CLASP1

Summary

CLASP1 (cytoplasmic linker associated protein 1, HGNC:17088) is a protein-coding gene on chromosome 2q14.2-q14.3, encoding CLIP-associating protein 1 (Q7Z460). Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules.

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

Source: NCBI Gene 23332 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 23
• Clinical variants (ClinVar): 1,056 total — 12 pathogenic, 21 likely-pathogenic (top 3% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 8 regions constrained (≈1% of expected missense variation)
• GTEx eGene: eQTL in 14 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 19
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.24 (highly constrained)
• MANE Select transcript: NM_001395891

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17088
Approved symbol	CLASP1
Name	cytoplasmic linker associated protein 1
Location	2q14.2-q14.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0622, MAST1
Ensembl gene	ENSG00000074054
Ensembl biotype	protein_coding
OMIM	605852
Entrez	23332

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 43 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000696935

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

ENST00000696935, ENST00000263710, ENST00000409078, ENST00000418989, ENST00000430234, ENST00000449975, ENST00000452274, ENST00000455322, ENST00000463621, ENST00000472776, ENST00000474065, ENST00000480007, ENST00000485112, ENST00000491646, ENST00000541377, ENST00000700754, ENST00000700755, ENST00000877407, ENST00000877408, ENST00000961907, ENST00000961908, ENST00000961909, ENST00000961910, ENST00000961911, ENST00000961912, ENST00000961913, ENST00000961914, ENST00000961915, ENST00000961916, ENST00000961917, ENST00000961918, ENST00000961919, ENST00000961920, ENST00000961921, ENST00000961922, ENST00000961923, ENST00000961924, ENST00000961925, ENST00000961926, ENST00000961927, ENST00000961928, ENST00000961929, ENST00000961930, ENST00000961931, ENST00000961932, ENST00000961933, ENST00000961934, ENST00000961935, ENST00000961936, ENST00000988971, ENST00001145473

RefSeq mRNA: 8 — MANE Select: NM_001395891 NM_001142273, NM_001142274, NM_001207051, NM_001378003, NM_001378004, NM_001378005, NM_001395891, NM_015282

CCDS: CCDS92851, CCDS92852, CCDS92853, CCDS92854

Canonical transcript exons

ENST00000696935 — 41 exons

Exon	Start	End
ENSE00000857213	121448276	121448325
ENSE00000963879	121530247	121530325
ENSE00001020860	121427404	121427430
ENSE00001275221	121448953	121449120
ENSE00001275227	121450913	121450990
ENSE00001341077	121605701	121606180
ENSE00001363713	121430073	121430177
ENSE00001363830	121447337	121447507
ENSE00001363849	121451790	121451849
ENSE00001363854	121457687	121457757
ENSE00001584912	121649372	121649462
ENSE00001614542	121337776	121340947
ENSE00002363734	121404371	121404434
ENSE00002370767	121458840	121458975
ENSE00002407519	121407471	121407715
ENSE00002444616	121401868	121401870
ENSE00003463416	121363172	121363300
ENSE00003469214	121387763	121387906
ENSE00003514732	121348512	121348718
ENSE00003539726	121347038	121347154
ENSE00003551470	121515665	121515762
ENSE00003563240	121462532	121462605
ENSE00003574373	121398322	121398400
ENSE00003582522	121469808	121469960
ENSE00003586143	121461101	121461193
ENSE00003589059	121365094	121365284
ENSE00003609948	121527799	121527890
ENSE00003612658	121387122	121387228
ENSE00003617302	121459980	121460125
ENSE00003625020	121377499	121377649
ENSE00003625435	121503167	121503234
ENSE00003634691	121525845	121525920
ENSE00003634998	121401509	121401672
ENSE00003639293	121528677	121528780
ENSE00003673163	121397140	121397283
ENSE00003688769	121367588	121367831
ENSE00003756210	121410866	121410969
ENSE00003757808	121425139	121425306
ENSE00003968979	121382208	121382324
ENSE00003968980	121418622	121418729
ENSE00003968981	121414141	121414203

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 96.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.1157 / max 1411.1280, expressed in 1820 samples.

Highest expression (Bgee): cortical plate, calcaneal tendon, dorsal motor nucleus of vagus nerve, adrenal tissue, dorsal root ganglion.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CLASP1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	4.9e-22	-0.61	2:121544987:T:C
Esophagus Muscularis	eqtl	4.3e-09	-0.22	2:121454098:G:C
Cells Cultured fibroblasts	eqtl	9.7e-06	-0.18	2:121667662:T:C
Muscle Skeletal	eqtl	5.7e-04	-0.17	2:121493101:T:C
Cells Cultured fibroblasts	sqtl	1.1e-03	-0.41	2:121439850:T:C
Brain Frontal Cortex BA9	eqtl	2.1e-03	-0.21	2:121307579:G:T
Esophagus Gastroesophageal Junction	eqtl	2.7e-03	-0.15	2:121517100:A:G
Thyroid	eqtl	7.1e-03	-0.14	2:121446645:C:T
Ovary	eqtl	8.5e-03	-0.38	2:121293654:A:C
Nerve Tibial	eqtl	9.0e-03	+0.52	2:121615120:A:C
Whole Blood	eqtl	2.4e-02	+0.12	2:120796661:G:A
Adipose Visceral Omentum	eqtl	3.1e-02	-0.28	2:121208334:A:T
Testis	eqtl	3.9e-02	-0.41	2:120952265:A:G
Skin Not Sun Exposed Suprapubic	sqtl	3.9e-02	-0.77	2:121740784:A:T
Liver	eqtl	4.3e-02	-0.61	2:121062382:C:T
Cells EBV-transformed lymphocytes	sqtl	4.5e-02	+0.67	2:121597809:T:C
Skin Sun Exposed Lower leg	eqtl	4.8e-02	-0.09	2:121336599:G:A

