CAPZA3

Summary

CAPZA3 (capping actin protein of muscle Z-line subunit alpha 3, HGNC:24205) is a protein-coding gene on chromosome 12p12.3, encoding F-actin-capping protein subunit alpha-3 (Q96KX2). 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.

This gene encodes an actin capping protein, one of the F-actin capping protein alpha subunit family. The encoded protein is predominantly localized to the neck region of ejaculated sperm, other immunohistochemical signals were found in the tail and postacrosomal regions. The encoded protein may also form heterodimers of alpha and beta subunits. This protein may be important in determining sperm architecture and male fertility.

Source: NCBI Gene 93661 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_033328

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24205
Approved symbol	CAPZA3
Name	capping actin protein of muscle Z-line subunit alpha 3
Location	12p12.3
Locus type	gene with protein product
Status	Approved
Aliases	Gsg3, CAPPA3
Ensembl gene	ENSG00000177938
Ensembl biotype	protein_coding
OMIM	608722
Entrez	93661

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000317658

RefSeq mRNA: 1 — MANE Select: NM_033328 NM_033328

CCDS: CCDS8681

Canonical transcript exons

ENST00000317658 — 1 exons

Exon	Start	End
ENSE00001276948	18738119	18739188

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 97.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1903 / max 179.3122, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124564	0.0904	3
124565	0.0856	3
124563	0.0144	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.56	gold quality
right testis	UBERON:0004534	97.35	gold quality
testis	UBERON:0000473	97.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.90	gold quality
right lobe of liver	UBERON:0001114	60.66	gold quality
skin of abdomen	UBERON:0001416	59.52	gold quality
zone of skin	UBERON:0000014	58.09	gold quality
skin of leg	UBERON:0001511	57.09	gold quality
body of stomach	UBERON:0001161	55.32	gold quality
lower esophagus mucosa	UBERON:0035834	53.90	gold quality
metanephros cortex	UBERON:0010533	52.73	gold quality
stomach	UBERON:0000945	52.45	gold quality
liver	UBERON:0002107	52.16	gold quality
adult mammalian kidney	UBERON:0000082	51.34	gold quality
fundus of stomach	UBERON:0001160	50.86	gold quality
right coronary artery	UBERON:0001625	48.74	gold quality
right uterine tube	UBERON:0001302	48.42	gold quality
kidney	UBERON:0002113	47.09	gold quality
thoracic mammary gland	UBERON:0005200	46.67	gold quality
cortex of kidney	UBERON:0001225	44.92	gold quality
gall bladder	UBERON:0002110	42.89	gold quality
colonic epithelium	UBERON:0000397	42.14	gold quality
cortical plate	UBERON:0005343	40.72	silver quality
esophagus mucosa	UBERON:0002469	39.61	gold quality
body of pancreas	UBERON:0001150	36.76	gold quality
left uterine tube	UBERON:0001303	36.56	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.98	gold quality
skeletal muscle tissue	UBERON:0001134	35.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.95
E-ANND-3	no	1.64

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Capping protein alpha3 may play a physiologically important role in sperm architecture as well as in fertility of the human male. (PMID:12029070)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Capza3	ENSMUSG00000041791
rattus_norvegicus	Capza3	ENSRNOG00000067096
drosophila_melanogaster	cpa	FBGN0034577
caenorhabditis_elegans		WBGENE00000292

Paralogs (2): CAPZA1 (ENSG00000116489), CAPZA2 (ENSG00000198898)

Protein

Protein identifiers

F-actin-capping protein subunit alpha-3 — Q96KX2 (reviewed: Q96KX2)

Alternative names: CapZ alpha-3, Germ cell-specific protein 3

All UniProt accessions (2): Q96KX2, A0A140VKF6

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 morphogenesis of spermatid.

Subunit / interactions. Component of the F-actin capping complex, composed of a heterodimer of an alpha and a beta subunit. 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.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed exclusively in testis and sperm. Highest expression is found in the neck region of ejaculated sperm with lower levels found in the tail and postacrosome region.

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

RefSeq proteins (1): NP_201585* (*=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 (3 total): chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KX2-F1	89.01	0.74

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 (1): 290

Function

Pathways and Gene Ontology

Reactome pathways

17 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-1280218	Adaptive 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-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-948021	Transport to the Golgi and subsequent modification

MSigDB gene sets: 108 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, KORKOLA_CHORIOCARCINOMA_DN, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, GOBP_MALE_GAMETE_GENERATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, KORKOLA_EMBRYONAL_CARCINOMA_DN

GO Biological Process (6): actin filament organization (GO:0007015), cytoplasm organization (GO:0007028), spermatid development (GO:0007286), actin cytoskeleton organization (GO:0030036), barbed-end actin filament capping (GO:0051016), actin filament capping (GO:0051693)

GO Molecular Function (2): actin filament binding (GO:0051015), actin binding (GO:0003779)

GO Cellular Component (8): nucleus (GO:0005634), cytosol (GO:0005829), F-actin capping protein complex (GO:0008290), membrane (GO:0016020), cortical cytoskeleton (GO:0030863), sperm head (GO:0061827), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Membrane Trafficking	2
Adaptive Immune System	1
Cellular responses to stress	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1
Immune System	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Cellular responses to stimuli	1
Post-translational protein modification	1
Metabolism of proteins	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
actin cytoskeleton organization	1
supramolecular fiber organization	1
cellular component organization	1
germ cell development	1
spermatid differentiation	1
cytoskeleton organization	1
actin filament-based process	1
actin filament capping	1
negative regulation of actin filament depolymerization	1
negative regulation of actin filament polymerization	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
actin cytoskeleton	1
protein-containing complex	1
cytoskeleton	1
cell cortex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPZA3	TMOD4	Q9NZQ9	963
CAPZA3	PLCZ1	Q86YW0	625
CAPZA3	CAPZB	P47756	552
CAPZA3	SPACA1	Q9HBV2	492
CAPZA3	ROPN1	Q9HAT0	483
CAPZA3	C22orf23	Q9BZE7	476
CAPZA3	TSSK1B	Q9BXA7	465
CAPZA3	ACTR6	Q9GZN1	461
CAPZA3	CABS1	Q96KC9	460
CAPZA3	GARIN1B	Q96KD3	445
CAPZA3	ACTRT2	Q8TDY3	444
CAPZA3	ODF1	Q14990	431
CAPZA3	DPY19L2	Q6NUT2	430
CAPZA3	FAM170B	A6NMN3	427
CAPZA3	TSSK6	Q9BXA6	421

