Human Disease Model Report: xeroderma pigmentosum, complementation group D

General Information

Name

xeroderma pigmentosum, complementation group D

FlyBase ID

FBhh0000205

Disease Ontology Term

xeroderma pigmentosum group D

Parent Disease

xeroderma pigmentosum

OMIM

XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP D; XPD

Overview

This report describes xeroderma pigmentosum, complementation group D (XPD), which is a subtype of xeroderma pigmentosum; XPD exhibits autosomal recessive inheritance. The human gene implicated in this disease is Excision Repair Cross-Complementation Group 2 (ERCC2), which is encodes a DNA helicase that is a component of the TFIIH basal transcription factor. There is a single fly ortholog, Xpd, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. ERCC2 is also implicated in several other human diseases, including a subtype of trichothiodystrophy (TTD; see MIM:126340 and human disease model report FBhh0000709).

The human ERCC2 gene has not been introduced into flies.

Variant(s) implicated in human disease tested (as analogous mutation in fly gene): R112H in the fly Xpd gene (corresponds to R112H in the human ERCC2 gene); R683W in the fly Xpd gene (corresponds to R683W in the human ERCC2 gene); D234N in the fly Xpd gene (corresponds to D234N in the human ERCC2 gene); G47R in the fly Xpd gene (corresponds to G47R in the human ERCC2 gene); G675R in the fly Xpd gene (corresponds to G675R in the human ERCC2 gene); R601L in the fly Xpd gene (corresponds to R601L in the human ERCC2 gene). In addition, a variant analogous to one implicated in TTD1 has been characterized; see FBhh0000709.

Amorphic alleles of the Drosophila Xpd gene are lethal during late embryogenesis; embryonic phenotypes, including radiation sensitivity, have been assayed. Physical and genetic interactions of Dmel\Xpd have been described; see below and in the Xpd gene report.

[updated Jan. 2018 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: xeroderma pigmentosum

Symptoms and phenotype

Xeroderma pigmentosum is characterized by increased sensitivity to sunlight with the development of carcinomas at an early age. Some patients develop neurologic symptoms or a more severe clinical phenotype known as de Sanctis-Cacchione syndrome (MIM:278800) (Satokata et al., 1992; pubmed:1372102). [from MIM:278700; 2016.03.09]

(OMIM, 2013-)

Xeroderma pigmentosum (XP) is an inherited condition characterized by an extreme sensitivity to ultraviolet (UV) rays from sunlight, affecting repeatedly exposed skin and the eyes, and by a greatly increased risk of developing skin cancer. About 30 percent of people with xeroderma pigmentosum also develop progressive neurological abnormalities. [from Genetics Home Reference, Xeroderma pigmentosum; 2016.03.23]

(FlyBase Curators, 2013-)

Specific Disease Summary: xeroderma pigmentosum, complementation group D

OMIM report

[XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP D; XPD](https://omim.org/entry/278730)

Human gene(s) implicated

[ERCC EXCISION REPAIR 2, TFIIH CORE COMPLEX HELICASE SUBUNIT; ERCC2](https://omim.org/entry/126340)

Symptoms and phenotype

See general description above.

(OMIM, 2013-)

Genetics

Xeroderma pigmentosum complementation group D (XPD) is caused by homozygous or compound heterozygous mutation in the excision repair gene ERCC2. [from MIM:278730; 2016.03.09]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

ERCC2 encodes an ATP-dependent DNA helicase that functions in nucleotide excision repair as a component of the core-TFIIH basal transcription factor. ERCC2 belongs to the RAD3/XPD subfamily of helicases. [from Gene Cards, ERCC2; 2016.03.23]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): ERCC2
Gene Cards: ERCC2
GeneReviews, NCBI Bookshelf: Xeroderma Pigmentosum
MedlinePlus (condition): Xeroderma pigmentosum
MedlinePlus (gene): ERCC2
MARRVEL (human gene): ERCC2
NCBI MedGen: Xeroderma pigmentosum, group D (XPD)
NCBI (Entrez) gene: ERCC2; ERCC excision repair 2, TFIIH core complex helicase subunit
National Organization for Rare Disorders: Xeroderma Pigmentosum

Disease synonyms

xeroderma pigmentosum

xeroderma pigmentosum/Cockayne syndrome

xeroderma pigmentosum IV

XP/CS

XPD

XPDC

Related Diseases

Related human health report(s)

trichothiodystrophy 1, photosensitive

Related Specific Diseases

OMIM phenotypic series

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[XPA](https://omim.org/entry/278700)

[XPA](https://omim.org/entry/611153)

[XPB](https://omim.org/entry/610651)

[ERCC3](https://omim.org/entry/133510)

xeroderma pigmentosum, complementation group B

[XPC](https://omim.org/entry/278720)

[XPC](https://omim.org/entry/613208)

[XPD](https://omim.org/entry/278730)

[ERCC2](https://omim.org/entry/126340)

xeroderma pigmentosum, complementation group D

[XPE](https://omim.org/entry/278740)

[DDB2](https://omim.org/entry/600811)

[XPF](https://omim.org/entry/278760)

[ERCC4](https://omim.org/entry/133520)

