CASZ1

Chr 1

castor zinc finger 1

Also known as: CAS11, CST, SRG, ZNF693, dJ734G22.1

NCBI Gene: 54897 ENSG00000130940 UniProt: Q86V15 OMIM: 609895

The protein is a zinc finger transcription factor that activates transcription and regulates vascular assembly and morphogenesis through direct transcriptional regulation of EGFL7. Mutations cause autosomal dominant neurodevelopmental disorder with seizures, microcephaly, and brain malformations, typically presenting in early infancy. The gene is highly constrained against loss-of-function variants, reflecting its critical role in normal development.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.15

Clinical Summary— CASZ1

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Gene-Disease Validity (ClinGen)

congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

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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.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 361 VUS of 683 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.15LOEUF

pLI 1.000

Z-score 6.72

OE 0.07 (0.03–0.15)

Highly constrained

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

Missense Constraint?

2.61Z-score

OE missense 0.78 (0.74–0.82)

866 obs / 1110.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.15)

0≤0.351.4

Missense OE?0.78 (0.74–0.82)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 4 / 60.3Missense obs/exp: 866 / 1110.3Syn Z: 0.50

This gene — mechanism propensity

0.2598th %ile

GOF

0.2198th %ile

LOF

0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 86% of P/LP variants are LoF · LOEUF 0.15

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

683 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic3

VUS361

Likely Benign193

Benign76

Conflicting13

Pathogenic

Likely Pathogenic

361

VUS

193

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	1	0	0	4
Likely Pathogenic	3	0	0	0	3
VUS	13	342	5	1	361
Likely Benign	0	29	33	131	193
Benign	0	14	34	28	76
Conflicting	—				13
Total	19	386	72	160	650

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 56) ClinVar copy-number / structural variants overlap CASZ1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →