CAPZA1

Summary

CAPZA1 (capping actin protein of muscle Z-line subunit alpha 1, HGNC:1488) is a protein-coding gene on chromosome 1p13.2, encoding F-actin-capping protein subunit alpha-1 (P52907). F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends.

CAPZA1 is a member of the F-actin capping protein alpha subunit family. This gene encodes the alpha subunit of the barbed-end actin binding protein. The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments.

Source: NCBI Gene 829 — RefSeq curated summary.

At a glance

• GWAS associations: 36
• Clinical variants (ClinVar): 70 total
• Druggable target: yes
• MANE Select transcript: NM_006135

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1488
Approved symbol	CAPZA1
Name	capping actin protein of muscle Z-line subunit alpha 1
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	CAPPA1
Ensembl gene	ENSG00000116489
Ensembl biotype	protein_coding
OMIM	601580
Entrez	829

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000263168, ENST00000466066, ENST00000476820, ENST00000476936, ENST00000485542, ENST00000498626, ENST00000904626, ENST00000904627, ENST00000904628, ENST00000904629, ENST00000917725, ENST00000917726, ENST00000917727, ENST00000917728, ENST00000967625

RefSeq mRNA: 1 — MANE Select: NM_006135 NM_006135

CCDS: CCDS30805

Canonical transcript exons

ENST00000263168 — 10 exons

Exon	Start	End
ENSE00001344117	112619832	112619883
ENSE00001929239	112669992	112671616
ENSE00003479895	112654465	112654671
ENSE00003480570	112659022	112659101
ENSE00003488752	112647210	112647273
ENSE00003580903	112653598	112653661
ENSE00003583937	112649418	112649469
ENSE00003602948	112659701	112659779
ENSE00003630790	112667074	112667145
ENSE00003673353	112669543	112669605

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 176.5034 / max 4675.7169, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4688	165.3565	1827
4687	8.1568	1698
4686	2.0986	1254
4684	0.8195	295
4685	0.0719	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	99.33	gold quality
nasopharynx	UBERON:0001728	99.32	gold quality
gingival epithelium	UBERON:0001949	99.08	gold quality
gingiva	UBERON:0001828	98.96	gold quality
bone marrow	UBERON:0002371	98.93	gold quality
pharyngeal mucosa	UBERON:0000355	98.85	gold quality
germinal epithelium of ovary	UBERON:0001304	98.85	gold quality
monocyte	CL:0000576	98.83	gold quality
mononuclear cell	CL:0000842	98.82	gold quality
tongue squamous epithelium	UBERON:0006919	98.80	gold quality
leukocyte	CL:0000738	98.79	gold quality
trabecular bone tissue	UBERON:0002483	98.79	gold quality
upper leg skin	UBERON:0004262	98.75	gold quality
oral cavity	UBERON:0000167	98.74	gold quality
bone element	UBERON:0001474	98.73	gold quality
squamous epithelium	UBERON:0006914	98.67	gold quality
bone marrow cell	CL:0002092	98.66	gold quality
skin of hip	UBERON:0001554	98.66	gold quality
palpebral conjunctiva	UBERON:0001812	98.65	gold quality
esophagus squamous epithelium	UBERON:0006920	98.61	gold quality
penis	UBERON:0000989	98.59	gold quality
caecum	UBERON:0001153	98.57	gold quality
amniotic fluid	UBERON:0000173	98.56	gold quality
vermiform appendix	UBERON:0001154	98.56	gold quality
lower esophagus mucosa	UBERON:0035834	98.52	gold quality
lymph node	UBERON:0000029	98.48	gold quality
colonic mucosa	UBERON:0000317	98.39	gold quality
pylorus	UBERON:0001166	98.39	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.38	gold quality
blood	UBERON:0000178	98.28	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	14285.60
E-MTAB-7249	no	26719.59
E-MTAB-7037	no	431.25
E-MTAB-6524	no	227.63
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

164 targeting CAPZA1, 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-9-5P	100.00	72.28	2361
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-551B-5P	99.96	71.28	3493

Literature-anchored findings (GeneRIF, showing 13)

• V-1, a protein expressed transiently during murine cerebellar development, regulates actin polymerization via interaction with capping protein (PMID:12488317)
• Cd2 antigen is linked to this protein via CMS and CIN85. (PMID:12690097)
• CKIP-1 has a role in cell morphology that depends on its interaction with actin-capping protein (PMID:16987810)
• Damaging exercise induced the expression of capZalpha, MCIP1, CARP1, DNAJB2, c-myc, and junD, each of which are likely involved in skeletal muscle growth, remodeling, and stress management. (PMID:18321953)
• CAPAZA1 is over expressed in malignant melanoma. (PMID:21566537)
• The present study suggests that CAPZA1 could be a marker of good prognosis in gastric cancer and shows that CAPZA1 is associated with decreased cancer cell migration and invasion. (PMID:23545944)
• mDia1 displaced from the barbed end by CapZ Actin Capping Protein can randomly slide along the actin filament and later return. (PMID:26566078)
• Disease causing mutations in inverted formin 2 regulate its binding to G-actin, F-actin capping protein (CapZ alpha-1) and profilin 2. (PMID:26764407)
• Data show that CAPZA1 inhibits EMT in hepatocellular carcinoma (HCC cells by regulating actin cytoskeleton remodeling, thereby reducing the metastatic ability of the cells. (PMID:28093067)
• in CAPZA1-overexpressing gastric epithelial cells infected with H. pylori, autolysosome formation is inhibited and CagA escapes autophagic degradation. (PMID:30176157)
• A barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks. (PMID:34504078)
• Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors. (PMID:34796874)
• Exosome-Delivered circSTAU2 Inhibits the Progression of Gastric Cancer by Targeting the miR-589/CAPZA1 Axis. (PMID:36643863)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	capza1a	ENSDARG00000034240
danio_rerio	capza1b	ENSDARG00000056090
mus_musculus	Capza1b	ENSMUSG00000055357
mus_musculus	Capza1	ENSMUSG00000070372
rattus_norvegicus	4933400A11Rik	ENSRNOG00000003688
rattus_norvegicus	Capza1	ENSRNOG00000013538
drosophila_melanogaster	cpa	FBGN0034577
caenorhabditis_elegans		WBGENE00000292

Paralogs (2): CAPZA3 (ENSG00000177938), CAPZA2 (ENSG00000198898)

Protein

Protein identifiers

F-actin-capping protein subunit alpha-1 — P52907 (reviewed: P52907)

Alternative names: CapZ alpha-1

All UniProt accessions (1): P52907

UniProt curated annotations — full annotation on UniProt →

Function. F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. May play a role in the formation of epithelial cell junctions. Forms, with CAPZB, the barbed end of the fast growing ends of actin filaments in the dynactin complex and stabilizes dynactin structure. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules.

Subunit / interactions. Component of the F-actin capping complex, composed of a heterodimer of an alpha and a beta subunit. Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin. Component of the WASH complex, composed of F-actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-actin-capping protein subunit beta (CAPZB), WASH (WASHC1, WASH2P, WASH3P, WASH4P, WASH5P or WASH6P), WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5. Interacts with S100A. Interacts with S100B. Interacts with SH3BP1; recruits CAPZA1 to forming cell junctions. Interacts with CD2AP. Directly interacts with CRACD; this interaction decreases binding to actin.

Subcellular location. Cytoplasm. Cytoskeleton.

Similarity. Belongs to the F-actin-capping protein alpha subunit family.

RefSeq proteins (1): NP_006126* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002189	CapZ_alpha	Family
IPR017865	F-actin_cap_asu_CS	Conserved_site
IPR037282	CapZ_alpha/beta	Homologous_superfamily
IPR042276	CapZ_alpha/beta_2	Homologous_superfamily
IPR042489	CapZ_alpha_1	Homologous_superfamily

Pfam: PF01267

UniProt features (33 total): strand 11, helix 10, turn 4, modified residue 4, initiator methionine 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
9YIM	ELECTRON MICROSCOPY	2.62
8F8Q	ELECTRON MICROSCOPY	2.79
9Y9L	ELECTRON MICROSCOPY	3.06
9Y9M	ELECTRON MICROSCOPY	3.06
7T5Q	ELECTRON MICROSCOPY	3.4
9EC0	ELECTRON MICROSCOPY	3.4
9B85	ELECTRON MICROSCOPY	3.47
9B7J	ELECTRON MICROSCOPY	3.49
1MQ1	SOLUTION NMR
1MWN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52907-F1	93.19	0.85

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 (4): 2, 9, 19, 97

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic
R-HSA-879415	Advanced glycosylation endproduct receptor signaling
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-2262752	Cellular responses to stress
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9020591	Interleukin-12 signaling
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9659379	Sensory processing of sound
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 299 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_MSN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MORF_SNRP70, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, MORF_HDAC1, HSIAO_HOUSEKEEPING_GENES, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, MORF_HDAC2, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (5): actin cytoskeleton organization (GO:0030036), cell junction assembly (GO:0034329), barbed-end actin filament capping (GO:0051016), protein-containing complex assembly (GO:0065003), actin filament capping (GO:0051693)

