GTF2H4

general transcription factor IIH subunit 4, the group of General transcription factor IIH complex subunits|Nucleotide excision repair

Basic information

Region (hg38): 6:30908207-30914106

Links

ENSG00000213780 ∙ NCBI:2968 ∙ OMIM:601760 ∙ HGNC:4658 ∙ Uniprot:Q92759 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GTF2H4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GTF2H4 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					1	1
missense			14			14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1		1
Total	0	0	14	1	1

Variants in GTF2H4

This is a list of pathogenic ClinVar variants found in the GTF2H4 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-30909070-G-A		not specified	Uncertain significance (Jul 20, 2021)
6-30909124-G-A		not specified	Likely benign (Aug 28, 2024)
6-30909152-C-G		not specified	Uncertain significance (Dec 16, 2023)
6-30909439-C-T		not specified	Uncertain significance (Dec 27, 2023)
6-30909933-G-A		not specified	Uncertain significance (Sep 01, 2024)
6-30909963-G-A		not specified	Uncertain significance (Mar 21, 2023)
6-30910060-G-A		not specified	Uncertain significance (Dec 07, 2024)
6-30910665-G-A		not specified	Likely benign (Dec 10, 2024)
6-30910671-G-C		not specified	Uncertain significance (Feb 28, 2024)
6-30910864-C-G		not specified	Uncertain significance (Aug 12, 2024)
6-30910869-T-C		not specified	Uncertain significance (Dec 16, 2023)
6-30910940-A-G		not specified	Uncertain significance (Jun 16, 2024)
6-30911703-T-G		not specified	Uncertain significance (Oct 02, 2023)
6-30912331-C-T		not specified	Uncertain significance (Aug 10, 2021)
6-30912342-A-G		not specified	Uncertain significance (Jul 09, 2024)
6-30912376-A-T		not specified	Uncertain significance (Oct 16, 2024)
6-30912434-C-T			Benign (Jun 22, 2018)
6-30913143-G-A		not specified	Uncertain significance (Jan 24, 2024)
6-30913327-A-C		not specified	Uncertain significance (Apr 12, 2023)
6-30913336-G-A		not specified	Uncertain significance (Nov 15, 2024)
6-30913337-A-C		not specified	Uncertain significance (Nov 27, 2024)
6-30913345-C-G		not specified	Uncertain significance (Oct 18, 2021)
6-30913859-T-C		not specified	Uncertain significance (Dec 19, 2022)
6-30913882-G-A		not specified	Uncertain significance (Oct 16, 2024)
6-30913925-C-A		not specified	Uncertain significance (Aug 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GTF2H4	protein_coding	protein_coding	ENST00000259895	13	5923

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.24e-7	0.990	125672	0	76	125748	0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	221	272	0.813	0.0000154	2985
Missense in Polyphen		85	106.03	0.80168		1144
Synonymous	2.19	79	108	0.732	0.00000583	953
Loss of Function	2.34	15	28.5	0.527	0.00000153	285

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000800	0.000791
Ashkenazi Jewish	0.00110	0.00109
East Asian	0.000219	0.000217
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000234	0.000229
Middle Eastern	0.000219	0.000217
South Asian	0.0000986	0.0000980
Other	0.000326	0.000326

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. {ECO:0000269|PubMed:9852112}.
• Pathway: Nucleotide excision repair - Homo sapiens (human);Basal transcription factors - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Eukaryotic Transcription Initiation;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;AndrogenReceptor;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: 0.124

Intolerance Scores

• loftool: 0.617
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.36

Haploinsufficiency Scores

• pHI: 0.267
• hipred: Y
• hipred_score: 0.747
• ghis: 0.578

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gtf2h4

Gene ontology

• Biological process: DNA repair;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;transcription initiation from RNA polymerase I promoter;termination of RNA polymerase I transcription;transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;transcription elongation from RNA polymerase II promoter;7-methylguanosine mRNA capping;positive regulation of ATPase activity;nucleotide-excision repair, DNA incision;phosphorylation of RNA polymerase II C-terminal domain;global genome nucleotide-excision repair
• Cellular component: core TFIIH complex portion of holo TFIIH complex;transcription factor TFIIH core complex;nucleus;nucleoplasm;transcription factor TFIID complex;transcription factor TFIIH holo complex;nuclear speck
• Molecular function: ATPase activator activity;double-stranded DNA binding;DNA-binding transcription factor activity;protein kinase activity;protein binding;DNA-dependent ATPase activity;RNA polymerase II CTD heptapeptide repeat kinase activity