IntAct

0 interactions, top by confidence:

BioGRID (1): CAPZA3 (Proximity Label-MS)

ESM2 similar proteins: A0A7H0DNF0, A1A5R7, B7F7B9, B9A014, F1MIW6, F4HZD1, F4JLK2, O14138, O14423, O23702, O60106, P0DSU9, P0DSV0, P24915, P34751, P36052, P38960, P49777, P52924, P70190, P86452, Q196W7, Q1L6Q1, Q4R7M8, Q5Q0E6, Q6IND4, Q6TEQ0, Q80HX3, Q80TC5, Q84RQ9, Q8CDS7, Q8CFL8, Q8L7T6, Q8QMP8, Q8V4S4, Q96KX2, Q9BR11, Q9DCE9, Q9FFN9, Q9FFP1

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

189 predictions. Top by Δscore:

Variant	Effect	Δscore
12:18738757:A:T	donor_gain	0.8300
12:18738801:T:G	donor_gain	0.5800
12:18738932:GCTC:G	donor_gain	0.5800
12:18738828:G:GT	donor_gain	0.5600
12:18738778:G:GT	donor_gain	0.5500
12:18738828:G:T	donor_gain	0.5500
12:18738779:A:T	donor_gain	0.5400
12:18738854:TTCAG:T	donor_loss	0.5400
12:18738855:TCAG:T	donor_loss	0.5400
12:18738857:AGG:A	donor_loss	0.5400
12:18738858:GG:G	donor_loss	0.5400
12:18738860:T:G	donor_loss	0.5300
12:18738931:GGCTC:G	donor_gain	0.5200
12:18738546:A:G	acceptor_gain	0.5000
12:18738756:G:GT	donor_gain	0.5000
12:18738708:G:GG	donor_gain	0.4800
12:18738840:TGCAA:T	acceptor_gain	0.4700
12:18738841:GCAAG:G	acceptor_gain	0.4700
12:18738842:CAAGC:C	acceptor_gain	0.4700
12:18738550:T:G	acceptor_gain	0.4600
12:18738652:T:G	acceptor_gain	0.4500
12:18738935:C:CG	donor_gain	0.4500
12:18738938:A:G	acceptor_gain	0.4400
12:18739003:G:GT	donor_gain	0.4400
12:18738710:AAGG:A	donor_gain	0.4300
12:18738711:AGGA:A	donor_gain	0.4300
12:18738712:GGAG:G	donor_gain	0.4300
12:18738767:A:T	donor_gain	0.4300
12:18738702:TCAA:T	donor_gain	0.4200
12:18738843:AAGC:A	acceptor_gain	0.4200

AlphaMissense

1991 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:18738788:T:A	W174R	0.996
12:18738788:T:C	W174R	0.996
12:18738782:T:C	S172P	0.993
12:18739075:G:C	W269C	0.993
12:18739075:G:T	W269C	0.993
12:18739073:T:A	W269R	0.992
12:18739073:T:C	W269R	0.992
12:18738542:T:C	F92L	0.991
12:18738544:C:A	F92L	0.991
12:18738544:C:G	F92L	0.991
12:18738515:T:C	F83L	0.990
12:18738517:T:A	F83L	0.990
12:18738517:T:G	F83L	0.990
12:18739042:G:C	R258S	0.990
12:18739042:G:T	R258S	0.990
12:18738543:T:C	F92S	0.989
12:18738790:G:C	W174C	0.989
12:18738790:G:T	W174C	0.989
12:18738776:T:A	W170R	0.988
12:18738776:T:C	W170R	0.988
12:18738783:C:T	S172F	0.985
12:18738854:T:C	F196L	0.984
12:18738856:C:A	F196L	0.984
12:18738856:C:G	F196L	0.984
12:18738868:C:A	N200K	0.984
12:18738868:C:G	N200K	0.984
12:18738483:T:C	L72S	0.983
12:18738966:A:T	E233V	0.982
12:18738347:T:C	F27L	0.981
12:18738349:T:A	F27L	0.981

dbSNP variants (sampled 300 via entrez): RS1002777400 (12:18739526 A>G,T), RS1002857290 (12:18738275 C>A,T), RS1002995382 (12:18738563 A>C), RS1004405209 (12:18736817 T>G), RS1006289730 (12:18738035 C>T), RS1006330566 (12:18738229 A>G), RS1006602063 (12:18738928 A>G,T), RS1009057068 (12:18736168 T>A,C), RS1009421336 (12:18737649 C>T), RS1009601724 (12:18736463 A>AT), RS1011167352 (12:18737655 A>C,G), RS1013518420 (12:18736797 A>G), RS1014591179 (12:18736520 T>C), RS1014623736 (12:18736754 G>C), RS1015310479 (12:18736818 T>A)

Disease associations

OMIM: gene MIM:608722 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002111_7	Personality dimensions	8.000000e-06
GCST003518_20	Daytime sleep phenotypes	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
bisphenol A	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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