CAPZA2

protein-coding

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

Gene summary

The protein encoded by this gene is a member of the F-actin capping protein alpha subunit family. It is the alpha subunit of the barbed-end actin binding protein Cap Z. By capping the barbed end of actin filaments, Cap Z regulates the growth of the actin filaments at the barbed end. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006136.3

Inheritance

ClinVar variants

P:3U:54

Top phenotype

Intellectual disability

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr7:116,811,070-116,922,049

External References & Databases

Ensembl (ENSG00000198898)

Transcript & Mutation Effects

hg38 • Region Span ~111.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CAPZA2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 26

not providedTotal: 22

Intellectual disabilityTotal: 2

Neurodevelopmental disorderTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006136.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense	1 clinvar	2 clinvar	39 clinvar			42
nonsense			2 clinvar			2
start loss			1 clinvar			1
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	1	2	54	0	0	57

Highest pathogenic variant AF is 6.872871e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006136.3	RefSeq	NP_006127.1	10	MANE Select
ENST00000361183.8	Ensembl	ENSP00000354947.2	10	MANE Select
ENST00000426421.5	Ensembl	ENSP00000395395.1	7	Standard
ENST00000449080.5	Ensembl	ENSP00000408150.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Vesicle-mediated transport
Membrane Trafficking
Factors involved in megakaryocyte development and platelet production
Post-translational protein modification

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

Molecular Function

actin filament binding

Cellular Component

extracellular region
cytosol
brush border
F-actin capping protein complex
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361183
Coding exons: 10
Length: 110980
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.84	86	149	0.576	0.00000758	1893
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.221

Intolerance Scores

RVIS EVS: 0.19
RVIS percentile EVS: 66.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.370

Gene Damage Prediction

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