CLASP1

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

Basic information

Region (hg38): 2:121337775-121649476

Links

ENSG00000074054 ∙ NCBI:23332 ∙ OMIM:605852 ∙ HGNC:17088 ∙ Uniprot:Q7Z460 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (No Known Disease Relationship), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLASP1 gene.

• not provided (225 variants)
• Roifman syndrome (15 variants)
• Osteodysplastic primordial dwarfism, type 1 (14 variants)
• Inborn genetic diseases (13 variants)
• RNU4ATAC-related condition (6 variants)
• Lowry-Wood syndrome (6 variants)
• Roifman syndrome;Lowry-Wood syndrome;Osteodysplastic primordial dwarfism, type 1 (4 variants)
• CLASP1-related condition (3 variants)
• RNU4ATAC-related spliceosomopathies (2 variants)
• Intellectual disability;Short stature (2 variants)
• Osteodysplastic primordial dwarfism, type 1;Roifman syndrome;Lowry-Wood syndrome (2 variants)
• Spondyloepiphyseal dysplasia congenita (2 variants)
• not specified (1 variants)
• Osteodysplastic primordial dwarfism, type 1;Lowry-Wood syndrome (1 variants)
• Lowry-Wood syndrome;Osteodysplastic primordial dwarfism, type 1;Roifman syndrome (1 variants)
• Lowry-Wood syndrome;Roifman syndrome;Osteodysplastic primordial dwarfism, type 1 (1 variants)
• Neurodevelopmental delay;Cardiomyopathy;Craniosynostosis syndrome;Microcephaly;Short stature (1 variants)
• Lowry-Wood syndrome;Osteodysplastic primordial dwarfism, type 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLASP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	2	3
missense			17	1		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding	5	12	171	14	10	212
Total	5	12	188	16	12

Highest pathogenic variant AF is 0.0000853

Variants in CLASP1

This is a list of pathogenic ClinVar variants found in the CLASP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-121340859-C-T		CLASP1-related disorder	Likely benign (Mar 04, 2019)
2-121363243-C-T		CLASP1-related disorder	Uncertain significance (Dec 15, 2023)
2-121363281-G-A		not specified	Uncertain significance (Jan 09, 2024)
2-121365083-CA-C		CLASP1-related disorder	Likely benign (Apr 08, 2019)
2-121365164-C-T		not specified	Uncertain significance (Jul 05, 2023)
2-121365227-T-C		not specified	Uncertain significance (Feb 06, 2024)
2-121365282-G-A		not specified	Uncertain significance (Feb 21, 2024)
2-121367637-G-A			Benign (Feb 20, 2018)
2-121367676-C-T		CLASP1-related disorder	Likely benign (May 28, 2019)
2-121367677-G-A		CLASP1-related disorder	Likely benign (Mar 28, 2023)
2-121367755-G-A		not specified	Uncertain significance (Dec 15, 2023)
2-121367762-G-A		not specified	Uncertain significance (Jun 12, 2023)
2-121367786-C-G		not specified	Uncertain significance (Jan 04, 2024)
2-121367797-G-T		CLASP1-related disorder	Benign (Feb 11, 2020)
2-121377533-G-T		not specified	Uncertain significance (Feb 12, 2024)
2-121377551-T-A		CLASP1-related disorder	Uncertain significance (Feb 05, 2024)
2-121377584-G-A			Uncertain significance (Apr 09, 2021)
2-121377593-C-T		not specified	Uncertain significance (Jun 11, 2021)
2-121382300-G-A		CLASP1-related disorder	Likely benign (Feb 19, 2020)
2-121382317-A-G		not specified	Uncertain significance (Apr 26, 2023)
2-121382323-G-A		not specified	Uncertain significance (Dec 21, 2023)
2-121387203-C-T		not specified	Uncertain significance (Aug 28, 2023)
2-121387866-G-C		not specified	Uncertain significance (May 31, 2023)
2-121397160-T-C		CLASP1-related disorder	Uncertain significance (Mar 31, 2023)
2-121397216-T-C		not specified	Uncertain significance (Mar 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLASP1	protein_coding	protein_coding	ENST00000263710	39	311812

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.72e-8	124642	0	13	124655	0.0000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.61	560	858	0.653	0.0000496	9926
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000648	0.0000646
Ashkenazi Jewish	0.00	0.00
East Asian	0.000115	0.000111
Finnish	0.00	0.00
European (Non-Finnish)	0.0000737	0.0000708
Middle Eastern	0.000115	0.000111
South Asian	0.0000656	0.0000654
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Signaling by ROBO receptors;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;Axon guidance;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Role of ABL in ROBO-SLIT signaling;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.147

Haploinsufficiency Scores

• pHI: 0.297
• hipred: Y
• hipred_score: 0.804
• ghis: 0.612

Essentials

• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.950

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clasp1

Zebrafish Information Network

• Gene name: clasp1b
• Affected structure: anatomical system
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;microtubule cytoskeleton organization;microtubule bundle formation;vesicle targeting;microtubule nucleation;negative regulation of microtubule depolymerization;Golgi organization;mitotic spindle organization;establishment or maintenance of cell polarity;regulation of G2/M transition of mitotic cell cycle;exit from mitosis;regulation of gastrulation;positive regulation of epithelial cell migration;regulation of epithelial to mesenchymal transition;astral microtubule organization;microtubule organizing center organization;negative regulation of microtubule polymerization or depolymerization;positive regulation of microtubule polymerization;microtubule anchoring;establishment of mitotic spindle localization;positive regulation of exocytosis;establishment of spindle orientation;cell division;negative regulation of stress fiber assembly;regulation of focal adhesion assembly;regulation of microtubule cytoskeleton organization;positive regulation of extracellular matrix disassembly;establishment of epithelial cell polarity;mitotic spindle assembly;ciliary basal body-plasma membrane docking;negative regulation of wound healing, spreading of epidermal cells;positive regulation of basement membrane assembly involved in embryonic body morphogenesis
• Cellular component: kinetochore;condensed chromosome kinetochore;Golgi apparatus;centrosome;kinetochore microtubule;cytosol;spindle microtubule;cytoplasmic microtubule;focal adhesion;cell cortex;membrane;cortical microtubule cytoskeleton;centrosomal corona;microtubule plus-end;basal cortex
• Molecular function: dystroglycan binding;protein binding;microtubule binding;kinetochore binding;microtubule plus-end binding