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NM_001957.4(EDNRA):c.907G>A (p.Glu303Lys) AND Mandibulofacial dysostosis with alopecia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 2, 2015
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:
RCV000170510.4

Allele description [Variation Report for NM_001957.4(EDNRA):c.907G>A (p.Glu303Lys)]

NM_001957.4(EDNRA):c.907G>A (p.Glu303Lys)

Gene:
EDNRA:endothelin receptor type A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q31.23
Genomic location:
Preferred name:
NM_001957.4(EDNRA):c.907G>A (p.Glu303Lys)
HGVS:
  • NC_000004.12:g.147539823G>A
  • NG_013343.1:g.63907G>A
  • NM_001166055.2:c.580G>A
  • NM_001957.4:c.907G>AMANE SELECT
  • NP_001159527.1:p.Glu194Lys
  • NP_001948.1:p.Glu303Lys
  • NC_000004.11:g.148460975G>A
  • NM_001957.3:c.907G>A
  • NR_045958.2:n.1058G>A
  • NR_148963.2:n.767G>A
  • NR_148964.2:n.568G>A
  • P25101:p.Glu303Lys
Protein change:
E194K; GLU303LYS
Links:
UniProtKB: P25101#VAR_073789; OMIM: 131243.0003; dbSNP: rs876657388
NCBI 1000 Genomes Browser:
rs876657388
Molecular consequence:
  • NM_001166055.2:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001957.4:c.907G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_045958.2:n.1058G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148963.2:n.767G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148964.2:n.568G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Mandibulofacial dysostosis with alopecia (MFDA)
Identifiers:
MONDO: MONDO:0014608; MedGen: C4225349; Orphanet: 443995; OMIM: 616367

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000222942OMIM
no assertion criteria provided
Pathogenic
(Apr 2, 2015) 		unknownliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Johnson-McMillin syndrome: report of a new case with novel features.

Cushman LJ, Torres-Martinez W, Weaver DD.

Birth Defects Res A Clin Mol Teratol. 2005 Sep;73(9):638-41.

PubMed [citation]
PMID:
16116593

Mutations in the endothelin receptor type A cause mandibulofacial dysostosis with alopecia.

Gordon CT, Weaver KN, Zechi-Ceide RM, Madsen EC, Tavares AL, Oufadem M, Kurihara Y, Adameyko I, Picard A, Breton S, Pierrot S, Biosse-Duplan M, Voisin N, Masson C, Bole-Feysot C, Nitschké P, Delrue MA, Lacombe D, Guion-Almeida ML, Moura PP, Garib DG, Munnich A, et al.

Am J Hum Genet. 2015 Apr 2;96(4):519-31. doi: 10.1016/j.ajhg.2015.01.015. Epub 2015 Mar 12.

PubMed [citation]
PMID:
25772936
PMCID:
PMC4385188

Details of each submission

From OMIM, SCV000222942.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a girl with mandibulofacial dysostosis and alopecia (MFDA; 616367) who was originally described by Cushman et al. (2005), Gordon et al. (2015) identified heterozygosity for a de novo c.907G-A transition (c.907G-A, NM_001957.3) in the EDNRA gene, resulting in a glu303-to-lys (E303K) substitution at a highly conserved residue in the C-terminal portion of the third intracellular loop. Analysis of exome sequencing reads indicated a 75%:25% bias in reference- versus variant-containing reads in the patient; Sanger sequencing showed a similar bias in wildtype versus mutant chromatogram peak height, suggesting that the patient was somatic mosaic for E303K. In vitro and in vivo analysis indicated that the E303K variant has the capacity to perturb EDNRA activity in an endothelin ligand-dependent manner.

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

Last Updated: Apr 23, 2022