CLIP3

Summary

CLIP3 (CAP-Gly domain containing linker protein 3, HGNC:24314) is a protein-coding gene on chromosome 19q13.12, encoding CAP-Gly domain-containing linker protein 3 (Q96DZ5). Functions as a cytoplasmic linker protein.

This gene encodes a member of the cytoplasmic linker protein 170 family. Members of this protein family contain a cytoskeleton-associated protein glycine-rich domain and mediate the interaction of microtubules with cellular organelles. The encoded protein plays a role in T cell apoptosis by facilitating the association of tubulin and the lipid raft ganglioside GD3. The encoded protein also functions as a scaffold protein mediating membrane localization of phosphorylated protein kinase B. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 25999 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 78 total
• Regional missense constraint (gnomAD): 2 of 5 regions constrained (≈14% of expected missense variation)
• GTEx eGene: eQTL in 27 tissues, sQTL in 18 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.40 (moderately constrained)
• MANE Select transcript: NM_015526
• Notable: 78 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24314
Approved symbol	CLIP3
Name	CAP-Gly domain containing linker protein 3
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	CLIPR-59, RSNL1
Ensembl gene	ENSG00000105270
Ensembl biotype	protein_coding
OMIM	607382
Entrez	25999

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000360535

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

ENST00000360535, ENST00000585466, ENST00000586457, ENST00000590559, ENST00000592017, ENST00000593074, ENST00000904679, ENST00000904680, ENST00000923666, ENST00001063807

RefSeq mRNA: 2 — MANE Select: NM_015526 NM_001199570, NM_015526

CCDS: CCDS12486

Canonical transcript exons

ENST00000360535 — 14 exons

Exon	Start	End
ENSE00001057348	36019171	36019306
ENSE00001057351	36018898	36019026
ENSE00001151412	36016907	36016979
ENSE00001151418	36017386	36017450
ENSE00001151425	36017655	36017778
ENSE00001151432	36017848	36017991
ENSE00001151451	36026147	36026265
ENSE00001151457	36026586	36026747
ENSE00001265900	36024396	36024632
ENSE00001430168	36014660	36016212
ENSE00002502399	36027132	36027271
ENSE00002695934	36032192	36032415
ENSE00002959485	36032724	36032873
ENSE00003789288	36026952	36027045

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 99.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.7782 / max 990.3994, expressed in 1244 samples.

Highest expression (Bgee): cortical plate, ganglionic eminence, prefrontal cortex, lateral nuclear group of thalamus, hemisphere of cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CLIP3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 18 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 45 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	7.7e-44	+0.48	19:36030167:C:T
Brain Cerebellar Hemisphere	sqtl	2.9e-33	+1.12	19:36018561:A:G
Brain Cerebellum	sqtl	5.9e-31	-1.13	19:36018561:A:G
Thyroid	eqtl	1.1e-26	+0.41	19:36032857:G:T
Nerve Tibial	sqtl	5.8e-24	-0.82	19:36018561:A:G
Skin Sun Exposed Lower leg	eqtl	1.6e-21	+0.29	19:36030167:C:T
Adipose Subcutaneous	eqtl	1.7e-19	+0.41	19:36030167:C:T
Muscle Skeletal	eqtl	1.8e-17	+0.33	19:36032857:G:T
Skin Not Sun Exposed Suprapubic	eqtl	6.1e-16	+0.30	19:36030167:C:T
Heart Left Ventricle	eqtl	1.8e-15	+0.40	19:36030167:C:T
Artery Aorta	eqtl	1.3e-12	+0.29	19:36030167:C:T
Lung	eqtl	1.9e-12	+0.26	19:36032857:G:T
Adipose Visceral Omentum	eqtl	6.1e-12	+0.27	19:36030167:C:T
Testis	eqtl	7.8e-10	+0.22	19:36121324:C:T
Esophagus Gastroesophageal Junction	sqtl	2.8e-09	-0.58	19:36018561:A:G
Whole Blood	eqtl	4.4e-09	+0.33	19:36030167:C:T
Esophagus Muscularis	eqtl	1.2e-08	+0.19	19:36030167:C:T
Cells Cultured fibroblasts	eqtl	2.6e-08	+0.13	19:36069583:C:T
Brain Hypothalamus	sqtl	6.5e-08	-0.74	19:36018561:A:G
Cells Cultured fibroblasts	sqtl	9.0e-08	-0.46	19:36018561:A:G

