CIZ1

Chr 9

CDKN1A interacting zinc finger protein 1

Also known as: LSFR1, NP94, ZNF356

NCBI Gene: 25792 ENSG00000148337 UniProt: Q9ULV3 OMIM: 611420

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.40

LOEUF

—

Mechanism

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

Background carrier burden — how many people carry a rare variant somewhere in CIZ1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,083 rare PASS variants

Rare truncating (LoF)

1 in 1,700

144 rare PASS variants

Rare synonymous (reference)

1 in 83

509 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CIZ1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 70	1 in 1,900
South Asian	~43k	1 in 58	1 in 560
Remaining (unassigned)	~30k	1 in 48	1 in 670
European (Finnish)	~27k	1 in 140	1 in 2,600
Admixed American	~22k	1 in 48	1 in 1,200
African / African American	~21k	1 in 58	1 in 2,400
East Asian	~20k	1 in 48	1 in 800
Ashkenazi Jewish	~13k	1 in 240	none seen
Middle Eastern	~2,884	1 in 80	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 16 coding exons well covered in gnomAD exomes; exon 4 poorly covered; exon 17 marginal. Genomes: 15 of 16 (exon 4 below).? see exons ↓