CAPZA2

Chr 7

capping actin protein of muscle Z-line subunit alpha 2

Also known as: CAPPA2, CAPZ

NCBI Gene: 830ENSG00000198898UniProt: P47755

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]

83
ClinVar variants
28
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CAPZA2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 54 VUS of 83 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.16LOEUF
pLI 0.998
Z-score 3.99
OE 0.00 (0.00–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.84Z-score
OE missense 0.58 (0.48–0.69)
86 obs / 149.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.58 (0.48–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.72
0≤1.21.6
LoF obs/exp: 0 / 18.6Missense obs/exp: 86 / 149.3Syn Z: 1.56

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic3
VUS54
Conflicting1
25
Pathogenic
3
Likely Pathogenic
54
VUS
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
1
2
0
3
VUS
7
36
11
0
54
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Conflicting
—1
Total73738083

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CAPZA2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.
Zhang XM et al.·J Hum Genet
2024Review
Molecular-assisted immunohistochemical optimization.
Mohd Omar MF et al.·Acta Histochem
2010
Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations.
Klubíčková N et al.·J Pathol
2024
WNT2B: comparative integromics and clinical applications (Review).
Katoh M·Int J Mol Med
2005Review
A de novo inframe deletion variant in CAPZA2 tentacle domain with global developmental delay and secondary microcephaly.
Pi S et al.·Clin Genet
2022Case report
Tankyrase-Binding Protein TNKS1BP1 Regulates Actin Cytoskeleton Rearrangement and Cancer Cell Invasion.
Ohishi T et al.·Cancer Res
2017
MET gene alterations predict poor survival following chemotherapy in patients with advanced cancer.
Ko J et al.·Pathol Oncol Res
2022Cohort
Genes and variants in hematopoiesis-related pathways are associated with gemcitabine/carboplatin-induced thrombocytopenia.
Björn N et al.·Pharmacogenomics J
2020
The University of Wisconsin Undiagnosed Disease Program: Unveiling Rare Neurodevelopmental Disorders in Exome-Negative Patients.
Heilmann JM et al.·WMJ
2024Case report
A subgroup of anaplastic thyroid carcinomas harbors MET alterations with potential therapeutic options.
Theurer S et al.·Pathol Res Pract
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools