CLASP2

Summary

CLASP2 (cytoplasmic linker associated protein 2, HGNC:17078) is a protein-coding gene on chromosome 3p22.3, encoding CLIP-associating protein 2 (O75122). Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. It is a selective cancer dependency (DepMap: 11.7% of cell lines).

Enables cytoskeletal protein binding activity; dystroglycan binding activity; and protein tyrosine kinase binding activity. Involved in several processes, including cytoskeleton organization; positive regulation of extracellular matrix organization; and regulation of supramolecular fiber organization. Located in several cellular components, including basal cortex; focal adhesion; and microtubule cytoskeleton. Is active in glutamatergic synapse.

Source: NCBI Gene 23122 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 179 total
• Cancer dependency (DepMap): dependent in 11.7% of screened cell lines
• MANE Select transcript: NM_001365631

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17078
Approved symbol	CLASP2
Name	cytoplasmic linker associated protein 2
Location	3p22.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0627
Ensembl gene	ENSG00000163539
Ensembl biotype	protein_coding
OMIM	605853
Entrez	23122

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 21 protein_coding, 7 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000313350, ENST00000333778, ENST00000399362, ENST00000461133, ENST00000462878, ENST00000464961, ENST00000467956, ENST00000468888, ENST00000475576, ENST00000476251, ENST00000476433, ENST00000480013, ENST00000480385, ENST00000482896, ENST00000485378, ENST00000486796, ENST00000487200, ENST00000487553, ENST00000491045, ENST00000493577, ENST00000494261, ENST00000496954, ENST00000498331, ENST00000635664, ENST00000650653, ENST00000682230, ENST00000895686, ENST00000912538, ENST00000912539, ENST00000912540, ENST00000912541, ENST00000946013

RefSeq mRNA: 53 — MANE Select: NM_001365631 NM_001207044, NM_001365627, NM_001365628, NM_001365629, NM_001365630, NM_001365631, NM_001365632, NM_001365633, NM_001365634, NM_001375694, NM_001375697, NM_001375700, NM_001375701, NM_001375703, NM_001375705, NM_001375713, NM_001375715, NM_001375716, NM_001375718, NM_001375720, NM_001400405, NM_001400406, NM_001400407, NM_001400408, NM_001400409, NM_001400410, NM_001400411, NM_001400412, NM_001400413, NM_001400414, NM_001400415, NM_001400416, NM_001400417, NM_001400418, NM_001400419, NM_001400420, NM_001400421, NM_001400422, NM_001400423, NM_001400424, NM_001400425, NM_001400427, NM_001400428, NM_001400429, NM_001400430, NM_001400431, NM_001400432, NM_001400433, NM_001400434, NM_001400435, NM_001400436, NM_001400437, NM_015097

CCDS: CCDS93232, CCDS93233, CCDS93234, CCDS93235, CCDS93237

Canonical transcript exons

ENST00000682230 — 39 exons

Exon	Start	End
ENSE00001141092	33602952	33603125
ENSE00001141097	33604154	33604209
ENSE00001250595	33592395	33592496
ENSE00001619214	33570727	33570790
ENSE00001622909	33560808	33560971
ENSE00001625094	33559307	33559385
ENSE00001654741	33535233	33535461
ENSE00001676639	33544698	33544841
ENSE00001687439	33581821	33581928
ENSE00001695537	33576169	33576275
ENSE00001696563	33551252	33551395
ENSE00001713113	33594951	33594968
ENSE00001788597	33596711	33596734
ENSE00001806316	33584750	33584920
ENSE00003459947	33622135	33622280
ENSE00003476776	33607384	33607461
ENSE00003496209	33608567	33608626
ENSE00003513922	33612001	33612071
ENSE00003517475	33516023	33516151
ENSE00003523070	33543433	33543539
ENSE00003531576	33663445	33663515
ENSE00003539336	33688277	33688368
ENSE00003541942	33496245	33498717
ENSE00003548398	33516981	33517174
ENSE00003554797	33684359	33684456
ENSE00003555043	33687060	33687135
ENSE00003562089	33689829	33689932
ENSE00003564019	33538789	33538942
ENSE00003572288	33619603	33619738
ENSE00003593483	33626988	33627080
ENSE00003593723	33573110	33573354
ENSE00003633438	33632292	33632371
ENSE00003638109	33644757	33644903
ENSE00003638794	33510558	33510764
ENSE00003639122	33696855	33696933
ENSE00003658184	33501652	33501768
ENSE00003671913	33606591	33606758
ENSE00003848352	33566732	33566734
ENSE00003918974	33717808	33718254