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
180644	31.5654	1244
180643	0.1649	69
180642	0.0479	14

Top tissues by expression

showing 100 of 279 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.08	gold quality
ganglionic eminence	UBERON:0004023	98.99	gold quality
prefrontal cortex	UBERON:0000451	98.94	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.89	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.87	gold quality
cerebellar hemisphere	UBERON:0002245	98.86	gold quality
cerebellar cortex	UBERON:0002129	98.82	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.82	gold quality
right frontal lobe	UBERON:0002810	98.80	gold quality
substantia nigra pars compacta	UBERON:0001965	98.78	gold quality
entorhinal cortex	UBERON:0002728	98.78	gold quality
postcentral gyrus	UBERON:0002581	98.77	gold quality
cerebellum	UBERON:0002037	98.76	gold quality
parietal lobe	UBERON:0001872	98.72	gold quality
frontal cortex	UBERON:0001870	98.68	gold quality
ventricular zone	UBERON:0003053	98.66	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.56	gold quality
neocortex	UBERON:0001950	98.47	gold quality
lateral globus pallidus	UBERON:0002476	98.35	gold quality
temporal lobe	UBERON:0001871	98.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.34	gold quality
cerebral cortex	UBERON:0000956	98.33	gold quality
amygdala	UBERON:0001876	98.17	gold quality
superior frontal gyrus	UBERON:0002661	98.08	gold quality
cingulate cortex	UBERON:0003027	98.08	gold quality
anterior cingulate cortex	UBERON:0009835	98.07	gold quality
superior vestibular nucleus	UBERON:0007227	98.05	gold quality
hypothalamus	UBERON:0001898	98.03	gold quality
pons	UBERON:0000988	97.98	gold quality
telencephalon	UBERON:0001893	97.98	gold quality
nucleus accumbens	UBERON:0001882	97.92	gold quality
orbitofrontal cortex	UBERON:0004167	97.91	gold quality
Ammon’s horn	UBERON:0001954	97.77	gold quality
CA1 field of hippocampus	UBERON:0003881	97.65	gold quality
brain	UBERON:0000955	97.64	gold quality
forebrain	UBERON:0001890	97.60	gold quality
caudate nucleus	UBERON:0001873	97.54	gold quality
medulla oblongata	UBERON:0001896	97.47	gold quality
putamen	UBERON:0001874	97.38	gold quality
dorsal root ganglion	UBERON:0000044	97.30	gold quality
ventral tegmental area	UBERON:0002691	97.24	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.22	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.14	gold quality
middle temporal gyrus	UBERON:0002771	96.99	gold quality
inferior olivary complex	UBERON:0002127	96.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.63	gold quality
spinal cord	UBERON:0002240	96.50	gold quality
olfactory bulb	UBERON:0002264	96.49	gold quality
occipital lobe	UBERON:0002021	96.45	gold quality
midbrain	UBERON:0001891	96.30	gold quality
subthalamic nucleus	UBERON:0001906	96.20	gold quality
substantia nigra	UBERON:0002038	96.18	gold quality
mucosa of stomach	UBERON:0001199	95.93	gold quality
primary visual cortex	UBERON:0002436	95.93	gold quality
trigeminal ganglion	UBERON:0001675	95.58	gold quality
inferior vagus X ganglion	UBERON:0005363	95.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.01	gold quality
stromal cell of endometrium	CL:0002255	94.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.89	gold quality
lower esophagus	UBERON:0013473	94.85	gold quality
body of uterus	UBERON:0009853	94.63	gold quality
embryo	UBERON:0000922	94.37	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.16	gold quality
adult organism	UBERON:0007023	93.84	gold quality
myometrium	UBERON:0001296	93.51	gold quality
endocervix	UBERON:0000458	93.50	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.45	gold quality
pituitary gland	UBERON:0000007	93.32	gold quality
smooth muscle tissue	UBERON:0001135	93.14	gold quality
adenohypophysis	UBERON:0002196	93.07	gold quality
right ovary	UBERON:0002118	92.99	gold quality
left ovary	UBERON:0002119	92.83	gold quality
tibial nerve	UBERON:0001323	92.82	gold quality
popliteal artery	UBERON:0002250	91.92	gold quality
tibial artery	UBERON:0007610	91.91	gold quality
descending thoracic aorta	UBERON:0002345	91.69	gold quality
aorta	UBERON:0000947	91.58	gold quality
thoracic aorta	UBERON:0001515	91.19	gold quality
right coronary artery	UBERON:0001625	91.13	gold quality
ascending aorta	UBERON:0001496	91.07	gold quality
ovary	UBERON:0000992	90.95	gold quality
left uterine tube	UBERON:0001303	90.85	gold quality
left coronary artery	UBERON:0001626	90.10	gold quality
coronary artery	UBERON:0001621	90.00	gold quality
globus pallidus	UBERON:0001875	89.97	gold quality
ectocervix	UBERON:0012249	89.78	gold quality
corpus callosum	UBERON:0002336	89.55	gold quality
cerebellar vermis	UBERON:0004720	89.18	gold quality
gall bladder	UBERON:0002110	89.01	gold quality
colonic epithelium	UBERON:0000397	88.92	gold quality
endothelial cell	CL:0000115	88.82	silver quality
urinary bladder	UBERON:0001255	88.82	gold quality
type B pancreatic cell	CL:0000169	88.43	gold quality
cranial nerve II	UBERON:0000941	88.39	gold quality
decidua	UBERON:0002450	88.36	gold quality
medial globus pallidus	UBERON:0002477	88.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.13	gold quality
cauda epididymis	UBERON:0004360	87.69	gold quality
sural nerve	UBERON:0015488	87.48	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	22.73
E-ANND-3	yes	9.10
E-GEOD-93593	yes	6.89
E-MTAB-7037	no	34.47
E-CURD-112	no	2.44
E-MTAB-9543	no	2.43

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Locus coeruleus	tissue	358.7
Frontal cortex	tissue	341.1
Postcentral gyrus	tissue	292.5
Prefrontal cortex	tissue	264.9
Cerebral cortex	tissue	264.9
Caudate putamen	tissue	258.5
Hippocampus	tissue	245.6
Thalamus	tissue	237.6
Occipital cortex	tissue	237.2
Motor cortex	tissue	237.1
Somatosensory cortex	tissue	236.3
Pons	tissue	234.8
Spinal cord	tissue	234.3
Hippocampal formation	tissue	230.2
Midbrain	tissue	228.4
Substantia nigra	tissue	223.8
Temporal cortex	tissue	211.3
Medulla oblongata	tissue	209.1
Retrosplenial cortex	tissue	208.9
Nucleus accumbens	tissue	207.8
Entorhinal cortex	tissue	207.7
Retrosplenial and cingulate cortex	tissue	204.7
Insular cortex	tissue	202.5
Basal ganglia	tissue	201.3
Putamen	tissue	199.9
Superior colliculi	tissue	199.3
Ventral forebrain	tissue	194.2
Hypothalamus	tissue	192.2
Cerebellum	tissue	184.1
Periaqueductal gray	tissue	182.5
Amygdala	tissue	181.5
Septum	tissue	170.0
Corpus callosum	tissue	160.2
Olfactory bulb	tissue	153.5
Choroid plexus	tissue	52.0
Retina	tissue	50.9
Pituitary gland	tissue	44.0
Ovary	tissue	39.7
Smooth muscle	tissue	35.4
Seminal vesicle	tissue	31.4
Endometrium 1	tissue	30.9
Vagina	tissue	30.3
Gallbladder	tissue	22.0
Cervix	tissue	21.3
Prostate	tissue	20.1
Esophagus	tissue	15.3
Urinary bladder	tissue	15.2
Adrenal gland	tissue	12.8
Epididymis	tissue	12.0
Fallopian tube	tissue	12.0
Appendix	tissue	9.2
Placenta	tissue	8.8
Thymus	tissue	8.8
Colon	tissue	8.2
Rectum	tissue	8.1
Spleen	tissue	7.4
Testis	tissue	7.3
Adipose tissue	tissue	7.3
Lymph node	tissue	6.5
Small intestine	tissue	6.3

