GTF2E2

protein-coding

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

Gene summary

The general transcription factor IIE (TFIIE) is part of the RNA polymerase II transcription initiation complex, recruiting TFIIH and being essential for promoter clearance by RNA polymerase II. TFIIE is a heterodimer (and sometimes heterotetramer) of alpha and beta subunits. The protein encoded by this gene represents the beta subunit of TFIIE. [provided by RefSeq, Jan 2017]

MANE transcript

NM_002095.6

Inheritance

ClinVar variants

P:2U:73B:54

Top phenotype

Trichothiodystrophy 6, nonphotosensitive

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr8:30,578,318-30,658,236

External References & Databases

Ensembl (ENSG00000197265)

Transcript & Mutation Effects

hg38 • Region Span ~79.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

trichothiodystrophy 6, nonphotosensitiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014841

Submitter: G2P

trichothiodystrophy 6, nonphotosensitiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014841

Submitter: PanelApp Australia

trichothiodystrophySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018053

Submitter: Orphanet

trichothiodystrophy 6, nonphotosensitiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014841

Submitter: Genomics England PanelApp

trichothiodystrophy 6, nonphotosensitiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014841

Submitter: Ambry Genetics

trichothiodystrophy 6, nonphotosensitiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014841

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Trichothiodystrophy 6, nonphotosensitiveAR

Manifestation: Dermatologic; Hematologic; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 26996949

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GTF2E2 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 145

Inborn genetic diseasesTotal: 32

not specifiedTotal: 16

GTF2E2-related disorderTotal: 5

Trichothiodystrophy 6, nonphotosensitiveTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002095.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				50 clinvar	1 clinvar	51
missense	2 clinvar		67 clinvar	3 clinvar		72
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	2	0	73	53	1	129

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002095.6	RefSeq	NP_002086.1	7	MANE Select
ENST00000355904.9	Ensembl	ENSP00000348168.4	7	MANE Select
NM_001348353.1	RefSeq	NP_001335282.1	6	Standard
ENST00000518445.1	Ensembl	ENSP00000429312.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Basal transcription factors - Homo sapiens (human)
Viral carcinogenesis - Homo sapiens (human)
Epstein-Barr virus infection - Homo sapiens (human)
Eukaryotic Transcription Initiation
Disease

Biological Process

transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter
snRNA transcription by RNA polymerase II

Molecular Function

TFIIH-class transcription factor complex binding
DNA binding
RNA binding
protein binding

Cellular Component

nucleus
nucleoplasm
transcription factor TFIID complex
transcription factor TFIIE complex
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355904
Coding exons: 7
Length: 79934
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125741
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.901	121	152	0.794	0.00000789	1882
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.594
RVIS EVS: 0.06
RVIS percentile EVS: 58.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.876

Gene Damage Prediction

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