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; regulation of cell migration; 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 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 180 total
• GTEx eGene: eQTL in 11 tissues, sQTL in 2 (q < 0.05)
• Cancer dependency (DepMap): dependent in 11.7% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.36 (moderately constrained)
• MANE Select transcript: NM_001365631
• Notable: 180 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 43 — 31 protein_coding, 7 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000682230

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 3: 3, TSL 4: 6, TSL 5: 9

ENST00000682230, 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, ENST00000895686, ENST00000912538, ENST00000912539, ENST00000912540, ENST00000912541, ENST00000946013, ENST00001007019, ENST00001045962, ENST00001045963, ENST00001045964, ENST00001108353, ENST00001108354, ENST00001112532, ENST00001112533, ENST00001112534, ENST00001112535, ENST00001145262

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.

Highest expression (Bgee): corpus callosum, cortical plate, paraflocculus, middle frontal gyrus, Brodmann (1909) area 10.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CLASP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.4e-03	+0.17	3:33783255:T:G
Nerve Tibial	sqtl	3.1e-03	-0.29	3:33480156:A:G
Colon Sigmoid	eqtl	8.7e-03	-0.17	3:34611526:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.1e-02	+0.12	3:33498401:A:G
Brain Cerebellar Hemisphere	sqtl	1.7e-02	-1.88	3:33936687:A:G
Breast Mammary Tissue	eqtl	2.2e-02	+0.23	3:33601427:A:T
Brain Cortex	eqtl	2.6e-02	+0.22	3:33318775:C:T
Stomach	eqtl	2.7e-02	+0.14	3:34632034:G:A
Brain Putamen basal ganglia	eqtl	3.2e-02	+0.13	3:34363322:T:G
Brain Anterior cingulate cortex BA24	eqtl	4.0e-02	+0.22	3:33731877:G:A
Esophagus Mucosa	eqtl	4.1e-02	+0.38	3:32779525:C:T
Brain Cerebellum	eqtl	4.3e-02	+0.12	3:33893592:G:A
Testis	eqtl	4.8e-02	+0.06	3:33193004:C:CTGTT

FANTOM5 promoters

showing 10 of 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

showing 100 of 302 tissues 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
medial globus pallidus	UBERON:0002477	96.98	gold quality
frontal cortex	UBERON:0001870	96.91	gold quality
occipital lobe	UBERON:0002021	96.77	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.67	gold quality
orbitofrontal cortex	UBERON:0004167	96.66	gold quality
primary visual cortex	UBERON:0002436	96.56	gold quality
spinal cord	UBERON:0002240	96.55	gold quality
neocortex	UBERON:0001950	96.53	gold quality
CA1 field of hippocampus	UBERON:0003881	96.40	gold quality
entorhinal cortex	UBERON:0002728	96.36	gold quality
cerebral cortex	UBERON:0000956	96.35	gold quality
sural nerve	UBERON:0015488	96.30	gold quality
inferior olivary complex	UBERON:0002127	96.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.14	gold quality
midbrain	UBERON:0001891	96.04	gold quality
central nervous system	UBERON:0001017	96.02	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.02	gold quality
brain	UBERON:0000955	96.00	gold quality
Ammon’s horn	UBERON:0001954	95.99	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.98	gold quality
telencephalon	UBERON:0001893	95.91	gold quality
substantia nigra	UBERON:0002038	95.88	gold quality
forebrain	UBERON:0001890	95.71	gold quality
middle temporal gyrus	UBERON:0002771	95.69	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.65	gold quality
temporal lobe	UBERON:0001871	95.61	gold quality
right frontal lobe	UBERON:0002810	95.50	gold quality
cerebellar vermis	UBERON:0004720	95.38	gold quality
hypothalamus	UBERON:0001898	95.26	gold quality
colonic epithelium	UBERON:0000397	95.01	gold quality
amygdala	UBERON:0001876	95.00	gold quality
caudate nucleus	UBERON:0001873	94.98	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.98	gold quality
cingulate cortex	UBERON:0003027	94.84	gold quality
anterior cingulate cortex	UBERON:0009835	94.80	gold quality
putamen	UBERON:0001874	94.52	gold quality
vastus lateralis	UBERON:0001379	94.22	gold quality
nucleus accumbens	UBERON:0001882	94.16	gold quality
embryo	UBERON:0000922	94.06	gold quality
adrenal tissue	UBERON:0018303	94.03	gold quality
cranial nerve II	UBERON:0000941	93.94	gold quality
nerve	UBERON:0001021	93.79	gold quality
tibial nerve	UBERON:0001323	93.79	gold quality
pituitary gland	UBERON:0000007	93.60	gold quality
dorsal root ganglion	UBERON:0000044	93.49	gold quality
biceps brachii	UBERON:0001507	93.48	gold quality
trigeminal ganglion	UBERON:0001675	93.43	gold quality
choroid plexus epithelium	UBERON:0003911	93.38	gold quality
quadriceps femoris	UBERON:0001377	93.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.17	gold quality
adenohypophysis	UBERON:0002196	93.14	gold quality
skeletal muscle tissue	UBERON:0001134	92.76	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.68	gold quality
muscle tissue	UBERON:0002385	92.24	gold quality
muscle organ	UBERON:0001630	92.20	gold quality
skeletal muscle organ	UBERON:0014892	92.20	gold quality
bone marrow cell	CL:0002092	92.01	gold quality
muscle of leg	UBERON:0001383	91.82	gold quality
mucosa of stomach	UBERON:0001199	91.75	gold quality
tibial artery	UBERON:0007610	91.67	gold quality
popliteal artery	UBERON:0002250	91.66	gold quality
ascending aorta	UBERON:0001496	91.62	gold quality
aorta	UBERON:0000947	91.58	gold quality
diaphragm	UBERON:0001103	91.57	gold quality
thoracic aorta	UBERON:0001515	91.57	gold quality
artery	UBERON:0001637	91.49	gold quality
secondary oocyte	CL:0000655	91.40	gold quality
tendon	UBERON:0000043	91.35	gold quality
gastrocnemius	UBERON:0001388	91.09	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Corpus callosum	tissue	230.5
Postcentral gyrus	tissue	211.6
Locus coeruleus	tissue	207.1
Thalamus	tissue	206.4
Nucleus accumbens	tissue	204.9
Midbrain	tissue	204.9
Pons	tissue	190.9
Medulla oblongata	tissue	182.8
Cerebral cortex	tissue	179.5
Somatosensory cortex	tissue	179.5
Superior colliculi	tissue	177.8
Occipital cortex	tissue	173.5
Spinal cord	tissue	173.1
Hippocampus	tissue	170.6
Motor cortex	tissue	168.9
Hippocampal formation	tissue	163.9
Putamen	tissue	162.3
Substantia nigra	tissue	161.5
Entorhinal cortex	tissue	158.9
Retrosplenial and cingulate cortex	tissue	158.3
Prefrontal cortex	tissue	157.5
Retrosplenial cortex	tissue	156.9
Temporal cortex	tissue	151.4
Ventral forebrain	tissue	151.1
Periaqueductal gray	tissue	150.2
Hypothalamus	tissue	145.4
Septum	tissue	145.1
Cerebellum	tissue	143.2
Insular cortex	tissue	142.3
Amygdala	tissue	134.4
Basal ganglia	tissue	124.7
Retina	tissue	117.3
Olfactory bulb	tissue	112.9
Frontal cortex	tissue	92.9
Caudate putamen	tissue	81.9
Choroid plexus	tissue	81.4
Skeletal muscle	tissue	61.0
Tongue	tissue	60.5
Heart muscle	tissue	38.4
Adrenal gland	tissue	23.6
Ovary	tissue	21.1
Cervix	tissue	20.4
Pituitary gland	tissue	20.4
Seminal vesicle	tissue	19.6
Endometrium 1	tissue	19.0
Smooth muscle	tissue	18.2
Esophagus	tissue	16.8
Gallbladder	tissue	16.8
Kidney	tissue	16.7
Parathyroid gland	tissue	16.3
Prostate	tissue	15.3
Fallopian tube	tissue	15.0
Thymus	tissue	14.7
Tonsil	tissue	14.7
Breast	tissue	14.3
Placenta	tissue	14.3
Lung	tissue	14.3
Lymph node	tissue	14.2
Spleen	tissue	13.5
Urinary bladder	tissue	13.4

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (465.9), Corpus callosum, genu (white matter) (414.9), Corpus callosum, splenium (white matter) (404.0), Temporal white matter (385.5), Occipital cortex (white matter) (370.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

Targeting CLASP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 261 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.365, missense Z 2.54 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000682230 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
3:33,498,634–33,592,410	732 / 987.9	0.74	no
3:33,592,411–33,606,669	174 / 179.0	0.97	no
3:33,606,670–33,644,831	207 / 331.4	0.62	no
3:33,644,832–33,718,002	332 / 325.3	1.02	no
DepMap (CRISPR cell-line fitness): dependent in 11.7% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): PA-TU-8988S (-0.912), OS186 (-0.838), NRH-UPS3 (-0.681), SKM-1 (-0.604), LAI-5S (-0.573), NRH-GCT2 (-0.534), NRH-OS2 (-0.515), SW 620 (-0.509), C337 (-0.508).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923749) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal cell migration	1
abnormal cell physiology	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus tropicalis	A1A5G0	95.6%	Diamond
Xenopus laevis	Q4U0G1	95.6%	Diamond
Caenorhabditis briggsae	Q61QN4	82.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FBXL2	protein-coding	25827
UBP1	protein-coding	7342
PDCD6IP	protein-coding	10015
PDCD6IP-DT	ncRNA	105377023
LINC01811	ncRNA	101928114

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): O75122, A0A0U1RQI6, A0A804HJG7, B3KR06, C9J668, 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, PF23271

UniProt features (120 total): helix 34, 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 by resolution:

PDB	Title	Method	Resolution (Å)
5NR4	Crystal structure of Clasp2 TOG1 domain	X-RAY DIFFRACTION	1.2
8WHJ	Crystal structure of CLASP2 TOG4 fused with LL5beta	X-RAY DIFFRACTION	1.4
8WHI	Crystal structure of native CLASP2 in complex with CLIP170	X-RAY DIFFRACTION	1.85
3WOY	Crystal structure of CLASP2 TOG domain (TOG2)	X-RAY DIFFRACTION	2.1
8WHK	Crystal structure of CLASP2 in complex with LL5beta	X-RAY DIFFRACTION	2.4
8WHL	Crystal structure of CLASP2 in complex with CENP-E	X-RAY DIFFRACTION	3.2
8WHH	Crystal structure of Se-Met derivative CLASP2 in complex with CLIP170	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; cytosol

Antibody reliability (HPA): IF supported

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)

Type	Positions
Phosphoserine	8, 14, 316, 327, 330, 360, 368, 370, 407, 455, 459, 463, 478, 489, 507, 525, 529, 585, 587, 596, 621, 627, 892, 952, 955, 1013, 1029
Phosphothreonine	787

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 microtubule plus ends …
499	phosphomimetic mutant that reduces mapre1 binding; when associated with d-503; d-507; d-525; d-529; d-533; d-537 and d-541.
503	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-507; d-525; d-529; d-533; d-537 and d-541.
507	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-525; d-529; d-533; d-537 and d-541.
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 microtubule plus ends …
525	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-507; d-529; d-533; d-537 and d-541.
529	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-507; d-525; d-533; d-537 and d-541.
533	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-507; d-525; d-529; d-537 and d-541.
537	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-507; d-525; d-529; d-533 and d-541.
541	phosphomimetic mutant that reduces mapre1 binding; when associated with d-499; d-503; d-507; d-525; d-529; d-533 and d-537.
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

6 curated (TAS) of 23; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

23 pathways:

ID	Pathway	Evidence
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	curated
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation	curated
R-HSA-68877	Mitotic Prometaphase	curated
R-HSA-5663220	RHO GTPases Activate Formins	curated
R-HSA-2500257	Resolution of Sister Chromatid Cohesion	curated
R-HSA-2467813	Separation of Sister Chromatids	curated
R-HSA-141424	Amplification of signal from the kinetochores	—
R-HSA-422475	Axon guidance	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69620	Cell Cycle Checkpoints	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-1266738	Developmental Biology	—
R-HSA-68886	M Phase	—
R-HSA-68882	Mitotic Anaphase	—
R-HSA-2555396	Mitotic Metaphase and Anaphase	—
R-HSA-69618	Mitotic Spindle Checkpoint	—
R-HSA-9675108	Nervous system development	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-428890	Role of ABL in ROBO-SLIT signaling	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-376176	Signaling by ROBO receptors	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—