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.3199 / max 631.5590, expressed in 1797 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41643	11.0478	1768
41634	8.3217	760
41631	3.5110	236
41633	1.2416	205
41632	0.9900	140
41642	0.9230	534
41641	0.3626	165
41635	0.2801	127
41636	0.2734	91
41637	0.1117	56

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.17	gold quality
cortical plate	UBERON:0005343	99.02	gold quality
paraflocculus	UBERON:0005351	98.87	gold quality
middle frontal gyrus	UBERON:0002702	98.84	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.82	gold quality
frontal pole	UBERON:0002795	98.60	gold quality
endothelial cell	CL:0000115	98.56	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.18	gold quality
ganglionic eminence	UBERON:0004023	97.99	gold quality
subthalamic nucleus	UBERON:0001906	97.98	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.90	gold quality
cerebellar cortex	UBERON:0002129	97.81	gold quality
cerebellar hemisphere	UBERON:0002245	97.81	gold quality
inferior vagus X ganglion	UBERON:0005363	97.81	gold quality
cerebellum	UBERON:0002037	97.71	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.70	gold quality
prefrontal cortex	UBERON:0000451	97.64	gold quality
postcentral gyrus	UBERON:0002581	97.53	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.48	gold quality
superior vestibular nucleus	UBERON:0007227	97.48	gold quality
calcaneal tendon	UBERON:0003701	97.47	gold quality
parietal lobe	UBERON:0001872	97.43	gold quality
substantia nigra pars compacta	UBERON:0001965	97.41	gold quality
pons	UBERON:0000988	97.38	gold quality
lateral globus pallidus	UBERON:0002476	97.25	gold quality
medulla oblongata	UBERON:0001896	97.22	gold quality
superior frontal gyrus	UBERON:0002661	97.16	gold quality
ventricular zone	UBERON:0003053	97.14	gold quality
globus pallidus	UBERON:0001875	97.07	gold quality
ventral tegmental area	UBERON:0002691	97.01	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	81.98
E-ANND-3	yes	5.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

261 targeting CLASP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 31)

• propose that CLASP1 and CLASP2 can mediate interactions between microtubule plus ends and the cell cortex and act as local rescue factors, possibly through forming a complex with EB1 at microtubule tips (PMID:15631994)
• These results demonstrate the striking difference of the microtubule cytoskeleton in the lamella as compared with the cell body and provide the first direct observation of subcellular regulation of a microtubule-associated protein in migrating cells. (PMID:15955847)
• CLASPs provide apparent stabilization of microtubules by locally reducing the amplitude of growth/shortening episodes at the microtubule ends. (PMID:16866869)
• Together, our data support that the partial redundancy of CLASPs during mitosis acts as a possible mechanism to prevent aneuploidy in mammals. (PMID:16914514)
• GSK3beta phosphorylation modulates CLASP-microtubule association and lamella microtubule attachment. (PMID:19289791)
• A role for microtubules that form at the Golgi membranes is identified in a manner dependent on the microtubule regulators CLASPs. (PMID:19701196)
• Data report that NEK1 and CLASP2 colocalize with FEZ1 in a perinuclear region in mammalian cells, and observed that coiled-coil interactions occur between FEZ1/CLASP2 and FEZ1/NEK1 in vitro. (PMID:19924516)
• Regulation of microtubule dynamics by TOG-domain proteins XMAP215/Dis1 and CLASP (PMID:21782439)
• Data show that CENP-E-mediated traction forces on misaligned chromosomes are responsible for the irreversible loss of spindle-pole integrity in CLASP1/2-depleted cells. (PMID:22307330)
• Multisite phosphorylation disrupts arginine-glutamate salt bridge networks required for binding of cytoplasmic linker-associated protein 2 (CLASP2) to end-binding protein 1 (EB1). (PMID:22467876)
• Overexpression of human CLASP2 in mouse neurons caused the formation of multiple axons, enhanced dendritic branching, & Golgi condensation. These morphogenetic changes led to significant functional alterations in synaptic transmission. (PMID:23035100)
• propose that Cdk1 and Plk1 mediate a fine CLASP2 “phospho-switch” that temporally regulates kinetochore-microtubule attachment stability (PMID:23045552)
• The epiblast epithelial status was maintained by anchoring microtubules to the basal cortex via CLIP2, a microtubule plus-end tracking protein, and Dystroglycan, a transmembrane protein that bridges the cytoskeleton and basement membrane (BM). (PMID:23940118)
• Results suggest a previously unidentified role for the scaffolding protein 4.1R in locally controlling CLASP2 behavior, CLASP2 cortical platform turnover and GSK3 activity, enabling correct MT organization and dynamics essential for cell polarity. (PMID:23943871)
• Interstitial deletion of 3p22.3p22.2 encompassing ARPP21 and CLASP2 is a potential pathogenic factor for a syndromic form of intellectual disability. (PMID:24127197)
• Propose that CLASPs couple microtubule organization, vesicle transport and cell interactions with the ECM, establishing a local secretion pathway that facilitates focal adhesion turnover by severing cell-matrix connections. (PMID:24859005)
• GSK3B-dependent phosphorylation and the level of CLASP2 play a role in the maintenance of acetylcholine receptor cluster size through the regulated capture and release of microtubule plus-ends. (PMID:25231989)
• PAR3 and aPKC control the organization of the Golgi through CLASP2 phosphorylation. (PMID:25518939)
• Prickle1 localized to the membrane through its farnesyl moiety, and the membrane localization was necessary for Prickle1 to regulate migration, to bind to CLASPs and LL5beta, and to promote microtubule targeting of focal adhesions. (PMID:27378169)
• These findings reveal a new role for Clasp2 in governing keratinocyte undifferentiated features. (PMID:28069833)
• CLASP2 is involved in the epithelial-mesenchymal transition and progression of bladder urothelial cancer. Simultaneous urine-based detection of CLASP2 and E-cadherin mRNA can efficiently discriminate patients with or without 2-years progression after transurethral resection of the bladder tumor. (PMID:28166762)
• this study shows that GSK3-mediated phosphorylation of CLASP2alpha largely abolishes CLASP2alpha-microtubule association in metaphase thus contributing to correct chromosome dynamics (PMID:28232523)
• microtubules grown with CLASP2 display greater variability in growth rates. (PMID:29540526)
• Significance of CLASP2 expression in prognosis for muscle-invasive bladder cancer patients: A propensity score-based analysis. (PMID:31130343)
• CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments. (PMID:31757788)
• CLASP Mediates Microtubule Repair by Restricting Lattice Damage and Regulating Tubulin Incorporation. (PMID:32359430)
• HIV-1 Exploits CLASP2 To Induce Microtubule Stabilization and Facilitate Virus Trafficking to the Nucleus. (PMID:32376623)
• SOCS3-microtubule interaction via CLIP-170 and CLASP2 is critical for modulation of endothelial inflammation and lung injury. (PMID:33372035)
• Cyclical phosphorylation of LRAP35a and CLASP2 by GSK3beta and CK1delta regulates EB1-dependent MT dynamics in cell migration. (PMID:34525355)
• CLASP2 facilitates dynamic actin filament organization along the microtubule lattice. (PMID:36598814)
• CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state-sensitive manner. (PMID:36598991)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	clasp2	ENSDARG00000020345
mus_musculus	Clasp2	ENSMUSG00000033392
rattus_norvegicus	Clasp2	ENSRNOG00000009161
drosophila_melanogaster	chb	FBGN0021760
caenorhabditis_elegans		WBGENE00000549
caenorhabditis_elegans		WBGENE00013847
caenorhabditis_elegans		WBGENE00015580

Paralogs (3): CLASP1 (ENSG00000074054), TOGARAM2 (ENSG00000189350), TOGARAM1 (ENSG00000198718)

Protein

Protein identifiers

CLIP-associating protein 2 — O75122 (reviewed: O75122)

Alternative names: Cytoplasmic linker-associated protein 2, Protein Orbit homolog 2

All UniProt accessions (15): A0A0U1RQI6, A0A804HJG7, B3KR06, C9J668, O75122, D6RBU8, E3W994, E7ENG2, E7ERI8, E7EW49, H7C4I5, H7C4M5, H7C4X8, H7C5M8, J3KR49

UniProt curated annotations — full annotation on UniProt →

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. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex.

Subunit / interactions. Interacts with microtubules. Interacts with MAPRE1; probably required for targeting to the growing microtubule plus ends. Interacts with CLIP2, ERC1, MAPRE3, PHLDB2 and RSN. The interaction with ERC1 may be mediated by PHLDB2. Interacts with GCC2; recruits CLASP2 to Golgi membranes. Interacts with MACF1. Interacts with mtcl2 and MTCL1.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Chromosome. Centromere. Kinetochore. Spindle. Golgi apparatus. trans-Golgi network. Cell membrane. Cell projection. Ruffle membrane. Cell cortex.

Tissue specificity. Brain-specific.

Post-translational modifications. Phosphorylated by GSK3B. Phosphorylation reduces MAPRE1 binding. Phosphorylation by GSK3B may negatively regulate binding to microtubule lattices in lamella.

Domain organisation. The two SXIP sequence motifs mediate interaction with MAPRE1; this is necessary for targeting to growing microtubule plus ends. Two TOG regions display structural characteristics similar to HEAT repeat domains and mediate interaction with microtubules.

Similarity. Belongs to the CLASP family.

Isoforms (3)

UniProt ID	Names	Canonical?
O75122-1	1, CLASP2 gamma	yes
O75122-2	2, CLASP2 beta
O75122-3	3

RefSeq proteins (53): NP_001193973, NP_001352556, NP_001352557, NP_001352558, NP_001352559, NP_001352560, NP_001352561, NP_001352562, NP_001352563, NP_001362623, NP_001362626, NP_001362629, NP_001362630, NP_001362632, NP_001362634, NP_001362642, NP_001362644, NP_001362645, NP_001362647, NP_001362649, NP_001387334, NP_001387335, NP_001387336, NP_001387337, NP_001387338, NP_001387339, NP_001387340, NP_001387341, NP_001387342, NP_001387343, NP_001387344, NP_001387345, NP_001387346, NP_001387347, NP_001387348, NP_001387349, NP_001387350, NP_001387351, NP_001387352, NP_001387353, NP_001387354, NP_001387356, NP_001387357, NP_001387358, NP_001387359, NP_001387360, NP_001387361, NP_001387362, NP_001387363, NP_001387364, NP_001387365, NP_001387366, NP_055912 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR024395	CLASP_N_dom	Domain
IPR034085	TOG	Domain
IPR057546	HEAT_GCN1	Domain

