CAPZA2

capping actin protein of muscle Z-line subunit alpha 2, the group of Dynactin subunits

Basic information

Region (hg38): 7:116811070-116922049

Links

ENSG00000198898 ∙ NCBI:830 ∙ OMIM:601571 ∙ HGNC:1490 ∙ Uniprot:P47755 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAPZA2 gene.

• not_specified (22 variants)
• not_provided (20 variants)
• Intellectual_disability (2 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAPZA2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006136.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense	1	2	31			34
nonsense			1			1
start loss			1			1
frameshift			3			3
splice donor/acceptor (+/-2bp)			3			3
Total	1	2	39	0	0

Highest pathogenic variant AF is 6.872871e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAPZA2	protein_coding	protein_coding	ENST00000361183	10	110980

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00172	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.84	86	149	0.576	0.00000758	1893
Missense in Polyphen		7	40.841	0.17139		564
Synonymous	1.56	35	48.9	0.716	0.00000244	493
Loss of Function	3.99	0	18.6	0.00	8.50e-7	230

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Pathway: Endocytosis - Homo sapiens (human);Vesicle-mediated transport;Membrane Trafficking;Factors involved in megakaryocyte development and platelet production;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Hemostasis;COPI-independent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;COPI-mediated anterograde transport;Advanced glycosylation endproduct receptor signaling;ER to Golgi Anterograde Transport;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.221

Intolerance Scores

• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.82

Haploinsufficiency Scores

• pHI: 0.524
• hipred: Y
• hipred_score: 0.725
• ghis: 0.475

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.370

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Capza2
• Phenotype: normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; skeleton phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• Biological process: endoplasmic reticulum to Golgi vesicle-mediated transport;blood coagulation;antigen processing and presentation of exogenous peptide antigen via MHC class II;actin cytoskeleton organization;innate immune response;barbed-end actin filament capping;protein-containing complex assembly
• Cellular component: extracellular region;cytosol;brush border;F-actin capping protein complex;actin cytoskeleton;membrane;actin cortical patch;extracellular exosome
• Molecular function: actin filament binding