CLIP1

Summary

CLIP1 (CAP-Gly domain containing linker protein 1, HGNC:10461) is a protein-coding gene on chromosome 12q24.31, encoding CAP-Gly domain-containing linker protein 1 (P30622). Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton.

The protein encoded by this gene links endocytic vesicles to microtubules. This gene is highly expressed in Reed-Sternberg cells of Hodgkin disease. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6249 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive non-syndromic intellectual disability (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 27
• Clinical variants (ClinVar): 251 total — 1 pathogenic
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• MANE Select transcript: NM_001247997

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10461
Approved symbol	CLIP1
Name	CAP-Gly domain containing linker protein 1
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	CYLN1, CLIP170, CLIP, CLIP-170
Ensembl gene	ENSG00000130779
Ensembl biotype	protein_coding
OMIM	179838
Entrez	6249

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 26 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000302528, ENST00000358808, ENST00000361654, ENST00000501271, ENST00000514271, ENST00000535290, ENST00000536634, ENST00000537004, ENST00000537123, ENST00000537178, ENST00000538120, ENST00000539080, ENST00000540304, ENST00000540539, ENST00000541108, ENST00000541410, ENST00000543205, ENST00000545889, ENST00000620786, ENST00000648993, ENST00000859888, ENST00000859889, ENST00000859890, ENST00000859891, ENST00000859892, ENST00000971569, ENST00000971570, ENST00000971571, ENST00000971572, ENST00000971573, ENST00000971574, ENST00000971575, ENST00000971576, ENST00000971577, ENST00000971578

RefSeq mRNA: 4 — MANE Select: NM_001247997 NM_001247997, NM_001389291, NM_002956, NM_198240

CCDS: CCDS58285, CCDS9232, CCDS9233

Canonical transcript exons

ENST00000620786 — 26 exons

Exon	Start	End
ENSE00000939786	122355115	122355312
ENSE00000939790	122340753	122341697
ENSE00001121508	122347375	122347479
ENSE00001121513	122351111	122351143
ENSE00001222056	122328261	122328426
ENSE00002332882	122332987	122333143
ENSE00002375305	122334027	122334110
ENSE00002379195	122363983	122364107
ENSE00002411192	122354453	122354556
ENSE00002425386	122377389	122377960
ENSE00003503944	122316749	122316855
ENSE00003532278	122278154	122278203
ENSE00003546268	122360959	122361181
ENSE00003554864	122309762	122309882
ENSE00003593203	122319232	122319348
ENSE00003601072	122288489	122288541
ENSE00003608614	122279028	122279145
ENSE00003628806	122336632	122336748
ENSE00003633525	122334648	122334705
ENSE00003658082	122352726	122352786
ENSE00003660226	122274038	122274162
ENSE00003688269	122278792	122278942
ENSE00003692668	122327947	122328162
ENSE00003835511	122380368	122380558
ENSE00003910343	122422521	122422669
ENSE00003912975	122271469	122273100