Pfam: PF12348, PF21040, PF23271

UniProt features (115 total): helix 29, modified residue 28, mutagenesis site 18, region of interest 12, compositionally biased region 10, repeat 8, splice variant 7, short sequence motif 2, chain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5NR4	X-RAY DIFFRACTION	1.2
8WHJ	X-RAY DIFFRACTION	1.4
8WHI	X-RAY DIFFRACTION	1.85
3WOY	X-RAY DIFFRACTION	2.1
8WHK	X-RAY DIFFRACTION	2.4
8WHL	X-RAY DIFFRACTION	3.2
8WHH	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75122-F1	66.98	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (28): 8, 14, 316, 327, 330, 360, 368, 370, 407, 455, 459, 463, 478, 489, 507, 525, 529, 585, 587, 596 …

Mutagenesis-validated functional residues (18):

Position	Phenotype
106	decreases affinity for microtubules; when associated with a-191; e-667; e-833; a-838 and a-839.
191	decreases affinity for microtubules; when associated with e-106; e-667; e-833; a-838 and a-839.
496–497	no effect on mapre1 binding. abolishes interaction with mapre1; when associated with 519-a-a-520.
496–497	reduced targeting to the growing microtubule plus ends. loss of interaction with mapre1 and targeting to the growing mic
499	phosphomimetic mutant that reduces mapre1 binding; when associated with d-503; d-507; d-525; d-529; d-533; d-537 and d-5
503	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-507; d-525; d-529; d-533; d-537 and d-5
507	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-525; d-529; d-533; d-537 and d-5
519–520	no effect on mapre1 binding. abolishes interaction with mapre1; when associated with 496-a-a-497.
519–520	reduced targeting to the growing microtubule plus ends. loss of interaction with mapre1 and targeting to the growing mic
525	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-507; d-529; d-533; d-537 and d-5
529	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-507; d-525; d-533; d-537 and d-5
533	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-507; d-525; d-529; d-537 and d-5
537	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-507; d-525; d-529; d-533 and d-5
541	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-507; d-525; d-529; d-533 and d-5
667	decreases affinity for microtubules; when associated with e-106; a-191; e-833; a-838 and a-839.
833	decreases affinity for microtubules; when associated with e-106; a-191; e-667; a-838 and a-839.
838	decreases affinity for microtubules; when associated with e-106; a-191; e-667; e-833 and a-839.
839	decreases affinity for microtubules; when associated with e-106; a-191; e-667; e-833 and a-838.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-428890	Role of ABL in ROBO-SLIT signaling
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 443 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GCACCTT_MIR18A_MIR18B, GOBP_CHROMOSOME_ORGANIZATION, GCM_MAP4K4, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GCM_PTPRD, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_VESICLE_LOCALIZATION, GOBP_MICROTUBULE_ANCHORING

GO Biological Process (34): microtubule cytoskeleton organization (GO:0000226), obsolete vesicle targeting (GO:0006903), microtubule nucleation (GO:0007020), negative regulation of microtubule depolymerization (GO:0007026), Golgi organization (GO:0007030), mitotic spindle organization (GO:0007052), establishment or maintenance of cell polarity (GO:0007163), exit from mitosis (GO:0010458), positive regulation of epithelial cell migration (GO:0010634), regulation of axon extension (GO:0030516), microtubule organizing center organization (GO:0031023), regulation of microtubule polymerization or depolymerization (GO:0031110), regulation of microtubule polymerization (GO:0031113), regulation of microtubule-based process (GO:0032886), regulation of actin cytoskeleton organization (GO:0032956), microtubule anchoring (GO:0034453), platelet-derived growth factor receptor-beta signaling pathway (GO:0035791), establishment of mitotic spindle localization (GO:0040001), positive regulation of exocytosis (GO:0045921), cell division (GO:0051301), negative regulation of stress fiber assembly (GO:0051497), negative regulation of focal adhesion assembly (GO:0051895), basement membrane organization (GO:0071711), positive regulation of extracellular matrix disassembly (GO:0090091), mitotic spindle assembly (GO:0090307), presynaptic cytoskeleton organization (GO:0099187), negative regulation of wound healing, spreading of epidermal cells (GO:1903690), regulation of gastrulation (GO:0010470), regulation of epithelial to mesenchymal transition (GO:0010717), establishment of cell polarity (GO:0030010), negative regulation of cytoskeleton organization (GO:0051494), regulation of focal adhesion assembly (GO:0051893), negative regulation of supramolecular fiber organization (GO:1902904), obsolete positive regulation of basement membrane assembly involved in embryonic body morphogenesis (GO:1904261)

