CLTC clathrin heavy chain [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLTCprovided by HGNC
Official Full Name: clathrin heavy chainprovided by HGNC
Primary source: HGNC:HGNC:2092
See related: Ensembl:ENSG00000141367 MIM:118955; AllianceGenome:HGNC:2092
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: Hc; CHC; CHC17; MRD56; CLH-17; CLTCL2
Summary: Clathrin is a major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits. These specialized organelles are involved in the intracellular trafficking of receptors and endocytosis of a variety of macromolecules. The basic subunit of the clathrin coat is composed of three heavy chains and three light chains. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in brain (RPKM 67.0), thyroid (RPKM 49.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q23.1

Exon count:: 32

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (59619895..59696956)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (60488657..60565708)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (57697256..57774317)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Expanding Our Knowledge of Molecular Pathogenesis in Histiocytoses: Solitary Soft Tissue Histiocytomas in Children With a Novel CLTC::SYK Fusion.
Title: Expanding Our Knowledge of Molecular Pathogenesis in Histiocytoses: Solitary Soft Tissue Histiocytomas in Children With a Novel CLTC::SYK Fusion.
Knockout of CLTC gene reduces but not completely block SFTSV infection.
Title: Knockout of CLTC gene reduces but not completely block SFTSV infection.
Molecular investigation of ALK-rearranged epithelioid fibrous histiocytomas identifies CLTC as a novel fusion partner and evidence of fusion-independent transcription activation.
Title: Molecular investigation of ALK-rearranged epithelioid fibrous histiocytomas identifies CLTC as a novel fusion partner and evidence of fusion-independent transcription activation.
Novel CLTC variants cause new brain and kidney phenotypes.
Title: Novel CLTC variants cause new brain and kidney phenotypes.
Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF-beta and AKT/mTOR signaling pathways.
Title: Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF-beta and AKT/mTOR signaling pathways.
Clathrin: the molecular shape shifter.
Title: Clathrin: the molecular shape shifter.
SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis.
Title: SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis.
De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy.
Title: De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy.
Clathrin switches transforming growth factor-beta role to pro-tumorigenic in liver cancer.
Title: Clathrin switches transforming growth factor-β role to pro-tumorigenic in liver cancer.
Pluripotency of embryonic stem cells lacking clathrin-mediated endocytosis cannot be rescued by restoring cellular stiffness.
Title: Pluripotency of embryonic stem cells lacking clathrin-mediated endocytosis cannot be rescued by restoring cellular stiffness.

Submit: New GeneRIF Correction See all GeneRIFs (64)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Intellectual disability, autosomal dominant 56 MedGen: C4693389 OMIM: 617854 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2022-09-27) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2022-09-27) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify heavy chain of clathrin (CLTC), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into Staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	env	HIV-1 matrix and gp120 co-localize with clathrin in primary T lymphocytes	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify heavy chain of clathrin (CLTC), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into Staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	gag-pol	HIV-1 particles incorporate the clathrin heavy chain together with associated light chains through HIV-1 Gag-Pol in an IN-dependent manner	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify heavy chain of clathrin (CLTC), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into Staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	nef	The leucine-based motif of Nef is required for targeting into clathrin-associated AP complexes and the Nef-mediated alterations of trafficking of CD4 receptor	PubMed
	nef	Knocking down either AP-1 gamma, AP-1 mu1, or clathrin strongly inhibits Nef-induced downregulation of HLA-A2	PubMed
	nef	HIV-1 Nef induces the formation of clathrin-coated pits in the presence of CD4 in human lymphocytes by interacting with components of the clathrin-coated surface domain	PubMed
Pol	gag-pol	Clathrin stabilizes HIV-1 Pol proteins in HIV-1 infected cells	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify heavy chain of clathrin (CLTC), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into Staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of clathrin, heavy chain (CLTC) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed
	vpr	HIV-1 Vpr C-terminus (residues 52-96) entry into cells is mediated through clathrin- and caveolae/raft-dependent endocytosis	PubMed
integrase	gag-pol	Deletion of the HIV-1 IN C-terminal domain and the IN N184L/F185K mutation abolish clathrin incorporation into virions	PubMed
	gag-pol	HIV-1 particles incorporate the clathrin heavy chain together with associated light chains through HIV-1 Gag-Pol in an IN-dependent manner	PubMed
matrix	gag	HIV-1 matrix and gp120 co-localize with clathrin in primary T lymphocytes	PubMed
reverse transcriptase	gag-pol	Mutations in HIV-1 RT, including L234A, that inhibit RT dimerization abolish clathrin incorporation into virions	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH11769 (e-PCR)
- UniSTS:65808

WI-19130 (e-PCR)
- UniSTS:10535

G42611 (e-PCR)
- UniSTS:94512

G42377 (e-PCR)
- UniSTS:94283

SHGC-80819 (e-PCR)
- UniSTS:102480

WI-18090 (e-PCR)
- UniSTS:17549

RH81083 (e-PCR)
- UniSTS:91535

G42242 (e-PCR)
- UniSTS:93345

MARC_20665-20666:1025269998:3 (e-PCR)
- UniSTS:268467

SHGC-36454 (e-PCR)
- UniSTS:17092

D17S1600 (e-PCR)
- UniSTS:153545

RH25272 (e-PCR)
- UniSTS:72661

D17S2052 (e-PCR)
- UniSTS:4316

RH46414 (e-PCR)
- UniSTS:63456

SGC30655 (e-PCR)
- UniSTS:60898

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables clathrin light chain binding	IBA Inferred from Biological aspect of Ancestor more info
enables clathrin light chain binding	IPI Inferred from Physical Interaction more info	PubMed
enables disordered domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables double-stranded RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables low-density lipoprotein particle receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	ISS Inferred from Sequence or Structural Similarity more info
enables structural molecule activity	NAS Non-traceable Author Statement more info	PubMed
enables ubiquitin-specific protease binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in amyloid-beta clearance by transcytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in autophagy	IEA Inferred from Electronic Annotation more info
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in clathrin coat assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in clathrin coat assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in clathrin coat disassembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in clathrin-dependent endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular protein transport	NAS Non-traceable Author Statement more info	PubMed
involved_in mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of hyaluronan biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of hyaluronan biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in osteoblast differentiation	HDA more info	PubMed
involved_in receptor internalization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in receptor-mediated endocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in receptor-mediated endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of mitotic spindle organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in retrograde transport, endosome to Golgi	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transferrin transport	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of clathrin coat	IMP Inferred from Mutant Phenotype more info	PubMed
part_of clathrin coat	NAS Non-traceable Author Statement more info	PubMed
part_of clathrin coat of coated pit	IEA Inferred from Electronic Annotation more info
part_of clathrin coat of trans-Golgi network vesicle	IEA Inferred from Electronic Annotation more info
part_of clathrin complex	IBA Inferred from Biological aspect of Ancestor more info
part_of clathrin complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in clathrin-coated endocytic vesicle	IBA Inferred from Biological aspect of Ancestor more info
located_in clathrin-coated endocytic vesicle	NAS Non-traceable Author Statement more info	PubMed
located_in clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in clathrin-coated vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in endolysosome membrane	TAS Traceable Author Statement more info
located_in endosome	IDA Inferred from Direct Assay more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular vesicle	HDA more info	PubMed
located_in focal adhesion	HDA more info	PubMed
located_in lysosome	IDA Inferred from Direct Assay more info
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed
located_in mitotic spindle	IDA Inferred from Direct Assay more info
located_in mitotic spindle microtubule	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in spindle	IBA Inferred from Biological aspect of Ancestor more info
located_in spindle	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: clathrin heavy chain 1

Names: clathrin heavy chain on chromosome 17; clathrin, heavy polypeptide (Hc); clathrin, heavy polypeptide-like 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_047043.1 RefSeqGene

Range

5207..82268

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001288653.2 → NP_001275582.1 clathrin heavy chain 1 isoform 2

See identical proteins and their annotated locations for NP_001275582.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The resulting protein (isoform 2) is longer compared to isoform 1.

Source sequence(s)

AC091271, AK127134

Consensus CDS

CCDS74115.1

UniProtKB/TrEMBL

A0A087WVQ6, A0A8V8TQ14, J3KSQ2

Related

ENSP00000462592.2, ENST00000580081.2

Conserved Domains (6) summary

smart00299
Location:1278 → 1420

CLH; Clathrin heavy chain repeat homology

sd00006
Location:1109 → 1135

TPR; TPR repeat [structural motif]

pfam01394
Location:202 → 238

Clathrin_propel; Clathrin propeller repeat

pfam00637
Location:1431 → 1565

Clathrin; Region in Clathrin and VPS

pfam09268
Location:335 → 358

Clathrin-link; Clathrin, heavy-chain linker

pfam13838
Location:360 → 425

Clathrin_H_link; Clathrin-H-link
NM_004859.4 → NP_004850.1 clathrin heavy chain 1 isoform 1

See identical proteins and their annotated locations for NP_004850.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript and encodes the shorter protein (isoform 1).

Source sequence(s)

AC091271, BC054489

Consensus CDS

CCDS32696.1

UniProtKB/Swiss-Prot

D3DU00, Q00610, Q6N0A0, Q86TF2

UniProtKB/TrEMBL

A0A8V8TR47

Related

ENSP00000269122.3, ENST00000269122.8

Conserved Domains (6) summary

smart00299
Location:1274 → 1416

CLH; Clathrin heavy chain repeat homology

sd00006
Location:1105 → 1131

TPR; TPR repeat [structural motif]

pfam00637
Location:979 → 1119

Clathrin; Region in Clathrin and VPS

pfam01394
Location:198 → 234

Clathrin_propel; Clathrin propeller repeat

pfam09268
Location:331 → 354

Clathrin-link; Clathrin, heavy-chain linker

pfam13838
Location:356 → 421

Clathrin_H_link; Clathrin-H-link