IKBKG |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- IKBKG (HGNC:5961) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- inhibitor of nuclear factor kappa B kinase regulatory subunit gamma
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- IP2, IP1
- Alias symbols
- IKK-gamma, NEMO, Fip3p, FIP-3, FIP3, ZC2HC9, IKKAP1, IKKG
- %HI
- 41.6(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.08(Read more about gnomAD pLI score)
- LOEUF
- 1.37(Read more about gnomAD LOEUF score)
- Cytoband
- Xq28
- Genomic Coordinates
-
GRCh37/hg19: chrX:153769453-153793261 NCBI Ensembl UCSC GRCh38/hg38: chrX:154541238-154565046 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001099857.5 ENST00000594239.6 (Read more about MANE Select)
- Function
- Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor (PubMed:9751060, PubMed:14695475, PubMed:20724660, PubMed:21518757). Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways (PubMed:16547522, PubMed:18287044, PubMed:19033441, PubMed:21606507, PubMed:27777308, PubMed:19185524, PubMed... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- incontinentia pigmenti Monarch
-
PUBMED:
15229184
Fusco et al. (2004) assessed 122 subjects with Incontinentia Pigmenti (IP) using PCR-based assays and DHPLC analysis. A recurrent exon 4-10 deletion was identified in 73 of 122 patients (59.8%). Single nucleotide variants and indels were identified in an additional 10 of 122 patients (8.2%), and included three missense variants, three stopgain variants, one frameshift insertion, two frameshift deletions, and one in-frame deletion.
-
PUBMED:
10839543
The International Incontinentia Pigmenta (IP) Consortium (2000) assessed 47 subjects with IP using restriction enzyme mapping and PCR-based assays. The recurrent exon 4-10 deletion was identified in 38 of 47 subjects (80.8%). An additional 6 of 47 subjects harboured small indels, missense and stopgain mutations.
-
PUBMED:
22121116
Fusco et al. (2012) describe non-recurrent deletions identified in 7 of 20 IP who did not harbour the recurrent exon 4-10 deletion. Non-recurrent deletions ranged in size from approximately 4.8 kb to 115 kb, and overlapped partially or fully the exonic coding sequence of IKBKG and upstream G6PD.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
-
PUBMED: 24721901
van Asbeck et al. (2014) describe a 167 kb de novo duplication within the Xq28 region that was identified in a female patient by microarray analysis and confirmed by qPCR. The patient presented with immune deficiency, skin abnormalities, macrocephaly, gastroparesis, peripheral small-fiber neuropathy, and benign tumors. The duplication encompasses the entire IKBKG gene, in addition to FAM3A, G6PD, GAB3, CTAG1A, CTAG1B, and CTAG2. The duplication does not include GDI1 or MECP2. The authors suggest that the Xq28 duplication identified in their patient represents a novel contiguous gene syndrome, with triplosensitivity of IKBKG being associated with skin abnormalities and immune deficiency specifically.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.