CLTC (clathrin heavy polypeptide)

2005-04-01 Pedram Argani , Marc Ladanyi Affiliation

Identity

HGNC

CLTC

LOCATION

17q23.1

LOCUSID

1213

ALIAS

CHC,CHC17,CLH-17,CLTCL2,Hc,MRD56

FUSION GENES

Show Gene Fusions

DNA/RNA

Transcription

32 exons, 6111 bp mRNA

Proteins

Description

Clathrin is the major protein constituent of the coat that surrounds organelles (cytoplasmic vesicles) to mediate selective protein transport. Clathrin coats are involved in receptor-mediated endocytosis and intracellular trafficking and recycling of receptors, which accounts for its characteristic punctate cytoplasmic and perinuclear cellular distribution. Structurally, clathrin is a triskelion (three-legged) shaped protein complex that is composed of a trimer of heavy chains (CLTC) each bound to a single light chain. CLTC is a 1675 amino acid residue protein encoded by a gene consisting of 32 exons. Its known domains include a N-terminal globular domain (residues 1-494) that interacts with adaptor proteins (AP-1, AP-2, b-arrestin), a light chain-binding region (residues 1074-1552), and a trimerization domain (residues 1550-1600) near the C-terminus.

Localisation

Cytoplasmic vesicles

Function

mediate endocytosis of transmembrane receptors.

Implicated in

Entity name

Anaplasic large cell lymphoma (ALCL) with t(2;17)(p23;q23) --> ALK - CLTC

Disease

ALCL are high grade non Hodgkin lymphomas; ALK+ ALCL are ALCL where ALK is involved in a fusion gene; ALK+ ALCL represent 50 to 60 % of ALCL cases (they are CD30+, ALK+;); belong to the "cytoplasmic ALK+" subset.

Prognosis

Although presenting as a high grade tumour, a 80% five yr survival is associated with this anomaly

Hybrid gene

5 CLTC - 3 ALK

Fusion protein

NH2 CLTC - COOH ALK

Entity name

Inflammatory myofibroblastic tumors with t(2;17)(p23;q23)

Note

In these tumors, the fusion point in CLTC is identical, being at amino acid 1634 (corresponding to the 3 end of exon 31 of CLTC), such that almost all of CLTC is included in the fusion protein, including its trimerization domain . As a fusion partner, CLTC has been postulated to provide CLTC-ALK with deregulated expression driven by its constitutively activated promoter and constitutive oligomerization of the chimeric protein via the CLTC multimerization domains normally used for clathrin coat assembly. Since ALK is a tyrosine kinase that is activated by cross-phosphorylation following ligand binding, CLTC-ALK-induced oligomerization may result in a constitutively activated ALK tyrosine kinase domain. In this sense, CLTC is likely to function in CLTC-ALK as other prototypical "dimerizing translocation partners" in fusions involving tyrosine kinase genes.

Disease

rare soft tissue tumour found in children and young adults

Prognosis

good prognosis

Hybrid gene

5 CLTC - 3 ALK

Entity name

Xp11 renal translocation carcinoma with t(X;17)(p11;q23)

Note

In the CLTC-TFE3 fusion, the fusion point on CLTC is at amino acid 932 (corresponding to the end of exon 17), thereby excluding the CLTC trimerization domain from the predicted fusion protein. As in other TFE3 gene fusions, the nuclear localization and DNA binding domains of TFE3 are retained in CLTC-TFE3. Based on these features and existing data on other TFE3 fusion proteins, CLTC-TFE3 may act as an aberrant transcription factor, with the CLTC promoter driving constitutive expression.

Disease

rare renal carcinoma (single case report)

Prognosis

Unknown prognosis

Hybrid gene

5 CLTC 3TFE3

Breakpoints

Article Bibliography

Pubmed ID	Last Year	Title	Authors
12917640	2003	A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23).	Argani P et al
11485898	2001	Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor.	Bridge JA et al
12112524	2002	Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor.	Cools J et al
1765375	1991	Human clathrin heavy chain (CLTC): partial molecular cloning, expression, and mapping of the gene to human chromosome 17q11-qter.	Dodge GR et al
10966473	2000	Clathrin.	Kirchhausen T et al
9242916	1997	Clathrin-coated vesicle formation and protein sorting: an integrated process.	Schmid SL et al
10360576	1999	Clathrin self-assembly is mediated by a tandemly repeated superhelix.	Ybe JA et al

Other Information

Locus ID:

NCBI: 1213
MIM: 118955
HGNC: 2092
Ensembl: ENSG00000141367

Variants:

dbSNP: 1213
ClinVar: 1213
TCGA: ENSG00000141367
COSMIC: CLTC

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000141367	ENST00000269122	Q00610
ENSG00000141367	ENST00000393043	Q00610
ENSG00000141367	ENST00000472651	K7EJJ5
ENSG00000141367	ENST00000475458	J3KRF5
ENSG00000141367	ENST00000483176	J3KTN1
ENSG00000141367	ENST00000579456	J3KS13
ENSG00000141367	ENST00000580081	J3KSQ2
ENSG00000141367	ENST00000584313	J3QL20
ENSG00000141367	ENST00000621829	A0A087WVQ6

Expression (GTEx)