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Orbitofrontal gyrus, anterior (399.5), Median raphe nucleus (397.3), Precentral gyrus (332.0), Lateral hypothalamic area (316.2), Inferior frontal gyrus, opercular (310.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CLIP3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 120 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-6752-5P	99.59	67.32	1243

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.397, missense Z 3.66 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000360535 splits into 5 regions with different missense tolerance; 2 are missense-constrained (≈14% 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
19:36,016,161–36,016,920	6 / 27.0	0.22	yes (p 5.3e-05)
19:36,016,921–36,018,987	179 / 226.2	0.79	no
19:36,018,988–36,026,747	194 / 327.8	0.59	no
19:36,026,952–36,027,202	26 / 79.5	0.33	yes (p 1.9e-09)
19:36,027,203–36,032,357	90 / 105.2	0.86	no

Literature-anchored findings (GeneRIF, showing 8)

• play an important role in membrane-microtubule interactions. (PMID:11854307)
• CLIPR-59 prevents microtubule-raft interactions (PMID:15262990)
• CLIPR-59 may act as a typical chaperone, allowing a prompt interaction between tubulin and the raft component GD3 during cell apoptosis triggered by CD95/Fas (PMID:20052288)
• CLIPR-59 modulates ubiquitination of RIP1, resulting in the formation of Complex-II and thus promoting Caspase-8 activation to induce apoptosis by TNF-alpha. (PMID:22297296)
• DHHC17 is a ClipR-59 palmitoyltransferase that modulates ClipR-59 plasma membrane binding. (PMID:24001771)
• CLIPR-59 interacts with Spy1 resulting in its decreased association with a de-ubiquitinating enzyme in glioblastoma cells. (PMID:26017671)
• this study indicates that inhibition of miRNA-593-3p by insulin promotes glucose metabolism through the regulation of Slc38a1 and CLIP3 expression, and provides a new insight into the role and mechanism of insulin-induced glycolysis. (PMID:27613819)
• Downregulated CLIP3 induces radioresistance by enhancing stemness and glycolytic flux in glioblastoma. (PMID:34488821)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	clip3	ENSDARG00000054456
mus_musculus	Clip3	ENSMUSG00000013921
rattus_norvegicus	Clip3	ENSRNOG00000050104

Paralogs (4): CLIP2 (ENSG00000106665), CLIP4 (ENSG00000115295), CLIP1 (ENSG00000130779), DCTN1 (ENSG00000204843)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923936) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
impaired muscle contractility	1
abnormal innervation pattern to muscle	1
abnormal neuromuscular synapse morphology	1
abnormal phrenic nerve morphology	1
cyanosis	1
respiratory failure	1
abnormal diaphragm morphology	1
neonatal lethality, complete penetrance	1
abnormal phrenic nerve innervation pattern to diaphragm	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
Drosophila melanogaster	Q9VJE5	57.6%	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
THAP8	protein-coding	199745
WDR62	protein-coding	284403
POLR2I	protein-coding	5438
OVOL3	protein-coding	728361
ALKBH6	protein-coding	84964
SYNE4	protein-coding	163183
SDHAF1	protein-coding	644096
TBCB	protein-coding	1155

Protein

Protein identifiers

CAP-Gly domain-containing linker protein 3 — Q96DZ5 (reviewed: Q96DZ5)

Alternative names: Cytoplasmic linker protein 170-related 59 kDa protein

All UniProt accessions (2): Q96DZ5, K7ESF3

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a cytoplasmic linker protein. Involved in TGN-endosome dynamics. May modulate the cellular compartmentalization of AKT kinase family and promote its cell membrane localization, thereby playing a role in glucose transport in adipocytes.

Subunit / interactions. Homodimer. Interacts with AKT1 and AKT2; when AKT1 and AKT2 are phosphorylated and activated, affinity is higher for AKT2. Interacts with ZDHHC13 (via ANK repeats). Interacts with ZDHHC17 (via ANK repeats).

Subcellular location. Cell membrane. Cytoplasm. Golgi apparatus. Golgi stack.

Post-translational modifications. Palmitoylation by ZDHHC17 regulates association with the plasma membrane.

Domain organisation. Microtubule association is inhibited by the ANK repeats and the Golgi localization region (GoLD).

Miscellaneous. The N-terminal half is dispensable for proper Golgi targeting, whereas the GoLD region is required.

RefSeq proteins (2): NP_001186499, NP_056341* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000938	CAP-Gly_domain	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR036859	CAP-Gly_dom_sf	Homologous_superfamily

Pfam: PF01302, PF12796

UniProt features (31 total): strand 8, compositionally biased region 4, repeat 3, region of interest 3, modified residue 2, lipid moiety-binding region 2, mutagenesis site 2, helix 2, domain 2, chain 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2CP0	Solution structure of the 1st CAP-Gly domain in human CLIP-170-related protein CLIPR59	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DZ5-F1	74.93	0.43

Human Protein Atlas

Protein class: Predicted intracellular 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 (4)

Type	Positions
Phosphothreonine	374
Phosphoserine	401
S-palmitoyl cysteine	534, 535

Mutagenesis-validated functional residues (2)

Position	Phenotype
509	inhibits interaction with zdhhc13 and zdhhc17.
534–535	strongly reduced plasma membrane association and decrease in the levels of akt at the plasma membrane.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-5357905	Regulation of TNFR1 signaling	curated
R-HSA-73887	Death Receptor Signaling	—
R-HSA-162582	Signal Transduction	—
R-HSA-75893	TNF signaling	—

MSigDB gene sets: 273 (showing top): GCACCTT_MIR18A_MIR18B, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GNF2_RTN1, GCM_MAP4K4, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_LIPOPROTEIN_METABOLIC_PROCESS

GO Biological Process (11): positive regulation of protein phosphorylation (GO:0001934), positive regulation of D-glucose transmembrane transport (GO:0010828), peptidyl-L-cysteine S-palmitoylation (GO:0018230), negative regulation of microtubule polymerization (GO:0031115), cytoplasmic microtubule organization (GO:0031122), positive regulation of apoptotic process (GO:0043065), membrane biogenesis (GO:0044091), fat cell differentiation (GO:0045444), positive regulation of endocytosis (GO:0045807), protein transport along microtubule (GO:0098840), positive regulation of protein localization to plasma membrane (GO:1903078)

GO Molecular Function (4): microtubule binding (GO:0008017), ganglioside binding (GO:0035594), microtubule plus-end binding (GO:0051010), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), Golgi stack (GO:0005795), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), early endosome membrane (GO:0031901), trans-Golgi network membrane (GO:0032588), microtubule plus-end (GO:0035371), membrane raft (GO:0045121), recycling endosome membrane (GO:0055038), cytoplasm (GO:0005737)

Reactome top-level categories

3 top-level categories:

Category	Pathways
TNF signaling	1
Signal Transduction	1
Death Receptor Signaling	1

GO top-level categories

50 GO namespaces:

Category	Terms
Golgi apparatus subcompartment	2
cytoplasm	2
cellular anatomical structure	2
cell periphery	2
endosome membrane	2
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
regulation of D-glucose transmembrane transport	1
positive regulation of transmembrane transport	1
D-glucose transmembrane transport	1
protein palmitoylation	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
negative regulation of protein polymerization	1
microtubule polymerization	1
negative regulation of supramolecular fiber organization	1
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
cellular component biogenesis	1
cell differentiation	1
endocytosis	1
regulation of endocytosis	1
positive regulation of transport	1
positive regulation of cellular component organization	1
intracellular protein transport	1
transport along microtubule	1
microtubule-based protein transport	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
positive regulation of protein localization to cell periphery	1
positive regulation of protein localization to membrane	1
tubulin binding	1
glycosphingolipid binding	1
ceramide binding	1
microtubule binding	1
binding	1
intracellular membrane-bounded organelle	1
membrane	1
early endosome	1
trans-Golgi network	1
organelle membrane	1
microtubule end	1
membrane microdomain	1
recycling endosome	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
membrane biogenesis	BP	mutant phenotype
negative regulation of microtubule polymerization	BP	mutant phenotype
peptidyl-L-cysteine S-palmitoylation	BP	mutant phenotype
positive regulation of apoptotic process	BP	mutant phenotype
positive regulation of endocytosis	BP	mutant phenotype
protein transport along microtubule	BP	mutant phenotype
early endosome membrane	CC	direct assay
membrane raft	CC	direct assay
plasma membrane	CC	direct assay
recycling endosome membrane	CC	direct assay
trans-Golgi network membrane	CC	direct assay
ganglioside binding	MF	direct assay
microtubule binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 675 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLIP3	TTC38	Q5R3I4	464
CLIP3	MALRD1	Q5VYJ5	446
CLIP3	GMEB2	Q9UKD1	438
CLIP3	CHST8	Q9H2A9	433
CLIP3	ZDHHC17	Q8IUH5	412
CLIP3	APLP1	P51693	394
CLIP3	PHKB	Q93100	370
CLIP3	ZBTB7C	A1YPR0	370
CLIP3	ADCY7	P51828	370
CLIP3	SUCLG2	Q96I99	370
CLIP3	RD3L	P0DJH9	369
CLIP3	ZDHHC13	Q8IUH4	368
CLIP3	ZBTB7B	O15156	367
CLIP3	MAMDC4	Q6UXC1	361
CLIP3	CIDEC	Q96AQ7	360

IntAct

Human interaction partners of CLIP3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
CEP83	physical association	0.560	3
GOLGA2	physical association	0.560	3
GRN	physical association	0.560	3
HSPB1	physical association	0.560	3
KIF1B	physical association	0.560	3
RNF11	physical association	0.560	3
TLE5	physical association	0.560	3
WFS1	physical association	0.560	3
FMR1	physical association	0.000	1

BioGRID (25 interactions; top human partners by supporting records): AKT1 (Affinity Capture-Western; 3 records), AKT2 (Affinity Capture-Western; 3 records), CYLD (Affinity Capture-Western; 3 records), SPDYA (Affinity Capture-Western; 2 records), TNFRSF1A (Two-hybrid; 2 records), AES (Two-hybrid), CASP8 (Affinity Capture-Western), CEP83 (Two-hybrid), FADD (Affinity Capture-Western), FBXO7 (Biochemical Activity), GOLGA2 (Two-hybrid), HNRNPH1 (Affinity Capture-RNA), PARP16 (Proximity Label-MS), RIPK1 (Affinity Capture-Western), SETD3 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for CLIP3: 78 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	3
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 764):

Position(s)	Effect	Δscore	Sites
19:36016213–36016214	acceptor_loss	1.0000	5
19:36016980–36016981	acceptor_loss	1.0000	6
19:36017380	donor_gain	1.0000
19:36017384	donor_loss	1.0000	2
19:36017451–36017452	acceptor_loss	1.0000	4
19:36017653–36017654	donor_loss	1.0000	5
19:36017846–36017847	donor_loss	1.0000	4
19:36017867	donor_gain	1.0000
19:36017992–36017993	acceptor_loss	1.0000	6
19:36017998	acceptor_gain	1.0000

AlphaMissense

1,714 missense substitutions predicted likely pathogenic (of 3,542 scored), across 389 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
M119	9	0.985	0.999
M162	9	0.981	0.999
F440	8	0.999	1.000
D114	8	0.998	0.999
F476	8	0.998	1.000
F318	8	0.997	1.000
F354	8	0.997	1.000
D112	8	0.996	0.999
F345	8	0.996	1.000
F171	8	0.993	1.000
H166	8	0.992	0.998
F467	8	0.990	1.000
D118	8	0.986	0.999
F60	8	0.984	0.999
H203	8	0.984	0.997
F59	8	0.983	1.000
D61	8	0.978	0.998
F82	8	0.977	0.998
F57	8	0.975	0.997
N335	8	0.974	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Glioblastoma Multiforme)

Disease associations

OMIM: gene MIM:607382 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression, affects expression, increases expression	5
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	increases expression, decreases expression, increases abundance, affects cotreatment	3
afuresertib	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	increases phosphorylation	1
moringin	decreases expression	1
bisphenol A	increases expression	1
lead acetate	affects cotreatment, increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
cyfluthrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Aspirin	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cannabidiol	decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Chlorpyrifos	increases expression	1
Mustard Gas	increases expression	1

Clinical trials (associated diseases)

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