GO Molecular Function (4): actin binding (GO:0003779), cadherin binding (GO:0045296), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), cytosol (GO:0005829), cytoskeleton (GO:0005856), F-actin capping protein complex (GO:0008290), actin cytoskeleton (GO:0015629), cortical cytoskeleton (GO:0030863), extracellular exosome (GO:0070062), WASH complex (GO:0071203), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Immune System	3
Adaptive Immune System	1
Cellular responses to stress	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1
Innate Immune System	1
Interleukin-12 signaling	1
Sensory processing of sound	1
Hemostasis	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Cellular responses to stimuli	1
Post-translational protein modification	1
Signaling by Interleukins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular component assembly	2
cytoplasm	2
protein-containing complex	2
cytoskeleton	2
cytoskeleton organization	1
actin filament-based process	1
cell junction organization	1
actin filament capping	1
protein-containing complex organization	1
negative regulation of actin filament depolymerization	1
negative regulation of actin filament polymerization	1
cytoskeletal protein binding	1
cell adhesion molecule binding	1
actin binding	1
protein-containing complex binding	1
binding	1
intracellular membraneless organelle	1
actin cytoskeleton	1
cell cortex	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2266 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPZA1	CAPZB	P47756	985
CAPZA1	TPPP	O94811	893
CAPZA1	TMOD4	Q9NZQ9	885
CAPZA1	NEB	P20929	872
CAPZA1	RCSD1	Q6JBY9	868
CAPZA1	ACTR10	Q9NZ32	822
CAPZA1	DCTN2	Q13561	821
CAPZA1	DCTN1	Q14203	815
CAPZA1	TMOD1	P28289	814
CAPZA1	ACTR3C	Q9C0K3	808
CAPZA1	ACTR3B	Q9P1U1	798
CAPZA1	TMOD3	Q9NYL9	796
CAPZA1	TMOD2	Q9NZR1	791
CAPZA1	CD2AP	Q9Y5K6	771
CAPZA1	DCTN5	Q9BTE1	743

IntAct

279 interactions, top by confidence:

A	B	Type	Score
CNOT7	CNOT1	psi-mi:“MI:0914”(association)	0.880
CNOT6L	CNOT1	psi-mi:“MI:0914”(association)	0.810
DCTN1	DCTN6	psi-mi:“MI:0914”(association)	0.780
CNOT11	CNOT1	psi-mi:“MI:0914”(association)	0.770
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
CAPZA1	CAPZB	psi-mi:“MI:0915”(physical association)	0.740
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
DCTN2	DCTN6	psi-mi:“MI:0914”(association)	0.730
DCTN2	DCTN3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
CAPZB	CNOT1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
S100B	CAPZA1	psi-mi:“MI:0407”(direct interaction)	0.610
CAPZA1	S100B	psi-mi:“MI:0915”(physical association)	0.610
Dctn2	DCTN6	psi-mi:“MI:0914”(association)	0.560

BioGRID (503): CAPZA1 (Affinity Capture-MS), CAPZA1 (Affinity Capture-RNA), CAPZA1 (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), ACTR2 (Co-fractionation), ARHGAP1 (Co-fractionation), ARPC2 (Co-fractionation), CAPZA1 (Co-fractionation), CAPZA1 (Co-fractionation), CAPZA1 (Co-fractionation)

ESM2 similar proteins: A0M8R8, A0M8S9, A0M8V0, A0PFK5, A1X151, A4D7Q3, A4D7S9, A4FUA8, B2GUZ5, P13127, P25229, P28497, P47753, P47754, P47755, P47757, P52907, P79136, Q00PJ7, Q07DV7, Q07DY0, Q07DZ0, Q07E00, Q07E23, Q07E36, Q07E47, Q09YH6, Q09YJ9, Q09YL0, Q09YN4, Q108U5, Q29221, Q2IBA7, Q2IBB9, Q2IBE7, Q2QL78, Q2QL88, Q2QL99, Q2QLA8, Q2QLB9