100

150

200

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Huntington's disease	KEGG	ko05016
Huntington's disease	KEGG	hsa05016
Lysosome	KEGG	ko04142
Lysosome	KEGG	hsa04142
Endocytosis	KEGG	ko04144
Endocytosis	KEGG	hsa04144
Bacterial invasion of epithelial cells	KEGG	ko05100
Bacterial invasion of epithelial cells	KEGG	hsa05100
Endocrine and other factor-regulated calcium reabsorption	KEGG	ko04961
Endocrine and other factor-regulated calcium reabsorption	KEGG	hsa04961
Synaptic vesicle cycle	KEGG	ko04721
Synaptic vesicle cycle	KEGG	hsa04721
Disease	REACTOME	R-HSA-1643685
Infectious disease	REACTOME	R-HSA-5663205
Influenza Infection	REACTOME	R-HSA-168254
Influenza Life Cycle	REACTOME	R-HSA-168255
Entry of Influenza Virion into Host Cell via Endocytosis	REACTOME	R-HSA-168275
Immune System	REACTOME	R-HSA-168256
Adaptive Immune System	REACTOME	R-HSA-1280218
MHC class II antigen presentation	REACTOME	R-HSA-2132295
Signal Transduction	REACTOME	R-HSA-162582
Signalling by NGF	REACTOME	R-HSA-166520
NGF signalling via TRKA from the plasma membrane	REACTOME	R-HSA-187037
Retrograde neurotrophin signalling	REACTOME	R-HSA-177504
Signaling by Wnt	REACTOME	R-HSA-195721
Beta-catenin independent WNT signaling	REACTOME	R-HSA-3858494
PCP/CE pathway	REACTOME	R-HSA-4086400
WNT5A-dependent internalization of FZD4	REACTOME	R-HSA-5099900
WNT5A-dependent internalization of FZD2, FZD5 and ROR2	REACTOME	R-HSA-5140745
Vesicle-mediated transport	REACTOME	R-HSA-5653656
Membrane Trafficking	REACTOME	R-HSA-199991
trans-Golgi Network Vesicle Budding	REACTOME	R-HSA-199992
Clathrin derived vesicle budding	REACTOME	R-HSA-421837
Golgi Associated Vesicle Biogenesis	REACTOME	R-HSA-432722
Lysosome Vesicle Biogenesis	REACTOME	R-HSA-432720
Gap junction trafficking and regulation	REACTOME	R-HSA-157858
Gap junction trafficking	REACTOME	R-HSA-190828
Gap junction degradation	REACTOME	R-HSA-190873
Formation of annular gap junctions	REACTOME	R-HSA-196025
Metabolism	REACTOME	R-HSA-1430728
Metabolism of lipids and lipoproteins	REACTOME	R-HSA-556833
Lipid digestion, mobilization, and transport	REACTOME	R-HSA-73923
Lipoprotein metabolism	REACTOME	R-HSA-174824
LDL-mediated lipid transport	REACTOME	R-HSA-171052
Developmental Biology	REACTOME	R-HSA-1266738
Axon guidance	REACTOME	R-HSA-422475
L1CAM interactions	REACTOME	R-HSA-373760
Recycling pathway of L1	REACTOME	R-HSA-437239
EPH-Ephrin signaling	REACTOME	R-HSA-2682334
EPH-ephrin mediated repulsion of cells	REACTOME	R-HSA-3928665
VLDL interactions	REACTOME	R-HSA-8855121
VLDLR internalisation and degradation	REACTOME	R-HSA-8866427
Clathrin-mediated endocytosis	REACTOME	R-HSA-8856828
Cargo recognition for clathrin-mediated endocytosis	REACTOME	R-HSA-8856825

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
37522373	2023	Expanding Our Knowledge of Molecular Pathogenesis in Histiocytoses: Solitary Soft Tissue Histiocytomas in Children With a Novel CLTC::SYK Fusion.	0
37624798	2023	Knockout of CLTC gene reduces but not completely block SFTSV infection.	0
37522373	2023	Expanding Our Knowledge of Molecular Pathogenesis in Histiocytoses: Solitary Soft Tissue Histiocytomas in Children With a Novel CLTC::SYK Fusion.	0
37624798	2023	Knockout of CLTC gene reduces but not completely block SFTSV infection.	0
34230591	2022	Novel CLTC variants cause new brain and kidney phenotypes.	3
35289445	2022	Molecular investigation of ALK-rearranged epithelioid fibrous histiocytomas identifies CLTC as a novel fusion partner and evidence of fusion-independent transcription activation.	1
34230591	2022	Novel CLTC variants cause new brain and kidney phenotypes.	3
35289445	2022	Molecular investigation of ALK-rearranged epithelioid fibrous histiocytomas identifies CLTC as a novel fusion partner and evidence of fusion-independent transcription activation.	1
33476648	2021	SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis.	261
34185412	2021	Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF-beta and AKT/mTOR signaling pathways.	5
34436540	2021	Clathrin: the molecular shape shifter.	9
33476648	2021	SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis.	261
34185412	2021	Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF-beta and AKT/mTOR signaling pathways.	5
34436540	2021	Clathrin: the molecular shape shifter.	9
31562907	2020	Clathrin switches transforming growth factor-β role to pro-tumorigenic in liver cancer.	22

Citation

Pedram Argani ; Marc Ladanyi

CLTC (clathrin heavy polypeptide)

Atlas Genet Cytogenet Oncol Haematol. 2005-04-01

Online version: http://atlasgeneticsoncology.org/gene/360/cltc-(clathrin-heavy-polypeptide)

Historical Card

2003-08-01 CLTC (clathrin heavy polypeptide) by Jean-Loup Huret,Sylvie Senon Affiliation

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

2001-08-01 CLTC (clathrin heavy polypeptide) by Jean-Loup Huret Affiliation

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France