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UniProtKB/Swiss-Prot P54760: Variant p.Arg739Gln

Ephrin type-B receptor 4
Gene: EPHB4
Chromosomal location: 7q22
Variant information

Variant position:  739
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Glutamine (Q) at position 739 (R739Q, p.Arg739Gln).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from large size and basic (R) to medium size and polar (Q)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Hydrops fetalis, non-immune, and/or atrial septal defect (HFASD) [MIM:617300]: A form of non-immune hydrops fetalis, a condition characterized by fluid accumulation in at least 2 fetal compartments, including abdominal cavities, pleura, and pericardium, or in body tissue. The majority of hydrops fetalis cases are non-immune conditions that present with generalized edema of the fetus. Approximately 15% of non-immune cases result from a lymphatic abnormality. HFASD is an autosomal dominant, lymphatic-related form with variable expressivity. Some patients suffer from severe manifestations that can result in early death, whereas others have milder clinical features, such as atrial septal defect or varicose veins as adults. The hydrops and/or swelling improves spontaneously in those who survive the neonatal period. {ECO:0000269|PubMed:27400125}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HFASD; loss of kinase activity.
Any additional useful information about the variant.



Sequence information

Variant position:  739
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  987
The length of the canonical sequence.

Location on the sequence:   GMLRGIASGMRYLAEMSYVH  R DLAARNILVNSNLVCKVSDF
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         GMLRGIASGMRYLAEMSYVHRDLAARNILVNSNLVCKVSDF

Mouse                         GMLRGIASGMRYLAEMSYVHRDLAARNILVNSNLVCKVSDF

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 16 – 987 Ephrin type-B receptor 4
Topological domain 561 – 987 Cytoplasmic
Domain 615 – 899 Protein kinase
Active site 740 – 740 Proton acceptor
Alternative sequence 307 – 987 Missing. In isoform 3.
Alternative sequence 415 – 987 Missing. In isoform 4.
Alternative sequence 517 – 987 Missing. In isoform 2.


Literature citations

EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis.
Martin-Almedina S.; Martinez-Corral I.; Holdhus R.; Vicente A.; Fotiou E.; Lin S.; Petersen K.; Simpson M.A.; Hoischen A.; Gilissen C.; Jeffery H.; Atton G.; Karapouliou C.; Brice G.; Gordon K.; Wiseman J.W.; Wedin M.; Rockson S.G.; Jeffery S.; Mortimer P.S.; Snyder M.P.; Berland S.; Mansour S.; Makinen T.; Ostergaard P.;
J. Clin. Invest. 126:3080-3088(2016)
Cited for: INVOLVEMENT IN HFASD; VARIANTS HFASD GLN-739 AND SER-782; CHARACTERIZATION OF VARIANTS HFASD GLU-739 AND SER-782; FUNCTION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.