CASZ1

protein-coding

castor zinc finger 1, the group of Zinc fingers C2H2-type

Gene summary

The protein encoded by this gene is a zinc finger transcription factor. The encoded protein may function as a tumor suppressor, and single nucleotide polymorphisms in this gene are associated with blood pressure variation. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

MANE transcript

NM_001079843.3

Inheritance

ClinVar variants

P:16U:361B:288

Top phenotype

CASZ1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr1:10,636,604-10,796,650

External References & Databases

Ensembl (ENSG00000130940)

Transcript & Mutation Effects

hg38 • Region Span ~160.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital heart diseaseLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005453

Submitter: ClinGen

**CASZ1** was first reported in relation to autosomal dominant congenital heart disease in 2016 (Huang et al., PMID: 27693370). 2 variants (missense) that have been reported in 5 probands in 2 publications (PMIDs: 27693370, 28641477) are included in this curation. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (mouse model, expression-level evidence) (PMID: 25190801, NCBI Fetal Expression Data). Homozygous mutant mice show structural congenital heart anomalies. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date 8/12/2024 (SOP Version 10).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CASZ1 variants in ClinVar

9 Conditions Cataloged

not providedTotal: 450

not specifiedTotal: 415

CASZ1-related disorderTotal: 19

Primary dilated cardiomyopathyTotal: 2

CardiomyopathyTotal: 2

CASZ1-associated cardiomyopathyTotal: 1

Autism spectrum disorderTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001079843.3. 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			6 clinvar	191 clinvar	14 clinvar	211
missense	1 clinvar		338 clinvar	76 clinvar	7 clinvar	422
nonsense	1 clinvar	6 clinvar	5 clinvar			12
start loss						0
frameshift	3 clinvar	2 clinvar	8 clinvar			13
splice donor/acceptor (+/-2bp)		3 clinvar	4 clinvar			7
Total	5	11	361	267	21	665

Highest pathogenic variant AF is 0.000008893657

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001079843.3	RefSeq	NP_001073312.1	18	MANE Select
ENST00000377022.8	Ensembl	ENSP00000366221.3	18	MANE Select
NM_017766.5	RefSeq	NP_060236.3	13	Standard
ENST00000344008.5	Ensembl	ENSP00000339445.5	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
multicellular organism development
positive regulation of transcription, DNA-templated

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
metal ion binding

Cellular Component

nucleoplasm
cytosol
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377022
Coding exons: 18
Length: 160047
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125745
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.61	866	1.11e+3	0.780	0.0000782	11414
Missense (PolyPhen)		387	576.91	0.67082		5772
Synonymous	0.499	508	523	0.972	0.0000438	3571
Loss of Function	6.72	4	60.3	0.0663	0.00000293	718

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
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)	0.000027	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional activator (PubMed:23639441, PubMed:27693370). Involved in vascular assembly and morphogenesis through direct transcriptional regulation of EGFL7 (PubMed:23639441). {ECO:0000269|PubMed:23639441, ECO:0000269|PubMed:27693370}.;

Recessive Scores

pRec: 0.275

Intolerance Scores

LoFtool: 0.00200
RVIS EVS: -2.42
RVIS percentile EVS: 1.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.532

Gene Damage Prediction

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