GO Molecular Function (7): dystroglycan binding (GO:0002162), microtubule binding (GO:0008017), microtubule plus-end binding (GO:0051010), actin filament binding (GO:0051015), protein tyrosine kinase binding (GO:1990782), protein binding (GO:0005515), tubulin binding (GO:0015631)

GO Cellular Component (29): kinetochore (GO:0000776), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), centrosome (GO:0005813), microtubule organizing center (GO:0005815), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), microtubule (GO:0005874), spindle microtubule (GO:0005876), cytoplasmic microtubule (GO:0005881), plasma membrane (GO:0005886), cell cortex (GO:0005938), membrane (GO:0016020), cortical microtubule cytoskeleton (GO:0030981), cell leading edge (GO:0031252), ruffle membrane (GO:0032587), axonal growth cone (GO:0044295), basal cortex (GO:0045180), glutamatergic synapse (GO:0098978), cortical microtubule plus-end (GO:1903754), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), spindle (GO:0005819), cytoskeleton (GO:0005856), focal adhesion (GO:0005925), microtubule cytoskeleton (GO:0015630), cell projection (GO:0042995), mitotic spindle (GO:0072686)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Mitotic Prometaphase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
Signaling by ROBO receptors	1
RHO GTPase Effectors	1
M Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
microtubule-based process	3
microtubule cytoskeleton organization	3
microtubule cytoskeleton	3
microtubule polymerization	2
mitotic cell cycle	2
microtubule cytoskeleton organization involved in mitosis	2
cellular process	2
microtubule	2
cell periphery	2
cytoskeleton organization	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
organelle organization	1
endomembrane system organization	1
spindle organization	1
mitotic cell cycle phase transition	1
mitotic nuclear division	1
epithelial cell migration	1
regulation of epithelial cell migration	1
positive regulation of cell migration	1
regulation of developmental growth	1
axon extension	1
regulation of extent of cell growth	1
cellular component organization	1
microtubule polymerization or depolymerization	1
regulation of microtubule cytoskeleton organization	1
regulation of microtubule polymerization or depolymerization	1
regulation of protein polymerization	1
regulation of supramolecular fiber organization	1
regulation of cellular process	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
platelet-derived growth factor receptor signaling pathway	1
establishment of spindle localization	1

Protein interactions and networks

STRING

1240 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLASP2	CLIP1	P30622	984
CLASP2	CLASRP	Q8N2M8	959
CLASP2	CLIP2	Q9UDT6	955
CLASP2	PHLDB2	Q86SQ0	882
CLASP2	CTNND1	O60716	714
CLASP2	GCC2	Q8IWJ2	708
CLASP2	MAPRE1	Q15691	686
CLASP2	GSK3B	P49841	668
CLASP2	CKAP5	Q14008	645
CLASP2	MAPRE3	Q9UPY8	643
CLASP2	MACF1	Q9UPN3	603
CLASP2	MAP4	P27816	572
CLASP2	MARK2	Q7KZI7	572
CLASP2	SLAIN2	Q9P270	529
CLASP2	CENPE	Q02224	524

IntAct

161 interactions, top by confidence:

