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UniProtKB/Swiss-Prot P00740: Variant p.Arg43Gln

Coagulation factor IX
Gene: F9
Variant information

Variant position:  43
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Arginine (R) to Glutamine (Q) at position 43 (R43Q, p.Arg43Gln).
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

Variant description:  In HEMB; severe; San Dimas, Oxford-3, Strasbourg-2; impairs removal of propeptide.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  43
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  461
The length of the canonical sequence.

Location on the sequence:   LLSAECTVFLDHENANKILN  R PKRYNSGKLEEFVQGNLERE
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                         LLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNLERE

                              LLSAECAVFLDRENATKILSRPKRYNSGKLEEFVRGNLERE

Chimpanzee                    LLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNLERE

Mouse                         LLSTECAVFLDRENATKILTRPKRYNSGKLEEFVRGNLERE

Rat                           LLSTECAVFLDRENATKILTRPKRYNSGKLEEFVQGNLERE

Bovine                        LLSAECTVFLDRENATKILHRPKRYNSGKLEEFVRGNLERE

Cat                           LLGADCTVFLDHEDATKVLSRPKRYNSGKLEEFVQGNLERE

Chicken                       FLGAESTVFIENKEASTVLSRTRRGNSNRLEELIPGNLERE

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
Propeptide 29 – 46
Metal binding 47 – 47 Calcium 1; via carbonyl oxygen
Metal binding 48 – 48 Calcium 2
Metal binding 53 – 53 Calcium 1; via 4-carboxyglutamate
Metal binding 53 – 53 Calcium 2; via 4-carboxyglutamate
Metal binding 54 – 54 Calcium 2; via 4-carboxyglutamate
Metal binding 54 – 54 Calcium 3; via 4-carboxyglutamate
Metal binding 61 – 61 Calcium 4 or magnesium 1; via 4-carboxyglutamate
Metal binding 63 – 63 Calcium 1; via 4-carboxyglutamate
Metal binding 63 – 63 Calcium 2; via 4-carboxyglutamate
Metal binding 63 – 63 Calcium 3; via 4-carboxyglutamate
Modified residue 53 – 53 4-carboxyglutamate
Modified residue 54 – 54 4-carboxyglutamate
Modified residue 61 – 61 4-carboxyglutamate
Modified residue 63 – 63 4-carboxyglutamate


Literature citations

The Arg-4 mutant factor IX Strasbourg 2 shows a delayed activation by factor XIa.
de la Salle C.; Charmantier J.L.; Ravanat C.; Ohlmann P.; Hartmann M.L.; Schuhler S.; Bischoff R.; Ebel C.; Roecklin D.; Balland A.;
Nouv. Rev. Fr. Hematol. 35:473-480(1993)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 30-84; VARIANT HEMB GLN-43; FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; PROTEOLYTIC CLEAVAGE;

Modification of the N-terminus of human factor IX by defective propeptide cleavage or acetylation results in a destabilized calcium-induced conformation: effects on phospholipid binding and activation by factor XIa.
Wojcik E.G.; Van Den Berg M.; Poort S.R.; Bertina R.M.;
Biochem. J. 323:629-636(1997)
Cited for: PROTEIN SEQUENCE OF 47-52; TISSUE SPECIFICITY; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS HEMB GLN-43; LEU-43 AND TRP-43; CALCIUM-BINDING; PROTEOLYTIC CLEAVAGE;

Defective propeptide processing of blood clotting factor IX caused by mutation of arginine to glutamine at position -4.
Bentley A.K.; Rees D.J.; Rizza C.; Brownlee G.G.;
Cell 45:343-348(1986)
Cited for: VARIANT HEMB GLN-43; CHARACTERIZATION OF VARIANT HEMB GLN-43;

Factor IX San Dimas. Substitution of glutamine for Arg-4 in the propeptide leads to incomplete gamma-carboxylation and altered phospholipid binding properties.
Ware J.; Diuguid D.L.; Liebman H.A.; Rabiet M.J.; Kasper C.K.; Furie B.C.; Furie B.; Stafford D.W.;
J. Biol. Chem. 264:11401-11406(1989)
Cited for: VARIANT HEMB GLN-43;

Germline mutations in Peruvian patients with hemophilia B: pattern of mutation in Amerindians is similar to the putative endogenous germline pattern.
Heit J.A.; Thorland E.C.; Ketterling R.P.; Lind T.J.; Daniels T.M.; Zapata R.E.; Ordonez S.M.; Kasper C.K.; Sommer S.S.;
Hum. Mutat. 11:372-376(1998)
Cited for: VARIANTS HEMB GLN-43; TRP-43; THR-46; SER-106; CYS-115; PHE-155; GLN-379; GLU-387; VAL-432 AND CYS-450;

Molecular pathology of haemophilia B in Turkish patients: identification of a large deletion and 33 independent point mutations.
Onay U.V.; Kavakli K.; Kilinc Y.; Gurgey A.; Aktuglu G.; Kemahli S.; Ozbek U.; Caglayan S.H.;
Br. J. Haematol. 120:656-659(2003)
Cited for: VARIANTS HEMB TYR-28; LEU-43; GLN-43; SER-52; ASP-106; LYS-124; TYR-134; GLN-226; GLY-226; TRP-226; LYS-241; TYR-252; GLN-294; PHE-316; ARG-318; GLY-379; ILE-383; PHE-383; ILE-395; PHE-396; ARG-407 AND GLU-412;

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.