere	eqtl	1.0e-02	+0.14	6:17404947:T:A
Lung	eqtl	1.0e-02	-0.13	6:17393550:T:TC
Spleen	eqtl	1.8e-02	+0.17	6:17446864:G:A
Adipose Visceral Omentum	eqtl	2.0e-02	+0.44	6:17177315:A:G
Liver	eqtl	4.3e-02	-0.22	6:17415833:G:A

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
66145	10.0223	1279
66143	2.3313	784
66144	0.9874	430
66142	0.8509	349
66139	0.5920	275
66141	0.4580	222
66140	0.1644	71

Top tissues by expression

showing 100 of 300 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.44	gold quality
biceps brachii	UBERON:0001507	99.43	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.38	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.35	gold quality
vastus lateralis	UBERON:0001379	99.32	gold quality
quadriceps femoris	UBERON:0001377	99.27	gold quality
endothelial cell	CL:0000115	99.25	gold quality
skeletal muscle tissue	UBERON:0001134	99.16	gold quality
gluteal muscle	UBERON:0002000	99.15	gold quality
deltoid	UBERON:0001476	99.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.02	gold quality
gastrocnemius	UBERON:0001388	98.98	gold quality
frontal pole	UBERON:0002795	98.90	gold quality
tibialis anterior	UBERON:0001385	98.72	gold quality
triceps brachii	UBERON:0001509	98.66	gold quality
muscle organ	UBERON:0001630	98.58	gold quality
skeletal muscle organ	UBERON:0014892	98.58	gold quality
middle temporal gyrus	UBERON:0002771	98.54	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.52	gold quality
diaphragm	UBERON:0001103	98.41	gold quality
primary visual cortex	UBERON:0002436	98.34	gold quality
muscle of leg	UBERON:0001383	98.33	gold quality
orbitofrontal cortex	UBERON:0004167	98.06	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.06	gold quality
muscle tissue	UBERON:0002385	97.80	gold quality
superior frontal gyrus	UBERON:0002661	97.78	gold quality
occipital lobe	UBERON:0002021	97.49	gold quality
heart right ventricle	UBERON:0002080	97.47	gold quality
prefrontal cortex	UBERON:0000451	97.13	gold quality
entorhinal cortex	UBERON:0002728	97.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.87	gold quality
postcentral gyrus	UBERON:0002581	96.86	gold quality
parietal lobe	UBERON:0001872	96.77	gold quality
blood vessel layer	UBERON:0004797	96.76	gold quality
body of tongue	UBERON:0011876	96.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.46	gold quality
CA1 field of hippocampus	UBERON:0003881	96.36	gold quality
cortical plate	UBERON:0005343	96.30	gold quality
cerebral cortex	UBERON:0000956	96.25	gold quality
frontal lobe	UBERON:0016525	96.17	gold quality
frontal cortex	UBERON:0001870	96.16	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.14	gold quality
left ventricle myocardium	UBERON:0006566	96.12	gold quality
neocortex	UBERON:0001950	96.06	gold quality
myocardium	UBERON:0002349	95.84	gold quality
Ammon’s horn	UBERON:0001954	95.68	gold quality
cingulate cortex	UBERON:0003027	95.51	gold quality
anterior cingulate cortex	UBERON:0009835	95.51	gold quality
telencephalon	UBERON:0001893	94.84	gold quality
temporal lobe	UBERON:0001871	94.79	gold quality
cardiac ventricle	UBERON:0002082	94.27	gold quality
heart left ventricle	UBERON:0002084	94.19	gold quality
popliteal artery	UBERON:0002250	94.09	gold quality
tibial artery	UBERON:0007610	94.09	gold quality
secondary oocyte	CL:0000655	93.97	gold quality
choroid plexus epithelium	UBERON:0003911	93.94	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.84	gold quality
right coronary artery	UBERON:0001625	93.62	gold quality
heart	UBERON:0000948	93.44	gold quality
amygdala	UBERON:0001876	93.37	gold quality
bronchial epithelial cell	CL:0002328	93.12	gold quality
nucleus accumbens	UBERON:0001882	93.03	gold quality
right frontal lobe	UBERON:0002810	92.92	gold quality
caudate nucleus	UBERON:0001873	92.86	gold quality
forebrain	UBERON:0001890	92.74	gold quality
middle frontal gyrus	UBERON:0002702	92.59	gold quality
cardiac atrium	UBERON:0002081	92.31	gold quality
right atrium auricular region	UBERON:0006631	92.13	gold quality
aorta	UBERON:0000947	92.03	gold quality
putamen	UBERON:0001874	92.01	gold quality
ganglionic eminence	UBERON:0004023	91.89	gold quality
smooth muscle tissue	UBERON:0001135	91.86	gold quality
brain	UBERON:0000955	91.64	gold quality
adult organism	UBERON:0007023	91.49	gold quality
cerebellar vermis	UBERON:0004720	91.47	gold quality
saphenous vein	UBERON:0007318	91.31	gold quality
central nervous system	UBERON:0001017	91.13	gold quality
pons	UBERON:0000988	91.10	gold quality
ventricular zone	UBERON:0003053	91.00	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.29	gold quality
seminal vesicle	UBERON:0000998	90.26	gold quality
hypothalamus	UBERON:0001898	90.26	gold quality
coronary artery	UBERON:0001621	90.12	gold quality
left coronary artery	UBERON:0001626	90.06	gold quality
apex of heart	UBERON:0002098	89.67	gold quality
parietal pleura	UBERON:0002400	89.62	gold quality
pigmented layer of retina	UBERON:0001782	89.55	gold quality
retina	UBERON:0000966	89.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.46	gold quality
ascending aorta	UBERON:0001496	89.42	gold quality
lower esophagus	UBERON:0013473	89.40	gold quality
epithelium of bronchus	UBERON:0002031	89.38	gold quality
thoracic aorta	UBERON:0001515	89.33	gold quality
stromal cell of endometrium	CL:0002255	89.04	gold quality
tongue	UBERON:0001723	88.76	gold quality
paraflocculus	UBERON:0005351	88.70	gold quality
bronchus	UBERON:0002185	88.63	gold quality
cauda epididymis	UBERON:0004360	88.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.27	gold quality
descending thoracic aorta	UBERON:0002345	88.03	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	3013.46
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 155 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	539.5	medium
Tongue	tissue	291.8
Cerebral cortex	tissue	229.0	medium
Somatosensory cortex	tissue	229.0
Prefrontal cortex	tissue	219.6
Occipital cortex	tissue	218.9
Motor cortex	tissue	206.2
Hippocampal formation	tissue	200.7
Entorhinal cortex	tissue	200.7
Temporal cortex	tissue	193.0
Retrosplenial and cingulate cortex	tissue	180.2
Frontal cortex	tissue	173.1
Basal ganglia	tissue	169.6	high
Putamen	tissue	158.6
Caudate putamen	tissue	157.2
Insular cortex	tissue	153.2
Retrosplenial cortex	tissue	151.1
Postcentral gyrus	tissue	144.4
Ventral forebrain	tissue	128.2
Hippocampus	tissue	114.7	high
Heart muscle	tissue	106.3	high
Cerebellum	tissue	90.1	high
Amygdala	tissue	89.5
Septum	tissue	88.5
Urinary bladder	tissue	69.6	medium
Nucleus accumbens	tissue	63.1
Thalamus	tissue	62.8
Midbrain	tissue	53.8
Superior colliculi	tissue	52.4
Locus coeruleus	tissue	45.7
Pons	tissue	45.6
Colon	tissue	40.8	medium
Rectum	tissue	40.3	medium
Smooth muscle	tissue	39.8	medium
Choroid plexus	tissue	38.3
Hypothalamus	tissue	37.4
Substantia nigra	tissue	32.8
Esophagus	tissue	32.3	medium
Medulla oblongata	tissue	30.1
Stomach 1	tissue	29.6	medium
Seminal vesicle	tissue	28.8	not detected
Olfactory bulb	tissue	28.6
Endometrium 1	tissue	26.5	not detected
Spinal cord	tissue	24.0
Duodenum	tissue	23.9	medium
Prostate	tissue	23.5	not detected
Periaqueductal gray	tissue	22.9
Small intestine	tissue	21.1	medium
Esophagus	tissue	20.4	not detected
Corpus callosum	tissue	19.9
Epididymis	tissue	16.8	not detected
Adipose tissue	tissue	16.7	not detected
Fallopian tube	tissue	15.8	not detected
Vagina	tissue	15.7	medium
Cervix	tissue	15.6
Cervix	tissue	14.4	not detected
Tonsil	tissue	14.0	medium
Gallbladder	tissue	13.4	medium
Urinary bladder	tissue	13.2	not detected
Adrenal gland	tissue	10.9	low

