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NM_001099857.5(IKBKG):c.863C>G (p.Ala288Gly) AND Ectodermal dysplasia and immunodeficiency 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 10, 2006
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000012221.17

Allele description [Variation Report for NM_001099857.5(IKBKG):c.863C>G (p.Ala288Gly)]

NM_001099857.5(IKBKG):c.863C>G (p.Ala288Gly)

Gene:
IKBKG:inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_001099857.5(IKBKG):c.863C>G (p.Ala288Gly)
HGVS:
  • NC_000023.11:g.154562904C>G
  • NG_009896.1:g.25661C>G
  • NM_001099856.6:c.1067C>G
  • NM_001099857.5:c.863C>GMANE SELECT
  • NM_001145255.4:c.616-655C>G
  • NM_001321396.3:c.863C>G
  • NM_001321397.3:c.860C>G
  • NM_001377312.1:c.863C>G
  • NM_001377313.1:c.860C>G
  • NM_001377314.1:c.707C>G
  • NM_001377315.1:c.494C>G
  • NM_003639.4:c.863C>G
  • NP_001093326.2:p.Ala356Gly
  • NP_001093327.1:p.Ala288Gly
  • NP_001308325.1:p.Ala288Gly
  • NP_001308326.1:p.Ala287Gly
  • NP_001364241.1:p.Ala288Gly
  • NP_001364242.1:p.Ala287Gly
  • NP_001364243.1:p.Ala236Gly
  • NP_001364244.1:p.Ala165Gly
  • NP_003630.1:p.Ala288Gly
  • LRG_70:g.25661C>G
  • NC_000023.10:g.153791119C>G
  • NR_165197.1:n.732C>G
  • Q9Y6K9:p.Ala288Gly
Protein change:
A165G; ALA288GLY
Links:
UniProtKB: Q9Y6K9#VAR_011322; OMIM: 300248.0020; dbSNP: rs137853330
NCBI 1000 Genomes Browser:
rs137853330
Molecular consequence:
  • NM_001145255.4:c.616-655C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001099856.6:c.1067C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099857.5:c.863C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321396.3:c.863C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321397.3:c.860C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377312.1:c.863C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377313.1:c.860C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377314.1:c.707C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377315.1:c.494C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003639.4:c.863C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_165197.1:n.732C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Ectodermal dysplasia and immunodeficiency 1 (EDAID1)
Synonyms:
Ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis, and lymphedema; ECTODERMAL DYSPLASIA AND IMMUNE DEFICIENCY 1; Hyper-IgM immunodeficiency, X-linked, with hypohidrotic ectodermal dysplasia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0020740; MedGen: C1846008; Orphanet: 238468; Orphanet: 98813; OMIM: 300291

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000032455OMIM
no assertion criteria provided
Pathogenic
(Mar 10, 2006) 		germlineliterature only

Doffinger, R., Smahi, A., Bessia, C., Geissmann, F., Feinberg, J., Durandy, A., Bodemer, C., Kenwrick, S., Dupuis-Girod, S., Blanche, S., Wood, P., Rabia, S. H., and 16 others X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappa-B signaling. Nature Genet. 27: 277-285, 2001.

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Details of each submission

From OMIM, SCV000032455.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature onlynot provided

Description

In a 2-year-old boy (patient 10) with anhidrotic ectodermal dysplasia and immunodeficiency-1 (EDAID1; 300291), Doffinger et al. (2001) identified a hemizygous c.863C-G transversion in the IKBKG gene, resulting in an ala288-to-gly (A288G) substitution in the second coiled-coil domain. The mutation was not found in 200 control chromosomes, and the patient's mother, who carried the mutation, showed skewed X inactivation in her blood cells. Functional studies of the variant were not performed.

Using temperature-induced unfolding, Vinolo et al. (2006) demonstrated that the A281G murine mutation in NEMO, corresponding to the human A288G mutation, causes an important loss in oligomer stability. Fluorescence studies showed that the tyrosine located in the adjacent zinc finger domain exhibits an alteration in its spectral properties. Functional complementation assays using NEMO-deficient pre-B and T lymphocytes showed that the pathogenic mutation reduces TNF-alpha (191160) and lipopolysaccharide-induced NFKB (see 164011) activation by altering the assembly of the IKK complex.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 30, 2023