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 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 253 total — 1 pathogenic
• Regional missense constraint (gnomAD): 1 of 6 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 16 tissues, sQTL in 10 (q < 0.05)
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.46 (moderately constrained)
• MANE Select transcript: NM_001247997
• Interaction hub: 1,918 STRING partners (top 8% of genes corpus-wide)
• Notable: 253 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 45 — 32 protein_coding, 6 retained_intron, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000620786

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

ENST00000620786, ENST00000302528, ENST00000358808, ENST00000361654, ENST00000501271, ENST00000514271, ENST00000535290, ENST00000536634, ENST00000537004, ENST00000537123, ENST00000537178, ENST00000538120, ENST00000539080, ENST00000540304, ENST00000540539, ENST00000541108, ENST00000541410, ENST00000543205, ENST00000545889, ENST00000648993, ENST00000859888, ENST00000859889, ENST00000859890, ENST00000859891, ENST00000859892, ENST00000971569, ENST00000971570, ENST00000971571, ENST00000971572, ENST00000971573, ENST00000971574, ENST00000971575, ENST00000971576, ENST00000971577, ENST00000971578, ENST00001003394, ENST00001003395, ENST00001018825, ENST00001018827, ENST00001018828, ENST00001018829, ENST00001108932, ENST00001108933, ENST00001113449, ENST00001137308

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.

Highest expression (Bgee): biceps brachii, buccal mucosa cell, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, gastrocnemius.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CLIP1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 10 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 26 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	sqtl	9.0e-33	-0.37	12:122280127:C:G
Heart Left Ventricle	sqtl	2.9e-32	+0.67	12:122223961:C:T
Pancreas	eqtl	8.5e-20	+0.59	12:122361593:G:A
Heart Atrial Appendage	sqtl	2.8e-15	+0.56	12:122275937:G:GCC
Skin Sun Exposed Lower leg	sqtl	5.1e-07	+0.34	12:122278057:T:C
Artery Tibial	eqtl	1.6e-06	+0.09	12:122454221:A:G
Testis	sqtl	5.5e-06	+0.46	12:122319709:T:C
Stomach	eqtl	1.7e-05	+0.20	12:122392229:C:T
Adipose Subcutaneous	eqtl	6.9e-04	+0.09	12:122324503:T:C
Brain Cerebellar Hemisphere	eqtl	1.9e-03	-0.14	12:122337102:G:T
Skin Not Sun Exposed Suprapubic	sqtl	2.1e-03	-0.29	12:122204634:C:G
Brain Cerebellum	eqtl	4.4e-03	-0.19	12:122357568:GC:G
Adrenal Gland	eqtl	5.9e-03	-0.32	12:122598621:G:A
Esophagus Muscularis	eqtl	7.5e-03	-0.07	12:122454411:T:C
Brain Cortex	eqtl	8.0e-03	-0.17	12:122269554:T:C
Cells Cultured fibroblasts	eqtl	8.5e-03	-0.10	12:122420964:T:C
Ovary	eqtl	8.9e-03	+0.51	12:123225237:AGT:A
Muscle Skeletal	eqtl	9.5e-03	-0.27	12:122468591:G:A
Cells Cultured fibroblasts	sqtl	1.4e-02	-0.98	12:122681807:G:A
Brain Putamen basal ganglia	sqtl	2.4e-02	-0.35	12:121774112:C:T

