ZC3HC1

protein-coding

zinc finger C3HC-type containing 1, the group of Zinc fingers

Gene summary

This gene encodes an F-box-containing protein that is a component of an SCF-type E3 ubiquitin ligase complex that regulates the onset of cell division. The G2/M transition in the cell cycle requires the interaction of the proteins cyclin B1 and cyclin-dependent kinase 1. The activated ubiquitin ligase complex targets the protein cyclin B1 for degradation, preventing this transition to mitosis. [provided by RefSeq, Aug 2013]

MANE transcript

NM_016478.5

Inheritance

—

ClinVar variants

U:73B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr7:130,018,287-130,051,401

External References & Databases

Ensembl (ENSG00000091732)

Transcript & Mutation Effects

hg38 • Region Span ~33.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZC3HC1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 69

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016478.5. 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			2 clinvar			2
missense			66 clinvar	4 clinvar		70
nonsense			1 clinvar			1
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)						0
Total	0	0	73	4	0	77

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 69 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016478.5	RefSeq	NP_057562.3	10	MANE Select
ENST00000358303.9	Ensembl	ENSP00000351052.4	10	MANE Select
NM_001282190.2	RefSeq	NP_001269119.1	11	Standard
NM_001282191.1	RefSeq	NP_001269120.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell cycle
protein ubiquitination
cell division
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Molecular Function

protein binding
zinc ion binding
protein kinase binding

Cellular Component

nucleus
nuclear membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358303
Coding exons: 10
Length: 33166
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 43
Defined: 125747
p: 0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	234	286	0.818	0.0000154	3264
Missense (PolyPhen)		58	76.983	0.75341		818
Synonymous	0.257	104	107	0.968	0.00000555	1020
Loss of Function	2.97	11	27.9	0.394	0.00000178	275

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00029	0.00029	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential component of a SCF-type E3 ligase complex, SCF(NIPA), a complex that controls mitotic entry by mediating ubiquitination and subsequent degradation of cyclin B1 (CCNB1). Its cell-cycle-dependent phosphorylation regulates the assembly of the SCF(NIPA) complex, restricting CCNB1 ubiquitination activity to interphase. Its inactivation results in nuclear accumulation of CCNB1 in interphase and premature mitotic entry. May have an antiapoptotic role in NPM-ALK-mediated signaling events. {ECO:0000269|PubMed:16009132}.;

Intolerance Scores

LoFtool: 0.760
RVIS EVS: 0.24
RVIS percentile EVS: 69.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.877

Gene Damage Prediction

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