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1460 / max 214.1511, expressed in 1791 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133818	11.7900	1772
133819	1.4851	965
133820	0.6123	345
133814	0.4727	198
133815	0.2996	148
133807	0.1950	57
133808	0.1125	16
133813	0.0715	19
133810	0.0429	10
133809	0.0300	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	98.88	gold quality
buccal mucosa cell	CL:0002336	98.73	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.57	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.51	gold quality
gastrocnemius	UBERON:0001388	98.50	gold quality
muscle of leg	UBERON:0001383	98.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.97	gold quality
tendon of biceps brachii	UBERON:0008188	97.90	gold quality
cauda epididymis	UBERON:0004360	97.78	gold quality
gingival epithelium	UBERON:0001949	97.66	gold quality
gingiva	UBERON:0001828	97.60	gold quality
tendon	UBERON:0000043	97.44	gold quality
amniotic fluid	UBERON:0000173	97.36	gold quality
tongue squamous epithelium	UBERON:0006919	97.31	gold quality
epithelium of nasopharynx	UBERON:0001951	97.24	gold quality
nasopharynx	UBERON:0001728	97.22	gold quality
diaphragm	UBERON:0001103	97.20	gold quality
gluteal muscle	UBERON:0002000	97.13	gold quality
skeletal muscle organ	UBERON:0014892	97.02	gold quality
muscle organ	UBERON:0001630	97.01	gold quality
calcaneal tendon	UBERON:0003701	96.85	gold quality
cerebellar hemisphere	UBERON:0002245	96.60	gold quality
cerebellar cortex	UBERON:0002129	96.55	gold quality
squamous epithelium	UBERON:0006914	96.47	gold quality
esophagus squamous epithelium	UBERON:0006920	96.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.22	gold quality
colonic epithelium	UBERON:0000397	96.13	gold quality
cerebellum	UBERON:0002037	96.07	gold quality
popliteal artery	UBERON:0002250	96.06	gold quality
tibial artery	UBERON:0007610	96.06	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	40.61
E-GEOD-75367	no	1685.82
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF3, ESR1, TP53

miRNA regulators (miRDB)

103 targeting CLIP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
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-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
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-3646	100.00	73.56	5283
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-4531	99.99	69.70	3181
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 40)

• LIS1, CLIP-170’s key to the dynein/dynactin pathway (PMID:11940666)
• The cytoplasmic linker protein CLIP-170 is a human autoantigen (PMID:11966772)
• Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170. (PMID:12110184)
• expressed at high levels in monocyte-derived dendritic cells and IL-4 + CD40L-activated B cells and is involved in the trafficking of macropinosomes to the cytoskeleton, a crucial step in antigen presentation (PMID:12433698)
• neogenin and restin have roles in proproliferation/survival action on ovarian cancer cells (PMID:12833147)
• The restin gene was amplified from retinoic acid-treated promyelocytic cell line HL-60 by RT-PCR and cloned into a prokaryotic expression vector. (PMID:15862147)
• these data explain observations that CLIP-170 localizes to newly polymerized microtubules in vitro but cannot track microtubule plus-ends in vitro. These observations have implications for the functions of CLIP-170 in regulating microtubule dynamics (PMID:16120651)
• CLIP-170 facilitates the formation of kinetochore-microtubule attachments, possibly through direct capture of microtubules at the kinetochore. (PMID:16362039)
• STAT-1alpha plays an important role in the atRA-induced transcriptional up-regulation of restin (PMID:16574066)
• The function of CLIP-170 in membrane trafficking is not associated with plus-end localization. (PMID:16772339)
• A structural basis for tubulin recognition by CLIP-170 and its autoinhibition is provided. (PMID:17563362)
• Data use the complex formed between the CAP-Gly domain of p150(glued) and the C-terminal zinc knuckle of CLIP170 as a model system to explore the structure-function relationship of CAP-Gly-mediated protein interactions. (PMID:17828277)
• Crystal structures of the tubulin binding domains of XMAP215 (yeast Stu2p and Drosophila Msps), EB1 (yeast Bim1p and human EB1), and CLIP-170 (human), which reveal diverse tubulin binding interfaces, are reported. (PMID:17889670)
• The results suggest that promotion of lamellipodia formation and invasion by HGF or serum requires PI3K-dependent release of IQGAP1 and kinesin from Rac1-CLIP-170 complex. (PMID:18237546)
• CLIP-170 was expressed in differentiated keratinocytes, first at the periphery of the nucleus then with a granular cytoplasmic labeling evocative of lamellar bodies (PMID:18622020)
• Amphiphysin 2/BIN1 participates in the tubulation of traffic intermediates and intracellular organelles first via its intrinsic tubulating potential and second via its ability to bind CLIP-170 and microtubules. (PMID:19004523)
• these results suggest that complexes of dynein, Lis1 and CLIP-170 crosslink and slide microtubules within the spindle, thereby producing an inward force that pulls centrosomes together. (PMID:19020519)
• EB1 is both necessary and sufficient to mediate microtubule plus-end tracking by CLIP-170. (PMID:19126680)
• Cdc2-mediated phosphorylation of CLIP-170 is essential for the normal function of this protein during cell cycle progression (PMID:19687009)
• Herein, the authors have identified polo-like kinase 1 (Plk1) and casein kinase 2 (CK2) as two kinases of CLIP-170 and mapped S195 and S1318 as their respective phosphorylation sites. (PMID:20664522)
• These results demonstrate that CLIP-170 mediates paclitaxel sensitivity in breast cancer via a microtubule-dependent mechanism. (PMID:21989536)
• End-binding proteins interact with the CAP-Gly domains of CLIP-170 and p150(glued). (PMID:22119847)
• results suggest that EB1 and ClipCG12 act cooperatively to regulate microtubule dynamics (CLIP-170) (PMID:22424550)
• We further demonstrate that this binding was prevented when the C-terminal tyrosine of EB1 was absent in the peptidic probes. (PMID:22543185)
• Depletion of CLIP-170 significantly impaired vascular endothelial tube formation and sprouting in vitro and inhibited breast tumor growth in mice by decreasing tumor vascularization. (PMID:23549612)
• CLIP-170 phosphorylation by Plk1 regulates proper chromosome alignment (PMID:24451569)
• HDAC6 interacts with cytoplasmic linker protein 170 (CLIP-170) and that these two proteins function together to stimulate the migration of pancreatic cancer cells. (PMID:24474193)
• siRNA-mediated knockdown of the cytoplasmic linker protein compromised the assembly and branching of capillary-like blood vessels and neovascularization in vivo. It was critical for the motility abilities of HUVECs through its actions on cell polarity. (PMID:24530770)
• A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability. (PMID:24569606)
• Data suggest that CLIP-170 acts as a novel recruiter and spatial regulator of PLK1 at kinetochores during early mitosis, promoting K-fiber stability and chromosome alignment for error-free chromosome segregation. (PMID:24777477)
• We find that LRRK1-mediated phosphorylation of CLIP-170 causes the accumulation of p150(Glued) (also known as DCTN1) a subunit of dynactin, at microtubule plus ends, thereby facilitating the migration of EGFR-containing endosomes. (PMID:25413345)
• Restin inhibits epithelial-mesenchymal transition and tumor metastasis by controlling the expression of the tumor metastasis suppressor mir-200a/b via association with p73. (PMID:25972084)
• CLIP-170 tethers kinetochores to microtubule ends against the dynein-mediated poleward force to slide kinetochores along microtubules (PMID:26231764)
• herpesvirus particles are absolutely dependent on CLIP-170-mediated capture to initiate transport in primary human cells. (PMID:26504169)
• We show that AMPH-1/BIN1 binds to nesprin and actin, as well as to the microtubule-binding protein CLIP170 in both species. We propose that BIN1 has a direct and evolutionarily conserved role in nuclear positioning, altered in myopathies. (PMID:26506308)
• single-molecule fluorescence microscopy showed that the microtubule plus-end-associated protein CLIP-170 binds tightly to formins to accelerate actin filament elongation. (PMID:27199431)
• ASK1- induced phosphorylation of EB1 not only increases its plus end-tracking ability, but also promotes its recruitment of CLIP170 and p150glued to astral microtubules. (PMID:28039481)
• we report an unexpected finding that CLIP170 negatively regulates TLR4 signaling by the targeted ubiquitination and degradation of TIRAP. Furthermore, we observed that CLIP170 expression is modulated by LPS to maintain the cellular homeostasis. (PMID:29222167)
• finding that CLIP-170 has multiple non-CAP-Gly EB1-binding modules may explain why autoinhibition of CLIP-170 GAP-Gly domains does not fully abrogate its microtubule plus-end localization. This work expands our understanding of EB1-binding motifs and their multivalent networks. (PMID:30455356)
• CLIP-170 plays an indispensable role in MTOC repositioning and full activation of T cells by regulating dynein localisation. (PMID:30487641)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	clip1a	ENSDARG00000078722
danio_rerio		ENSDARG00000079483
mus_musculus	Clip1	ENSMUSG00000049550
rattus_norvegicus	Clip1	ENSRNOG00000001247
drosophila_melanogaster	CLIP-190	FBGN0020503

