CLIP2

Summary

CLIP2 (CAP-Gly domain containing linker protein 2, HGNC:2586) is a protein-coding gene on chromosome 7q11.23, encoding CAP-Gly domain-containing linker protein 2 (Q9UDT6). Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions.

The protein encoded by this gene belongs to the family of cytoplasmic linker proteins, which have been proposed to mediate the interaction between specific membranous organelles and microtubules. This protein was found to associate with both microtubules and an organelle called the dendritic lamellar body. This gene is hemizygously deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants.

Source: NCBI Gene 7461 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 199 total — 2 pathogenic, 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 27 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 186
• Constraint (gnomAD): pLI 0.99 (loss-of-function intolerant), LOEUF 0.48 (moderately constrained)
• MANE Select transcript: NM_003388
• Notable: 199 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2586
Approved symbol	CLIP2
Name	CAP-Gly domain containing linker protein 2
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	CLIP-115, KIAA0291, WSCR4, CLIP, WSCR3
Ensembl gene	ENSG00000106665
Ensembl biotype	protein_coding
OMIM	603432
Entrez	7461

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 26 protein_coding, 4 retained_intron, 4 nonsense_mediated_decay

MANE Select: ENST00000223398

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

ENST00000223398, ENST00000361545, ENST00000474962, ENST00000482424, ENST00000487091, ENST00000487447, ENST00000491075, ENST00000493166, ENST00000884298, ENST00000884299, ENST00000884300, ENST00000884301, ENST00000930626, ENST00000930627, ENST00000930628, ENST00000930629, ENST00000930630, ENST00000941414, ENST00000941415, ENST00000941416, ENST00000941417, ENST00000941418, ENST00000941419, ENST00000941420, ENST00000941421, ENST00000941422, ENST00000941423, ENST00001048402, ENST00001048403, ENST00001048404, ENST00001048405, ENST00001112568, ENST00001112569, ENST00001141314

RefSeq mRNA: 2 — MANE Select: NM_003388 NM_003388, NM_032421

CCDS: CCDS5569, CCDS5570

Canonical transcript exons

ENST00000223398 — 17 exons

Exon	Start	End
ENSE00000691488	74400370	74400555
ENSE00000691492	74380806	74380863
ENSE00000691493	74375887	74376822
ENSE00001039248	74403837	74405935
ENSE00001039278	74372932	74373036
ENSE00001128453	74317480	74317667
ENSE00001148381	74397074	74397233
ENSE00001148391	74389103	74389259
ENSE00001148405	74364255	74364315
ENSE00001148414	74356410	74356623
ENSE00001148424	74353880	74354004
ENSE00001148434	74338448	74339004
ENSE00001400047	74401505	74401567
ENSE00002467763	74357280	74357477
ENSE00002512403	74360175	74360278
ENSE00003486023	74386521	74386604
ENSE00003896646	74289407	74289734

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 96.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4973 / max 187.9459, expressed in 1721 samples.

Highest expression (Bgee): cortical plate, C1 segment of cervical spinal cord, ganglionic eminence, spinal cord, dorsal motor nucleus of vagus nerve.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CLIP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 29 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	3.7e-58	+0.42	7:74290347:T:C
Artery Aorta	eqtl	9.5e-35	-0.49	7:74318598:A:G
Esophagus Muscularis	eqtl	1.3e-22	+0.28	7:74290347:T:C
Esophagus Gastroesophageal Junction	eqtl	1.7e-21	+0.34	7:74290347:T:C
Nerve Tibial	eqtl	2.4e-19	+0.18	7:74290347:T:C
Colon Sigmoid	eqtl	8.8e-11	+0.26	7:74290347:T:C
Cells Cultured fibroblasts	eqtl	3.5e-10	-0.26	7:74290507:G:C
Brain Caudate basal ganglia	eqtl	4.0e-07	+0.17	7:74290347:T:C
Heart Left Ventricle	eqtl	4.6e-06	+0.28	7:74283553:C:T
Artery Coronary	eqtl	7.3e-06	-0.25	7:74328973:T:C
Brain Cortex	eqtl	7.8e-06	+0.18	7:74290347:T:C
Skin Not Sun Exposed Suprapubic	eqtl	1.0e-05	+0.14	7:74290347:T:C
Whole Blood	eqtl	7.9e-04	+0.19	7:74283553:C:T
Breast Mammary Tissue	eqtl	2.2e-03	+0.14	7:74290347:T:C
Colon Transverse	eqtl	2.5e-03	+0.10	7:74290347:T:C
Brain Anterior cingulate cortex BA24	eqtl	2.5e-03	+0.16	7:74290347:T:C
Lung	eqtl	4.7e-03	-0.16	7:74228548:A:G
Skin Sun Exposed Lower leg	eqtl	5.9e-03	+0.10	7:74290347:T:C
Brain Frontal Cortex BA9	eqtl	9.4e-03	+0.15	7:74290347:T:C
Esophagus Mucosa	eqtl	1.2e-02	+0.13	7:74290347:T:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
79085	13.4973	1721

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.22	gold quality
ganglionic eminence	UBERON:0004023	95.79	gold quality
spinal cord	UBERON:0002240	95.64	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.16	gold quality
prefrontal cortex	UBERON:0000451	95.05	gold quality
inferior olivary complex	UBERON:0002127	94.87	gold quality
cranial nerve II	UBERON:0000941	94.62	gold quality
right frontal lobe	UBERON:0002810	94.51	gold quality
amygdala	UBERON:0001876	94.19	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.89	gold quality
postcentral gyrus	UBERON:0002581	93.87	gold quality
frontal cortex	UBERON:0001870	93.85	gold quality
anterior cingulate cortex	UBERON:0009835	93.83	gold quality
cingulate cortex	UBERON:0003027	93.82	gold quality
neocortex	UBERON:0001950	93.59	gold quality
hypothalamus	UBERON:0001898	93.31	gold quality
parietal lobe	UBERON:0001872	93.21	gold quality
Ammon’s horn	UBERON:0001954	92.99	gold quality
cerebral cortex	UBERON:0000956	92.96	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.93	gold quality
substantia nigra	UBERON:0002038	92.71	gold quality
sural nerve	UBERON:0015488	92.71	gold quality
ventricular zone	UBERON:0003053	92.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.62	gold quality
telencephalon	UBERON:0001893	92.61	gold quality
temporal lobe	UBERON:0001871	92.57	gold quality
midbrain	UBERON:0001891	92.48	gold quality
putamen	UBERON:0001874	92.35	gold quality
corpus callosum	UBERON:0002336	92.17	gold quality
superior frontal gyrus	UBERON:0002661	92.15	gold quality
inferior vagus X ganglion	UBERON:0005363	92.11	gold quality
caudate nucleus	UBERON:0001873	92.02	gold quality
nucleus accumbens	UBERON:0001882	91.89	gold quality
middle frontal gyrus	UBERON:0002702	91.64	gold quality
forebrain	UBERON:0001890	91.57	gold quality
paraflocculus	UBERON:0005351	91.49	gold quality
central nervous system	UBERON:0001017	91.36	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.36	gold quality
brain	UBERON:0000955	91.22	gold quality
medulla oblongata	UBERON:0001896	91.21	gold quality
entorhinal cortex	UBERON:0002728	91.17	gold quality
stromal cell of endometrium	CL:0002255	90.76	gold quality
ventral tegmental area	UBERON:0002691	90.68	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.23	gold quality
frontal pole	UBERON:0002795	90.07	gold quality
decidua	UBERON:0002450	90.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.01	gold quality
substantia nigra pars compacta	UBERON:0001965	89.61	gold quality
superior vestibular nucleus	UBERON:0007227	89.50	gold quality
subthalamic nucleus	UBERON:0001906	89.35	gold quality
cerebellar cortex	UBERON:0002129	89.29	gold quality
cerebellar hemisphere	UBERON:0002245	89.27	gold quality
cerebellum	UBERON:0002037	89.01	gold quality
lateral globus pallidus	UBERON:0002476	88.82	gold quality
mucosa of transverse colon	UBERON:0004991	88.82	gold quality
colonic epithelium	UBERON:0000397	87.53	gold quality
orbitofrontal cortex	UBERON:0004167	87.53	gold quality
dorsal plus ventral thalamus	UBERON:0001897	87.37	gold quality
CA1 field of hippocampus	UBERON:0003881	87.13	gold quality
occipital lobe	UBERON:0002021	86.77	gold quality
primary visual cortex	UBERON:0002436	86.28	gold quality
tibial nerve	UBERON:0001323	85.79	gold quality
transverse colon	UBERON:0001157	85.52	gold quality
cartilage tissue	UBERON:0002418	85.46	gold quality
dorsal root ganglion	UBERON:0000044	85.26	gold quality
cerebellar vermis	UBERON:0004720	85.02	gold quality
ascending aorta	UBERON:0001496	84.84	gold quality
thoracic aorta	UBERON:0001515	84.83	gold quality
embryo	UBERON:0000922	84.78	gold quality
descending thoracic aorta	UBERON:0002345	84.75	gold quality
pons	UBERON:0000988	84.60	gold quality
body of stomach	UBERON:0001161	83.60	gold quality
right coronary artery	UBERON:0001625	83.37	gold quality
metanephros cortex	UBERON:0010533	83.35	gold quality
aorta	UBERON:0000947	83.01	gold quality
colon	UBERON:0001155	83.00	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.98	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.70	gold quality
large intestine	UBERON:0000059	82.67	gold quality
stomach	UBERON:0000945	82.52	gold quality
monocyte	CL:0000576	82.50	gold quality
right ovary	UBERON:0002118	82.35	gold quality
trigeminal ganglion	UBERON:0001675	82.31	gold quality
middle temporal gyrus	UBERON:0002771	82.30	gold quality
left ovary	UBERON:0002119	82.27	gold quality
mononuclear cell	CL:0000842	82.21	gold quality
mucosa of stomach	UBERON:0001199	82.14	gold quality
body of pancreas	UBERON:0001150	82.06	gold quality
gall bladder	UBERON:0002110	81.93	gold quality
endocervix	UBERON:0000458	81.91	gold quality
leukocyte	CL:0000738	81.85	gold quality
left coronary artery	UBERON:0001626	81.82	gold quality
intestine	UBERON:0000160	81.75	gold quality
popliteal artery	UBERON:0002250	81.72	gold quality
tibial artery	UBERON:0007610	81.70	gold quality
coronary artery	UBERON:0001621	81.66	gold quality
apex of heart	UBERON:0002098	81.58	gold quality
adenohypophysis	UBERON:0002196	81.44	gold quality
ectocervix	UBERON:0012249	81.29	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.29
E-GEOD-111727	no	308.50