A	B	Type	Score
GSK3B	AXIN1	psi-mi:“MI:0914”(association)	0.980
MAPRE1	CLASP2	psi-mi:“MI:0914”(association)	0.850
MAPRE1	CLASP2	psi-mi:“MI:0915”(physical association)	0.850
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CLASP2	YWHAZ	psi-mi:“MI:0914”(association)	0.670
CLASP2	YWHAE	psi-mi:“MI:0915”(physical association)	0.650
PPP4C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
CENPE	CLASP2	psi-mi:“MI:0914”(association)	0.530
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CSGALNACT2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
KLHDC3	DPYSL4	psi-mi:“MI:0914”(association)	0.530
CSGALNACT2	TPST1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530

BioGRID (236): CLASP2 (Affinity Capture-RNA), CLASP2 (Affinity Capture-RNA), CLASP2 (Reconstituted Complex), CLASP2 (Affinity Capture-MS), CLASP2 (Affinity Capture-MS), GOPC (Affinity Capture-MS), FAM43A (Affinity Capture-MS), CLASP2 (Affinity Capture-MS), Clip1 (Affinity Capture-Western), CLASP2 (Two-hybrid), CLASP2 (Biochemical Activity), CLASP2 (Proximity Label-MS), CLASP2 (Proximity Label-MS), CLASP2 (Affinity Capture-MS), CLASP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K2P5, A0JNJ1, B1WAP7, G9CGD6, O14640, O75122, O88382, O95049, O97758, P34908, P39447, P51141, P54792, P70175, Q05AS8, Q07157, Q16825, Q5F488, Q5IS48, Q5SGD7, Q5TCQ9, Q5XI81, Q61062, Q62136, Q62728, Q62936, Q6DKE2, Q6P9H4, Q6ZM86, Q812E4, Q86UL8, Q8BMA3, Q8IVH8, Q8JHI3, Q8TDW5, Q920B0, Q924I2, Q925T6, Q92997, Q95168

Diamond homologs: A1A5G0, A1A5K2, O75122, Q4U0G1, Q61J98, Q61QN4, Q6NYW6, Q7Z460, Q80TV8, Q8BRT1, Q99JD4, Q9NBD7, Q9PT63, Q03609, Q61KX5, P32744, Q95YF0

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
CLASP2	“up-regulates activity”	CLIP2	binding
CDK1	“up-regulates activity”	CLASP2	phosphorylation
PLK1	“up-regulates activity”	CLASP2	phosphorylation
ABL1	“up-regulates quantity”	CLASP2	phosphorylation
GSK3B	“down-regulates activity”	CLASP2	phosphorylation
CLASP2	“up-regulates activity”	CLIP1	binding
CLASP2	“up-regulates activity”	IQGAP1	binding
CLASP2	“up-regulates activity”	MAPRE1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 152 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	8	58.0×	8e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	44.8×	8e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	44.8×	8e-09
Activation of BH3-only proteins	8	37.8×	2e-09
Intrinsic Pathway for Apoptosis	8	22.3×	9e-08
RHO GTPases activate PKNs	7	21.1×	9e-07
FOXO-mediated transcription	6	19.2×	1e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	12	17.6×	6e-10

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of microtubule polymerization	5	27.0×	1e-03
protein targeting	5	14.7×	4e-03
mitotic spindle organization	6	13.1×	3e-03
intracellular protein localization	9	7.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

179 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	16
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

6535 predictions. Top by Δscore:

