GTF2H5

general transcription factor IIH subunit 5, the group of General transcription factor IIH complex subunits|Nucleotide excision repair

Basic information

Region (hg38): 6:158168349-158199344

Previous symbols: [ "C6orf175", "TTD" ]

Links

ENSG00000272047 ∙ NCBI:404672 ∙ OMIM:608780 ∙ HGNC:21157 ∙ Uniprot:Q6ZYL4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• trichothiodystrophy 1, photosensitive (Definitive), mode of inheritance: AR
• trichothiodystrophy 3, photosensitive (Strong), mode of inheritance: AR
• trichothiodystrophy 3, photosensitive (Strong), mode of inheritance: AR
• trichothiodystrophy 3, photosensitive (Moderate), mode of inheritance: AR
• trichothiodystrophy (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Trichothiodystrophy 3, photosensitive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	2189905; 8783572; 15220921; 18470933; 18603627

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GTF2H5 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GTF2H5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				14		14
missense			26			26
nonsense		1				1
start loss		1				1
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1	1		2
non coding				4	5	9
Total	1	3	26	18	5

Variants in GTF2H5

This is a list of pathogenic ClinVar variants found in the GTF2H5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-158168365-C-T			Likely benign (Feb 26, 2021)
6-158168401-T-G			Uncertain significance (Aug 26, 2015)
6-158170256-C-G			Benign (Jul 09, 2018)
6-158170266-A-C			Likely benign (Jul 10, 2018)
6-158170446-A-G			Benign (Jul 09, 2018)
6-158170505-T-C			Likely pathogenic (Aug 27, 2022)
6-158170509-C-G			Likely benign (Jan 24, 2024)
6-158170515-C-T			Likely benign (May 23, 2023)
6-158170531-A-G			Uncertain significance (Aug 24, 2021)
6-158170532-T-A		Trichothiodystrophy 3, photosensitive	Pathogenic (Aug 10, 2020)
6-158170533-A-T			Likely benign (Dec 06, 2022)
6-158170546-G-T			Likely benign (Jul 15, 2022)
6-158170587-T-G			Benign (Jul 05, 2018)
6-158191681-A-G			Benign (Jul 06, 2018)
6-158191958-CAT-C			Likely benign (Aug 25, 2023)
6-158191963-G-A			Likely benign (Feb 02, 2023)
6-158191975-A-G		Trichothiodystrophy 3, photosensitive	Likely pathogenic (Aug 07, 2018)
6-158191982-C-A			Uncertain significance (Jun 25, 2022)
6-158191983-TG-T			Pathogenic (Aug 19, 2022)
6-158191987-A-G			Uncertain significance (Dec 24, 2020)
6-158191990-A-T		Trichothiodystrophy 3, photosensitive	Pathogenic (Aug 10, 2020)
6-158191996-T-C			Uncertain significance (Jul 07, 2023)
6-158191999-C-G			Uncertain significance (May 03, 2021)
6-158192001-G-T			Likely benign (Aug 19, 2022)
6-158192003-T-C		Trichothiodystrophy 3, photosensitive	Pathogenic (Jul 01, 2004)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GTF2H5	protein_coding	protein_coding	ENST00000607778	2	30993

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0452	0.687	125729	0	14	125743	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.123	40	37.9	1.06	0.00000186	470
Missense in Polyphen		6	7.3692	0.8142		124
Synonymous	-0.319	17	15.4	1.10	8.63e-7	133
Loss of Function	0.576	2	3.09	0.646	2.15e-7	31

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000967	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre- initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. Necessary for the stability of the TFIIH complex and for the presence of normal levels of TFIIH in the cell. {ECO:0000269|PubMed:15220921}.
• Disease: DISEASE: Trichothiodystrophy 3, photosensitive (TTD3) [MIM:616395]: A form of trichothiodystrophy, an autosomal recessive disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non- photosensitive forms of the disorder. {ECO:0000269|PubMed:15220921}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Nucleotide excision repair - Homo sapiens (human);Basal transcription factors - Homo sapiens (human);DNA Repair;Disease;RNA Pol II CTD phosphorylation and interaction with CE during HIV infection;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Formation of the HIV-1 Early Elongation Complex;Epigenetic regulation of gene expression;Gene expression (Transcription);Formation of HIV-1 elongation complex containing HIV-1 Tat;Tat-mediated elongation of the HIV-1 transcript;HIV Transcription Elongation;Formation of HIV elongation complex in the absence of HIV Tat;Generic Transcription Pathway;Transcription of the HIV genome;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;RNA Polymerase II HIV Promoter Escape;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Transcription Initiation;RNA Polymerase II Transcription Initiation And Promoter Clearance;RNA Pol II CTD phosphorylation and interaction with CE;Formation of RNA Pol II elongation complex ;RNA Polymerase I Promoter Clearance;HIV Transcription Initiation;RNA Polymerase II Transcription;Metabolism of RNA;Infectious disease;RNA Polymerase I Transcription Termination;RNA Polymerase I Transcription;RNA Polymerase II Transcription Elongation;RNA Polymerase I Transcription Initiation;RNA Polymerase I Promoter Escape;RNA Polymerase II Promoter Escape;RNA Polymerase I Chain Elongation;RNA Polymerase II Transcription Pre-Initiation And Promoter Opening;TP53 Regulates Transcription of DNA Repair Genes;Transcriptional Regulation by TP53;mRNA Capping;Formation of the Early Elongation Complex;Formation of Incision Complex in GG-NER;Dual Incision in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Formation of TC-NER Pre-Incision Complex;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• loftool: 0.517
• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.79

Haploinsufficiency Scores

• pHI: 0.0771
• hipred: Y
• hipred_score: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gtf2h5
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: transcription-coupled nucleotide-excision repair;nucleotide-excision repair;nucleotide-excision repair, preincision complex stabilization;nucleotide-excision repair, preincision complex assembly;nucleotide-excision repair, DNA incision, 5'-to lesion;regulation of transcription, DNA-templated;transcription initiation from RNA polymerase I promoter;transcription elongation from RNA polymerase I promoter;termination of RNA polymerase I transcription;rRNA processing;transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;transcription elongation from RNA polymerase II promoter;7-methylguanosine mRNA capping;nucleotide-excision repair, DNA incision;phosphorylation of RNA polymerase II C-terminal domain;global genome nucleotide-excision repair;cellular response to gamma radiation
• Cellular component: transcription factor TFIIH core complex;nucleoplasm;transcription factor TFIID complex;transcription factor TFIIH holo complex;nucleolus
• Molecular function: rDNA binding;protein binding