Paralogs (4): CLIP3 (ENSG00000105270), CLIP2 (ENSG00000106665), CLIP4 (ENSG00000115295), DCTN1 (ENSG00000204843)

Protein

Protein identifiers

CAP-Gly domain-containing linker protein 1 — P30622 (reviewed: P30622)

Alternative names: Cytoplasmic linker protein 1, Cytoplasmic linker protein 170 alpha-2, Reed-Sternberg intermediate filament-associated protein, Restin

All UniProt accessions (10): P30622, A0A3B3IS27, A0A3B3ISJ8, A0A3B3ITA2, F5H0N7, F5H1T5, F5H270, F5H367, F5H6A0, J3KP58

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking.

Subunit / interactions. Interacts with MTOR; phosphorylates and regulates CLIP1. Interacts (via CAP-Gly domains) with tubulin. Interacts with SLAIN2. Interacts (via zinc finger) with DCTN1. Interacts with TUBA1B, MAPRE1 and MAPRE3. Binds preferentially to tyrosinated microtubules, and only marginally to detyrosinated microtubules.

Subcellular location. Cytoplasm. Cytoskeleton. Cytoplasmic vesicle membrane. Cell projection. Ruffle.

Tissue specificity. Detected in dendritic cells (at protein level). Highly expressed in the Reed-Sternberg cells of Hodgkin disease.

Post-translational modifications. Phosphorylated. Phosphorylation induces conformational changes by increasing the affinity of the N-terminus for C-terminus, resulting in inhibition of its function thus decreasing its binding to microtubules and DCTN1. Exhibits a folded, autoinhibited conformation when phosphorylated and an open conformation when dephosphorylated with increased binding affinity to microtubules and DCTN1. Phosphorylation regulates its recruitment to tyrosinated microtubules and the recruitment of vesicular cargo to microtubules in neurons. Phosphorylation by MTOR may positively regulate CLIP1 association with microtubules.

Domain organisation. Intramolecular interaction between the zinc finger domain and the CAP-Gly domains may inhibit interaction with tubulin.

Isoforms (3)

UniProt ID	Names	Canonical?
P30622-3	1	yes
P30622-1	2, Long
P30622-2	3, Short

RefSeq proteins (4): NP_001234926, NP_001376220, NP_002947, NP_937883 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000938	CAP-Gly_domain	Domain
IPR032108	CLIP1_ZNF	Domain
IPR036859	CAP-Gly_dom_sf	Homologous_superfamily

Pfam: PF01302, PF16641

UniProt features (75 total): strand 19, modified residue 17, sequence variant 6, region of interest 6, sequence conflict 6, compositionally biased region 5, turn 5, helix 3, domain 2, splice variant 2, chain 1, coiled-coil region 1, zinc finger region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2E3H	X-RAY DIFFRACTION	1.45
3RDV	X-RAY DIFFRACTION	1.75
2HQH	X-RAY DIFFRACTION	1.8
8WHI	X-RAY DIFFRACTION	1.85
2E3I	X-RAY DIFFRACTION	2
2QK0	X-RAY DIFFRACTION	2
3E2U	X-RAY DIFFRACTION	2.6
8WHH	X-RAY DIFFRACTION	3.8
2CP5	SOLUTION NMR
2CP6	SOLUTION NMR
2E4H	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30622-F1	72.16	0.13

