UniProtKB/SwissProt variant VAR

Variant information

Variant position:

294

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 294 (R294Q, p.Arg294Gln).

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; mild to moderate; Dreihacken, Penafiel and Seattle-4.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137852249 [ dbSNP | Ensembl ]

Sequence information

Variant position:

294

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:

KITVVAGEHNIEETEHTEQK R NVIRIIPHHNYNAAINKYNH

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                         KITVVAGEHNIEETEHTEQKRNVIRIIPHHNYNAAINKYNH

                              KITIVAGEHNTEKREHTEQKRNVIRTILHHSYNATINKYNH

Chimpanzee                    KITVVAGEHNIEETEHTEQKRNVIRIIPHHNYNAAINKYNH

Mouse                         KIEVVAGEYNIDKKEDTEQRRNVIRTIPHHQYNATINKYSH

Rat                           KIEVVAGEHNIDEKEDTEQRRNVIRTIPHHQYNATINKYSH

Bovine                        KITVVAGEHNTEKPEPTEQKRNVIRAIPYHSYNASINKYSH

Cat                           EITVVAGEHNTEETEHTEQKRNVIRTILHHSYNASVNKYSH

Chicken                       NVTAVAGEYNTKEDDHTEQRRQVVKILPYPTYNRTRNKHHN

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
Chain	227 – 461	Coagulation factor IXa heavy chain
Domain	227 – 459	Peptidase S1
Metal binding	281 – 281	Calcium 8
Metal binding	283 – 283	Calcium 8; via carbonyl oxygen
Metal binding	286 – 286	Calcium 8; via carbonyl oxygen
Metal binding	288 – 288	Calcium 8
Metal binding	291 – 291	Calcium 8
Disulfide bond	178 – 335	Interchain (between light and heavy chains)
Mutagenesis	305 – 305	Y -> F. Strongly increases enzyme activity with a synthetic peptide substrate; when associated with T-311; A-365 and T-391.
Mutagenesis	311 – 311	K -> T. Strongly increases enzyme activity with a synthetic peptide substrate; when associated with F-305; A-365 and T-391.
Mutagenesis	312 – 312	Y -> A. Strongly decreases enzyme activity with a synthetic peptide substrate.
Beta strand	292 – 301

Literature citations

Three point mutations in the factor IX genes of five hemophilia B patients. Identification strategy using localization by altered epitopes in their hemophilic proteins.
Chen S.H.; Thompson A.R.; Zhang M.; Scott C.R.;
J. Clin. Invest. 84:113-118(1989)
Cited for: VARIANTS HEMB LYS-73; SER-106 AND GLN-294;

Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX.
Ludwig M.; Sabharwal A.K.; Brackmann H.H.; Olek K.; Smith K.J.; Birktoft J.J.; Bajaj S.P.;
Blood 79:1225-1232(1992)
Cited for: VARIANTS HEMB VAL-291; GLN-294; HIS-410; GLY-411 AND ILE-411;

Single-strand conformation polymorphism (SSCP) analysis of the molecular pathology of hemophilia B.
David D.; Rosa H.A.V.; Pemberton S.; Diniz M.J.; Campos M.; Lavinha J.;
Hum. Mutat. 2:355-361(1993)
Cited for: VARIANTS HEMB ARG-253; GLN-294; GLN-379; PRO-426 AND ILE-TYR-THR-445 INS;

Identification of mutations in four hemophilia B patients of Turkish origin, including a novel deletion of base 6411.
Caglayan S.H.; Vielhaber E.; Guersel T.; Aktuglu G.; Sommer S.S.;
Hum. Mutat. 4:163-165(1994)
Cited for: VARIANTS HEMB GLN-294 AND ARG-413;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00740: Variant p.Arg294Gln