DSP desmoplakin [Homo sapiens (human)] - Gene

Summary

Official Symbol: DSPprovided by HGNC
Official Full Name: desmoplakinprovided by HGNC
Primary source: HGNC:HGNC:3052
See related: Ensembl:ENSG00000096696 MIM:125647; AllianceGenome:HGNC:3052
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: DP; DCWHKTA
Summary: This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
Expression: Biased expression in skin (RPKM 438.1), esophagus (RPKM 191.0) and 7 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p24.3

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (7541671..7586714)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (7410711..7455759)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (7541904..7586947)

Chromosome 6 - NC_000006.12 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 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?

The Desmoplakin Phenotype Spectrum: Is the Inflammation the "Fil Rouge" Linking Myocarditis, Arrhythmogenic Cardiomyopathy, and Uncommon Autoinflammatory Systemic Disease?
Title: The Desmoplakin Phenotype Spectrum: Is the Inflammation the "Fil Rouge" Linking Myocarditis, Arrhythmogenic Cardiomyopathy, and Uncommon Autoinflammatory Systemic Disease?
Epidermal growth factor receptor inhibition leads to cellular phenotype correction of DSP-mutated keratinocytes.
Title: Epidermal growth factor receptor inhibition leads to cellular phenotype correction of DSP-mutated keratinocytes.
Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (DSP) Truncating Variant.
Title: Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (DSP) Truncating Variant.
DSP-Related Cardiomyopathy as a Distinct Clinical Entity? Emerging Evidence from an Italian Cohort.
Title: DSP-Related Cardiomyopathy as a Distinct Clinical Entity? Emerging Evidence from an Italian Cohort.
Colocalization of Gene Expression and DNA Methylation with Genetic Risk Variants Supports Functional Roles of MUC5B and DSP in Idiopathic Pulmonary Fibrosis.
Title: Colocalization of Gene Expression and DNA Methylation with Genetic Risk Variants Supports Functional Roles of MUC5B and DSP in Idiopathic Pulmonary Fibrosis.
Analysis of incidental findings in Qatar genome participants reveals novel functional variants in LMNA and DSP.
Title: Analysis of incidental findings in Qatar genome participants reveals novel functional variants in LMNA and DSP.
Clinical profile and long-term follow-up of a cohort of patients with desmoplakin cardiomyopathy.
Title: Clinical profile and long-term follow-up of a cohort of patients with desmoplakin cardiomyopathy.
A novel desmoplakin mutation causes dilated cardiomyopathy with palmoplantar keratoderma as an early clinical sign.
Title: A novel desmoplakin mutation causes dilated cardiomyopathy with palmoplantar keratoderma as an early clinical sign.
Missense Mutations in Desmoplakin Plakin Repeat Domains Have Dramatic Effects on Domain Structure and Function.
Title: Missense Mutations in Desmoplakin Plakin Repeat Domains Have Dramatic Effects on Domain Structure and Function.
Desmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis.
Title: Desmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis.

Submit: New GeneRIF Correction See all GeneRIFs (99)

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

Professional guidelines

Description
Professional guideline ACMG 2013 The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in DSP that are pathogenic or expected to be pathogenic. GuidelinePubMed

Associated conditions

Description	Tests
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma MedGen: C1854063 OMIM: 605676 GeneReviews: Not available	not available
Arrhythmogenic right ventricular cardiomyopathy MedGen: C0349788 GeneReviews: Arrhythmogenic Right Ventricular Cardiomyopathy Overview	not available
Arrhythmogenic right ventricular dysplasia 8 MedGen: C1843896 OMIM: 607450 GeneReviews: Arrhythmogenic Right Ventricular Cardiomyopathy Overview	not available
Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis MedGen: C4014393 OMIM: 615821 GeneReviews: Not available	not available
Keratosis palmoplantaris striata 2 MedGen: C1852127 OMIM: 612908 GeneReviews: Not available	not available
Lethal acantholytic epidermolysis bullosa MedGen: C1864826 OMIM: 609638 GeneReviews: Not available	not available

Copy number response

Description
Copy number response Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-10-12) ClinGen Genome Curation PagePubMed Triplosensitivity No evidence available (Last evaluated 2021-10-12) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. EBI GWAS Catalog EBI GWAS CatalogPubMed

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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Replication interactions

Interaction	Pubs
Knockdown of desmoplakin (DSP) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	The expression of desmoplakin (DSP) gene is upregulated in both Jurkat-Tat101 and Jurkat-Tat72 cells	PubMed
integrase	gag-pol	HIV-1 IN is identified to have a physical interaction with desmoplakin (DSP) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	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

DSP__4785 (e-PCR)
- UniSTS:462884

GDB:185731 (e-PCR)
- UniSTS:155458

MARC_16807-16808:1042836779:1 (e-PCR)
- UniSTS:268126

STS-T89283 (e-PCR)
- UniSTS:73576

SHGC-35221 (e-PCR)
- UniSTS:4990

D6S2178 (e-PCR)
- UniSTS:63628

RH46616 (e-PCR)
- UniSTS:19881

A004I41 (e-PCR)
- UniSTS:27361

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication	IC Inferred by Curator more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase C binding	IPI Inferred from Physical Interaction more info	PubMed
enables scaffold protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables structural constituent of cytoskeleton	TAS Traceable Author Statement more info	PubMed
enables structural molecule activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in adherens junction organization	IEA Inferred from Electronic Annotation more info
involved_in bundle of His cell-Purkinje myocyte adhesion involved in cell communication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in desmosome organization	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in epidermis development	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within epithelial cell-cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intermediate filament cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in intermediate filament organization	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in keratinocyte differentiation	IDA Inferred from Direct Assay more info
involved_in peptide cross-linking	IDA Inferred from Direct Assay more info
involved_in protein localization to cell-cell junction	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of heart rate by cardiac conduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of ventricular cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in skin development	IBA Inferred from Biological aspect of Ancestor more info
involved_in ventricular compact myocardium morphogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in wound healing	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in adherens junction	ISS Inferred from Sequence or Structural Similarity more info
located_in basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
located_in cornified envelope	IDA Inferred from Direct Assay more info
located_in cornified envelope	TAS Traceable Author Statement more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in desmosome	IDA Inferred from Direct Assay more info	PubMed
located_in desmosome	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular exosome	HDA more info	PubMed
located_in fascia adherens	IEA Inferred from Electronic Annotation more info
located_in ficolin-1-rich granule membrane	TAS Traceable Author Statement more info
is_active_in intercalated disc	IBA Inferred from Biological aspect of Ancestor more info
located_in intercalated disc	IDA Inferred from Direct Assay more info	PubMed
located_in intercalated disc	ISS Inferred from Sequence or Structural Similarity more info
colocalizes_with intermediate filament	IBA Inferred from Biological aspect of Ancestor more info
colocalizes_with intermediate filament	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in nucleus	HDA more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: desmoplakin

Names: 250/210 kDa paraneoplastic pemphigus antigen

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_008803.1 RefSeqGene

Range

5001..50077

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_423

mRNA and Protein(s)

NM_001008844.3 → NP_001008844.1 desmoplakin isoform II

See identical proteins and their annotated locations for NP_001008844.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. The resulting isoform (II) is shorter than isoform I.

Source sequence(s)

AI304615, AK296756, AL713599, AL713610, AW890985, BF435232, CN282963, J05211, M77830

Consensus CDS

CCDS47368.1

UniProtKB/TrEMBL

Q4LE79

Related

ENSP00000396591.2, ENST00000418664.3

Conserved Domains (5) summary

smart00250
Location:1485 → 1522

PLEC; Plectin repeat

cd00176
Location:285 → 450

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam00681
Location:1767 → 1808

Plectin; Plectin repeat

pfam13863
Location:1159 → 1281

DUF4200; Domain of unknown function (DUF4200)

pfam14662
Location:1018 → 1202

KASH_CCD; Coiled-coil region of CCDC155 or KASH
NM_001319034.2 → NP_001305963.1 desmoplakin isoform Ia

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. The resulting isoform (Ia) is shorter than isoform I.

Source sequence(s)

AK296756, BF435232, HM151899

UniProtKB/TrEMBL

Q4LE79

Related

ENSP00000518230.1, ENST00000710359.2

Conserved Domains (5) summary

smart00250
Location:1641 → 1678

PLEC; Plectin repeat

cd00176
Location:285 → 450

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

TIGR02101
Location:1182 → 1366

IpaC_SipC; type III secretion target, IpaC/SipC family

pfam00681
Location:1923 → 1964

Plectin; Plectin repeat

pfam14662
Location:1018 → 1206

KASH_CCD; Coiled-coil region of CCDC155 or KASH
NM_001406591.1 → NP_001393520.1 desmoplakin isoform 4

Status: REVIEWED

Source sequence(s)

AL031058, KF458095

UniProtKB/TrEMBL

A0AAQ5BH43

Related

ENSP00000519209.1, ENST00000713910.1
NM_004415.4 → NP_004406.2 desmoplakin isoform I

See identical proteins and their annotated locations for NP_004406.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (I).

Source sequence(s)

AI304615, AK296756, AL713599, AL713610, AW890985, BF435232, CN282963, J05211, M77830

Consensus CDS

CCDS4501.1

UniProtKB/Swiss-Prot

B2RTT2, D7RX09, O75993, P15924, Q14189, Q9UHN4

UniProtKB/TrEMBL

A0AAQ5BH40

Related

ENSP00000369129.3, ENST00000379802.8

Conserved Domains (10) summary

smart00250
Location:2084 → 2121

PLEC; Plectin repeat

PRK03918
Location:770 → 1251

PRK03918; chromosome segregation protein; Provisional

cd00176
Location:285 → 450

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam00681
Location:2366 → 2407

Plectin; Plectin repeat

pfam09728
Location:1517 → 1832

Taxilin; Myosin-like coiled-coil protein

pfam10174
Location:1025 → 1674

Cast; RIM-binding protein of the cytomatrix active zone

pfam12761
Location:1507 → 1655

End3; Actin cytoskeleton-regulatory complex protein END3

cd16269
Location:1375 → 1386

GBP_C; coiled coil [structural motif]

cl02488
Location:190 → 366

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

cl20817
Location:1311 → 1405

GBP_C; Guanylate-binding protein, C-terminal domain