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 (17): 48, 50, 140, 143, 147, 182, 195, 197, 200, 204, 310, 312, 315, 348, 1236, 1310, 1364

Mutagenesis-validated functional residues (1):

Position	Phenotype
98–99	abolishes interaction with tubulin. abolishes localization at the microtubule plus end.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5626467	RHO GTPases activate IQGAPs
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-9842640	Signaling by LTK in cancer

MSigDB gene sets: 336 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, RORA1_01, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, TGACCTY_ERR1_Q2, GOCC_RUFFLE, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5, GOCC_MICROTUBULE_ORGANIZING_CENTER, CEBPB_01

GO Biological Process (4): mitotic cell cycle (GO:0000278), microtubule bundle formation (GO:0001578), positive regulation of microtubule polymerization (GO:0031116), cytoplasmic microtubule organization (GO:0031122)

GO Molecular Function (7): microtubule binding (GO:0008017), zinc ion binding (GO:0008270), tubulin binding (GO:0015631), identical protein binding (GO:0042802), microtubule plus-end binding (GO:0051010), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (18): kinetochore (GO:0000776), ruffle (GO:0001726), nucleus (GO:0005634), centrosome (GO:0005813), cytosol (GO:0005829), microtubule (GO:0005874), intermediate filament (GO:0005882), plasma membrane (GO:0005886), cell cortex (GO:0005938), microtubule cytoskeleton (GO:0015630), cytoplasmic vesicle membrane (GO:0030659), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), microtubule plus-end (GO:0035371), cell projection (GO:0042995), macropinosome (GO:0044354)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Mitotic Prometaphase	2
RHO GTPase Effectors	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
M Phase	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
microtubule cytoskeleton organization	2
intracellular membraneless organelle	2
polymeric cytoskeletal fiber	2
cell periphery	2
cell cycle	1
mitotic nuclear division	1
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
positive regulation of protein polymerization	1
microtubule polymerization	1
positive regulation of supramolecular fiber organization	1
supramolecular fiber organization	1
tubulin binding	1
transition metal ion binding	1
cytoskeletal protein binding	1
protein binding	1
microtubule binding	1
binding	1
cation binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1
intermediate filament cytoskeleton	1
membrane	1
cytoskeleton	1
vesicle membrane	1
cytoplasmic vesicle	1
intracellular anatomical structure	1
intracellular vesicle	1
microtubule end	1
pinosome	1

Protein interactions and networks

STRING

2202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLIP1	IQGAP1	P46940	998
CLIP1	CLASP2	O75122	984
CLIP1	CLASRP	Q8N2M8	973
CLIP1	DCTN1	Q14203	955
CLIP1	CLASP1	Q7Z460	954
CLIP1	CDC42	P21181	946
CLIP1	MAPRE1	Q15691	885
CLIP1	TTL	Q8NG68	846
CLIP1	MAPRE3	Q9UPY8	837
CLIP1	PAFAH1B1	P43034	792
CLIP1	MACF1	Q9UPN3	759
CLIP1	APC	P25054	750
CLIP1	CKAP5	Q14008	696
CLIP1	CPN1	P15169	649
CLIP1	KIF2C	Q99661	644

IntAct

76 interactions, top by confidence:

A	B	Type	Score
MAPRE1	CLASP2	psi-mi:“MI:0914”(association)	0.850
CLIP1	MAPRE1	psi-mi:“MI:0407”(direct interaction)	0.750
TUBA4A	CLIP1	psi-mi:“MI:0407”(direct interaction)	0.620
CLIP1	TUBA4A	psi-mi:“MI:0407”(direct interaction)	0.620
DCTN1	CLIP1	psi-mi:“MI:0403”(colocalization)	0.590
CLIP1	REL	psi-mi:“MI:0915”(physical association)	0.560
CLIP1		psi-mi:“MI:0915”(physical association)	0.550
CSNK1E	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
BMP1	TLL1	psi-mi:“MI:0914”(association)	0.530
GORASP1	PPP6R2	psi-mi:“MI:0914”(association)	0.530
SDCBP	TARS3	psi-mi:“MI:0914”(association)	0.530
CLIP1	SERBP1	psi-mi:“MI:0915”(physical association)	0.400
CLIP1	PLK1	psi-mi:“MI:0915”(physical association)	0.400
CSNK2B	CLIP1	psi-mi:“MI:0915”(physical association)	0.400
	CLIP1	psi-mi:“MI:0915”(physical association)	0.370
CLIP1	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	CLIP1	psi-mi:“MI:0915”(physical association)	0.370
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	CCDC22	psi-mi:“MI:0914”(association)	0.350
CFTR	POTEF	psi-mi:“MI:0914”(association)	0.350
MED13L	IGKV1-8	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350

BioGRID (233): CLIP1 (Affinity Capture-Western), HDAC6 (Affinity Capture-Western), CLIP1 (Affinity Capture-MS), CHD4 (Co-fractionation), GPS1 (Co-fractionation), CLIP1 (Proximity Label-MS), CLIP1 (Affinity Capture-MS), CLIP1 (Affinity Capture-MS), CLIP1 (Affinity Capture-MS), CLIP1 (Affinity Capture-MS), CLIP1 (Two-hybrid), CLIP1 (Affinity Capture-Western), CLIP1 (Co-localization), CLIP1 (Affinity Capture-MS), CLIP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M9PQ61, A6QR54, B2RZ86, E9Q7G0, F1R4Y7, O42184, O55156, P30622, P35458, Q11102, Q13439, Q14789, Q14980, Q15075, Q29RS0, Q3SWS9, Q5DTN8, Q5RI56, Q5U312, Q5U4E6, Q5VZ66, Q60952, Q66H89, Q6PCJ1, Q7Z7A1, Q7ZW57, Q861Q8, Q8BL66, Q8BVL9, Q8CDI7, Q8CGB3, Q8N998, Q8NB25, Q8S2T0, Q8VDC1, Q91VW5, Q922J3, Q92805, Q95KA2, Q96N16

Diamond homologs: A0A287B8J2, B9EHT4, O08788, O42184, O42667, O55156, P28023, P30622, P33420, P35458, Q10235, Q14203, Q20728, Q54Z01, Q5E951, Q5R686, Q5U243, Q66HD5, Q6PCJ1, Q8CI96, Q8N3C7, Q922J3, Q96DZ5, Q99426, Q9D1E6, Q9JK25, Q9NQT8, Q9UDT6, Q9VJE5, Q9Z0H8, E9Q309, P13496, P34531, Q01397, Q15813, Q32KS0, Q55CN0, Q5FVQ9, Q5RBD9, Q5U378

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
PRKCA	down-regulates	CLIP1	phosphorylation
CSNK2A1	up-regulates	CLIP1	phosphorylation
PLK1	up-regulates	CLIP1	phosphorylation
CLIP1	“up-regulates activity”	DCTN1	binding
PAFAH1B1	“up-regulates activity”	CLIP1	binding
CLASP1	“up-regulates activity”	CLIP1	binding
MTOR	“up-regulates activity”	CLIP1	phosphorylation
CLIP1	“down-regulates activity”	TIRAP	binding
PLK1	“down-regulates activity”	CLIP1	phosphorylation
CLASP2	“up-regulates activity”	CLIP1	binding
CLIP1	up-regulates	Microtubule_polimerization	binding
LRRK1	“up-regulates activity”	CLIP1	phosphorylation
CDK1	“up-regulates activity”	CLIP1	phosphorylation
CyclinB/CDK1	“up-regulates activity”	CLIP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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
Loss of Nlp from mitotic centrosomes	8	20.8×	2e-07
Loss of proteins required for interphase microtubule organization from the centrosome	8	20.8×	2e-07
Centrosome maturation	5	20.8×	6e-05
AURKA Activation by TPX2	8	20.0×	3e-07
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	6	19.0×	1e-05
Recruitment of mitotic centrosome proteins and complexes	8	17.8×	6e-07
Kinesins	6	17.6×	2e-05
Recruitment of NuMA to mitotic centrosomes	9	17.2×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle organization	5	16.8×	2e-03
microtubule cytoskeleton organization	7	10.5×	2e-03
mitotic cell cycle	6	9.9×	2e-03
cell division	10	5.7×	2e-03
protein transport	10	5.4×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — CESC, ESCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	172
Likely benign	32
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
599504	NM_001247997.2(CLIP1):c.430C>T (p.Arg144Ter)	Pathogenic