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Locus coeruleus	tissue	135.4
Hippocampus	tissue	109.7	high
Postcentral gyrus	tissue	99.0
Nucleus accumbens	tissue	94.4
Frontal cortex	tissue	45.0
Choroid plexus	tissue	44.7
Corpus callosum	tissue	33.7
Spinal cord	tissue	33.0
Cerebral cortex	tissue	29.7	high
Motor cortex	tissue	29.7
Insular cortex	tissue	29.3
Prefrontal cortex	tissue	28.5
Caudate putamen	tissue	28.5
Temporal cortex	tissue	26.6
Retrosplenial cortex	tissue	26.0
Midbrain	tissue	25.6
Medulla oblongata	tissue	25.5
Somatosensory cortex	tissue	25.5
Hippocampal formation	tissue	25.3
Entorhinal cortex	tissue	25.3
Thalamus	tissue	25.1
Retrosplenial and cingulate cortex	tissue	25.1
Substantia nigra	tissue	24.2
Pons	tissue	23.9
Amygdala	tissue	23.7
Ventral forebrain	tissue	22.1
Occipital cortex	tissue	21.8
Hypothalamus	tissue	20.8
Superior colliculi	tissue	20.5
Basal ganglia	tissue	19.2	medium
Olfactory bulb	tissue	18.8
Putamen	tissue	18.5
Septum	tissue	18.2
Periaqueductal gray	tissue	16.8
Ovary	tissue	16.7	medium
Colon	tissue	15.8	high
Small intestine	tissue	12.8	high
Pancreas	tissue	11.8	high
Pituitary gland	tissue	11.1
Stomach 1	tissue	10.8	high
Duodenum	tissue	10.7	high
Vagina	tissue	10.5	low
Gallbladder	tissue	10.2	high
Appendix	tissue	10.0	high
Cerebellum	tissue	9.9	high
Rectum	tissue	9.4	high
Skin 1	tissue	9.1	medium
Seminal vesicle	tissue	8.7	medium
Endometrium 1	tissue	8.4	medium
Placenta	tissue	8.2	high
Urinary bladder	tissue	7.9	medium
Cervix	tissue	7.6	low
Smooth muscle	tissue	7.6	low
Tonsil	tissue	6.8	high
Adrenal gland	tissue	6.7	high
Spleen	tissue	6.2	medium
Adipose tissue	tissue	6.0	low
Esophagus	tissue	6.0	low
Lung	tissue	5.8	low
Lymph node	tissue	5.1	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Area postrema (178.4), Temporal white matter (175.6), Parieto-temporal junction (white matter) (166.7), Inferior olive (165.8), Lateral vestibular nucleus (165.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CLIP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 111 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6851-5P	100.00	65.63	1294
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-4455	100.00	65.48	1587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-378G	99.71	64.90	1106

Functional genomics

gnomAD constraint: pLI 0.993, LOEUF 0.476, missense Z 2.26 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000223398 splits into 5 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
7:74,317,547–74,338,993	301 / 315.2	0.96	no
7:74,338,994–74,357,309	110 / 185.2	0.59	no
7:74,357,310–74,357,385	3 / 29.0	0.10	yes (p 1.4e-06)
7:74,357,386–74,372,941	70 / 114.9	0.61	no
7:74,372,942–74,403,845	676 / 777.8	0.87	no

Literature-anchored findings (GeneRIF, showing 8)

• Data show that gene CLIP2 was specifically overexpressed in the exposed cases. (PMID:21606360)
• CLIP2 haploinsufficiency by itself does not lead to the physical or cognitive characteristics of the Williams-Beuren syndrome; GTF2IRD1 and GTF2I are the main genes causing the cognitive defects (PMID:22608712)
• CLIP2 protein expression is elevated in papillary thyroid carcinomas from patients exposed to radioiodine fallout compared with a nonexposed control group. (PMID:25284583)
• A clear radiation dose-response relationship for the CLIP2 marker expression in post-Chernobyl papillary thyroid carcinomas (PMID:25957251)
• Cross checking with epidemiological estimates and model validation suggests that CLIP2 is a marker of high precision. CLIP2 leaves an imprint in the epidemiological incidence data which is typical for a driver gene. (PMID:27729373)
• CILP-2 is a novel secreted protein and demonstrated that circulating CILP-2 levels were elevated in both IGT and nT2DM subjects and associated with IR. CILP-2 overexpression promoted hepatic IR in HFD-fed mice, increased PEPCK expression and suppressed insulin signaling in hepatocytes. (PMID:30896018)
• Whole exome sequencing identifies three novel gene mutations in patients with the triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis. (PMID:32734598)
• Clinical, pathologic, and genomic characteristics of two pediatric glioneuronal tumors with a CLIP2::MET fusion. (PMID:38650040)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	clip2	ENSDARG00000059596
mus_musculus	Clip2	ENSMUSG00000063146
rattus_norvegicus	Clip2	ENSRNOG00000021611

Paralogs (4): CLIP3 (ENSG00000105270), CLIP4 (ENSG00000115295), CLIP1 (ENSG00000130779), DCTN1 (ENSG00000204843)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1313136) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 21 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart morphology	1
enlarged heart	1
abnormal cell morphology	1
abnormal spleen morphology	1
abnormal thymus morphology	1
enlarged thymus	1
decreased corpus callosum size	1
decreased body length	1
decreased body weight	1
impaired coordination	1
abnormal contextual conditioning behavior	1
postnatal growth retardation	1
impaired synaptic plasticity	1
abnormal seminal vesicle morphology	1
abnormal bone marrow morphology	1
abnormal epididymis morphology	1
abnormal bone structure	1
abnormal skeleton morphology	1
increased grip strength	1
increased effector memory CD8-positive, alpha-beta T cell number	1
dilated brain ventricle	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
WBSCR23	ncRNA	107986810
MIR10525	ncRNA	113218504
GTF2IRD1	protein-coding	9569
RFC2	protein-coding	5982
LAT2	protein-coding	7462
GTF2I-AS1	ncRNA	101926943
GTF2I	protein-coding	2969
MIR590	ncRNA	693175
EIF4H	protein-coding	7458

Protein

Protein identifiers

CAP-Gly domain-containing linker protein 2 — Q9UDT6 (reviewed: Q9UDT6)

Alternative names: Cytoplasmic linker protein 115, Cytoplasmic linker protein 2, Williams-Beuren syndrome chromosomal region 3 protein, Williams-Beuren syndrome chromosomal region 4 protein

All UniProt accessions (3): Q9UDT6, H7C4L6, H7C5H8

UniProt curated annotations — full annotation on UniProt →

Function. Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions. May operate in the control of brain-specific organelle translocations.

Subunit / interactions. Interacts with CLASP1 and CLASP2. Binds preferentially to tyrosinated microtubules, and only marginally to detyrosinated microtubules.

Subcellular location. Cytoplasm. Cytoskeleton.

Disease relevance. CLIP2 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of CLIP2 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease. However, it has been demonstrated that haploinsufficiency of this gene alone is not sufficient to cause any of the cognitive or facial features of WBS.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UDT6-1	1	yes
Q9UDT6-2	2

RefSeq proteins (2): NP_003379, NP_115797 (=MANE)

Domains & families (InterPro)

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

Pfam: PF01302, PF27241

UniProt features (49 total): strand 14, modified residue 8, compositionally biased region 7, region of interest 5, coiled-coil region 3, helix 3, turn 3, domain 2, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
2CP2	Solution structure of the 1st CAP-Gly domain in human CLIP-115/CYLN2	SOLUTION NMR
2CP3	Solution structure of the 2nd CAP-Gly domain in human CLIP-115/CYLN2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UDT6-F1	75.25	0.46

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Other congenital disorders, Chromosomal abnormalities

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; plasma membrane

Antibody reliability (HPA): IH enhanced · 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 (8)

Type	Positions
Phosphoserine	49, 202, 207, 211, 314, 923, 973, 979

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 593 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, FREAC2_01, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_493, BLALOCK_ALZHEIMERS_DISEASE_UP, PARK_HSC_VS_MULTIPOTENT_PROGENITORS_UP, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, HFH1_01, TTGGAGA_MIR5155P_MIR519E, FREAC4_01, chr7q11, YAGI_AML_RELAPSE_PROGNOSIS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_TURQUOISE_UP, SOX5_01

GO Biological Process (1): cytoplasmic microtubule organization (GO:0031122)

GO Molecular Function (2): microtubule binding (GO:0008017), microtubule plus-end binding (GO:0051010)

GO Cellular Component (8): nucleus (GO:0005634), microtubule associated complex (GO:0005875), cell cortex (GO:0005938), microtubule plus-end (GO:0035371), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630)

GO top-level categories

15 GO namespaces:

Category	Terms
microtubule cytoskeleton	2
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
tubulin binding	1
microtubule binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
cytoplasm	1
cell periphery	1
microtubule end	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
polymeric cytoskeletal fiber	1
cytoskeleton	1

Protein interactions and networks

STRING

showing 15 of 908 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLIP2	CLASP2	O75122	902
CLIP2	CLASP1	Q7Z460	898
CLIP2	CLASRP	Q8N2M8	880
CLIP2	LIMK1	P53667	850
CLIP2	GTF2IRD1	Q9UHL9	843
CLIP2	TBL2	Q9Y4P3	800
CLIP2	EIF4H	Q15056	798
CLIP2	GTF2I	P78347	746
CLIP2	FZD9	O00144	712
CLIP2	FKBP6	O75344	712
CLIP2	RFC2	P32846	705
CLIP2	FKBP10	Q96AY3	696
CLIP2	STX1A	Q16623	677
CLIP2	TRIM50	Q86XT4	654
CLIP2	BAZ1B	Q9UIG0	634

IntAct

Human interaction partners of CLIP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
BCAP31	physical association	0.400	1
ITSN1	physical association	0.000	1
MAX	physical association	0.000	1

BioGRID (50 interactions; top human partners by supporting records): CLASP1 (Affinity Capture-Western; 3 records), ITSN1 (Two-hybrid; 2 records), MAPRE1 (Affinity Capture-MS; 2 records), PRNP (Affinity Capture-MS; 2 records), AHNAK (Cross-Linking-MS (XL-MS)), APEX1 (Affinity Capture-RNA), ASB7 (Protein-peptide), C17orf59 (Affinity Capture-MS), CCDC88C (Cross-Linking-MS (XL-MS)), CDK9 (Cross-Linking-MS (XL-MS)), CLASP2 (Reconstituted Complex), CLIC1 (Affinity Capture-MS), COMT (Affinity Capture-MS), DOT1L (Affinity Capture-MS), EIF3A (Cross-Linking-MS (XL-MS))

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
CLASP1	“up-regulates activity”	CLIP2	binding
CLASP2	“up-regulates activity”	CLIP2	binding
CLIP2	up-regulates	Microtubule_polimerization

Disease & clinical

Genetic variants

Variant evidence for CLIP2: 199 ClinVar records (3 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	144
Likely benign	22
Benign	13

Top pathogenic / likely-pathogenic (3)

Showing all 3 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
523284	GRCh37/hg19 7q11.23(chr7:72772522-74133319)	Pathogenic	criteria provided, single submitter	1
563406	GRCh37/hg19 7q11.23(chr7:72612042-74574641)x1	Pathogenic	no assertion criteria provided	1
393774	GRCh37/hg19 7q11.23(chr7:73791725-74133273)x1	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CLIP2’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; 24 predictions of 1,653):

Position(s)	Effect	Δscore	Sites
7:74289735–74289736	donor_loss	1.0000	4
7:74317479	acceptor_loss	1.0000	2
7:74317665	donor_gain	1.0000
7:74339005–74339006	donor_loss	1.0000	5
7:74353975	donor_gain	1.0000
7:74354005–74354006	donor_loss	1.0000	5
7:74356569	donor_gain	1.0000
7:74357269	acceptor_gain	1.0000
7:74357478	donor_loss	1.0000	2
7:74360164–74360165	acceptor_gain	1.0000	2

AlphaMissense

2,022 missense substitutions predicted likely pathogenic (of 6,743 scored), across 587 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
F243	8	0.999	1.000
N260	8	0.999	1.000
F279	8	0.998	1.000
F139	8	0.997	1.000
F270	8	0.997	1.000
F103	8	0.994	1.000
F447	8	0.993	1.000
F130	8	0.992	0.999
N120	8	0.991	0.999
D444	8	0.990	0.998
D254	8	0.983	0.998
H367	8	0.979	0.999
D376	8	0.976	0.995
D458	8	0.976	0.993
D261	8	0.973	0.999
F290	8	0.964	0.998
D223	8	0.932	0.994
S316	8	0.920	0.999
H283	8	0.908	0.984
S324	8	0.896	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Disease associations

OMIM: gene MIM:603432 | disease phenotypes:

HPO phenotypes

showing 60 of 186 phenotypes (HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000025	Functional abnormality of male internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000121	Nephrocalcinosis
HP:0000125	Pelvic kidney
HP:0000147	Polycystic ovaries
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000389	Chronic otitis media
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000464	Abnormality of the neck
HP:0000485	Megalocornea
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000545	Myopia
HP:0000581	Blepharophimosis
HP:0000627	Posterior embryotoxon
HP:0000632	Lacrimation abnormality
HP:0000635	Blue irides
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000682	Abnormal dental enamel morphology
HP:0000689	Dental malocclusion
HP:0000691	Microdontia
HP:0000716	Depression
HP:0000717	Autism
HP:0000722	Compulsive behaviors
HP:0000739	Anxiety
HP:0000767	Pectus excavatum
HP:0000787	Kidney stone
HP:0000821	Hypothyroidism
HP:0000822	Hypertension
HP:0000826	Precocious puberty

GWAS associations

3 associations:

Study	Trait	p-value
GCST010584_1	Autism spectrum disorders (social interaction)	3e-8
GCST008771_2	Age at suicide	1e-7
GCST012256_21	SAPHO syndrome	4e-7

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0006882	suicide behaviour measurement
EFO:0005426	autism spectrum disorder symptom

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Cyclosporine	increases expression	3
Cisplatin	decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
ethylbenzene	affects cotreatment, decreases expression, increases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
ochratoxin A	increases acetylation	1
nickel sulfate	increases expression	1
beta-methylcholine	affects expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1

Clinical trials (associated diseases)

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

1 trials:

NCT	Phase	Status	Title
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.