FANTOM5 promoters

showing 10 of 11 alternative TSS:

Promoter ID	TPM avg	Samples expressed
30463	20.3271	1799
30460	4.1596	1417
30464	1.0720	680
30458	0.8142	483
30452	0.6678	117
30451	0.6188	113
30449	0.2182	76
30459	0.1915	60
30454	0.0305	15
30457	0.0083	3

Top tissues by expression

showing 100 of 298 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.66	gold quality
calcaneal tendon	UBERON:0003701	95.65	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.54	gold quality
adrenal tissue	UBERON:0018303	95.49	gold quality
dorsal root ganglion	UBERON:0000044	95.04	gold quality
CA1 field of hippocampus	UBERON:0003881	95.01	gold quality
postcentral gyrus	UBERON:0002581	94.77	gold quality
cerebellar vermis	UBERON:0004720	94.72	gold quality
corpus callosum	UBERON:0002336	94.70	gold quality
parietal lobe	UBERON:0001872	94.64	gold quality
inferior olivary complex	UBERON:0002127	93.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.58	gold quality
entorhinal cortex	UBERON:0002728	93.57	gold quality
superior vestibular nucleus	UBERON:0007227	93.29	gold quality
pons	UBERON:0000988	93.18	gold quality
superior frontal gyrus	UBERON:0002661	93.13	gold quality
ventral tegmental area	UBERON:0002691	93.08	gold quality
trigeminal ganglion	UBERON:0001675	93.00	gold quality
ganglionic eminence	UBERON:0004023	92.98	gold quality
medulla oblongata	UBERON:0001896	92.88	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.63	gold quality
sural nerve	UBERON:0015488	92.58	gold quality
renal medulla	UBERON:0000362	92.51	gold quality
substantia nigra pars compacta	UBERON:0001965	92.37	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.33	gold quality
left ventricle myocardium	UBERON:0006566	92.08	gold quality
inferior vagus X ganglion	UBERON:0005363	91.95	gold quality
colonic epithelium	UBERON:0000397	91.93	gold quality
lateral globus pallidus	UBERON:0002476	91.79	gold quality
body of tongue	UBERON:0011876	91.69	gold quality
subthalamic nucleus	UBERON:0001906	91.48	gold quality
ventricular zone	UBERON:0003053	91.42	gold quality
occipital lobe	UBERON:0002021	91.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.41	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.40	gold quality
orbitofrontal cortex	UBERON:0004167	91.40	gold quality
skeletal muscle tissue	UBERON:0001134	91.37	gold quality
vastus lateralis	UBERON:0001379	91.35	silver quality
embryo	UBERON:0000922	91.28	gold quality
muscle of leg	UBERON:0001383	91.28	gold quality
muscle organ	UBERON:0001630	91.20	gold quality
skeletal muscle organ	UBERON:0014892	91.20	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.03	gold quality
cerebellum	UBERON:0002037	90.97	gold quality
Brodmann (1909) area 10	UBERON:0013541	90.96	gold quality
gastrocnemius	UBERON:0001388	90.89	gold quality
primary visual cortex	UBERON:0002436	90.88	gold quality
muscle tissue	UBERON:0002385	90.81	gold quality
quadriceps femoris	UBERON:0001377	90.68	silver quality
cerebellar cortex	UBERON:0002129	90.64	gold quality
cerebellar hemisphere	UBERON:0002245	90.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.30	gold quality
middle temporal gyrus	UBERON:0002771	90.22	gold quality
heart right ventricle	UBERON:0002080	90.11	gold quality
bone marrow cell	CL:0002092	90.02	gold quality
seminal vesicle	UBERON:0000998	90.01	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.89	gold quality
biceps brachii	UBERON:0001507	89.70	gold quality
paraflocculus	UBERON:0005351	89.57	gold quality
myocardium	UBERON:0002349	89.47	gold quality
saphenous vein	UBERON:0007318	89.43	gold quality
urethra	UBERON:0000057	89.38	gold quality
temporal lobe	UBERON:0001871	89.38	gold quality
endothelial cell	CL:0000115	89.34	silver quality
superior surface of tongue	UBERON:0007371	89.24	gold quality
choroid plexus epithelium	UBERON:0003911	89.19	gold quality
cerebral cortex	UBERON:0000956	89.14	gold quality
frontal cortex	UBERON:0001870	89.08	gold quality
tonsil	UBERON:0002372	89.03	gold quality
neocortex	UBERON:0001950	88.93	gold quality
stromal cell of endometrium	CL:0002255	88.73	gold quality
tongue	UBERON:0001723	88.66	gold quality
deltoid	UBERON:0001476	88.65	silver quality
Ammon’s horn	UBERON:0001954	88.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.51	gold quality
brain	UBERON:0000955	88.46	gold quality
telencephalon	UBERON:0001893	88.43	gold quality
gluteal muscle	UBERON:0002000	88.37	gold quality
cardia of stomach	UBERON:0001162	88.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.33	gold quality
central nervous system	UBERON:0001017	88.29	gold quality
cardiac ventricle	UBERON:0002082	88.12	gold quality
tibialis anterior	UBERON:0001385	88.06	silver quality
forebrain	UBERON:0001890	87.99	gold quality
heart left ventricle	UBERON:0002084	87.99	gold quality
blood vessel layer	UBERON:0004797	87.98	gold quality
vena cava	UBERON:0004087	87.88	silver quality
prefrontal cortex	UBERON:0000451	87.84	gold quality
right frontal lobe	UBERON:0002810	87.76	gold quality
heart	UBERON:0000948	87.75	gold quality
penis	UBERON:0000989	87.65	gold quality
nipple	UBERON:0002030	87.65	gold quality
frontal pole	UBERON:0002795	87.54	gold quality
popliteal artery	UBERON:0002250	87.53	gold quality
tibial artery	UBERON:0007610	87.51	gold quality
midbrain	UBERON:0001891	87.48	gold quality
lower esophagus	UBERON:0013473	87.43	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	48.94
E-ANND-3	yes	5.85

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 133 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Postcentral gyrus	tissue	158.1
Locus coeruleus	tissue	89.5
Hippocampus	tissue	77.0	high
Postcentral gyrus	tissue	71.8
Locus coeruleus	tissue	61.1
Hippocampus	tissue	59.5	medium
Choroid plexus	tissue	56.9
Hippocampal formation	tissue	55.0
Olfactory bulb	tissue	51.1
Nucleus accumbens	tissue	49.5
Cerebral cortex	tissue	48.3	medium
Somatosensory cortex	tissue	48.3
Cerebellum	tissue	47.9	medium
Prefrontal cortex	tissue	46.2
Motor cortex	tissue	45.7
Occipital cortex	tissue	45.6
Entorhinal cortex	tissue	44.8
Spinal cord	tissue	44.6
Retrosplenial cortex	tissue	44.3
Temporal cortex	tissue	43.8
Insular cortex	tissue	43.8
Retrosplenial and cingulate cortex	tissue	43.2
Amygdala	tissue	42.3
Retina	tissue	42.1
Thalamus	tissue	41.1
Cerebral cortex	tissue	41.1	high
Somatosensory cortex	tissue	41.1
Skeletal muscle	tissue	40.2	low
Pons	tissue	39.7
Superior colliculi	tissue	39.0
Midbrain	tissue	38.7
Substantia nigra	tissue	37.3
Cerebellum	tissue	36.5	medium
Occipital cortex	tissue	36.2
Hypothalamus	tissue	36.0
Prefrontal cortex	tissue	35.3
Pons	tissue	35.3
Medulla oblongata	tissue	35.2
Motor cortex	tissue	35.0
Basal ganglia	tissue	34.7	low
Septum	tissue	34.5
Insular cortex	tissue	34.4
Thalamus	tissue	33.9
Hippocampal formation	tissue	33.9
Periaqueductal gray	tissue	33.8
Ventral forebrain	tissue	33.6
Retrosplenial and cingulate cortex	tissue	33.4
Entorhinal cortex	tissue	32.9
Temporal cortex	tissue	32.7
Retrosplenial cortex	tissue	31.9
Superior colliculi	tissue	30.5
Putamen	tissue	29.6
Amygdala	tissue	27.9
Hypothalamus	tissue	27.3
Midbrain	tissue	27.1
Spinal cord	tissue	26.7
Corpus callosum	tissue	25.0
Tongue	tissue	24.6
Frontal cortex	tissue	24.4
Medulla oblongata	tissue	22.3

Brain sub-regions (HPA Brain Atlas): detected in 381; highest nTPM — Precentral gyrus (173.8), Posterior insular cortex (129.5), Inferior frontal gyrus, opercular (124.7), Parietal operculum (122.6), Frontal eye field (119.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KAT5, ZHX2

miRNA regulators (miRDB)

Targeting CLASP1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 126 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
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-3163	100.00	77.23	8605
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-219A-5P	99.91	73.36	735

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.237, missense Z 3.48 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000263710 splits into 8 regions with different missense tolerance; 1 is missense-constrained (≈1% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:121,340,864–121,365,149	148 / 247.5	0.60	no
2:121,365,150–121,387,811	336 / 358.0	0.94	no
2:121,387,812–121,401,611	90 / 159.3	0.56	no
2:121,401,612–121,449,098	445 / 535.5	0.83	no
2:121,449,099–121,461,176	113 / 239.5	0.47	no
2:121,461,177–121,462,552	17 / 16.1	1.05	no
2:121,462,553–121,462,595	2 / 16.6	0.12	yes (p 3.4e-04)
2:121,462,596–121,605,895	282 / 359.9	0.78	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 17)

