UniProtKB/SwissProt variant VAR

Variant information

Variant position:

226

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 226 (R226Q, p.Arg226Gln).

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; Hilo and Novara; no effect on protein abundance; loss of function in blood coagulation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137852241 [ dbSNP | Ensembl ]

Sequence information

Variant position:

226

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:

EAETILDNITQSTQSFNDFT R VVGGEDAKPGQFPWQVVLNG

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                         EAETILDNITQSTQS-------------FNDFTRVVGGEDAKPGQFPWQV-VLNG

                              EVEKILDNVTQP----------------LNDFTRVVGGKDA

Chimpanzee                    EAETILDNITQSTQS-------------FNDFTRVVGGEDA

Mouse                         TDGAILNNVTESSES-------------LNDFTRVVGGENA

Rat                           TNSTILDNLTENSEP-------------INDFTRVVGGENA

Bovine                        EAEIIWDNVTQSNQS-------------FDEFSRVVGGEDA

Cat                           EAEKNVDNVTQP----------------LNDLTRIVGGKTA

Chicken                       HDEAL--DITEPPPPPTTSAAPAKIVPITKNDTRVVGGYDS

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.

Type	Positions	Description
Chain	47 – 461	Coagulation factor IX
Propeptide	192 – 226	Activation peptide
Site	226 – 227	Cleavage; by factor XIa
Glycosylation	213 – 213	N-linked (GlcNAc...) asparagine
Glycosylation	215 – 215	O-linked (GalNAc...) threonine
Glycosylation	225 – 225	O-linked (GalNAc...) threonine
Disulfide bond	178 – 335	Interchain (between light and heavy chains)

Literature citations

Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo.
Monroe D.M.; McCord D.M.; Huang M.N.; High K.A.; Lundblad R.L.; Kasper C.K.; Roberts H.R.;
Blood 73:1540-1544(1989)
Cited for: VARIANT HEMB GLN-226;

Mutations in hemophilia Bm occur at the Arg180-Val activation site or in the catalytic domain of factor IX.
Bertina R.M.; van der Linden I.K.; Mannucci P.M.; Reinalda-Poot H.H.; Cupers R.; Poort S.R.; Reitsma P.H.;
J. Biol. Chem. 265:10876-10883(1990)
Cited for: VARIANTS HEMB GLN-226; TRP-226; PHE-227 AND THR-414;

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;

Comprehensive analysis of phenotypes and genetics in 21 Chinese families with haemophilia B: characterization of five novel mutations.
Guo Z.P.; Yang L.H.; Qin X.Y.; Liu X.E.; Chen J.F.; Zhang Y.F.;
Haemophilia 20:859-865(2014)
Cited for: VARIANTS HEMB SER-20; TYR-28; SER-46; ASP-54; GLU-58; ARG-84; HIS-138; GLN-226; ILE-284 DEL; MET-296; LYS-328; TYR-328; THR-414 AND TYR-THR-LYS-VAL-447 INS; CHARACTERIZATION OF VARIANTS HEMB SER-20; TYR-28; SER-46; ASP-54; GLU-58; ARG-84; HIS-138; GLN-226; ILE-284 DEL; MET-296; LYS-328; TYR-328; THR-414 AND TYR-THR-LYS-VAL-447 INS;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00740: Variant p.Arg226Gln