[XPG](https://omim.org/entry/278780)

[ERCC5](https://omim.org/entry/133530)

[XPV](https://omim.org/entry/278750)

[POLH](https://omim.org/entry/603968)

xeroderma pigmentosum, variant type

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

ERCC2; ERCC excision repair 2, TFIIH core complex helicase subunit

D. melanogaster ortholog (based on DIOPT)

Dmel\Xpd

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Xpd

Gene Snapshot

Xeroderma pigmentosum D (Xpd) encodes a DNA helicase that is a subunit of the basal transcription and DNA repair factor TFIIH. [Date last reviewed: 2019-03-21]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human ERCC2 (1 Drosophila to 1 human). Dmel\Xpd shares 69% identity and 84% similarity with the human gene.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (11 groups)

Xpd

protein-protein

Interacting group

Assay

References

Xpd - Cdk7

anti bait coimmunoprecipitation, western blot

(Nag et al., 2018, Aguilar-Fuentes et al., 2006)

Xpd - Ciao1

anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot

(Jung et al., 2020)

Xpd - crb

anti tag coimmunoprecipitation, anti tag western blot

(Yeom et al., 2015)

Xpd - galla-2

anti bait coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, western blot

(Nag et al., 2018, Yeom et al., 2015)

Xpd - hay

anti bait coimmunoprecipitation, western blot

(Aguilar-Fuentes et al., 2006)

Xpd - Hsp23

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

Xpd - Hsp26

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

Xpd - Klp61F

pull down, anti tag western blot, anti tag coimmunoprecipitation

(Hwang et al., 2020)

Xpd - Mms19

anti tag coimmunoprecipitation, western blot

(Nag et al., 2018)

Xpd - Sams

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

Xpd - Ssl1

anti bait coimmunoprecipitation, western blot

(Aguilar-Fuentes et al., 2008)

Alleles Reported to Model Human Disease (Disease Ontology) (10 alleles)

Xpd

Models Based on Experimental Evidence ( 10 )

Allele

Disease

Evidence

References

Xpd^SH2137

model of xeroderma pigmentosum

CEA with Xpd^G675R

(Stettler et al., 2015)

CEA with Xpd^R601L

(Stettler et al., 2015)

CEA with Xpd^R683W

(Stettler et al., 2015)

CEA with Xpd^G47R

(Stettler et al., 2015)

CEA with Xpd^D234N

(Stettler et al., 2015)

model of Cockayne syndrome

CEA with Xpd^G47R

(Stettler et al., 2015)

CEA with Xpd^G675R

(Stettler et al., 2015)

model of photosensitive trichothiodystrophy

CEA with Xpd^R112H

(Stettler et al., 2015)

CEA with Xpd^R722W

(Stettler et al., 2015)

Xpd^D234N

model of xeroderma pigmentosum

CEA with Xpd^SH2137

(Stettler et al., 2015)

Xpd^R601L

model of xeroderma pigmentosum

CEA with Xpd^SH2137

(Stettler et al., 2015)

Xpd^R683W

model of xeroderma pigmentosum

CEA with Xpd^SH2137

(Stettler et al., 2015)

Xpd^G47R

model of xeroderma pigmentosum

CEA with Xpd^SH2137

(Stettler et al., 2015)

model of Cockayne syndrome

CEA with Xpd^SH2137

(Stettler et al., 2015)

Xpd^G675R

model of xeroderma pigmentosum

CEA with Xpd^SH2137

(Stettler et al., 2015)

model of Cockayne syndrome

CEA with Xpd^SH2137

(Stettler et al., 2015)

Xpd^R112H

model of photosensitive trichothiodystrophy

CEA with Xpd^SH2137

(Stettler et al., 2015)

Xpd^R722W

model of photosensitive trichothiodystrophy

CEA with Xpd^SH2137

(Stettler et al., 2015)

Xpd^{RNAi.UAS.012.1}

model of adenoid cystic carcinoma

CEA with Hsap\MYB^ΔC.UAS, N^UAS.cMa, ft^{RNAi.UAS.012.1}, kug^{RNAi.UAS.012.1}

(Bangi et al., 2021)

Xpd^{RNAi.UAS.012.2}

model of adenoid cystic carcinoma

CEA with Hsap\MYB^ΔC.UAS, N^UAS.cMa, ft^{RNAi.UAS.012.2}, kug^{RNAi.UAS.012.2}

(Bangi et al., 2021)

Modifiers Based on Experimental Evidence ( 0 )

Allele

Disease

Interaction

References

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Xpd^{RNAi.UAS.012.1}

P{UAS-MYBDeltaC,UAS-3sh(Xpd,ft,kug).012.1}

Xpd^{RNAi.UAS.012.2}

P{UAS-MYBDeltaC,UAS-3sh(Xpd,ft,kug).012.2}

Xpd^GD4206

P{GD4206}

w¹¹¹⁸ P{GD4206}v41021

y¹ v¹; P{TRiP.HMJ21396}attP40/CyO

Xpd^HMC06145

P{TRiP.HMC06145}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC06145}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Xpd^SH2137

P-element activity

w^*; P{lacW}Xpd^SH2137/CyO

References (8)

Report Sections

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