SpliceAI

5581 predictions. Top by Δscore:

Variant	Effect	Δscore
12:122273096:CATCA:C	acceptor_gain	1.0000
12:122273098:TCA:T	acceptor_gain	1.0000
12:122273099:CA:C	acceptor_gain	1.0000
12:122273099:CAC:C	acceptor_gain	1.0000
12:122273101:C:CC	acceptor_gain	1.0000
12:122273113:A:AC	acceptor_gain	1.0000
12:122273115:G:C	acceptor_gain	1.0000
12:122273115:G:GC	acceptor_gain	1.0000
12:122274168:T:C	acceptor_gain	1.0000
12:122274168:T:TC	acceptor_gain	1.0000
12:122276488:G:T	acceptor_gain	1.0000
12:122276492:C:CT	acceptor_gain	1.0000
12:122276493:A:T	acceptor_gain	1.0000
12:122279144:CT:C	acceptor_gain	1.0000
12:122288483:GCTTA:G	donor_loss	1.0000
12:122288484:CTTA:C	donor_loss	1.0000
12:122288485:TTAC:T	donor_loss	1.0000
12:122288486:TACCT:T	donor_loss	1.0000
12:122288487:A:AC	donor_gain	1.0000
12:122288488:C:CA	donor_loss	1.0000
12:122288488:C:CC	donor_gain	1.0000
12:122288538:CCAG:C	acceptor_gain	1.0000
12:122288539:CAG:C	acceptor_gain	1.0000
12:122288539:CAGC:C	acceptor_gain	1.0000
12:122288540:AG:A	acceptor_gain	1.0000
12:122288540:AGCT:A	acceptor_loss	1.0000
12:122288541:GCT:G	acceptor_loss	1.0000
12:122288542:C:CC	acceptor_gain	1.0000
12:122288542:CTAG:C	acceptor_loss	1.0000
12:122309757:CTGA:C	donor_loss	1.0000

AlphaMissense

9531 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:122273013:A:C	C1393W	1.000
12:122273014:C:G	C1393S	1.000
12:122273015:A:G	C1393R	1.000
12:122273015:A:T	C1393S	1.000
12:122273047:C:T	C1382Y	1.000
12:122273048:A:G	C1382R	1.000
12:122273055:A:C	C1379W	1.000
12:122273056:C:A	C1379F	1.000
12:122273056:C:G	C1379S	1.000
12:122273056:C:T	C1379Y	1.000
12:122273057:A:G	C1379R	1.000
12:122273057:A:T	C1379S	1.000
12:122274131:A:G	L1333P	1.000
12:122274140:A:T	I1330K	1.000
12:122274147:A:G	S1328P	1.000
12:122274152:A:G	L1326P	1.000
12:122352765:G:C	F443L	1.000
12:122352765:G:T	F443L	1.000
12:122352766:A:G	F443S	1.000
12:122352767:A:G	F443L	1.000
12:122352772:A:G	L441P	1.000
12:122354480:A:G	L427P	1.000
12:122355218:A:G	L367P	1.000
12:122361131:A:T	V278D	1.000
12:122361133:T:A	K277N	1.000
12:122361133:T:G	K277N	1.000
12:122361135:T:C	K277E	1.000
12:122361146:G:T	A273D	1.000
12:122361148:G:C	F272L	1.000
12:122361148:G:T	F272L	1.000

