CDC7

protein-coding

cell division cycle 7

Gene summary

This gene encodes a cell division cycle protein with kinase activity that is critical for the G1/S transition. The yeast homolog is also essential for initiation of DNA replication as cell division occurs. Overexpression of this gene product may be associated with neoplastic transformation for some tumors. Multiple alternatively spliced transcript variants that encode the same protein have been detected. [provided by RefSeq, Aug 2008]

Previous symbols:

CDC7L1

MANE transcript

NM_003503.4

Inheritance

—

ClinVar variants

U:85B:3

Top phenotype

Premature ovarian insufficiency

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr1:91,500,851-91,525,764

External References & Databases

Ensembl (ENSG00000097046)

Transcript & Mutation Effects

hg38 • Region Span ~24.9 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 CDC7 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 78

not providedTotal: 2

Premature ovarian insufficiencyTotal: 1

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003503.4. 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						0
missense			81 clinvar	3 clinvar		84
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	85	3	0	88

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 70 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003503.4	RefSeq	NP_003494.1	11	MANE Select
ENST00000234626.11	Ensembl	ENSP00000234626.6	11	MANE Select
NM_001134419.2	RefSeq	NP_001127891.1	11	Standard
NM_001134420.2	RefSeq	NP_001127892.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell cycle - Homo sapiens (human)
Cell Cycle
Retinoblastoma (RB) in Cancer
DNA Replication
Gene expression (Transcription)

Biological Process

G1/S transition of mitotic cell cycle
double-strand break repair via break-induced replication
DNA replication
positive regulation of cell population proliferation
positive regulation of nuclear cell cycle DNA replication

Molecular Function

protein kinase activity
protein serine/threonine kinase activity
protein binding
ATP binding
kinase activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
intercellular bridge
mitotic spindle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000428239
Coding exons: 11
Length: 24914
Individuals with no LoFs: 125662
Homozygous LoFs: 0
Heterozygous LoFs: 86
Defined: 125748
p: 0.000342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.686	265	298	0.888	0.0000142	3791
Missense (PolyPhen)		106	128.65	0.82393		1609
Synonymous	0.648	90	98.2	0.917	0.00000445	1063
Loss of Function	2.35	13	25.9	0.501	0.00000119	349

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00071	0.00068	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00042	0.00041	rare
South Asian	0.00020	0.00020	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Seems to phosphorylate critical substrates that regulate the G1/S phase transition and/or DNA replication. Can phosphorylates MCM2 and MCM3. {ECO:0000269|PubMed:12065429}.;

Recessive Scores

pRec: 0.194

Intolerance Scores

LoFtool: 0.941
RVIS EVS: -0.2
RVIS percentile EVS: 38.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.862

Gene Damage Prediction

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