GTF2E2

general transcription factor IIE subunit 2, the group of General transcription factor IIE complex subunits

Basic information

Region (hg38): 8:30578318-30658236

Links

ENSG00000197265 ∙ NCBI:2961 ∙ OMIM:189964 ∙ HGNC:4651 ∙ Uniprot:P29084 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• trichothiodystrophy 6, nonphotosensitive (Moderate), mode of inheritance: AR
• trichothiodystrophy 6, nonphotosensitive (Moderate), mode of inheritance: AR
• trichothiodystrophy 6, nonphotosensitive (Strong), 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 6, nonphotosensitive	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; Hematologic; Musculoskeletal; Neurologic	26996949

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GTF2E2 gene.

• Trichothiodystrophy 6, nonphotosensitive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GTF2E2 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				36	2	38
missense	1		47	2		50
nonsense			2			2
start loss						0
frameshift						0
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			2	6		8
non coding			6	19	13	38
Total	1	0	58	57	15

Variants in GTF2E2

This is a list of pathogenic ClinVar variants found in the GTF2E2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-30578931-G-C			Uncertain significance (Aug 09, 2022)
8-30578948-A-G			Likely benign (May 13, 2021)
8-30578952-T-C			Uncertain significance (Apr 11, 2022)
8-30578965-C-A			Uncertain significance (Nov 04, 2021)
8-30578975-G-A			Likely benign (Aug 02, 2023)
8-30578991-C-T			Uncertain significance (Apr 19, 2022)
8-30578992-G-A			Uncertain significance (Aug 20, 2022)
8-30578994-C-T			Uncertain significance (Oct 05, 2022)
8-30579031-T-C			Uncertain significance (Aug 23, 2022)
8-30579056-A-C			Likely benign (Apr 25, 2023)
8-30579262-C-T			Benign (Nov 12, 2018)
8-30579335-C-T			Benign (Nov 12, 2018)
8-30580122-C-T			Benign (Nov 12, 2018)
8-30580265-G-A			Likely benign (Mar 24, 2023)
8-30580273-T-C			Likely benign (Nov 27, 2023)
8-30580277-G-A			Uncertain significance (Jun 24, 2022)
8-30580290-T-C			Likely benign (May 23, 2023)
8-30580291-G-C			Uncertain significance (Nov 27, 2023)
8-30580307-T-A		Inborn genetic diseases	Uncertain significance (Apr 12, 2024)
8-30580345-T-G			Uncertain significance (Sep 27, 2022)
8-30580352-C-T			Uncertain significance (Mar 23, 2022)
8-30580353-G-A			Likely benign (Dec 11, 2023)
8-30580361-A-C			Uncertain significance (Mar 27, 2022)
8-30580362-A-G			Likely benign (Jun 09, 2023)
8-30580367-C-T			Uncertain significance (Feb 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GTF2E2	protein_coding	protein_coding	ENST00000355904	7	79934

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0393	0.959	125730	0	11	125741	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.901	121	152	0.794	0.00000789	1882
Missense in Polyphen		24	39.041	0.61474		461
Synonymous	-0.147	58	56.6	1.02	0.00000300	541
Loss of Function	2.83	6	19.5	0.308	0.00000126	216

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000798	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000661	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase. {ECO:0000269|PubMed:1956398, ECO:0000269|PubMed:1956404}.
• Disease: DISEASE: Trichothiodystrophy 6, non-photosensitive (TTD6) [MIM:616943]: A form of trichothiodystrophy, a 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. TTD6 patients do not manifest cutaneous photosensitivity. Inheritance pattern has been reported to be autosomal recessive. {ECO:0000269|PubMed:26996949}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Basal transcription factors - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Eukaryotic Transcription Initiation;Disease;Gene expression (Transcription);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;HIV Transcription Initiation;RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription;Infectious disease;RNA Polymerase II Promoter Escape;RNA Polymerase II Transcription Pre-Initiation And Promoter Opening (Consensus)

Recessive Scores

• pRec: 0.148

Intolerance Scores

• loftool: 0.594
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.53

Haploinsufficiency Scores

• pHI: 0.634
• hipred: Y
• hipred_score: 0.763
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.876

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gtf2e2
• 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 by RNA polymerase II;transcription initiation from RNA polymerase II promoter;snRNA transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;transcription factor TFIID complex;transcription factor TFIIE complex;cytosol;nuclear speck
• Molecular function: TFIIH-class transcription factor complex binding;DNA binding;RNA binding;protein binding