UniProtKB/Swiss-Prot P00451: Variant p.Arg2169His

Coagulation factor VIII
Gene: F8
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Variant information Variant position:

2169 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 Histidine (H) at position 2169 (R2169H, p.Arg2169His). 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 (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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 HEMA; severe/mild; affinity for VWF reduced 3-fold. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs137852461 [ dbSNP | Ensembl ]

Sequence information Variant position:

2169 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

2351 The length of the canonical sequence.
Location on the sequence:

VDSSGIKHNIFNPPIIARYI R LHPTHYSIRSTLRMELMGCD 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                         VDSSGIKHNIFNPPIIARYIRLHPTHYSIRSTLRMELMGCD

                              VDSSGIKHNIFNPPIIAQYIRLHPTHYSIRSTLRMELLGCD

Mouse                         VDSSGIKHNSFNPPIIARYIRLHPTHSSIRSTLRMELMGCD

Pig                           VDASGIKHNIFNPPIVARYIRLHPTHYSIRSTLRMELMGCD

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	20 – 2351	Coagulation factor VIII
Chain	1668 – 2351	Factor VIIIa light chain
Domain	2040 – 2188	F5/8 type C 1
Disulfide bond	2040 – 2188
Beta strand	2155 – 2178

Literature citations
Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.
Higuchi M.; Kazazian H.H. Jr.; Kasch L.; Warren T.C.; McGinniss M.J.; Phillips J.A. III; Kasper C.; Janco R.; Antonarakis S.E.;
Proc. Natl. Acad. Sci. U.S.A. 88:7405-7409(1991)
Cited for: VARIANTS HEMA THR-108; VAL-110; GLY-285; HIS-301; SER-312; ARG-444; HIS-492; GLY-561; CYS-612; THR-723; PHE-1699; HIS-1800; TYR-1803; ASP-1941; SER-1941; HIS-2169; GLN-2228 AND CYS-2323; Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.
Higuchi M.; Antonarakis S.E.; Kasch L.; Oldenburg J.; Economou-Petersen E.; Olek K.; Arai M.; Inaba H.; Kazazian H.H. Jr.;
Proc. Natl. Acad. Sci. U.S.A. 88:8307-8311(1991)
Cited for: VARIANTS HEMA THR-185; TRP-224; ALA-314; PHE-431; CYS-492; TRP-546; CYS-550; GLY-550; LYS-584; VAL-663; LYS-1057; SER-1844; ARG-1867; TRP-2016; LEU-2120; TYR-2138; HIS-2169; CYS-2178 AND LEU-2319; Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.
Diamond C.; Kogan S.; Levinson B.; Gitschier J.;
Hum. Mutat. 1:248-257(1992)
Cited for: VARIANTS HEMA VAL-30; VAL-89; VAL-92; ASP-104; VAL-164; MET-181; CYS-550; GLY-554; CYS-612; TRP-717; PHE-1808; SER-1941; ARG-2065; HIS-2169; CYS-2178 AND CYS-2248; Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients.
Arruda V.R.; Pieneman W.C.; Reitsma P.H.; Deutz-Terlouw P.P.; Annichino-Bizzacchi J.M.; Brieet E.; Costa F.F.;
Blood 86:3015-3020(1995)
Cited for: VARIANTS HEMA ARG-113; ASN-202; LEU-275; GLY-285; CYS-301; ASP-637; PHE-1808; PRO-1867; GLN-1960; HIS-2169; CYS-2178 AND THR-2281; VARIANT VAL-2257; Molecular characterization of haemophilia A in southern Chinese.
Chan V.; Pang A.; Chan T.P.T.; Chan V.W.-Y.; Chan T.K.;
Br. J. Haematol. 93:451-456(1996)
Cited for: VARIANTS HEMA LEU-189; SER-263; ARG-947; LYS-1057; SER-1610 AND HIS-2169; VARIANT MET-2242; Factor VIII gene analysis in Japanese CRM-positive and CRM-reduced haemophilia A patients by single-strand conformation polymorphism.
Morichika S.; Shima M.; Kamisue S.; Tanaka I.; Imanaka Y.; Suzuki H.; Shibata H.; Pemberton S.; Gale K.; McVey J.; Tuddenham E.G.D.; Yoshioka A.;
Br. J. Haematol. 98:901-906(1997)
Cited for: VARIANTS HEMA CYS-274; CYS-492; ARG-498; HIS-550; ARG-686; CYS-1708; GLN-1960; HIS-2169; CYS-2178; ALA-2264 AND VAL-2304; Molecular diagnostics of 15 hemophilia A patients: characterization of eight novel mutations in the factor VIII gene, two of which result in exon skipping.
Tavassoli K.; Eigel A.; Wilke K.; Pollmann H.; Horst J.;
Hum. Mutat. 12:301-303(1998)
Cited for: VARIANTS HEMA CYS-133; ARG-498; CYS-550; ASP-556; HIS-1708; VAL-1869; SER-2148; HIS-2169; VAL-2183 AND ASN-2209; Use of denaturing gradient gel blots to screen for point mutations in the factor VIII gene.
Laprise S.L.; Mak E.K.; Killoran K.A.; Layman L.C.; Gray M.R.;
Hum. Mutat. 12:393-402(1998)
Cited for: VARIANTS HEMA VAL-439; CYS-1800; HIS-2169; HIS-2182 AND SER-2319; Factor VIII inhibitors in mild and moderate-severity haemophilia A.
Hay C.R.M.; Ludlam C.A.; Colvin B.T.; Hill F.G.H.; Preston F.E.; Wasseem N.; Bagnall R.; Peake I.R.; Berntorp E.; Mauser Bunschoten E.P.; Fijnvandraat K.; Kasper C.K.; White G.; Santagostino E.;
Thromb. Haemost. 79:762-766(1998)
Cited for: VARIANTS HEMA CYS-612; PHE-682; ARG-2028; CYS-2124; HIS-2169; HIS-2182; ASP-2200; CYS-2248 AND ILE-2279; Screen of 55 Slovenian haemophilia A patients: identification of 2 novel mutations (S-1R and IVS23+1G-->A) and discussion of mutation spectrum.
Strmecki L.; Benedik-Dolnicar M.; Vouk K.; Komel R.;
Hum. Mutat. 13:413-413(1999)
Cited for: VARIANTS HEMA ARG-19; HIS-301; LEU-308; HIS-2169; GLN-2228 AND GLN-2326; Start of UK confidential haemophilia A database: analysis of 142 patients by solid phase fluorescent chemical cleavage of mismatch.
Waseem N.H.; Bagnall R.; Green P.M.; Giannelli F.;
Thromb. Haemost. 81:900-905(1999)
Cited for: VARIANTS HEMA CYS-24; ARG-26; TYR-113; SER-121; TRP-172; PRO-176; MET-181; VAL-214; THR-219; LYS-291; ALA-314; VAL-315; LYS-340; PHE-405; GLY-412; THR-470; GLU-474; ASN-478; CYS-484; GLY-490; ARG-498; TRP-546; CYS-550; HIS-561; ARG-584; THR-585; GLY-588; ASP-601; LYS-601; GLY-602; HIS-605; CYS-612; TRP-717; CYS-1708; GLN-1751; HIS-1800; CYS-1802; THR-1853; GLU-1864; PRO-1882; ILE-1888; LEU-1973; TRP-2016; ALA-2035; TYR-2040; CYS-2120; CYS-2145; HIS-2169; CYS-2178; HIS-2182; VAL-2183; VAL-2198; CYS-2248 AND GLY-2326; A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor.
Jacquemin M.; Lavend'homme R.; Benhida A.; Vanzieleghem B.; d'Oiron R.; Lavergne J.-M.; Brackmann H.H.; Schwaab R.; VandenDriessche T.; Chuah M.K.L.; Hoylaerts M.; Gilles J.G.G.; Peerlinck K.; Vermylen J.; Saint-Remy J.-M.R.;
Blood 96:958-965(2000)
Cited for: VARIANTS HEMA SER-2117; TYR-2138; SER-2148; HIS-2169 AND GLN-2172; CHARACTERIZATION OF VARIANTS HEMA SER-2117; TYR-2138 AND HIS-2169; Relationship between factor VIII mutation type and inhibitor development in a cohort of previously untreated patients treated with recombinant factor VIII (Recombinate).
Goodeve A.C.; Williams I.; Bray G.L.; Peake I.R.;
Thromb. Haemost. 83:844-848(2000)
Cited for: VARIANTS HEMA PRO-69; TYR-75; ARG-585; PRO-664; GLU-1779; ALA-2000; HIS-2169 AND PRO-2228; Site and type of mutations in the factor VIII gene in patients and carriers of haemophilia A.
Theophilus B.D.M.; Enayat M.S.; Williams M.D.; Hill F.G.H.;
Haemophilia 7:381-391(2001)
Cited for: VARIANTS HEMA ASP-132; LYS-141; GLU-466; THR-470; HIS-503; GLY-602; THR-1853; GLN-1985; ARG-2004; TRP-2016; TYR-2093; HIS-2169; HIS-2182; VAL-2198 AND GLN-2228; Rapid hemophilia A molecular diagnosis by a simple DNA sequencing procedure: identification of 14 novel mutations.
Vidal F.; Farssac E.; Altisent C.; Puig L.; Gallardo D.;
Thromb. Haemost. 85:580-583(2001)
Cited for: VARIANTS HEMA ARG-193; CYS-391; CYS-550; CYS-612; HIS-1705; ARG-1782; GLU-1872; TRP-2016; PRO-2016; HIS-2169 AND HIS-2182; Non-inversion factor VIII mutations in 80 hemophilia A families including 24 with alloimmune responses.
Liu M.-L.; Nakaya S.; Thompson A.R.;
Thromb. Haemost. 87:273-276(2002)
Cited for: VARIANTS HEMA GLU-67; 84-ARG-PRO-85 DEL; PRO-85 DEL; MET-181; TYR-186; GLY-220; LEU-262; ARG-412; PHE-438; ASP-439; ARG-470; SER-513; SER-541; CYS-550; GLY-554; SER-583; GLN-594; ILE-609; CYS-612; ASN-635; THR-699; ILE-701; ILE-721; ARG-1779; LEU-1780; THR-1791; PRO-1798; HIS-1800; GLY-1848; ARG-1907; CYS-1907; THR-1939; VAL-1939; ILE-1982; GLN-1985; CYS-2015; TRP-2016; SER-2038; HIS-2169; ILE-2192 AND LEU-2326; Thirty-four novel mutations detected in factor VIII gene by multiplex CSGE: modeling of 13 novel amino acid substitutions.
Habart D.; Kalabova D.; Novotny M.; Vorlova Z.;
J. Thromb. Haemost. 1:773-781(2003)
Cited for: VARIANTS HEMA ARG-26; PRO-326; PHE-329; HIS-391; GLY-401; TYR-522; THR-540; TRP-546; TYR-588; CYS-683; SER-720; TYR-1066; HIS-1768; PRO-1771; HIS-1800; ASP-1904; PRO-1980; CYS-2169; HIS-2169; ASP-2174; CYS-2178; HIS-2178; CYS-2182; GLY-2228; PHE-2229; LEU-2319; CYS-2323; HIS-2323 AND SER-2345;

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.