dbSNP variants (sampled 300 via entrez): RS1000006307 (12:122330991 G>A,C), RS1000054916 (12:122298964 A>C), RS1000073467 (12:122315983 A>G), RS1000082630 (12:122420060 G>A), RS1000095566 (12:122333647 C>T), RS1000111717 (12:122349886 GTTTT>G,GT,GTTT,GTTTTT), RS1000113787 (12:122393868 G>A), RS1000114773 (12:122364529 G>C,T), RS1000128466 (12:122305706 G>A), RS1000132607 (12:122312742 G>GC), RS1000133694 (12:122404057 G>A), RS1000141592 (12:122391452 G>A), RS1000145959 (12:122350091 G>A), RS1000170471 (12:122400713 T>G), RS1000177627 (12:122407449 C>G)

Disease associations

OMIM: gene MIM:179838 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive
intellectual disability	Limited	Autosomal recessive

Mondo (2): intellectual disability (MONDO:0001071), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (0):

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST002783_436	Body mass index	1.000000e-08
GCST002783_511	Body mass index	2.000000e-08
GCST002783_6	Body mass index	2.000000e-06
GCST004066_118	Hip circumference	2.000000e-10
GCST004066_14	Hip circumference	3.000000e-09
GCST006802_6	Body mass index	4.000000e-06
GCST007576_396	Chronotype	7.000000e-08
GCST008152_78	Weight	2.000000e-06
GCST010050_16	Adiponectin levels	3.000000e-14
GCST011122_75	Walking pace	4.000000e-08
GCST011336_11	Body mass index and HDL-C (pairwise)	1.000000e-18
GCST011344_11	Body fat percentage and HDL-C (pairwise)	4.000000e-13
GCST012227_561	Hip circumference adjusted for BMI	7.000000e-11
GCST012490_587	Femur bone mineral density x serum urate levels interaction	8.000000e-11
GCST90020024_243	A body shape index	1.000000e-11
GCST90020025_117	Waist-to-hip ratio adjusted for BMI	1.000000e-12
GCST90020025_118	Waist-to-hip ratio adjusted for BMI	4.000000e-09
GCST90020025_120	Waist-to-hip ratio adjusted for BMI	2.000000e-20
GCST90020026_29	Hip index	3.000000e-08
GCST90020026_30	Hip index	7.000000e-10
GCST90020027_1196	Waist-hip index	1.000000e-08
GCST90020027_1198	Waist-hip index	6.000000e-20
GCST90020028_1241	Hip circumference adjusted for BMI	2.000000e-19
GCST90020028_1242	Hip circumference adjusted for BMI	8.000000e-11
GCST90020028_1243	Hip circumference adjusted for BMI	5.000000e-11
GCST90020028_962	Hip circumference adjusted for BMI	2.000000e-09
GCST90020029_468	Waist circumference adjusted for body mass index	2.000000e-09

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008328	chronotype measurement
EFO:0004338	body weight
EFO:0004502	adiponectin measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007800	body fat percentage
EFO:0008039	BMI-adjusted hip circumference
EFO:0004531	urate measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	7
bisphenol A	affects expression, decreases expression, decreases methylation	3
trichostatin A	affects cotreatment, decreases expression	3
Cyclosporine	increases expression	3
methylmercuric chloride	increases expression	2
methacrylaldehyde	increases oxidation, decreases expression, increases abundance, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Acrolein	affects cotreatment, increases oxidation, decreases expression, increases abundance	2
Doxorubicin	increases expression	2
Ozone	affects cotreatment, increases oxidation, decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
moringin	decreases expression, affects cotreatment	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
afimoxifene	decreases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders