CIZ1

Chr 9

CDKN1A interacting zinc finger protein 1

Also known as: LSFR1, NP94, ZNF356

NCBI Gene: 25792 ENSG00000148337 UniProt: Q9ULV3

The protein encoded by CIZ1 is a zinc finger DNA binding protein that regulates the subcellular localization of CIP1/WAF1, a cell cycle regulator. Mutations cause autosomal dominant intellectual disability with variable features including developmental delay and behavioral abnormalities. This gene shows significant constraint against loss-of-function variants, suggesting that such mutations are likely to be pathogenic.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a zinc finger DNA binding protein that interacts with CIP1, part of a complex with cyclin E. The encoded protein may regulate the cellular localization of CIP1. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ResearchGenerating clinical summary…

LOEUF 0.40

Clinical Summary— CIZ1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 251 VUS of 530 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.40LOEUF

pLI 0.063

Z-score 4.98

OE 0.25 (0.16–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.99Z-score

OE missense 0.75 (0.69–0.82)

371 obs / 495.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.16–0.40)

0≤0.351.4

Missense OE?0.75 (0.69–0.82)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 13 / 51.7Missense obs/exp: 371 / 495.6Syn Z: 0.79

ClinVar Variant Classifications

530 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic5

VUS251

Likely Benign161

Benign65

Conflicting16

Pathogenic

Likely Pathogenic

251

VUS

161

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	0	0	2
Likely Pathogenic	0	5	0	0	5
VUS	4	230	14	3	251
Likely Benign	0	12	49	100	161
Benign	0	9	37	19	65
Conflicting	—				16
Total	5	257	100	122	500

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap CIZ1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →