CLASP1

protein-coding

cytoplasmic linker associated protein 1, the group of TOG domain containing

Gene summary

CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170; MIM 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003 [PubMed 12837247]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001395891.1

Inheritance

ClinVar variants

U:156B:13

Top phenotype

CLASP1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr2:121,337,776-121,649,476

External References & Databases

Ensembl (ENSG00000074054)

Transcript & Mutation Effects

hg38 • Region Span ~311.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Illumina

focal epilepsyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005384

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLASP1 variants in ClinVar

19 Conditions Cataloged

not providedTotal: 240

not specifiedTotal: 140

CLASP1-related disorderTotal: 39

RNU4ATAC-related disorderTotal: 33

RNU4ATAC spectrum disorderTotal: 32

Roifman syndromeTotal: 25

Osteodysplastic primordial dwarfism, type 1Total: 24

Lowry-Wood syndromeTotal: 22

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001395891.1. 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	6 clinvar	3 clinvar	11
missense			145 clinvar	2 clinvar	2 clinvar	149
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	156	8	5	169

Highest pathogenic variant AF is 0.0004972514

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 119 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001395891.1	RefSeq	NP_001382820.1	40	MANE Select
ENST00000696935.1	Ensembl	ENSP00000512981.1	40	MANE Select
NM_001142273.2	RefSeq	NP_001135745.1	39	Standard
NM_001142274.2	RefSeq	NP_001135746.1	38	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
clasp1b	Danio rerio	Structure: anatomical system Quality: quality abnormal

Gene / Model

Organism

Observed Phenotype

clasp1b

Danio rerio

Structure: anatomical system

Quality: quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of Microtubule Cytoskeleton
Splicing factor NOVA regulated synaptic proteins
Developmental Biology
Signal Transduction
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal

Biological Process

G2/M transition of mitotic cell cycle
microtubule cytoskeleton organization
microtubule bundle formation
vesicle targeting
microtubule nucleation

Molecular Function

dystroglycan binding
protein binding
microtubule binding
kinetochore binding
microtubule plus-end binding

Cellular Component

kinetochore
condensed chromosome kinetochore
Golgi apparatus
centrosome
kinetochore microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263710
Coding exons: 39
Length: 311812
Individuals with no LoFs: 124642
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 124655
p: 0.0000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.61	560	858	0.653	0.0000496	9926
Missense (PolyPhen)		160	339.72	0.47098		3918
Synonymous	0.300	316	323	0.979	0.0000188	3060
Loss of Function	7.86	9	89.0	0.101	0.00000562	986

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000074	0.000071	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:12837247, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864}.;

Recessive Scores

pRec: 0.147

Essentials

Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.950

Gene Damage Prediction

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