Diamond homologs: A0M8R8, A0M8S9, A0M8V0, A0PFK5, A1X151, A4D7Q3, A4D7S9, A4FUA8, B2GUZ5, O82631, P13022, P13127, P25229, P28495, P28497, P34685, P47753, P47754, P47755, P52907, P70190, P9WF01, Q00PJ7, Q07DV7, Q07DY0, Q07DZ0, Q07E00, Q07E23, Q07E36, Q07E47, Q09YH6, Q09YJ9, Q09YL0, Q09YN4, Q108U5, Q29221, Q2IBA7, Q2IBB9, Q2IBE7, Q2QL78

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	CAPZA1	phosphorylation
“1D-myo-inositol 1,4,5-trisphosphate”	“down-regulates activity”	CAPZA1	“chemical inhibition”
“phosphatidylinositol bisphosphate”	“down-regulates activity”	CAPZA1	“chemical inhibition”
CAPZA1	“up-regulates quantity”	F-actin_assembly	binding
RCSD1	up-regulates	CAPZA1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 202 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
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	7	27.7×	3e-06
Deadenylation of mRNA	7	23.5×	5e-06
RHO GTPases activate PAKs	5	20.8×	2e-04
M-decay: degradation of maternal mRNAs by maternally stored factors	7	17.4×	3e-05
RHO GTPases activate IQGAPs	6	15.8×	1e-04
Parasite infection	6	15.8×	1e-04
Leishmania phagocytosis	6	15.8×	1e-04
Sensory processing of sound	6	14.1×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA poly(A) tail shortening	7	33.0×	1e-06
barbed-end actin filament capping	6	28.3×	3e-05
regulatory ncRNA-mediated gene silencing	5	19.8×	2e-03
canonical NF-kappaB signal transduction	6	12.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2132 predictions. Top by Δscore:

Variant	Effect	Δscore
1:112619880:GAAG:G	donor_gain	1.0000
1:112619884:G:T	donor_loss	1.0000
1:112619885:T:G	donor_loss	1.0000
1:112647205:TTTA:T	acceptor_loss	1.0000
1:112647207:TA:T	acceptor_loss	1.0000
1:112647208:A:AC	acceptor_loss	1.0000
1:112647208:A:AG	acceptor_gain	1.0000
1:112647208:AG:A	acceptor_gain	1.0000
1:112647209:G:GA	acceptor_gain	1.0000
1:112647209:GG:G	acceptor_gain	1.0000
1:112647209:GGT:G	acceptor_gain	1.0000
1:112647209:GGTA:G	acceptor_gain	1.0000
1:112647209:GGTAC:G	acceptor_gain	1.0000
1:112647261:G:GT	donor_gain	1.0000
1:112647271:ATG:A	donor_gain	1.0000
1:112647272:TG:T	donor_gain	1.0000
1:112647272:TGGT:T	donor_loss	1.0000
1:112647273:GG:G	donor_gain	1.0000
1:112647274:G:GG	donor_gain	1.0000
1:112647275:T:A	donor_loss	1.0000
1:112649465:GCACA:G	donor_gain	1.0000
1:112649468:CA:C	donor_gain	1.0000
1:112649470:G:GG	donor_gain	1.0000
1:112654673:T:G	donor_gain	1.0000
1:112659696:AATAG:A	acceptor_gain	1.0000
1:112659698:TA:T	acceptor_loss	1.0000
1:112659699:A:AG	acceptor_gain	1.0000
1:112659699:A:AT	acceptor_loss	1.0000
1:112659700:G:GC	acceptor_loss	1.0000
1:112659700:G:GG	acceptor_gain	1.0000

AlphaMissense

1921 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:112647220:C:A	A17D	1.000
1:112647229:T:C	F20S	1.000
1:112647241:C:A	A24E	1.000
1:112647243:C:A	P25T	1.000
1:112647244:C:A	P25H	1.000
1:112647244:C:G	P25R	1.000
1:112647247:C:A	P26Q	1.000
1:112647247:C:G	P26R	1.000
1:112647249:G:A	G27R	1.000
1:112647249:G:C	G27R	1.000
1:112647249:G:T	G27W	1.000
1:112647250:G:A	G27E	1.000
1:112647250:G:T	G27V	1.000
1:112649421:T:A	V36D	1.000
1:112649424:G:C	R37P	1.000
1:112649430:T:A	L39Q	1.000
1:112649430:T:C	L39P	1.000
1:112649441:G:C	D43H	1.000
1:112649441:G:T	D43Y	1.000
1:112649442:A:C	D43A	1.000
1:112649442:A:T	D43V	1.000
1:112649451:T:A	L46H	1.000
1:112653624:A:C	Q61P	1.000
1:112659066:T:G	C157W	1.000
1:112659082:T:C	F163L	1.000
1:112659084:T:A	F163L	1.000
1:112659084:T:G	F163L	1.000
1:112659096:C:A	N167K	1.000
1:112659096:C:G	N167K	1.000
1:112659097:T:C	F168L	1.000

