CIZ1

protein-coding

CDKN1A interacting zinc finger protein 1

Gene summary

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]

MANE transcript

NM_001131016.2

Inheritance

ClinVar variants

U:209B:130

Top phenotype

Primary cervical dystonia, adult-onset

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr9:128,161,251-128,204,383

External References & Databases

Ensembl (ENSG00000148337)

Transcript & Mutation Effects

hg38 • Region Span ~43.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inherited dystoniaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0044807

Submitter: Ambry Genetics

dystonia 23MODERATE

Inheritance Pattern: Unknown

Disease ID:MONDO:0013928

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Primary cervical dystonia, adult-onsetAD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 22447717

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CIZ1 variants in ClinVar

7 Conditions Cataloged

Dystonic disorderTotal: 331

not specifiedTotal: 128

not providedTotal: 42

CIZ1-related disorderTotal: 12

Dystonia, primary cervicalTotal: 1

Variant of unknown significanceTotal: 1

Dystonia 23Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001131016.2. 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			5 clinvar	90 clinvar	10 clinvar	105
missense			197 clinvar	23 clinvar	7 clinvar	227
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	209	113	17	339

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 76 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001131016.2	RefSeq	NP_001124488.1	16	MANE Select
ENST00000372938.10	Ensembl	ENSP00000362029.5	16	MANE Select
NM_001131015.2	RefSeq	NP_001124487.1	17	Standard
NM_001131017.2	RefSeq	NP_001124489.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

nucleic acid binding
protein binding
zinc ion binding

Cellular Component

nucleus
nucleoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393608
Coding exons: 16
Length: 38320
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.99	371	496	0.749	0.0000286	5780
Missense (PolyPhen)		69	122.98	0.56105		1423
Synonymous	0.788	187	201	0.929	0.0000120	1773
Loss of Function	4.98	13	51.7	0.252	0.00000255	526

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00082	0.00082	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.00010	0.000098	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May regulate the subcellular localization of CIP/WAF1.;
Disease: DISEASE: Note=Defects in CIZ1 may be a cause of adult onset primary cervical dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Cervical dystonia or spasmodic torticollis, the most common form of focal dystonia, is characterized by involuntary contractions of the neck muscles, which produce abnormal posturing of the head upon the trunk.;

Recessive Scores

pRec: 0.0907

Intolerance Scores

LoFtool: 0.576
RVIS EVS: -0.35
RVIS percentile EVS: 29.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.934

Gene Damage Prediction

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