Brain sub-regions (HPA Brain Atlas): detected in 479; highest nTPM — Dorsal hippocampus (185.5), Posterior cingulate cortex (165.3), Hippocampus, CA1 (149.6), Hippocampus, CA3 (146.4), Ventral hippocampus (139.2).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 0.00309, LOEUF 0.763, missense Z 1.31 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000229922 — one region, missense o/e 0.85.

Literature-anchored findings (GeneRIF, showing 13)

• CAP2 is up-regulated in human cancers and that is possibly related to multistage hepatocarcinogenesis. (PMID:17000669)
• An important conserved function of CAP2 in higher vertebrates may be associated with the process of skeletal muscle development. (PMID:23022774)
• CAP2 overexpression is a novel prognostic marker in malignant melanoma. CAP2 expression seems to increase stepwise during tumor progression, suggesting the involvement of CAP2 in the aggressive behavior of malignant melanoma. (PMID:26374196)
• CAP2 is upregulated in breast cancer and is associated with the expression of progesterone receptor and patient survival (PMID:27573674)
• CAP2 is a Valuable Biomarker for Diagnosis and Prognostic in Patients with Gastric Cancer. (PMID:30047046)
• CAP2 joins other regulators of actin dynamics demonstrated to cause human genetic diseases. Our study is the first to demonstrate a mutation in CAP2 in human and a direct role for mutated CAP2 and perturbation of actin dynamics in the pathogenesis of DCM and possibly also conduction abnormalities in humans. (PMID:30518548)
• CAP2 is highly expressed in gastric cancer tissues in close relation with the tumor progression. CAP2 is an independent risk factor for 5-year survival rate after radical gastrectomy for gastric cancer. (PMID:31640951)
• Study used lysine-to-glutamine mutations to map the relevant lysines on actin for INF2 regulation. K50Q- and K61Q-actin, when bound to CAP2, inhibit full-length INF2 but not INF2 lacking inhibitory domain (DID). CAP WH2 domain binds INF2-DID with submicromolar affinity but has weak affinity for actin monomers, while INF2-C-terminal diaphanous autoregulatory domain binds CAP/K50Q-actin 5-fold better than CAP/WT-actin. (PMID:31871199)
• CAP2 expression in ovarian cancer is an independent prognostic factor for recurrence-free survival. (PMID:32211793)
• Endoplasmic Reticulum Stress Induces CAP2 Expression Promoting Epithelial-Mesenchymal Transition in Liver Cancer Cells. (PMID:34294609)
• Analysis of mRNA and Protein Levels of CAP2, DLG1 and ADAM10 Genes in Post-Mortem Brain of Schizophrenia, Parkinson’s and Alzheimer’s Disease Patients. (PMID:35163460)
• An association study of cyclase-associated protein 2 and frailty. (PMID:37537790)
• CAP2 contributes to Parkinson’s disease diagnosed by neutrophil extracellular trap-related immune activity. (PMID:38846945)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cap2	ENSDARG00000104478
mus_musculus	Cap2	ENSMUSG00000021373
rattus_norvegicus	Cap2	ENSRNOG00000043350
drosophila_melanogaster	capt	FBGN0261458
caenorhabditis_elegans		WBGENE00000294
caenorhabditis_elegans	cas-2	WBGENE00015975

Paralogs (1): CAP1 (ENSG00000131236)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914502) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 50 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	3
prolonged QT interval	3
premature death	2
dilated cardiomyopathy	2
decreased heart rate	2
prolonged QRS complex duration	2
prolonged RR interval	2
postnatal lethality, incomplete penetrance	2
abnormal heart morphology	1
enlarged heart	1
microphthalmia	1
cataract	1
small pupil	1
postnatal growth retardation	1
eye inflammation	1
increased susceptibility to infection	1
decreased circulating triglyceride level	1
dilated heart left ventricle	1
decreased aerobic running capacity	1
abnormal impulse conducting system conduction	1
dilated heart atrium	1
cardiac fibrosis	1
abnormal locomotor activation	1
increased heart rate variability	1
dilated heart right atrium	1

+25 more (showing top 25).

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
Pongo abelii	Q5R5X8	98.1%	Diamond
Macaca fascicularis	Q4R4I6	97.1%	Diamond
Bos taurus	Q3SYV4	92.0%	Diamond
Sus scrofa	P40125	48.4%	Diamond
Hydra viridissima	P40122	40.4%	Diamond
Dictyostelium discoideum	P54654	39.1%	Diamond
Arabidopsis thaliana	O65902	38.5%	Diamond
Saccharomyces cerevisiae S288C	P17555	37.9%	Diamond
Schizosaccharomyces pombe 972h-	P36621	37.2%	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
RBM24	protein-coding	221662
STMND1	protein-coding	401236
FAM8A1	protein-coding	51439
NUP153	protein-coding	9972

Protein

Protein identifiers

Adenylyl cyclase-associated protein 2 — P40123 (reviewed: P40123)

All UniProt accessions (5): P40123, B7Z385, E9PDI2, F8WDB9, F8WEW0

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of actin polymerization.

Subcellular location. Cell membrane.

Disease relevance. Cardiomyopathy, dilated, 2I (CMD2I) [MIM:620462] A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2I is an autosomal recessive, severe form characterized by onset in infancy or childhood. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CAP family.

Isoforms (3)

UniProt ID	Names	Canonical?
P40123-1	1	yes
P40123-2	2
P40123-3	3

RefSeq proteins (3): NP_001350462, NP_001350463, NP_006357* (*=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 (15 total): sequence variant 3, modified residue 3, splice variant 2, region of interest 2, compositionally biased region 2, initiator methionine 1, chain 1, domain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40123-F1	83.78	0.66

Human Protein Atlas

Protein class: Predicted intracellular proteins, Cancer-related genes, Mutated cancer genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm; plasma membrane

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3)

Type	Positions
N-acetylalanine	2
Phosphoserine	301, 309

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-422475	Axon guidance	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9675108	Nervous system development	—
R-HSA-428890	Role of ABL in ROBO-SLIT signaling	electronic
R-HSA-376176	Signaling by ROBO receptors	—

MSigDB gene sets: 225 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, MODULE_52, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOZGIT_ESR1_TARGETS_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, PATIL_LIVER_CANCER, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_ADENYLATE_CYCLASE_ACTIVITY, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1

GO Biological Process (7): cell morphogenesis (GO:0000902), actin filament organization (GO:0007015), establishment or maintenance of cell polarity (GO:0007163), signal transduction (GO:0007165), activation of adenylate cyclase activity (GO:0007190), presynaptic actin cytoskeleton organization (GO:0099140), cytoskeleton organization (GO:0007010)

GO Molecular Function (4): actin binding (GO:0003779), adenylate cyclase binding (GO:0008179), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), postsynaptic density (GO:0014069)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Signaling by ROBO receptors	1
Axon guidance	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

21 GO namespaces:

Category	Terms
actin cytoskeleton organization	2
cellular process	2
anatomical structure morphogenesis	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
presynaptic cytoskeleton organization	1
organelle organization	1
cytoskeletal protein binding	1
enzyme binding	1
protein binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 740 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAP2	WDR1	O75083	429
CAP2	PRRT1B	A0A1B0GWB2	411
CAP2	TWF2	Q6IBS0	405
CAP2	JDP2	Q8WYK2	370
CAP2	PFN4	Q8NHR9	368
CAP2	TWF1	Q12792	363
CAP2	CDC123	O75794	323
CAP2	CGA	P01215	313
CAP2	CFL2	Q9Y281	303
CAP2	PPIH	O43447	302
CAP2	STMND1	H3BQB6	300
CAP2	PPIL1	Q9Y3C6	300
CAP2	PPIL4	Q8WUA2	295
CAP2	CFL1	P23528	294
CAP2	SUN2	Q9UH99	293

