GTF2H3

general transcription factor IIH subunit 3, the group of Nucleotide excision repair|General transcription factor IIH complex subunits

Basic information

Region (hg38): 12:123633739-123662604

Links

ENSG00000111358NCBI:2967OMIM:601750HGNC:4657Uniprot:Q13889AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GTF2H3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GTF2H3 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
0
missense
14
clinvar
14
nonsense
0
start loss
1
clinvar
1
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
0
Total 0 0 14 1 0

Variants in GTF2H3

This is a list of pathogenic ClinVar variants found in the GTF2H3 region.

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

Position Type Phenotype Significance ClinVar
12-123633740-G-C Vanishing white matter disease Uncertain significance (Jan 13, 2018)307538
12-123633750-C-A Vanishing white matter disease Uncertain significance (Jan 13, 2018)307539
12-123633765-C-T Vanishing white matter disease Uncertain significance (Jan 12, 2018)307540
12-123633862-G-A Likely benign (Dec 31, 2019)778081
12-123639270-A-T not specified Uncertain significance (Dec 13, 2022)2334640
12-123639303-A-G not specified Uncertain significance (Feb 14, 2023)2483887
12-123648013-A-C not specified Uncertain significance (Dec 20, 2023)3103091
12-123651029-G-A not specified Uncertain significance (Jan 03, 2024)3103092
12-123652543-A-G not specified Uncertain significance (Nov 10, 2022)2208654
12-123654948-G-A not specified Uncertain significance (Oct 20, 2024)3523223
12-123654987-G-A not specified Uncertain significance (Aug 05, 2024)3523222
12-123655789-T-A not specified Uncertain significance (Dec 05, 2024)3523221
12-123655810-G-C not specified Uncertain significance (Dec 19, 2022)2223173
12-123659807-C-G not specified Uncertain significance (Jun 29, 2023)2607921
12-123659897-G-A not specified Uncertain significance (Nov 21, 2023)3103093
12-123659903-G-T not specified Uncertain significance (Aug 02, 2021)2218040
12-123659922-G-A not specified Uncertain significance (Dec 10, 2024)3523224
12-123660195-T-C not specified Uncertain significance (Nov 14, 2023)3103094

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
GTF2H3protein_codingprotein_codingENST00000543341 1328779
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
3.04e-80.7621257080391257470.000155
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.6521381610.8560.000007922024
Missense in Polyphen4249.6750.8455629
Synonymous-1.086958.51.180.00000330559
Loss of Function1.411522.10.6780.00000108268

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0008900.000888
Ashkenazi Jewish0.000.00
East Asian0.0002730.000272
Finnish0.000.00
European (Non-Finnish)0.00009690.0000967
Middle Eastern0.0002730.000272
South Asian0.0002040.000196
Other0.0001640.000163

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)

Intolerance Scores

loftool
0.431
rvis_EVS
-0.21
rvis_percentile_EVS
38.58

Haploinsufficiency Scores

pHI
0.297
hipred
Y
hipred_score
0.617
ghis
0.650

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.969

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Gtf2h3
Phenotype

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;translation;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;transcriptional preinitiation complex
Molecular function
damaged DNA binding;DNA-binding transcription factor activity;protein kinase activity;protein binding;DNA-dependent ATPase activity;translation factor activity, RNA binding;RNA polymerase II CTD heptapeptide repeat kinase activity;metal ion binding;protein N-terminus binding