UniProtKB/Swiss-Prot P35579: Variant p.Asp1424His

Myosin-9
Gene: MYH9
Chromosomal location: 22q13.1
Variant information

Variant position:  1424
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Aspartate (D) to Histidine (H) at position 1424 (D1424H, p.Asp1424His).
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 medium size and acidic (D) to medium size and polar (H)
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:  Fechtner syndrome (FTNS) [MIM:153640]: Autosomal dominant macrothrombocytopenia characterized by thrombocytopenia, giant platelets and leukocyte inclusions that are small and poorly organized. Additionally, FTNS is distinguished by Alport-like clinical features of sensorineural deafness, cataracts and nephritis. Note=The disease is 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.

Involvement in disease:  May-Hegglin anomaly (MHA) [MIM:155100]: A disorder characterized by thrombocytopenia, giant platelets and Dohle body-like inclusions in peripheral blood leukocytes. Appearing as highly parallel paracrystalline bodies. Note=The disease is 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 FTNS and MHA.
Any additional useful information about the variant.



Sequence information

Variant position:  1424
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1960
The length of the canonical sequence.

Location on the sequence:   KVAAYDKLEKTKTRLQQELD  D LLVDLDHQRQSACNLEKKQK
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                         KVAAYDKLEKTKTRLQQELDDLLVDLDHQRQSACNLEKKQK

Mouse                         KVAAYDKLEKTKTRLQQELDDLLVDLDHQRQSVSNLEKKQK

Rat                           KVAAYDKLEKTKTRLQQELDDLLVDLDHQRQSVSNLEKKQK

Dog                           KVAAYDKLEKTKTRLQQELDDLLVDLDHQRRTASNLEKKQK

Chicken                       KIAAYDKLEKTKTRLQQELDDIAVDLDHQRQTVSNLEKKQK

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 2 – 1960 Myosin-9
Coiled coil 837 – 1926
Modified residue 1404 – 1404 N6-acetyllysine
Modified residue 1410 – 1410 N6-acetyllysine


Literature citations

Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes.
Seri M.; Cusano M.; Gangarossa S.; Caridi G.; Bordo D.; Lo Nigro C.; Ghiggeri G.M.; Ravazzolo R.; Savino M.; Del Vecchio M.; d'Apolito M.; Iolascon A.; Zelante L.L.; Savoia A.; Balduini C.L.; Noris P.; Magrini U.; Belletti S.; Heath K.E.; Babcock M.; Glucksman M.J.; Aliprandis E.; Bizzaro N.; Desnick R.J.; Martignetti J.A.;
Nat. Genet. 26:103-105(2000)
Cited for: VARIANTS MHA/FTNS/SBS LYS-93; CYS-702; CYS-1165; HIS-1424 AND LYS-1841;

Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes.
Heath K.E.; Campos-Barros A.; Toren A.; Rozenfeld-Granot G.; Carlsson L.E.; Savige J.; Denison J.C.; Gregory M.C.; White J.G.; Barker D.F.; Greinacher A.; Epstein C.J.; Glucksman M.J.; Martignetti J.A.;
Am. J. Hum. Genet. 69:1033-1045(2001)
Cited for: VARIANTS MHA/SBS/FTNS/EPS/APSM ASN-373; CYS-702; HIS-702; PRO-1114; ASN-1424; HIS-1424 AND LYS-1841;

Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions.
Kunishima S.; Matsushita T.; Kojima T.; Amemiya N.; Choi Y.M.; Hosaka N.; Inoue M.; Jung Y.; Mamiya S.; Matsumoto K.; Miyajima Y.; Zhang G.; Ruan C.; Saito K.; Song K.S.; Yoon H.-J.; Kamiya T.; Saito H.;
J. Hum. Genet. 46:722-729(2001)
Cited for: VARIANTS MHA/FTNS/SBS THR-95; CYS-1165; LEU-1165; 1205-LEU--GLN-1207 DEL; HIS-1424; ASN-1424; TYR-1424 AND LYS-1841; VARIANT VAL-1626;

Immunofluorescence analysis of neutrophil nonmuscle myosin heavy chain-A in MYH9 disorders: association of subcellular localization with MYH9 mutations.
Kunishima S.; Matsushita T.; Kojima T.; Sako M.; Kimura F.; Jo E.-K.; Inoue C.; Kamiya T.; Saito H.;
Lab. Invest. 83:115-122(2003)
Cited for: VARIANT FTNS/SBS CYS-1165; VARIANTS SBS LEU-1165 AND 1205-LEU--GLN-1207 DEL; VARIANTS MHA HIS-1424; ASN-1424; TYR-1424 AND LYS-1841; VARIANT EPS VAL-1816; VARIANT FTNS/MHA LYS-1841;

MYH9-related disease: may-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness.
Seri M.; Pecci A.; Di Bari F.; Cusano R.; Savino M.; Panza E.; Nigro A.; Noris P.; Gangarossa S.; Rocca B.; Gresele P.; Bizzaro N.; Malatesta P.; Koivisto P.A.; Longo I.; Musso R.; Pecoraro C.; Iolascon A.; Magrini U.; Rodriguez Soriano J.; Renieri A.; Ghiggeri G.M.; Ravazzolo R.; Balduini C.L.; Savoia A.;
Medicine (Baltimore) 82:203-215(2003)
Cited for: VARIANT EPS HIS-702; VARIANTS FTNS GLN-910; ILE-1155 AND HIS-1424; VARIANTS MHA/SBS 1066-GLU--ALA-1072 DEL AND ASN-1424; VARIANT EPS/FTNS/MHA/SBS CYS-702;

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.