GTF2I

protein-coding

general transcription factor IIi, the group of General transcription factors

Gene summary

This gene encodes a phosphoprotein containing six characteristic repeat motifs. The encoded protein binds to the initiator element (Inr) and E-box element in promoters and functions as a regulator of transcription. This locus, along with several other neighboring genes, is deleted in Williams-Beuren syndrome. There are many closely related genes and pseudogenes for this gene on chromosome 7. This gene also has pseudogenes on chromosomes 9, 13, and 21. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2013]

Previous symbols:

WBSCR6

MANE transcript

NM_032999.4

Inheritance

—

ClinVar variants

U:69B:11

Top phenotype

GTF2I related condition

Max pathogenic AF

—

Genomic locus

chr7:74,650,231-74,760,692

External References & Databases

Ensembl (ENSG00000263001)

Transcript & Mutation Effects

hg38 • Region Span ~110.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GTF2I variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 43

not providedTotal: 25

GTF2I related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032999.4. 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			2 clinvar	8 clinvar		10
missense			55 clinvar	2 clinvar		57
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			10 clinvar	1 clinvar		11
Total	0	0	69	11	0	80

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 195 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032999.4	RefSeq	NP_127492.1	33	MANE Select
ENST00000573035.6	Ensembl	ENSP00000460070.1	33	MANE Select
NM_001163636.3	RefSeq	NP_001157108.1	32	Standard
NM_001280800.2	RefSeq	NP_001267729.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Basal transcription factors - Homo sapiens (human)
cGMP-PKG signaling pathway - Homo sapiens (human)
Herpes simplex infection - Homo sapiens (human)
B Cell Receptor Signaling Pathway
BCR

Biological Process

regulation of transcription, DNA-templated
transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter
signal transduction
negative regulation of angiogenesis

Molecular Function

DNA binding
DNA-binding transcription factor activity
protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
membrane

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Interacts with the basal transcription machinery by coordinating the formation of a multiprotein complex at the C-FOS promoter, and linking specific signal responsive activator complexes. Promotes the formation of stable high-order complexes of SRF and PHOX1 and interacts cooperatively with PHOX1 to promote serum-inducible transcription of a reporter gene deriven by the C- FOS serum response element (SRE). Acts as a coregulator for USF1 by binding independently two promoter elements, a pyrimidine-rich initiator (Inr) and an upstream E-box. Required for the formation of functional ARID3A DNA-binding complexes and for activation of immunoglobulin heavy-chain transcription upon B-lymphocyte activation. {ECO:0000269|PubMed:10373551, ECO:0000269|PubMed:11373296, ECO:0000269|PubMed:16738337}.;
Disease: DISEASE: Note=GTF2I is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of GTF2I may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease.;

Recessive Scores

pRec: 0.436

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.993

Gene Damage Prediction

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