IntAct

Human interaction partners of CAP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

19 partners by confidence:

Partner	Interaction type	MIscore	Records
ACTG1	physical association	0.860	12
ACTB	physical association	0.820	4
CFL1	association	0.640	2
TWF2	association	0.640	2
ACT1	physical association	0.560	3
ADO	physical association	0.560	3
AIP1	physical association	0.560	3
ALAS1	physical association	0.560	3
CFL2	physical association	0.560	3
GRXCR1	physical association	0.560	3
PS1TP5BP1	physical association	0.560	3
POTEI	association	0.530	2
PRPF40A	physical association	0.370	1
POTEF	association	0.350	1
DISC1	physical association	0.000	1
DSCAM	physical association	0.000	1
FMR1	physical association	0.000	1
PSPH	physical association	0.000	1
YWHAE	physical association	0.000	1

BioGRID (108 interactions; top human partners by supporting records): ACTB (Two-hybrid; 8 records), ACTG1 (Two-hybrid; 6 records), CFL1 (Affinity Capture-MS; 5 records), CAP1 (Affinity Capture-MS; 4 records), ACTA2 (Affinity Capture-MS; 3 records), ACTC1 (Affinity Capture-MS; 3 records), ACTA1 (Affinity Capture-MS; 2 records), ACTBL2 (Affinity Capture-MS; 2 records), BCL7A (Affinity Capture-MS; 2 records), BCL7C (Affinity Capture-MS; 2 records), POTEI (Affinity Capture-MS; 2 records), TWF2 (Affinity Capture-MS; 2 records), ADO (Two-hybrid), AGO2 (Affinity Capture-RNA), ALAS1 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for CAP2: 90 ClinVar records (4 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	73
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (4)

Showing all 4 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
4845338	NM_006366.3(CAP2):c.870del (p.Ser291fs)	Likely pathogenic	criteria provided, single submitter	1
2574649	NM_006366.3(CAP2):c.636+1G>A	Pathogenic	no assertion criteria provided	1
2574650	NM_006366.3(CAP2):c.948T>G (p.Tyr316Ter)	Pathogenic	no assertion criteria provided	1
2574651	NM_006366.3(CAP2):c.1288del (p.Cys430fs)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CAP2’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.

AlphaMissense

962 missense substitutions predicted likely pathogenic (of 3,147 scored), across 253 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
M159	9	0.892	0.981
F165	8	0.962	1.000
H132	8	0.935	0.993
F264	8	0.917	0.970
N441	8	0.883	0.984
D376	8	0.868	0.937
D161	8	0.852	0.972
H181	8	0.804	0.951
F82	8	0.776	0.980
W145	7	0.997	1.000
W184	7	0.994	0.999
W209	7	0.987	0.998
W332	7	0.985	0.998
F130	7	0.981	0.997
E138	7	0.980	0.994
R169	7	0.974	1.000
F60	7	0.962	0.990
S139	7	0.957	1.000
F49	7	0.938	0.976
S137	7	0.932	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.39e-06
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000137
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	0.000726

Disease associations

OMIM: gene MIM:618385 | disease phenotypes: MIM:620462

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
cardiomyopathy, dilated, 2I	Moderate	Autosomal recessive
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Paediatric or syndromic cardiomyopathy	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (2): cardiomyopathy, dilated, 2I (MONDO:0957545), (MONDO:0015470)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	8
Acetaminophen	decreases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression, increases expression	2
entinostat	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Nickel	decreases expression	2
Dronabinol	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
decabromobiphenyl ether	decreases expression	1
trimellitic anhydride	decreases expression	1
afimoxifene	decreases reaction, increases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
chloropicrin	increases expression	1
AM 251	decreases expression	1
corosolic acid	increases expression	1
K 7174	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1

Clinical trials (associated diseases)

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