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 (31): microtubule cytoskeleton organization (GO:0000226), 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), spindle organization (GO:0007051), establishment of cell polarity (GO:0030010), establishment or maintenance of microtubule cytoskeleton polarity (GO:0030951), microtubule polymerization (GO:0046785), regulation of focal adhesion assembly (GO:0051893)

GO Molecular Function (8): 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), microtubule plus end polymerase activity (GO:0061863)

GO Cellular Component (25): 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), spindle (GO:0005819), cytoskeleton (GO:0005856), focal adhesion (GO:0005925), mitotic spindle (GO:0072686)

Reactome top-level categories

15 top-level categories:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
Signaling by ROBO receptors	1
RHO GTPase Effectors	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Axon guidance	1
Nervous system development	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle	1
Cell Cycle Checkpoints	1

GO top-level categories

showing 60 of 77 GO namespaces:

Category	Terms
cellular anatomical structure	5
microtubule cytoskeleton organization	4
cytoplasm	4
microtubule-based process	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
exocytosis	1
regulation of exocytosis	1
positive regulation of secretion by cell	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
protein binding	1
tubulin binding	1
microtubule binding	1
actin binding	1
protein-containing complex binding	1
protein kinase binding	1
binding	1
cytoskeletal protein binding	1
transferase activity	1
catalytic activity, acting on a protein	1
condensed chromosome, centromeric region	1
intracellular membraneless organelle	1
supramolecular complex	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 39 of 65 annotations. The rest are phylogenetic / computational / electronic (IEA).

39 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi organization	BP	mutant phenotype
basement membrane organization	BP	mutant phenotype
exit from mitosis	BP	mutant phenotype
microtubule anchoring	BP	mutant phenotype
microtubule cytoskeleton organization	BP	mutant phenotype
microtubule nucleation	BP	mutant phenotype
microtubule organizing center organization	BP	mutant phenotype
mitotic spindle organization	BP	mutant phenotype
negative regulation of focal adhesion assembly	BP	mutant phenotype
negative regulation of stress fiber assembly	BP	mutant phenotype
negative regulation of wound healing, spreading of epidermal cells	BP	mutant phenotype
platelet-derived growth factor receptor-beta signaling pathway	BP	direct assay
positive regulation of epithelial cell migration	BP	mutant phenotype
positive regulation of exocytosis	BP	mutant phenotype
positive regulation of extracellular matrix disassembly	BP	mutant phenotype
presynaptic cytoskeleton organization	BP	direct assay
regulation of actin cytoskeleton organization	BP	direct assay
regulation of axon extension	BP	direct assay
regulation of microtubule polymerization	BP	direct assay
regulation of microtubule polymerization or depolymerization	BP	mutant phenotype
regulation of microtubule-based process	BP	mutant phenotype
Golgi apparatus	CC	direct assay
axonal growth cone	CC	direct assay
basal cortex	CC	direct assay
cell cortex	CC	direct assay
cell leading edge	CC	direct assay
cortical microtubule plus-end	CC	direct assay
cytoplasmic microtubule	CC	direct assay
glutamatergic synapse	CC	direct assay
membrane	CC	high-throughput assay
microtubule	CC	direct assay
plasma membrane	CC	direct assay
ruffle membrane	CC	direct assay
trans-Golgi network	CC	direct assay
actin filament binding	MF	direct assay
dystroglycan binding	MF	physical interaction
microtubule binding	MF	direct assay
microtubule plus-end binding	MF	direct assay
protein tyrosine kinase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,142 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLASP2	CLASRP	Q8N2M8	954
CLASP2	CLIP1	P30622	926
CLASP2	CLIP2	Q9UDT6	902
CLASP2	GSK3B	P49841	639
CLASP2	CKAP5	Q14008	616
CLASP2	MAPRE3	Q9UPY8	596
CLASP2	PHLDB2	Q86SQ0	572
CLASP2	MAP4	P27816	538
CLASP2	MACF1	Q9UPN3	536
CLASP2	GCC2	Q8IWJ2	535
CLASP2	SLAIN2	Q9P270	510
CLASP2	CENPE	Q02224	507
CLASP2	PIK3C3	Q8NEB9	503
CLASP2	BUB1B	O60566	499
CLASP2	CENPF	P49454	496

