GTF2IRD1

GTF2I repeat domain containing 1

Basic information

Region (hg38): 7:74453790-74602605

Previous symbols: [ "WBSCR11" ]

Links

ENSG00000006704 ∙ NCBI:9569 ∙ OMIM:604318 ∙ HGNC:4661 ∙ Uniprot:Q9UHL9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GTF2IRD1 gene.

• not_specified (131 variants)
• not_provided (55 variants)
• GTF2IRD1-related_disorder (24 variants)
• Childhood-onset_schizophrenia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GTF2IRD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005685.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	37	10	49
missense		1	121	8		130
nonsense			5			5
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8			8
Total	0	1	136	45	10

Highest pathogenic variant AF is 0.0000034267464

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GTF2IRD1	protein_coding	protein_coding	ENST00000455841	26	148812

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125731	0	16	125747	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.66	444	632	0.702	0.0000421	6309
Missense in Polyphen		114	200.23	0.56934		2020
Synonymous	0.327	269	276	0.975	0.0000201	2004
Loss of Function	5.36	10	51.5	0.194	0.00000282	578

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000294	0.0000294
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000233	0.000231
European (Non-Finnish)	0.0000531	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be a transcription regulator involved in cell-cycle progression and skeletal muscle differentiation. May repress GTF2I transcriptional functions, by preventing its nuclear residency, or by inhibiting its transcriptional activation. May contribute to slow-twitch fiber type specificity during myogenesis and in regenerating muscles. Binds troponin I slow-muscle fiber enhancer (USE B1). Binds specifically and with high affinity to the EFG sequences derived from the early enhancer of HOXC8 (By similarity). {ECO:0000250, ECO:0000269|PubMed:11438732}.
• Disease: DISEASE: Note=GTF2IRD1 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 GTF2IRD1 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease.
• Pathway: Basal transcription factors - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.160

Intolerance Scores

• loftool: 0.305
• rvis_EVS: -1.39
• rvis_percentile_EVS: 4.31

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.733

Gene Damage Prediction

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

Gene ontology

• Biological process: regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;multicellular organism development;transition between slow and fast fiber
• Cellular component: nucleus;nucleoplasm;cytosol
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding