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UniProtKB/Swiss-Prot O95259: Variant p.Ile494Val

Potassium voltage-gated channel subfamily H member 1
Gene: KCNH1
Chromosomal location: 1q32.1-q32.3
Variant information

Variant position:  494
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Isoleucine (I) to Valine (V) at position 494 (I494V, p.Ile494Val).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  3
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:  Zimmermann-Laband syndrome 1 (ZLS1) [MIM:135500]: A disorder characterized by gingival fibromatosis, dysplastic or absent nails, finger abnormalities, hepatosplenomegaly, and abnormalities of the cartilage of the nose and/or ears. {ECO:0000269|PubMed:25915598}. 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:  Temple-Baraitser syndrome (TMBTS) [MIM:611816]: A developmental disorder characterized by intellectual disability, epilepsy, hypoplasia or aplasia of the thumb and great toe nails, and broadening and/or elongation of the thumbs and halluces, which have a tubular aspect. Some patients show facial dysmorphism. {ECO:0000269|PubMed:25420144}. 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 TMBTS and ZLS1; gain-of-function effect; resulting in a decreased threshold of channel activation and slower deactivation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  494
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  989
The length of the canonical sequence.

Location on the sequence:   DIEKIFAVAIMMIGSLLYAT  I FGNVTTIFQQMYANTNRYHE
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                         DIEKIFAVAIMMIGSLLYATIFGNVTTIFQQMYANTNRYHE

Mouse                         DIEKIFAVAIMMIGSLLYATIFGNVTTIFQQMYANTNRYHE

Rat                           DIEKIFAVAIMMIGSLLYATIFGNVTTIFQQMYANTNRYHE

Bovine                        DIEKIFAVAIMMIGSLLYATIFGNVTTIFQQMYANTNRYHE

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 1 – 989 Potassium voltage-gated channel subfamily H member 1
Transmembrane 478 – 498 Helical; Name=Segment S6


Literature citations

Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy.
Simons C.; Rash L.D.; Crawford J.; Ma L.; Cristofori-Armstrong B.; Miller D.; Ru K.; Baillie G.J.; Alanay Y.; Jacquinet A.; Debray F.G.; Verloes A.; Shen J.; Yesil G.; Guler S.; Yuksel A.; Cleary J.G.; Grimmond S.M.; McGaughran J.; King G.F.; Gabbett M.T.; Taft R.J.;
Nat. Genet. 47:73-77(2015)
Cited for: INVOLVEMENT IN TMBTS; VARIANTS TMBTS ASN-217; PHE-489; VAL-494 AND ARG-503; CHARACTERIZATION OF VARIANTS TMBTS ASN-217; PHE-489; VAL-494 AND ARG-503;

Mutations in KCNH1 and ATP6V1B2 cause Zimmermann-Laband syndrome.
Kortuem F.; Caputo V.; Bauer C.K.; Stella L.; Ciolfi A.; Alawi M.; Bocchinfuso G.; Flex E.; Paolacci S.; Dentici M.L.; Grammatico P.; Korenke G.C.; Leuzzi V.; Mowat D.; Nair L.D.; Nguyen T.T.; Thierry P.; White S.M.; Dallapiccola B.; Pizzuti A.; Campeau P.M.; Tartaglia M.; Kutsche K.;
Nat. Genet. 47:661-667(2015)
Cited for: INVOLVEMENT IN ZLS1; VARIANTS ZLS1 TYR-352; ARG-375; VAL-379; LEU-383; VAL-494 AND ARG-496; CHARACTERIZATION OF VARIANTS ZLS1 TYR-352; ARG-375; VAL-379; LEU-383; VAL-494 AND ARG-496;

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.