CLIP4

Summary

CLIP4 (CAP-Gly domain containing linker protein family member 4, HGNC:26108) is a protein-coding gene on chromosome 2p23.2, encoding CAP-Gly domain-containing linker protein 4 (Q8N3C7).

Predicted to enable microtubule plus-end binding activity. Predicted to be involved in cytoplasmic microtubule organization. Located in intracellular membrane-bounded organelle.

Source: NCBI Gene 79745 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 104 total
• MANE Select transcript: NM_024692

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26108
Approved symbol	CLIP4
Name	CAP-Gly domain containing linker protein family member 4
Location	2p23.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21069
Ensembl gene	ENSG00000115295
Ensembl biotype	protein_coding
Entrez	79745

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 34 protein_coding, 14 nonsense_mediated_decay, 10 retained_intron

ENST00000320081, ENST00000401605, ENST00000401617, ENST00000404424, ENST00000415891, ENST00000438819, ENST00000449202, ENST00000456385, ENST00000471165, ENST00000481628, ENST00000491701, ENST00000493551, ENST00000685126, ENST00000685829, ENST00000686125, ENST00000686470, ENST00000686848, ENST00000687104, ENST00000687166, ENST00000687450, ENST00000687506, ENST00000687889, ENST00000687915, ENST00000688337, ENST00000688724, ENST00000689017, ENST00000689045, ENST00000689070, ENST00000689605, ENST00000689687, ENST00000690063, ENST00000690615, ENST00000691129, ENST00000691341, ENST00000691509, ENST00000691585, ENST00000691796, ENST00000691852, ENST00000693041, ENST00000693232, ENST00000693264, ENST00000693446, ENST00000693482, ENST00000693513, ENST00000693694, ENST00000881705, ENST00000881706, ENST00000881707, ENST00000949173, ENST00000949174, ENST00000949175, ENST00000949176, ENST00000949177, ENST00000949178, ENST00000949179, ENST00000949180, ENST00000949181, ENST00000949182

RefSeq mRNA: 4 — MANE Select: NM_024692 NM_001287527, NM_001287528, NM_001410747, NM_024692

CCDS: CCDS1770, CCDS74502, CCDS92728

Canonical transcript exons

ENST00000320081 — 16 exons

Exon	Start	End
ENSE00001614395	29157204	29157347
ENSE00001735118	29174373	29174445
ENSE00001836545	29115415	29115665
ENSE00001955568	29181572	29183808
ENSE00002289868	29121374	29121521
ENSE00003485496	29145232	29145367
ENSE00003492604	29132152	29132245
ENSE00003495558	29133655	29133816
ENSE00003504495	29167476	29167540
ENSE00003505071	29131258	29131397
ENSE00003552762	29156354	29156443
ENSE00003561365	29163831	29163954
ENSE00003569398	29152685	29152828
ENSE00003603269	29143709	29143945
ENSE00003619527	29160333	29160467
ENSE00003636961	29135548	29135666

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 98.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6450 / max 217.0966, expressed in 1628 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19533	13.6745	1543
19526	1.3984	421
19534	1.3430	649
19531	1.2687	597
19535	1.1068	607
19527	1.0260	283
19524	0.6676	256
19530	0.1932	56
19525	0.1395	69
19543	0.1252	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.37	gold quality
upper leg skin	UBERON:0004262	97.07	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.73	gold quality
germinal epithelium of ovary	UBERON:0001304	96.59	gold quality
oocyte	CL:0000023	96.52	gold quality
skin of hip	UBERON:0001554	96.49	gold quality
biceps brachii	UBERON:0001507	96.38	gold quality
gastrocnemius	UBERON:0001388	95.96	gold quality
sural nerve	UBERON:0015488	95.65	gold quality
skin of leg	UBERON:0001511	95.41	gold quality
skin of abdomen	UBERON:0001416	95.40	gold quality
muscle of leg	UBERON:0001383	95.15	gold quality
lateral globus pallidus	UBERON:0002476	95.10	gold quality
tibial nerve	UBERON:0001323	95.07	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.96	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.50	gold quality
globus pallidus	UBERON:0001875	94.46	gold quality
medial globus pallidus	UBERON:0002477	94.46	gold quality
parietal pleura	UBERON:0002400	94.44	gold quality
zone of skin	UBERON:0000014	94.39	gold quality
left lobe of thyroid gland	UBERON:0001120	94.16	gold quality
substantia nigra pars compacta	UBERON:0001965	94.07	gold quality
right lobe of thyroid gland	UBERON:0001119	93.96	gold quality
left ovary	UBERON:0002119	93.91	gold quality
thyroid gland	UBERON:0002046	93.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.57	gold quality
mucosa of stomach	UBERON:0001199	93.46	gold quality
postcentral gyrus	UBERON:0002581	93.27	gold quality
muscle organ	UBERON:0001630	93.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting CLIP4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 2)

• FOXC2 and CLIP4 activity correlates to the presence of </=7-cm clear cell renal cell carcinomas (ccRCCs) with synchronous metastasis and may be potential molecular predictors of synchronous metastasis of </=7-cm ccRCCs. (PMID:27283491)
• miR-135b-5p promotes gastric carcinogenesis by targeting CLIP4-mediated JAK2/STAT3 signal pathway. (PMID:39121973)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkeyp-47f9.4	ENSDARG00000096961
mus_musculus	Clip4	ENSMUSG00000024059
rattus_norvegicus	Clip4	ENSRNOG00000008806

Paralogs (4): CLIP3 (ENSG00000105270), CLIP2 (ENSG00000106665), CLIP1 (ENSG00000130779), DCTN1 (ENSG00000204843)

Protein

Protein identifiers

CAP-Gly domain-containing linker protein 4 — Q8N3C7 (reviewed: Q8N3C7)

Alternative names: Restin-like protein 2

All UniProt accessions (27): A0A8I5KRC7, A0A8I5KRK9, A0A8I5KRT4, A0A8I5KS79, A0A8I5KSB1, A0A8I5KT47, A0A8I5KTC6, A0A8I5KTN3, A0A8I5KTX2, Q8N3C7, A0A8I5KUB8, A0A8I5KVT2, A0A8I5KW63, A0A8I5KX39, A0A8I5KXU9, A0A8I5KYN5, A0A8I5QJ97, A0A8I5QKL4, A0A8I5QKM8, A0A8I5QKP4, A0A8I5QKV0, A0A8I5QKZ2, B5MCH3, C9IYE4, E7EW06, E9PBB1, G3XAK3

Isoforms (4)

UniProt ID	Names	Canonical?
Q8N3C7-1	1	yes
Q8N3C7-2	2
Q8N3C7-3	3
Q8N3C7-4	4

RefSeq proteins (4): NP_001274456, NP_001274457, NP_001397676, NP_078968* (*=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 (27 total): strand 6, splice variant 4, repeat 3, domain 3, compositionally biased region 2, modified residue 2, sequence variant 2, region of interest 2, chain 1, sequence conflict 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2Z0W	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3C7-F1	72.24	0.46

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 (2): 557, 609

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 186 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, BENPORATH_ES_WITH_H3K27ME3, TGCACTT_MIR519C_MIR519B_MIR519A, TATTATA_MIR374, DOANE_BREAST_CANCER_CLASSES_DN, VERNELL_RETINOBLASTOMA_PATHWAY_DN, MARTINEZ_RB1_TARGETS_DN, LASTOWSKA_COAMPLIFIED_WITH_MYCN, DOUGLAS_BMI1_TARGETS_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, HUANG_FOXA2_TARGETS_UP, TTTGCAC_MIR19A_MIR19B, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, DURCHDEWALD_SKIN_CARCINOGENESIS_DN

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

GO Molecular Function (2): microtubule plus-end binding (GO:0051010), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cell cortex (GO:0005938), microtubule plus-end (GO:0035371), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
microtubule binding	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cell periphery	1
microtubule end	1
cellular anatomical structure	1

Protein interactions and networks

STRING

615 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLIP4	MPG	P29372	572
CLIP4	C9orf50	Q5SZB4	571
CLIP4	GARIN5A	Q6IPT2	447
CLIP4	TSPYL6	Q8N831	390
CLIP4	ZNF529	Q6P280	380
CLIP4	CCDC57	Q2TAC2	377
CLIP4	NOS1AP	O75052	374
CLIP4	FBXO36	Q8NEA4	357
CLIP4	TOGARAM2	Q6ZUX3	348
CLIP4	PHKB	Q93100	347
CLIP4	MAP6D1	Q9H9H5	338
CLIP4	SLAIN2	Q9P270	337
CLIP4	MRPS12	O15235	335
CLIP4	KCNQ5	Q9NR82	325
CLIP4	TTC27	Q6P3X3	323

IntAct

90 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
CLIP4	ZNF114	psi-mi:“MI:0915”(physical association)	0.780
ZNF114	CLIP4	psi-mi:“MI:0915”(physical association)	0.780
JAKMIP2	CLIP4	psi-mi:“MI:0915”(physical association)	0.740
CLIP4	JAKMIP2	psi-mi:“MI:0915”(physical association)	0.740
CLIP4	TRIM32	psi-mi:“MI:0915”(physical association)	0.720
MAGEA12	CLIP4	psi-mi:“MI:0915”(physical association)	0.720
TRIM32	CLIP4	psi-mi:“MI:0915”(physical association)	0.720
CLIP4	rep	psi-mi:“MI:0915”(physical association)	0.660
CLIP4	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
KIFC3	CLIP4	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	CLIP4	psi-mi:“MI:0915”(physical association)	0.560
CLIP4	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
CLIP4	SIX2	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	CLIP4	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	CLIP4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (59): CLIP4 (Two-hybrid), CLIP4 (Two-hybrid), CLIP4 (Two-hybrid), CLIP4 (Two-hybrid), LZTS2 (Two-hybrid), ZNF114 (Two-hybrid), CLIP4 (Reconstituted Complex), CLIP4 (PCA), KIAA1161 (Affinity Capture-MS), AMPH (Affinity Capture-MS), TACC3 (Two-hybrid), CLIP4 (Affinity Capture-MS), CLIP4 (Two-hybrid), CLIP4 (Two-hybrid), TRIM32 (Two-hybrid)

ESM2 similar proteins: A0A7H0DN38, A3EX96, A5DK05, A7E2Z2, A8MQG7, B1H2Q2, D0Z5N4, F4JJE0, G5EEW9, G5EFD2, H2KY84, O01326, O01767, O15226, O45523, O74975, P0C530, P21081, P21605, P33863, P34541, Q03615, Q04688, Q06651, Q08BS4, Q10024, Q177G4, Q18008, Q18317, Q1A173, Q21341, Q28D84, Q4V863, Q5ICL9, Q5SVQ0, Q66HD5, Q6E3F0, Q6E3F2, Q6NUB7, Q8BY02

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Striated Muscle Contraction	7	61.7×	3e-09
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	22.1×	1e-04
EML4 and NUDC in mitotic spindle formation	6	15.9×	1e-04
Resolution of Sister Chromatid Cohesion	6	14.8×	1e-04
RHO GTPases Activate Formins	6	13.3×	2e-04
Mitotic Prometaphase	6	11.9×	3e-04
Separation of Sister Chromatids	6	10.4×	5e-04
RHO GTPase Effectors	5	9.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
sarcomere organization	6	46.9×	6e-07
microtubule cytoskeleton organization	10	24.7×	3e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4603 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:29131348:G:C	R75T	1.000
2:29131353:T:A	W77R	1.000
2:29131353:T:C	W77R	1.000
2:29131355:G:C	W77C	1.000
2:29131355:G:T	W77C	1.000
2:29132226:A:C	K116N	1.000
2:29132226:A:T	K116N	1.000
2:29133729:T:A	W148R	1.000
2:29133729:T:C	W148R	1.000
2:29143740:T:A	V227D	1.000
2:29160458:T:C	F509L	1.000
2:29160460:C:A	F509L	1.000
2:29160460:C:G	F509L	1.000
2:29163836:T:A	W514R	1.000
2:29163836:T:C	W514R	1.000
2:29163843:G:A	G516D	1.000
2:29163852:T:C	L519P	1.000
2:29163867:G:A	G524D	1.000
2:29163879:G:A	G528D	1.000
2:29163924:G:A	G543E	1.000
2:29163929:T:C	F545L	1.000
2:29163930:T:C	F545S	1.000
2:29163930:T:G	F545C	1.000
2:29163931:T:A	F545L	1.000
2:29163931:T:G	F545L	1.000
2:29163933:C:A	A546D	1.000
2:29131348:G:T	R75I	0.999
2:29131349:A:C	R75S	0.999
2:29131349:A:T	R75S	0.999
2:29131354:G:C	W77S	0.999

dbSNP variants (sampled 300 via entrez): RS1000050873 (2:29137188 C>G), RS1000092482 (2:29102884 C>T), RS1000122461 (2:29136176 TTTG>T), RS1000147276 (2:29151865 A>T), RS1000206859 (2:29156162 A>G), RS1000220722 (2:29179211 T>C), RS1000240143 (2:29139007 T>C), RS1000288220 (2:29118973 C>G), RS1000300280 (2:29157641 T>G), RS1000347407 (2:29118764 C>T), RS1000353045 (2:29169444 A>G), RS1000405194 (2:29115047 G>A), RS1000431144 (2:29161618 A>G), RS1000437251 (2:29163486 T>C), RS1000500879 (2:29150492 A>T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:613014

GenCC curated gene-disease

Mondo (1): neuroblastoma, susceptibility to, 3 (MONDO:0013083)

Orphanet (1): Neuroblastoma (Orphanet:635)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	7
Cyclosporine	increases expression	3
Cadmium Chloride	increases abundance, increases expression	3
bisphenol A	increases expression	2
entinostat	decreases expression, affects cotreatment	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	2
Cadmium	increases abundance, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression, affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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