CLSPN

protein-coding

claspin

Gene summary

The product of this gene is an essential upstream regulator of checkpoint kinase 1 and triggers a checkpoint arrest of the cell cycle in response to replicative stress or DNA damage. The protein is also required for efficient DNA replication during a normal S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

MANE transcript

NM_022111.4

Inheritance

—

ClinVar variants

U:180B:9

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr1:35,720,218-35,769,978

External References & Databases

Ensembl (ENSG00000092853)

Transcript & Mutation Effects

hg38 • Region Span ~49.8 kb

Loading mutation effect viewer...

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 CLSPN variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 178

not providedTotal: 4

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022111.4. 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				2 clinvar	1 clinvar	3
missense			177 clinvar	6 clinvar		183
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	180	8	1	189

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022111.4	RefSeq	NP_071394.2	25	MANE Select
ENST00000318121.8	Ensembl	ENSP00000312995.3	25	MANE Select
NM_001190481.2	RefSeq	NP_001177410.1	24	Standard
NM_001330490.2	RefSeq	NP_001317419.1	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
DNA Repair
DNA Double-Strand Break Repair
Homology Directed Repair
Post-translational protein modification

Biological Process

DNA damage checkpoint
DNA replication
DNA repair
mitotic G2 DNA damage checkpoint
protein deubiquitination

Molecular Function

DNA binding
protein binding
anaphase-promoting complex binding

Cellular Component

nucleoplasm
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318121
Coding exons: 25
Length: 49750
Individuals with no LoFs: 125591
Homozygous LoFs: 0
Heterozygous LoFs: 157
Defined: 125748
p: 0.000624

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.854	616	679	0.908	0.0000337	8905
Missense (PolyPhen)		173	213.18	0.81152		2822
Synonymous	-0.0902	248	246	1.01	0.0000123	2393
Loss of Function	5.61	19	69.4	0.274	0.00000381	890

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0042	0.0042	notable
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00012	0.00011	rare
Finnish	0.0025	0.0025	notable
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation. Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR- dependent phosphorylation of both proteins. Can also bind specifically to branched DNA structures and may associate with S- phase chromatin following formation of the pre-replication complex (pre-RC). This may indicate a role for this protein as a sensor which monitors the integrity of DNA replication forks. {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391}.;

Intolerance Scores

LoFtool: 0.701
RVIS EVS: 0.74
RVIS percentile EVS: 86.38

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.680

Gene Damage Prediction

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