FANTOM5 promoters

showing 10 of 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

showing 100 of 300 tissues 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
heart right ventricle	UBERON:0002080	95.96	gold quality
mammalian vulva	UBERON:0000997	95.91	gold quality
saphenous vein	UBERON:0007318	95.89	gold quality
body of tongue	UBERON:0011876	95.81	gold quality
seminal vesicle	UBERON:0000998	95.77	gold quality
pharyngeal mucosa	UBERON:0000355	95.62	gold quality
skin epidermis	UBERON:0001003	95.51	gold quality
hair follicle	UBERON:0002073	95.51	gold quality
skin of leg	UBERON:0001511	95.50	gold quality
zone of skin	UBERON:0000014	95.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.45	gold quality
skin of abdomen	UBERON:0001416	95.41	gold quality
lower esophagus	UBERON:0013473	95.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.40	gold quality
skeletal muscle tissue	UBERON:0001134	95.37	gold quality
epithelium of esophagus	UBERON:0001976	95.34	gold quality
esophagus	UBERON:0001043	95.27	gold quality
tongue	UBERON:0001723	95.18	gold quality
oral cavity	UBERON:0000167	95.17	gold quality
oviduct epithelium	UBERON:0004804	95.16	gold quality
esophagus mucosa	UBERON:0002469	95.01	gold quality
placenta	UBERON:0001987	94.98	gold quality
upper leg skin	UBERON:0004262	94.94	gold quality
cervix squamous epithelium	UBERON:0006922	94.88	gold quality
bronchial epithelial cell	CL:0002328	94.72	gold quality
aorta	UBERON:0000947	94.70	gold quality
sural nerve	UBERON:0015488	94.69	gold quality
right coronary artery	UBERON:0001625	94.66	gold quality
mucosa of stomach	UBERON:0001199	94.62	gold quality
tonsil	UBERON:0002372	94.61	gold quality
choroid plexus epithelium	UBERON:0003911	94.54	gold quality
vagina	UBERON:0000996	94.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.04	gold quality
urinary bladder	UBERON:0001255	94.03	gold quality
lower esophagus mucosa	UBERON:0035834	94.03	gold quality
sigmoid colon	UBERON:0001159	93.97	gold quality
left coronary artery	UBERON:0001626	93.91	gold quality
caput epididymis	UBERON:0004358	93.90	gold quality
blood vessel layer	UBERON:0004797	93.82	gold quality
coronary artery	UBERON:0001621	93.79	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.78	gold quality
skin of hip	UBERON:0001554	93.75	gold quality
vastus lateralis	UBERON:0001379	93.73	gold quality
cervix epithelium	UBERON:0004801	93.69	gold quality
lower lobe of lung	UBERON:0008949	93.68	gold quality
palpebral conjunctiva	UBERON:0001812	93.57	gold quality
superficial temporal artery	UBERON:0001614	93.53	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.38	gold quality
superior surface of tongue	UBERON:0007371	93.31	gold quality
thyroid gland	UBERON:0002046	93.29	gold quality
cortical plate	UBERON:0005343	93.27	gold quality
entorhinal cortex	UBERON:0002728	93.25	gold quality
smooth muscle tissue	UBERON:0001135	93.18	gold quality
quadriceps femoris	UBERON:0001377	93.18	gold quality
mouth mucosa	UBERON:0003729	93.12	gold quality
triceps brachii	UBERON:0001509	93.07	gold quality
postcentral gyrus	UBERON:0002581	93.07	gold quality
deltoid	UBERON:0001476	93.04	gold quality
middle temporal gyrus	UBERON:0002771	93.02	gold quality
left lobe of thyroid gland	UBERON:0001120	92.99	gold quality
thoracic aorta	UBERON:0001515	92.90	gold quality
medial globus pallidus	UBERON:0002477	92.88	gold quality
penis	UBERON:0000989	92.83	gold quality
ascending aorta	UBERON:0001496	92.83	gold quality
monocyte	CL:0000576	92.80	gold quality
primary visual cortex	UBERON:0002436	92.77	gold quality
uterine cervix	UBERON:0000002	92.75	gold quality
myometrium	UBERON:0001296	92.75	gold quality
descending thoracic aorta	UBERON:0002345	92.72	gold quality
left adrenal gland	UBERON:0001234	92.71	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	157.7
Skeletal muscle	tissue	154.8	low
Parathyroid gland	tissue	84.6	medium
Esophagus	tissue	66.5	medium
Thyroid gland	tissue	65.0	medium
Postcentral gyrus	tissue	61.0
Hippocampus	tissue	57.1	low
Choroid plexus	tissue	50.0
Locus coeruleus	tissue	49.3
Nucleus accumbens	tissue	47.7
Urinary bladder	tissue	45.1	medium
Liver	tissue	43.2	low
Seminal vesicle	tissue	41.8	medium
Cerebellum	tissue	41.8	low
Heart muscle	tissue	40.3	low
Smooth muscle	tissue	39.5	low
Frontal cortex	tissue	37.7
Skin 1	tissue	37.2	medium
Placenta	tissue	36.6	medium
Adrenal gland	tissue	34.7	medium
Vagina	tissue	33.1
Prefrontal cortex	tissue	31.0
Cerebral cortex	tissue	31.0	medium
Prostate	tissue	30.4	low
Occipital cortex	tissue	30.4
Hippocampal formation	tissue	30.1
Entorhinal cortex	tissue	30.1
Motor cortex	tissue	29.8
Retrosplenial and cingulate cortex	tissue	29.5
Somatosensory cortex	tissue	29.4
Temporal cortex	tissue	28.1
Retrosplenial cortex	tissue	27.8
Adipose tissue	tissue	27.7	medium
Kidney	tissue	27.7	medium
Insular cortex	tissue	27.3
Olfactory bulb	tissue	27.1
Lung	tissue	26.4	low
Appendix	tissue	26.2	low
Basal ganglia	tissue	26.1	low
Amygdala	tissue	26.0
Caudate putamen	tissue	25.6
Pancreas	tissue	25.3	low
Ventral forebrain	tissue	25.1
Retina	tissue	25.0
Putamen	tissue	25.0
Septum	tissue	24.8
Endometrium 1	tissue	24.5	medium
Salivary gland	tissue	23.7	low
Tonsil	tissue	23.7	medium
Testis	tissue	23.2	medium
Hypothalamus	tissue	22.4
Pons	tissue	22.1
Periaqueductal gray	tissue	21.9
Breast	tissue	21.7	medium
Thalamus	tissue	21.7
Cervix	tissue	21.4	medium
Midbrain	tissue	20.9
Gallbladder	tissue	20.9	medium
Superior colliculi	tissue	20.8
Substantia nigra	tissue	19.8

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar cortex (143.0), Flocculonodular lobe (140.1), Vermis (139.3), Anterior thalamic nucleus, ventral (62.7), Hippocampus, CA3 (62.0).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting CLIP1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 103 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.999, LOEUF 0.455, missense Z 3.46 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000620786 splits into 6 regions with different missense tolerance; 1 is missense-constrained (≈2% 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
12:122,272,878–122,351,143	948 / 1134.8	0.84	no
12:122,352,726–122,354,464	5 / 28.3	0.18	yes (p 1.2e-05)
12:122,354,465–122,377,438	211 / 295.1	0.72	no
12:122,377,439–122,377,712	119 / 112.0	1.06	no
12:122,377,713–122,377,867	27 / 64.1	0.42	no
12:122,377,868–122,380,452	66 / 67.8	0.97	no

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

4 orthologs

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

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1928401) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)	Records
reduced male fertility	1
teratozoospermia	1
abnormal spermatid morphology	1
abnormal sperm flagellum morphology	1
abnormal sperm head morphology	1
abnormal manchette morphology	1
ectopic manchette	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
Pongo abelii	Q5R686	99.8%	Diamond
Sus scrofa	A0A287B8J2	97.3%	Diamond
Bos taurus	Q5E951	87.7%	Diamond
Xenopus laevis	Q5U243	80.2%	Diamond
Gallus gallus	P35458	73.0%	Diamond
Neurospora crassa OR74A	Q01397	61.5%	Diamond
Dictyostelium discoideum	Q54Z01	58.2%	Diamond
Saccharomyces cerevisiae S288C	P33420	56.6%	Diamond
Schizosaccharomyces pombe 972h-	O42667	56.3%	Diamond
Caenorhabditis elegans	Q20728	56.3%	Diamond
Arabidopsis thaliana	Q67Z52	45.3%	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
CLIP1-AS1	ncRNA	100507066
DIABLO	protein-coding	56616
VPS33A	protein-coding	65082
ZCCHC8	protein-coding	55596
RSRC2	protein-coding	65117
LRRC43	protein-coding	254050
IL31	protein-coding	386653
B3GNT4	protein-coding	79369
KNTC1	protein-coding	9735
MLXIP	protein-coding	22877

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): A0A3B3IS27, A0A3B3ISJ8, A0A3B3ITA2, F5H0N7, F5H1T5, F5H270, F5H367, F5H6A0, J3KP58, P30622

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, PF27241

UniProt features (77 total): strand 19, modified residue 17, sequence variant 6, region of interest 6, sequence conflict 6, compositionally biased region 5, turn 5, helix 5, domain 2, splice variant 2, chain 1, coiled-coil region 1, zinc finger region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

11 structures by resolution:

PDB	Title	Method	Resolution (Å)
2E3H	Crystal structure of the CLIP-170 CAP-Gly domain 2	X-RAY DIFFRACTION	1.45
3RDV	Structure of the SLAIN2c-CLIPCG1 complex	X-RAY DIFFRACTION	1.75
2HQH	Crystal structure of p150Glued and CLIP-170	X-RAY DIFFRACTION	1.8
8WHI	Crystal structure of native CLASP2 in complex with CLIP170	X-RAY DIFFRACTION	1.85
2E3I	Crystal structure of the CLIP-170 CAP-Gly domain 1	X-RAY DIFFRACTION	2
2QK0	Structural Basis of Microtubule Plus End Tracking by XMAP215, CLIP-170 and EB1	X-RAY DIFFRACTION	2
3E2U	Crystal structure of the zink-knuckle 2 domain of human CLIP-170 in complex with CAP-Gly …	X-RAY DIFFRACTION	2.6
8WHH	Crystal structure of Se-Met derivative CLASP2 in complex with CLIP170	X-RAY DIFFRACTION	3.8
2CP5	Solution structure of the 1st CAP-Gly domain in human CLIP-170/restin	SOLUTION NMR
2CP6	Solution structure of the 2nd CAP-Gly domain in human CLIP-170/restin	SOLUTION NMR
2E4H	Solution structure of cytoskeletal protein in complex with tubulin tail	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Mutational cancer driver genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): microtubule ends; mid piece; cytosol; principal piece

Antibody reliability (HPA): IH approved · IF approved

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)

Type	Positions
Phosphoserine	48, 143, 147, 195, 197, 200, 204, 310, 312, 315, 348, 1236, 1364
Phosphothreonine	50, 140, 182, 1310

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 curated (TAS) of 22; 3 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

22 pathways:

ID	Pathway	Evidence
R-HSA-9842640	Signaling by LTK in cancer ⚕	curated
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	curated
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation	curated
R-HSA-68877	Mitotic Prometaphase	curated
R-HSA-5663220	RHO GTPases Activate Formins	curated
R-HSA-5626467	RHO GTPases activate IQGAPs	curated
R-HSA-2500257	Resolution of Sister Chromatid Cohesion	curated
R-HSA-2467813	Separation of Sister Chromatids	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-141424	Amplification of signal from the kinetochores	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69620	Cell Cycle Checkpoints	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-68886	M Phase	—
R-HSA-68882	Mitotic Anaphase	—
R-HSA-2555396	Mitotic Metaphase and Anaphase	—
R-HSA-69618	Mitotic Spindle Checkpoint	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—

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 (16): 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), cytoplasmic vesicle (GO:0031410), microtubule plus-end (GO:0035371), macropinosome (GO:0044354)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Mitotic Prometaphase	2
RHO GTPase Effectors	2
M Phase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Disease	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle	1
Cell Cycle Checkpoints	1

GO top-level categories

38 GO namespaces:

Category	Terms
cytoplasm	3
microtubule cytoskeleton organization	2
intracellular membraneless organelle	2
cellular anatomical structure	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
microtubule bundle formation	BP	mutant phenotype
positive regulation of microtubule polymerization	BP	mutant phenotype
centrosome	CC	direct assay
cytosol	CC	direct assay
microtubule	CC	mutant phenotype
microtubule cytoskeleton	CC	mutant phenotype
identical protein binding	MF	physical interaction
microtubule binding	MF	direct assay
microtubule plus-end binding	MF	direct assay
tubulin binding	MF	direct assay
zinc ion binding	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 1,918 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLIP1	CLASP2	O75122	926
CLIP1	CLASP1	Q7Z460	911
CLIP1	CLASRP	Q8N2M8	900
CLIP1	IQGAP1	P46940	886
CLIP1	TTL	Q8NG68	850
CLIP1	RBL2	Q08999	750
CLIP1	MAPRE3	Q9UPY8	748
CLIP1	CDC42	P21181	718
CLIP1	MACF1	Q9UPN3	701
CLIP1	CPN1	P15169	661
CLIP1	CKAP5	Q14008	643
CLIP1	MAPRE1	Q15691	620
CLIP1	SLAIN2	Q9P270	595
CLIP1	TBCD	Q9BTW9	579
CLIP1	APC	P25054	569
CLIP1	DCTN2	Q13561	569

IntAct

Human interaction partners of CLIP1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

14 partners by confidence:

Partner	Interaction type	MIscore	Records
MAPRE1	direct interaction	0.750	2
TUBA4A	direct interaction	0.620	3
DCTN1	colocalization	0.590	1
REL	physical association	0.560	3
CSNK2B	physical association	0.400	1
PLK1	physical association	0.400	1
SERBP1	physical association	0.400	1
ECE1	physical association	0.370	2
CADPS	association	0.350	1
RGPD3	association	0.350	1
SLK	association	0.350	1
NDC80	colocalization	0.270	2
CLIP4	physical association	0.000	1
NR3C1	physical association	0.000	1

BioGRID (235 interactions; top human partners by supporting records): PAFAH1B1 (Two-hybrid; 8 records), BIN1 (Two-hybrid; 6 records), MAPRE1 (Affinity Capture-MS; 5 records), MTOR (Affinity Capture-Western; 4 records), CADPS (Affinity Capture-MS; 3 records), CDK1 (Affinity Capture-Western; 3 records), CLASP1 (Proximity Label-MS; 3 records), DCTN1 (Proximity Label-MS; 3 records), ATPIF1 (Cross-Linking-MS (XL-MS); 2 records), BMP1 (Affinity Capture-MS; 2 records), CAPZB (Affinity Capture-MS; 2 records), CLASP2 (Proximity Label-MS; 2 records), DAB2IP (Affinity Capture-MS; 2 records), DYNC1H1 (Affinity Capture-MS; 2 records), GORASP1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 14 of 15 signaling 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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
APC-IQGAP1-CLIP-170 complex	3	APC, CLIP1, IQGAP1

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for CLIP1: 253 ClinVar records (1 pathogenic / likely pathogenic); 27 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	174
Likely benign	32
Benign	8

Top pathogenic / likely-pathogenic (1)

Showing all 1 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
599504	NM_001247997.2(CLIP1):c.430C>T (p.Arg144Ter)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CLIP1’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; 23 predictions of 2,965):

Position(s)	Effect	Δscore	Sites
12:122273115	acceptor_gain	1.0000
12:122274168	acceptor_gain	1.0000
12:122276488	acceptor_gain	1.0000
12:122276493	acceptor_gain	1.0000
12:122288487–122288488	donor_loss	1.0000	4
12:122288542–122288543	acceptor_loss	1.0000	2
12:122309760–122309761	donor_loss	1.0000	5
12:122309883–122309884	acceptor_loss	1.0000	6
12:122316756	donor_gain	1.0000
12:122316857	acceptor_gain	1.0000

AlphaMissense

2,872 missense substitutions predicted likely pathogenic (of 9,531 scored), across 737 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
F236	8	0.999	1.000
N253	8	0.999	1.000
F272	8	0.999	1.000
F263	8	0.998	1.000
F118	8	0.997	1.000
D254	8	0.997	1.000
F82	8	0.995	1.000
H1388	8	0.995	0.999
D247	8	0.994	0.999
F443	8	0.993	1.000
N99	8	0.992	0.999
F109	8	0.991	0.999
D1380	8	0.991	0.997
D1386	8	0.990	0.996
D440	8	0.989	0.997
F1385	8	0.986	0.999
F1325	8	0.984	0.999
F283	8	0.982	0.999
H1427	8	0.978	0.995
N1327	8	0.974	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000656
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.00085

Disease associations

OMIM: gene MIM:179838 | disease phenotypes:

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
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)

GWAS associations

27 associations:

Study	Trait	p-value
GCST90020025_1095	Waist-to-hip ratio adjusted for BMI	2e-20
GCST90020027_313	Waist-hip index	6e-20
GCST90020028_1560	Hip circumference adjusted for BMI	2e-19
GCST011336_9	Body mass index and HDL-C (pairwise)	1e-18
GCST010050_16	Adiponectin levels	3e-14
GCST011344_11	Body fat percentage and HDL-C (pairwise)	4e-13
GCST90020025_1092	Waist-to-hip ratio adjusted for BMI	1e-12
GCST90020024_841	A body shape index	1e-11
GCST90020028_1562	Hip circumference adjusted for BMI	5e-11
GCST012227_182	Hip circumference adjusted for BMI	7e-11
GCST012490_45	Femur bone mineral density x serum urate levels interaction	8e-11
GCST90020028_1561	Hip circumference adjusted for BMI	8e-11
GCST004066_34	Hip circumference	2e-10
GCST90020026_96	Hip index	7e-10
GCST90020028_1656	Hip circumference adjusted for BMI	2e-9
GCST90020029_1423	Waist circumference adjusted for body mass index	2e-9
GCST004066_14	Hip circumference	3e-9
GCST90020025_1093	Waist-to-hip ratio adjusted for BMI	4e-9
GCST002783_302	Body mass index	1e-8
GCST90020027_311	Waist-hip index	1e-8
GCST002783_38	Body mass index	2e-8
GCST90020026_95	Hip index	3e-8
GCST011122_50	Walking pace	4e-8
GCST007576_141	Chronotype	7e-8
GCST002783_381	Body mass index	2e-6
GCST008152_103	Weight	2e-6
GCST006802_6	Body mass index	4e-6

EFO canonical traits (from GWAS)

10 canonical traits:

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 disease descriptors:

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 (CPIC guideline: no)

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	decreases expression, decreases methylation, affects expression	3
trichostatin A	affects cotreatment, decreases expression	3
Ozone	affects cotreatment, increases oxidation, decreases expression, increases abundance, increases expression	3
Cyclosporine	increases expression	3
methylmercuric chloride	increases expression	2
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment, increases oxidation	2
Acetaminophen	increases expression, decreases expression	2
Acrolein	affects cotreatment, increases oxidation, decreases expression, increases abundance	2
Air Pollutants	increases oxidation, increases expression, affects cotreatment, increases abundance	2
Doxorubicin	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
moringin	affects cotreatment, decreases expression	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

Clinical trials (associated diseases)

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

showing 60 of 204 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	Phase 3	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	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	Phase 2/3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	Phase 1/2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	Early Phase 1	TERMINATED	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
NCT02862808	Not specified	COMPLETED	Molecular Diagnosis of Syndromic or Isolated Severe Intellectual Disability Using Whole Exome Sequencing : a Pilot Study
NCT02881333	Not specified	UNKNOWN	Various Type of Genetic Events in Patients With Intellectual Disability
NCT02889068	Not specified	COMPLETED	Targeted Next Generation Sequencing and Intellectual Disability
NCT02914951	Not specified	ENROLLING_BY_INVITATION	Cognitive-Behavioral Therapy for Irritability in Children With Autism Spectrum Disorder and Intellectual Disability
NCT02919826	Not specified	COMPLETED	Dialectical Behaviour Group Therapy for Adults With Intellectual Disabilities
NCT02934854	Not specified	WITHDRAWN	Biomarker for Creatine Deficiency Syndromes (BioCDS)
NCT03033797	Not specified	UNKNOWN	Augmentative and Alternative Communication in Games With Virtual Reality in Intellectual Disabilities
NCT03135236	Not specified	COMPLETED	Parents as the Primary Sexuality Educators for Their Young Adults With Down Syndrome
NCT03139760	Not specified	COMPLETED	POWERSforID: A Telehealth Weight Management System for Adults With Intellectual Disability
NCT03203226	Not specified	COMPLETED	The Feldenkrais Method for People With Intellectual Disability
NCT03212092	Not specified	COMPLETED	Reducing Aggression Among People With an Intellectual Disability
NCT03218462	Not specified	COMPLETED	Effect of Sensory Adapted Dental Environment on Dental Anxiety of Children With Intellectual and Developmental Disabilities
NCT03234231	Not specified	UNKNOWN	Supervised Brushing Programme for Intellectual Disabled Students
NCT03348124	Not specified	UNKNOWN	Prevention Among Young People With Intellectual Disability
NCT03424772	Not specified	UNKNOWN	Whole Genome Sequencing in the Detection of Rare Undiagnosed Genetic Diseases in Children in China
NCT03426059	Not specified	COMPLETED	Mapping the Phenotype in Adults With Phelan-McDermid Syndrome
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03501914	Not specified	COMPLETED	A Pilot Trial of Mindfulness Based Intervention Program for People With Intellectual Disabilities in a Low Income Setting
NCT03522337	Not specified	COMPLETED	Oral Health Promotion Among Preschool Children With Special Needs
NCT03525431	Not specified	COMPLETED	Clinical Utility of Pediatric Whole Exome Sequencing