• These results suggest that CLASP1 is required at kinetochores to regulate the dynamic behavior of attached microtubules. (PMID:14504462)
• 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)
• A fusion protein of the putative microtubule-binding domain (1-662 out of 1289 residues) of hOrbit1 & GFP was transfected into human cells. The GFP-hOrbit1 N-terminal fragment binds to the newly formed microtubules rather than the pre-formed ones. (PMID:16145243)
• CLASPs provide apparent stabilization of microtubules by locally reducing the amplitude of growth/shortening episodes at the microtubule ends. (PMID:16866869)
• Data propose that PRC1 forms a link between stabilization of CLASP1 association with central spindle microtubules and anti-parallel microtubule elongation. (PMID:19561070)
• A role for microtubules that form at the Golgi membranes is identified in a manner dependent on the microtubule regulators CLASPs. (PMID:19701196)
• Data show that CLASP1-astrin-Kif2b complex acts as a central switch at kinetochores that defines mitotic progression and promotes fidelity by temporally regulating kinetochore-microtuble attachments. (PMID:20852589)
• Data show that the tau-related protein MAP4 and the microtubule rescue factor CLASP1 are essential for maintaining spindle position and the correct cell-division axis. (PMID:21822276)
• 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)
• Acute silencing of CLASP1, a +TIP that participates in microtubule stabilization at the cell periphery, impairs trypomastigote internalization without diminishing the capacity for calcium-regulated lysosome exocytosis. (PMID:23107073)
• findings highlight the common mechanistic use of TOG domains in XMAP215 and CLASP families to regulate MT dynamics and suggest that differential TOG domain architecture may confer distinct functions to these critical cytoskeletal regulators (PMID:23727231)
• our data suggest a model for mitotic spindle positioning in which RanGTP and CLASP1 cooperate to align the spindle along the long axis of the dividing cell. (PMID:23783028)
• The epiblast epithelial status was maintained by anchoring microtubules to the basal cortex via CLIP1, a microtubule plus-end tracking protein, and Dystroglycan, a transmembrane protein that bridges the cytoskeleton and basement membrane (BM). (PMID:23940118)
• 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)
• 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)
• catastrophe inhibition by SLAIN2 and CLASP1 supports mesenchymal cell shape in soft 3D matrices by enabling microtubules to perform a load-bearing function. (PMID:27939686)
• Differential regulation of single microtubules and bundles by a three-protein module. (PMID:34083810)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	clasp1a	ENSDARG00000010280
danio_rerio		ENSDARG00000104358
danio_rerio		ENSDARG00000115906
mus_musculus	Clasp1	ENSMUSG00000064302
rattus_norvegicus	Clasp1	ENSRNOG00000002376

Paralogs (3): CLASP2 (ENSG00000163539), TOGARAM2 (ENSG00000189350), TOGARAM1 (ENSG00000198718)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923957) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal liver morphology	1
enlarged liver	1
abnormal spleen morphology	1
enlarged spleen	1
enlarged lymph nodes	1
abnormal testis morphology	1
small testis	1
hyperactivity	1
small heart	1
enlarged epididymis	1
hydrometra	1
preweaning lethality, complete penetrance	1
preweaning lethality, incomplete penetrance	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 elegans	Q03609	82.1%	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
CLASP1-AS1	ncRNA	107985942
NIFK-AS1	ncRNA	254128
TFCP2L1	protein-coding	29842
RNU4ATAC	snRNA	100151683
NIFK	protein-coding	84365
TSN	protein-coding	7247

Protein

Protein identifiers

CLIP-associating protein 1 — Q7Z460 (reviewed: Q7Z460)

Alternative names: Cytoplasmic linker-associated protein 1, Multiple asters homolog 1, Protein Orbit homolog 1

All UniProt accessions (8): A0A8V8TLP7, A0A8V8TQK9, A0A8V8TRF6, C9J151, C9JP76, Q7Z460, F8WA11, H0Y5T1

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.

Subunit / interactions. Interacts with CLIP2, ERC1, MAPRE1, MAPRE3, microtubules, PHLDB2 and RSN. The interaction with ERC1 may be mediated by PHLDB2. Interacts with GCC2; recruits CLASP1 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.

Similarity. Belongs to the CLASP family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q7Z460-1	1	yes
Q7Z460-2	2
Q7Z460-3	3
Q7Z460-4	4
Q7Z460-5	5

RefSeq proteins (8): NP_001135745, NP_001135746, NP_001193980, NP_001364932, NP_001364933, NP_001364934, NP_001382820, NP_056097 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR021133	HEAT_type_2	Repeat
IPR024395	CLASP_N_dom	Domain
IPR034085	TOG	Domain
IPR048491	XMAP215_CLASP_TOG	Domain
IPR057546	HEAT_GCN1	Domain

Pfam: PF12348, PF21041, PF23271

UniProt features (104 total): helix 35, modified residue 27, compositionally biased region 10, region of interest 9, splice variant 8, repeat 7, sequence conflict 2, turn 2, chain 1, coiled-coil region 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
6MQ7	Crystal structure of CLASP1 TOG2 domain at 1.78A resolution	X-RAY DIFFRACTION	1.78
4K92	A Cryptic TOG Domain with a Distinct Architecture Underlies CLASP-Dependent Bipolar …	X-RAY DIFFRACTION	2
6MQ5	Structure of human CLASP1 TOG1	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z460-F1	69.44	0.45

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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 (27)

Type	Positions
Phosphoserine	246, 545, 548, 558, 559, 568, 600, 636, 646, 647, 649, 684, 688, 695, 705, 714, 787, 797, 823, 1091, 1113, 1196, 1223
Phosphothreonine	656, 711, 1095, 1099

Function

Pathways and Gene Ontology

Reactome pathways

13 curated (TAS) of 35; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

35 pathways:

ID	Pathway	Evidence
R-HSA-8854518	AURKA Activation by TPX2	curated
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	curated
R-HSA-5620912	Anchoring of the basal body to the plasma membrane	curated
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation	curated
R-HSA-380259	Loss of Nlp from mitotic centrosomes	curated
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome	curated
R-HSA-68877	Mitotic Prometaphase	curated
R-HSA-5663220	RHO GTPases Activate Formins	curated
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes	curated
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes	curated
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition	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-380287	Centrosome maturation	—
R-HSA-5617833	Cilium Assembly	—
R-HSA-1266738	Developmental Biology	—
R-HSA-69275	G2/M Transition	—
R-HSA-68886	M Phase	—
R-HSA-68882	Mitotic Anaphase	—
R-HSA-453274	Mitotic G2-G2/M phases	—
R-HSA-2555396	Mitotic Metaphase and Anaphase	—
R-HSA-69618	Mitotic Spindle Checkpoint	—
R-HSA-9675108	Nervous system development	—
R-HSA-1852241	Organelle biogenesis and maintenance	—
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: 564 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, TAATAAT_MIR126, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, MYOGENIN_Q6, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_VESICLE_LOCALIZATION, GOBP_MICROTUBULE_ANCHORING

GO Biological Process (26): microtubule cytoskeleton organization (GO:0000226), microtubule bundle formation (GO:0001578), 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), astral microtubule organization (GO:0030953), microtubule organizing center organization (GO:0031023), negative regulation of microtubule polymerization or depolymerization (GO:0031111), positive regulation of microtubule polymerization (GO:0031116), microtubule anchoring (GO:0034453), establishment of mitotic spindle localization (GO:0040001), positive regulation of exocytosis (GO:0045921), establishment of spindle orientation (GO:0051294), cell division (GO:0051301), negative regulation of stress fiber assembly (GO:0051497), regulation of focal adhesion assembly (GO:0051893), basement membrane organization (GO:0071711), positive regulation of extracellular matrix disassembly (GO:0090091), mitotic spindle assembly (GO:0090307), negative regulation of wound healing, spreading of epidermal cells (GO:1903690), establishment of cell polarity (GO:0030010), regulation of microtubule polymerization or depolymerization (GO:0031110)

GO Molecular Function (6): dystroglycan binding (GO:0002162), microtubule binding (GO:0008017), kinetochore binding (GO:0043515), microtubule plus-end binding (GO:0051010), protein binding (GO:0005515), tubulin binding (GO:0015631)

GO Cellular Component (19): kinetochore (GO:0000776), Golgi apparatus (GO:0005794), centrosome (GO:0005813), microtubule organizing center (GO:0005815), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), spindle microtubule (GO:0005876), cytoplasmic microtubule (GO:0005881), cell cortex (GO:0005938), membrane (GO:0016020), cortical microtubule cytoskeleton (GO:0030981), centrosomal corona (GO:0031592), microtubule plus-end (GO:0035371), basal cortex (GO:0045180), mitotic spindle (GO:0072686), spindle (GO:0005819), cytoskeleton (GO:0005856), microtubule (GO:0005874), focal adhesion (GO:0005925)

Reactome top-level categories

12 top-level categories:

Category	Pathways
Mitotic Prometaphase	3
G2/M Transition	2
Centrosome maturation	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Signaling by ROBO receptors	1
Assembly of the 9+0 primary cilium	1
RHO GTPase Effectors	1
M Phase	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1

GO top-level categories

showing 60 of 66 GO namespaces:

Category	Terms
microtubule cytoskeleton organization	4
cytoplasm	4
microtubule cytoskeleton	4
cellular anatomical structure	4
intracellular membraneless organelle	3
microtubule-based process	2
microtubule polymerization	2
mitotic cell cycle	2
spindle organization	2
microtubule cytoskeleton organization involved in mitosis	2
cellular process	2
establishment of spindle localization	2
binding	2
spindle	2
microtubule	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
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
cytoplasmic microtubule organization	1
cellular component organization	1
microtubule polymerization or depolymerization	1
regulation of microtubule polymerization or depolymerization	1
negative regulation of cytoskeleton organization	1
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
positive regulation of protein polymerization	1
positive regulation of supramolecular fiber organization	1
exocytosis	1
regulation of exocytosis	1
positive regulation of secretion by cell	1
establishment of cell polarity	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of cell-substrate junction assembly	1
protein binding	1
tubulin binding	1
microtubule binding	1
cytoskeletal protein binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
endomembrane system	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
spindle microtubule	1
cell periphery	1
cortical cytoskeleton	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 35 of 52 annotations. The rest are phylogenetic / computational / electronic (IEA).

35 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi organization	BP	mutant phenotype
astral microtubule organization	BP	mutant phenotype
basement membrane organization	BP	mutant phenotype
cell division	BP	direct assay
establishment of mitotic spindle localization	BP	mutant phenotype
establishment of spindle orientation	BP	direct assay
exit from mitosis	BP	mutant phenotype
microtubule anchoring	BP	mutant phenotype
microtubule bundle formation	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 microtubule depolymerization	BP	mutant phenotype
negative regulation of microtubule polymerization or depolymerization	BP	mutant phenotype
negative regulation of stress fiber assembly	BP	mutant phenotype
negative regulation of wound healing, spreading of epidermal cells	BP	mutant phenotype
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
regulation of focal adhesion assembly	BP	mutant phenotype
Golgi apparatus	CC	direct assay
basal cortex	CC	direct assay
cell cortex	CC	direct assay
centrosomal corona	CC	direct assay
centrosome	CC	direct assay
cortical microtubule cytoskeleton	CC	direct assay
cytoplasmic microtubule	CC	direct assay
kinetochore	CC	direct assay
membrane	CC	high-throughput assay
spindle microtubule	CC	direct assay
dystroglycan binding	MF	physical interaction
kinetochore binding	MF	mutant phenotype
microtubule binding	MF	direct assay
microtubule plus-end binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,238 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLASP1	CLASRP	Q8N2M8	955
CLASP1	CLIP1	P30622	911
CLASP1	CLIP2	Q9UDT6	898
CLASP1	KIF2B	Q8N4N8	618
CLASP1	MAPRE3	Q9UPY8	616
CLASP1	PHLDB2	Q86SQ0	570
CLASP1	KNSTRN	Q9Y448	557
CLASP1	CLCN1	P35523	553
CLASP1	SLAIN2	Q9P270	549
CLASP1	KIF2C	Q99661	523
CLASP1	CENPE	Q02224	522
CLASP1	KIF18A	Q8NI77	517
CLASP1	CAMSAP1	Q5T5Y3	517
CLASP1	DCTN1	Q14203	514
CLASP1	NDC80	O14777	500

IntAct

Human interaction partners of CLASP1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

15 partners by confidence:

Partner	Interaction type	MIscore	Records
YWHAG	physical association	0.900	2
YWHAE	physical association	0.650	2
KIF1B	association	0.560	3
SPAG5	physical association	0.560	1
SFN	physical association	0.470	1
ARHGEF38	physical association	0.400	1
PHLDB2	physical association	0.400	1
SRP14	physical association	0.400	1
HTT	physical association	0.370	2
KIF2A	association	0.350	1
CBY1	physical association	0.000	1
DISC1	physical association	0.000	1
FMR1	physical association	0.000	1
MTNR1A	physical association	0.000	1
MTNR1B	physical association	0.000	1

BioGRID (199 interactions; top human partners by supporting records): YWHAG (Affinity Capture-MS; 7 records), YWHAB (Affinity Capture-MS; 6 records), YWHAE (Affinity Capture-MS; 5 records), YWHAH (Affinity Capture-MS; 5 records), YWHAQ (Affinity Capture-MS; 5 records), CENPJ (Proximity Label-MS; 4 records), CLASP2 (Affinity Capture-MS; 4 records), MAPRE1 (Reconstituted Complex; 4 records), CLIP1 (Proximity Label-MS; 3 records), CLIP2 (Affinity Capture-Western; 3 records), DCTN1 (Proximity Label-MS; 3 records), MARK3 (Affinity Capture-MS; 3 records), SYBU (Affinity Capture-MS; 3 records), YWHAZ (Affinity Capture-MS; 3 records), ARHGEF38 (Affinity Capture-MS; 2 records)

SIGNOR signaling

4 signaling interactions:

A	Effect	B	Mechanism
TPX2	“up-regulates activity”	CLASP1	binding
CLASP1	“up-regulates activity”	CLIP1	binding
CLASP1	“up-regulates activity”	CLIP2	binding
CLASP1	“up-regulates activity”	MAPRE1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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
Membrane Trafficking	5	16.9×	7e-05
Vesicle-mediated transport	5	15.8×	8e-05

Disease & clinical

Genetic variants

Variant evidence for CLASP1: 1,056 ClinVar records (33 pathogenic / likely pathogenic); 23 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,056 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	21
Uncertain significance	638
Likely benign	236
Benign	43

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 33 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
30179	NR_023343.3(RNU4ATAC):n.55G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	10
599361	NM_014975.3(MAST1):c.1549G>A (p.Gly517Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
30180	NR_023343.1:n.30G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	5
2580895	NM_014975.3(MAST1):c.3530C>T (p.Pro1177Leu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
30182	NC_000002.12:g.121530929G>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
812960	NC_000002.12:g.121530995A>T	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1319774	NM_014975.3(MAST1):c.873C>A (p.Cys291Ter)	Pathogenic	criteria provided, single submitter	1
1698956	NM_014975.3(MAST1):c.1568T>C (p.Leu523Pro)	Pathogenic	criteria provided, single submitter	1
599359	NM_014975.3(MAST1):c.826AAG[1] (p.Lys277del)	Likely pathogenic	criteria provided, single submitter	2
692040	NM_001395891.1(CLASP1):c.196-562G>T	Likely pathogenic	criteria provided, single submitter	2
977779	NR_023343.3(RNU4ATAC):n.120T>G	Likely pathogenic	criteria provided, single submitter	2
1224468	NM_001395891.1(CLASP1):c.196-677del	Likely pathogenic	criteria provided, single submitter	1
1679266	NM_014975.3(MAST1):c.1580C>A (p.Thr527Asn)	Likely pathogenic	criteria provided, single submitter	1
1805144	NM_014975.3(MAST1):c.1594G>C (p.Glu532Gln)	Likely pathogenic	criteria provided, single submitter	1
2501671	NM_014975.3(MAST1):c.1298T>C (p.Phe433Ser)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CLASP1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 6,615):

Position(s)	Effect	Δscore	Sites
19:12847451–12847452	donor_loss	1.0000	5
19:12847610–12847611	acceptor_loss	1.0000	5
19:12847674	donor_gain	1.0000
19:12847846–12847847	acceptor_loss	1.0000	5
19:12848058–12848059	donor_loss	1.0000	3
19:12851926	acceptor_gain	1.0000
19:12852220	donor_gain	1.0000
19:12852396–12852397	donor_loss	1.0000	5
19:12858529–12858530	acceptor_loss	1.0000	3
19:12858737	donor_gain	1.0000

AlphaMissense

5,904 missense substitutions predicted likely pathogenic (of 10,153 scored), across 1,293 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
M904	9	0.952	0.997
M1390	9	0.908	0.992
M1445	9	0.905	0.999
M1009	9	0.877	0.989
M980	9	0.856	0.997
M1511	9	0.843	0.977
D379	8	0.994	0.998
D178	8	0.992	0.999
F905	8	0.991	0.999
D985	8	0.991	0.999
F223	8	0.990	1.000
D907	8	0.990	0.998
F1069	8	0.989	1.000
D102	8	0.988	0.998
D497	8	0.987	0.996
F1381	8	0.986	0.999
F1486	8	0.986	1.000
F901	8	0.984	0.998
D1357	8	0.984	0.997
F914	8	0.983	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.88e-05
Lung Squamous Cell Carcinoma (validation)	favorable	0.000162
Rectum Adenocarcinoma (validation)	favorable	0.000246
Glioblastoma Multiforme (validation)	favorable	0.000275
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000952

Disease associations

OMIM: gene MIM:605852 | disease phenotypes: MIM:300258, MIM:616651, MIM:618273, MIM:210710, MIM:226960, MIM:236600, MIM:616331

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations	Strong	Autosomal dominant	4
focal epilepsy	Limited	Autosomal dominant
complex neurodevelopmental disorder	No Known Disease Relationship	Autosomal dominant

Mondo (10): RNU4ATAC spectrum disorder (MONDO:0100558), Roifman syndrome (MONDO:0014722), mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MONDO:0032648), microcephalic osteodysplastic primordial dwarfism type I (MONDO:0008871), Lowry-Wood syndrome (MONDO:0009191), retinal disorder (MONDO:0005283), hydrocephalus, nonsyndromic, autosomal recessive 1 (MONDO:0009360), autosomal dominant Robinow syndrome 2 (MONDO:0014591), focal epilepsy (MONDO:0005384), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (6): Roifman syndrome (Orphanet:353298), Lowry-Wood syndrome (Orphanet:1824), Microcephalic osteodysplastic primordial dwarfism types I and III (Orphanet:2636), Congenital hydrocephalus (Orphanet:2185), Autosomal dominant Robinow syndrome (Orphanet:3107), Robinow syndrome (Orphanet:97360)

HPO phenotypes

19 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000657	Oculomotor apraxia
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001344	Absent speech
HP:0002078	Truncal ataxia
HP:0002119	Ventriculomegaly
HP:0002317	Unsteady gait
HP:0002365	Hypoplasia of the brainstem
HP:0002540	Inability to walk
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0007074	Thick corpus callosum
HP:0007165	Periventricular heterotopia
HP:0009879	Simplified gyral pattern

GWAS associations

23 associations:

Study	Trait	p-value
GCST90002386_599	High light scatter reticulocyte percentage of red cells	5e-64
GCST90002392_612	Mean corpuscular volume	3e-33
GCST005993_60	Mean corpuscular hemoglobin	4e-26
GCST010204_213	Low density lipoprotein cholesterol levels	2e-24
GCST004612_209	High light scatter reticulocyte percentage of red cells	1e-21
GCST90002390_467	Mean corpuscular hemoglobin	1e-20
GCST005996_44	Red blood cell count	5e-19
GCST90002387_12	Immature fraction of reticulocytes	3e-18
GCST90002406_35	Reticulocyte fraction of red cells	1e-17
GCST90002397_784	Mean spheric corpuscular volume	3e-17
GCST004611_44	High light scatter reticulocyte count	4e-16
GCST90002396_119	Mean reticulocyte volume	2e-15
GCST006031_5	Potassium levels	2e-13
GCST90002393_69	Monocyte count	2e-13
GCST004625_208	Monocyte count	9e-10
GCST004049_10	Cough in response to angiotensin-converting enzyme inhibitor drugs	1e-9
GCST006030_2	Chloride levels	2e-9
GCST007281_1	HDL cholesterol x physical activity interaction (1df test)	8e-9
GCST010173_122	Triglyceride levels	8e-9
GCST005316_510	Intelligence (MTAG)	3e-8
GCST004049_9	Cough in response to angiotensin-converting enzyme inhibitor drugs	1e-7
GCST007282_15	HDL cholesterol x physical activity interaction (2df test)	4e-7
GCST009391_1793	Metabolite levels	7e-7

EFO canonical traits (from GWAS)

14 canonical traits:

EFO ID	Trait name
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0007986	reticulocyte count
EFO:0005091	monocyte count
EFO:0004337	intelligence
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0009283	potassium measurement
EFO:0003940	physical activity
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007805	HDL cholesterol change measurement
EFO:0010549	xanthosine measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors

4 disease descriptors:

Descriptor	Name	Tree numbers
D004828	Epilepsies, Partial	C10.228.140.490.360
D012164	Retinal Diseases	C11.768
C537038	Lowry Wood syndrome *(supp.)*
C535866	Roifman syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724765 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	3
Valproic Acid	decreases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	affects cotreatment, increases methylation	1
decabromobiphenyl ether	decreases expression	1
arsenite	decreases reaction, affects binding	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651121	Binding	Binding affinity to human CLASP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1M0	Abcam K-562 CLASP1 KO	Cancer cell line	Female
CVCL_D2IK	Abcam Raji CLASP1 KO	Cancer cell line	Male
CVCL_SJ13	HAP1 CLASP1 (-) 1	Cancer cell line	Male
CVCL_SJ14	HAP1 CLASP1 (-) 2	Cancer cell line	Male
CVCL_UQ32	Abcam Jurkat CLASP1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 402 trials:

NCT	Phase	Status	Title
NCT00438451	Phase 4	COMPLETED	Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs
NCT00522418	Phase 4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00855738	Phase 4	COMPLETED	A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice
NCT00955357	Phase 4	COMPLETED	Trial to Assess Lacosamide as the First add-on Anti-epileptic Drug Treatment in Patients With Partial-onset Seizures
NCT01190098	Phase 4	COMPLETED	Randomized Controlled Trial to Assess Effects of Lacosamide on Sleep and Wake in Adults With Focal Epilepsy
NCT01235403	Phase 4	COMPLETED	Trial to Assess Optimized Dosage of Lacosamide as add-on Therapy in Patients With Partial Onset Seizure
NCT02208492	Phase 4	COMPLETED	The Effects on Cognitive Function of Levetiracetam (Keppra®) Compared to Carbamazepine (Tegretol®, Carmazepine®) as Monotherapy for Children With Partial Seizure; A Multicentric Randomized Controlled Study
NCT03607851	Phase 4	COMPLETED	Efficacy and Safety of Rapid Titration Protocols of Lacosamide
NCT05748236	Phase 4	UNKNOWN	The Efficacy and Safety of Lamotrigine Versus Carbamazepine in Focal Epilepsy
NCT07193277	Phase 4	RECRUITING	Butylphthalide for Cognitive Impairment in Elderly Patients With Focal Epilepsy
NCT01955135	Phase 4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT07685886	Phase 4	NOT_YET_RECRUITING	MIRACLE-T2D Montelukast Intervention for Renal, Cardiovascular and Eye Health in Type 2 Diabetes
NCT00348530	Phase 4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	Phase 4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	Phase 4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	Phase 4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	Phase 4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	Phase 4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	Phase 4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	Phase 4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	Phase 4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	Phase 4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	Phase 4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	Phase 4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	Phase 4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	Phase 4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	Phase 4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	Phase 4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	Phase 4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05371496	Phase 4	COMPLETED	Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction
NCT05718128	Phase 4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	Phase 4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00391534	Phase 3	TERMINATED	EXTENT: EXtended Tolerability and Efficacy of a Novel Formulation of Oxcarbazepine in a Trial in Partial Epilepsy
NCT00522275	Phase 3	COMPLETED	Determine Safety and Efficacy of Long-term Oral Lacosamide in Patients With Partial Seizures
NCT00655486	Phase 3	COMPLETED	Study to Assess the Long-term Safety of Oral Lacosamide in Subjects With Partial-onset Seizures
NCT00655551	Phase 3	COMPLETED	Safety of Intravenous Lacosamide Dose Followed by Twice Daily Oral Lacosamide in Subjects With Partial-onset Seizures
NCT00908349	Phase 3	COMPLETED	Safety and Tolerability of OXC XR as Adjunctive Therapy in Subjects With Refractory Partial Epilepsy
NCT00957047	Phase 3	COMPLETED	Efficacy and Safety Study of BIA 2-093 in Combination With Other Anti-Epileptic Drugs to Treat Partial Epilepsy
NCT00957372	Phase 3	COMPLETED	Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Epilepsy
NCT00957684	Phase 3	COMPLETED	Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Seizures
NCT00988429	Phase 3	COMPLETED	Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures
NCT02076698	Phase 3	COMPLETED	Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy
NCT02535091	Phase 3	COMPLETED	Safety and Pharmacokinetic Study of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures
NCT05067634	Phase 3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study of Cenobamate in Pediatric Subjects 2-17 Years of Age With Partial-onset (Focal) Seizures
NCT05718817	Phase 3	ENROLLING_BY_INVITATION	An Open-label Study of XEN1101 in Epilepsy
NCT07505004	Phase 3	ACTIVE_NOT_RECRUITING	Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults With Focal Seizures
NCT07563881	Phase 3	RECRUITING	Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
NCT07594119	Phase 3	RECRUITING	Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
NCT07594158	Phase 3	RECRUITING	A Study to Evaluate the Safety, Efficacy, and PK of ONO-2017 in Japanese Patients With POS 2 to 17 Year Olds
NCT00170183	Phase 3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	Phase 3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	Phase 3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	Phase 3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	Phase 3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	Phase 3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	Phase 3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	Phase 3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	Phase 3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	Phase 3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	Phase 3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CLASP1 across ~30M SureChEMBL compounds — explore on Sugi Predict.