Variant	Effect	Δscore
3:33501647:CT:C	donor_loss	1.0000
3:33501648:TTAC:T	donor_loss	1.0000
3:33501649:TACTT:T	donor_loss	1.0000
3:33501650:A:AC	donor_gain	1.0000
3:33501650:ACTT:A	donor_loss	1.0000
3:33501651:C:CA	donor_gain	1.0000
3:33501651:CTTT:C	donor_gain	1.0000
3:33501651:CTTTA:C	donor_gain	1.0000
3:33516018:CTT:C	donor_loss	1.0000
3:33516020:TACC:T	donor_loss	1.0000
3:33516021:ACCT:A	donor_gain	1.0000
3:33516022:CCTC:C	donor_gain	1.0000
3:33516152:C:CC	acceptor_gain	1.0000
3:33516976:TTTA:T	donor_loss	1.0000
3:33516977:TTACC:T	donor_loss	1.0000
3:33516978:TAC:T	donor_loss	1.0000
3:33516979:A:AT	donor_loss	1.0000
3:33517057:T:TA	donor_gain	1.0000
3:33535457:CACAT:C	acceptor_gain	1.0000
3:33535459:CAT:C	acceptor_gain	1.0000
3:33538783:ACTTA:A	donor_loss	1.0000
3:33538785:TT:T	donor_loss	1.0000
3:33538786:TA:T	donor_loss	1.0000
3:33538787:A:AC	donor_gain	1.0000
3:33538787:ACTGA:A	donor_loss	1.0000
3:33538788:C:CG	donor_gain	1.0000
3:33538788:CT:C	donor_gain	1.0000
3:33538788:CTG:C	donor_gain	1.0000
3:33538788:CTGA:C	donor_gain	1.0000
3:33538788:CTGAA:C	donor_gain	1.0000

AlphaMissense

9801 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:33498701:A:G	L1272P	1.000
3:33498707:A:G	L1270P	1.000
3:33498710:A:G	L1269P	1.000
3:33501719:A:G	L1244P	1.000
3:33501724:G:C	F1242L	1.000
3:33501724:G:T	F1242L	1.000
3:33501726:A:G	F1242L	1.000
3:33501728:A:T	V1241D	1.000
3:33501736:T:A	K1238N	1.000
3:33501736:T:G	K1238N	1.000
3:33501737:T:A	K1238I	1.000
3:33501743:A:T	V1236D	1.000
3:33510565:A:G	L1225P	1.000
3:33510647:C:G	A1198P	1.000
3:33510652:A:G	L1196P	1.000
3:33510691:A:G	L1183P	1.000
3:33510751:G:T	A1163D	1.000
3:33510752:C:G	A1163P	1.000
3:33516069:A:G	L1143S	1.000
3:33516087:A:G	F1137S	1.000
3:33517003:A:G	L1108P	1.000
3:33517012:A:G	L1105P	1.000
3:33517024:T:A	K1101I	1.000
3:33517075:A:G	L1084P	1.000
3:33517126:A:G	L1067P	1.000
3:33551287:A:G	W828R	1.000
3:33551287:A:T	W828R	1.000
3:33551379:A:G	L797P	1.000
3:33570779:A:G	L692P	1.000
3:33573143:A:G	L677P	1.000

dbSNP variants (sampled 300 via entrez): RS1000000562 (3:33516916 A>T), RS1000019282 (3:33651612 C>A,T), RS1000031055 (3:33616094 A>G), RS1000037326 (3:33602340 T>C), RS1000073702 (3:33710240 A>T), RS1000082339 (3:33703668 C>T), RS1000118353 (3:33520499 G>A), RS1000123651 (3:33610664 C>A), RS1000127119 (3:33699661 A>G), RS1000127754 (3:33636217 G>A,C), RS1000128500 (3:33563186 G>T), RS1000131783 (3:33655837 A>G), RS1000160402 (3:33636555 A>G), RS1000176742 (3:33545681 A>G), RS1000192862 (3:33701384 A>G)

Disease associations

OMIM: gene MIM:605853 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009391_1083	Metabolite levels	1.000000e-06
GCST009391_1698	Metabolite levels	5.000000e-06
GCST012490_476	Femur bone mineral density x serum urate levels interaction	9.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010543	uridine diphosphate galactose measurement
EFO:0010544	uridine diphosphate glucose measurement
EFO:0010344	cholesteryl ester 18:1 measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	5
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	2
Estradiol	affects expression, affects binding, increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tretinoin	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
ochratoxin A	decreases acetylation, decreases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Atrazine	increases expression	1
Caffeine	affects phosphorylation	1
Demecolcine	increases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.