dbSNP variants (sampled 300 via entrez): RS1000007271 (1:112641907 T>A), RS1000128397 (1:112634194 T>C), RS1000137429 (1:112618272 T>A,C), RS1000212011 (1:112649572 G>A), RS1000228038 (1:112641491 A>G,T), RS1000344361 (1:112624224 A>T), RS1000459600 (1:112619414 C>CA,CG), RS1000511491 (1:112619190 G>A), RS1000562578 (1:112638895 T>A), RS1000568032 (1:112666884 TCTTAAA>T), RS1000704159 (1:112655124 A>G), RS1000773754 (1:112647370 C>A,G), RS1000798751 (1:112623808 A>G), RS1000864988 (1:112662024 A>T), RS1000923369 (1:112654815 G>A)

Disease associations

OMIM: gene MIM:601580 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST001072_3	Blood pressure	8.000000e-06
GCST001074_5	Blood pressure	1.000000e-08
GCST002647_87	Height	2.000000e-12
GCST003273_2	Diastolic blood pressure	6.000000e-07
GCST003273_5	Diastolic blood pressure	7.000000e-08
GCST004603_165	Platelet count	2.000000e-21
GCST004776_10	Systolic blood pressure	2.000000e-07
GCST004777_46	Diastolic blood pressure	2.000000e-08
GCST005580_14	Intraocular pressure	8.000000e-15
GCST005580_50	Intraocular pressure	2.000000e-12
GCST006258_50	Diastolic blood pressure	9.000000e-10
GCST006259_26	Systolic blood pressure	1.000000e-12
GCST006412_13	Intraocular pressure	6.000000e-10
GCST006614_55	Total cholesterol levels	2.000000e-08
GCST007094_48	Diastolic blood pressure	7.000000e-12
GCST007099_168	Systolic blood pressure	3.000000e-07
GCST007294_13	Body fat distribution (trunk fat ratio)	9.000000e-19
GCST007294_32	Body fat distribution (trunk fat ratio)	1.000000e-08
GCST007295_163	Body fat distribution (leg fat ratio)	8.000000e-07
GCST007295_7	Body fat distribution (leg fat ratio)	7.000000e-16
GCST007576_104	Chronotype	2.000000e-08
GCST007576_308	Chronotype	2.000000e-08
GCST007703_140	Systolic blood pressure	3.000000e-10
GCST007704_23	Diastolic blood pressure	6.000000e-09
GCST007706_87	Mean arterial pressure	9.000000e-11
GCST007707_25	Hypertension	1.000000e-10
GCST010696_10	Cortical thickness (min-P)	6.000000e-41
GCST010697_23	Cortical surface area (min-P)	1.000000e-08
GCST010698_26	Subcortical volume (min-P)	2.000000e-08
GCST010699_12	Brain morphology (min-P)	2.000000e-10

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004309	platelet count
EFO:0004695	intraocular pressure measurement
EFO:0004574	total cholesterol measurement
EFO:0004341	body fat distribution
EFO:0008328	chronotype measurement
EFO:0006340	mean arterial pressure
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295781 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12069113	CAPZA1, MOV10		0.00	0
rs12076902	CAPZA1		0.00	0

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	Kd	305.1	nM	CHEMBL3752910
6.51	ED50	311.5	nM	CHEMBL3752910
5.84	Kd	1457	nM	CHEMBL5653589
5.83	ED50	1487	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 11 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147995: Binding affinity to human CAPZA1 incubated for 45 mins by Kinobead based pull down assay	kd	0.3051	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147995: Binding affinity to human CAPZA1 incubated for 45 mins by Kinobead based pull down assay	kd	1.4571	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Air Pollutants	affects expression, affects cotreatment, increases abundance, increases oxidation	2
Ozone	affects expression, affects cotreatment, increases oxidation, increases abundance	2
Smoke	decreases expression	2
Tretinoin	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
methylselenic acid	decreases expression	1
sodium arsenate	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
ochratoxin A	decreases expression	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
diallyl trisulfide	decreases expression	1
microcystin RR	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
quinocetone	decreases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
bromovanin	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Aspirin	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118959	Binding	Binding affinity to CAPZA1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery