Human Disease Model Report: trichothiodystrophy 1, photosensitive

General Information

Name

trichothiodystrophy 1, photosensitive

FlyBase ID

FBhh0000709

Disease Ontology Term

photosensitive trichothiodystrophy

Parent Disease

trichothiodystrophy

OMIM

TRICHOTHIODYSTROPHY 1, PHOTOSENSITIVE; TTD1

Overview

This report describes trichothiodystrophy 1, photosensitive (TTD1), which is a subtype of trichothiodystrophy; TTD1 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 transcription and DNA repair complex. 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 xeroderma pigmentosum (see MIM:126340 and human disease model report FBhh0000205).

The human ERCC2 gene has not been introduced into flies.

Multiple variants of Dmel\Xpd analogous to variants implicated in human disease have been characterized. Most of these correspond to variants implicated in xeroderma pigmentosum, subtype XPD; see FBhh0000205. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): R722W in the fly Xpd gene (corresponds to R722W in the human ERCC2 gene, implicated in TTD1); R112H in the fly Xpd gene (corresponds to R112H in the human ERCC2 gene, implicated in both XPD and TTD1).

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: trichothiodystrophy

Symptoms and phenotype

Trichothiodystrophy (TTD) is a rare autosomal recessive disorder in which patients have brittle, sulfur-deficient hair that displays a diagnostic alternating light and dark banding pattern under polarizing microscopy. TTD patients display a wide variety of clinical features, including cutaneous, neurologic, and growth abnormalities. Common additional clinical features are ichthyosis (rough, thick, and scaly skin), intellectual/developmental disabilities, decreased fertility, ocular abnormalities, short stature, and infections. There are both photosensitive and non-photosensitive forms of the disorder. TTD patients have not been reported to have a predisposition to cancer (summary by Faghri et al., 2008; pubmed:18603627). [from MIM:601675; 2018.01.22]

(OMIM, 2013-)

Specific Disease Summary: trichothiodystrophy 1, photosensitive

OMIM report

[TRICHOTHIODYSTROPHY 1, PHOTOSENSITIVE; TTD1](https://omim.org/entry/601675)

Human gene(s) implicated

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

Symptoms and phenotype

TTD1 is a photosensitive form of trichothiodystrophy. [from MIM:601675; 2018.01.22]

(OMIM, 2013-)

Genetics

Photosensitive trichothiodystrophy-1 (TTD1) is caused by homozygous or compound heterozygous mutation in the ERCC2/XPD gene. [from MIM:601675; 2018.01.22]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

ERCC2 encodes a helicase subunit of transcription/repair factor TFIIH, which functions in nucleotide excision repair. [from MIM:601675, MIM:126340; 2018.01.22]

(OMIM, 2013-)

External links

Gene2Function (human gene): ERCC2
Gene Cards: ERCC2
MedlinePlus (gene): ERCC2
MARRVEL (human gene): ERCC2
NCBI MedGen: Trichothiodystrophy 1, photosensitive (TTD1)
NCBI (Entrez) gene: ERCC2; ERCC excision repair 2, TFIIH core complex helicase subunit

Disease synonyms

photosensitive trichothiodystrophy

TTD1

TTDP

Related Diseases

Related human health report(s)

xeroderma pigmentosum, complementation group D

Related Specific Diseases

OMIM phenotypic series

Trichothiodystrophy

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[TTD1](https://omim.org/entry/601675)

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

trichothiodystrophy 1, photosensitive

[TTD2](https://omim.org/entry/616390)

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

[TTD3](https://omim.org/entry/616395)

[GTF2H5](https://omim.org/entry/608780)

[TTD4](https://omim.org/entry/234050)

[MPLKIP](https://omim.org/entry/609188)

[TTD5](https://omim.org/entry/300953)

[RNF113A](https://omim.org/entry/300951)

[TTD6](https://omim.org/entry/616943)

[GTF2E2](https://omim.org/entry/189964)

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

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

(Jung et al., 2020)

Xpd - crb

anti tag coimmunoprecipitation, anti tag western blot

(Yeom et al., 2015)

Xpd - galla-2

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

(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 (7)

Report Sections

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