IntAct

Human interaction partners of CLASP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

17 partners by confidence:

Partner	Interaction type	MIscore	Records
MAPRE1	association	0.850	4
YWHAZ	association	0.670	1
YWHAE	physical association	0.650	2
CENPE	association	0.530	1
DCAF7	association	0.510	2
SFN	physical association	0.470	1
ADRB2	physical association	0.370	1
AKT1	physical association	0.370	1
CCR4	physical association	0.370	1
ERBB2	physical association	0.370	1
TUBA1A	association	0.350	3
APOD	association	0.350	1
ID2	association	0.350	1
PEA15	association	0.350	1
TAF5L	association	0.350	1
AKAP9	colocalization	0.270	1
PYGM	physical association	0.000	1

BioGRID (237 interactions; top human partners by supporting records): MAPRE1 (Reconstituted Complex; 9 records), YWHAB (Affinity Capture-MS; 6 records), YWHAE (Affinity Capture-MS; 5 records), YWHAG (Affinity Capture-MS; 5 records), YWHAH (Affinity Capture-MS; 5 records), YWHAQ (Affinity Capture-MS; 5 records), YWHAZ (Affinity Capture-MS; 5 records), CLASP1 (Affinity Capture-MS; 4 records), MARK3 (Affinity Capture-MS; 4 records), DCTN1 (Proximity Label-MS; 3 records), FAM43A (Affinity Capture-MS; 3 records), GSK3B (Affinity Capture-MS; 3 records), LYPD3 (Affinity Capture-MS; 3 records), MARK2 (Affinity Capture-MS; 3 records), ATG16L1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 8 of 9 signaling 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 17 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
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	45.4×	3e-06
Cell Cycle Checkpoints	5	26.0×	2e-05
RHO GTPase Effectors	6	24.0×	5e-06
Mitotic Prometaphase	5	20.4×	5e-05
M Phase	5	19.4×	5e-05
Cell Cycle, Mitotic	6	17.0×	2e-05
Cell Cycle	8	16.9×	6e-07
Membrane Trafficking	7	15.3×	6e-06

Disease & clinical

Genetic variants

Variant evidence for CLASP2: 180 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	16
Benign	11

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 3,456):

Position(s)	Effect	Δscore	Sites
3:33501650–33501651	donor_loss	1.0000	5
3:33516021–33516022	donor_loss	1.0000	4
3:33516979–33516980	donor_loss	1.0000	4
3:33538787–33538788	donor_loss	1.0000	4
3:33538945	acceptor_gain	1.0000
3:33544696–33544697	donor_loss	1.0000	5
3:33544842–33544843	acceptor_loss	1.0000	6
3:33551254	donor_gain	1.0000
3:33551396–33551397	acceptor_loss	1.0000	6
3:33559305–33559306	donor_loss	1.0000	5

AlphaMissense

4,513 missense substitutions predicted likely pathogenic (of 9,801 scored), across 979 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M702	9	0.935	0.993
M1201	9	0.905	0.999
M1146	9	0.857	0.985
M193	9	0.848	0.984
D147	8	0.994	0.998
D783	8	0.991	0.998
F1137	8	0.991	1.000
D265	8	0.986	0.995
F703	8	0.986	0.998
F1100	8	0.986	0.999
F1242	8	0.986	1.000
F867	8	0.984	0.999
F699	8	0.982	0.997
F715	8	0.982	0.999
F768	8	0.977	0.998
F712	8	0.975	0.996
D654	8	0.973	0.996
F856	8	0.972	0.999
D267	8	0.970	0.988
F722	8	0.970	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.78e-07
Rectum Adenocarcinoma (validation)	favorable	7.99e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000462
Kidney Chromophobe (TCGA)	unfavorable	0.000647

Disease associations

OMIM: gene MIM:605853 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST012490_168	Femur bone mineral density x serum urate levels interaction	9e-10
GCST009391_1208	Metabolite levels	1e-6
GCST009391_1823	Metabolite levels	5e-6

EFO canonical traits (from GWAS)

4 canonical traits:

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 (CPIC guideline: no)

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	affects cotreatment, decreases expression	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)

Via MONDO — disease-level, not drug-specific.