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UniProtKB/Swiss-Prot Q12809: Variant p.Thr65Pro

Potassium voltage-gated channel subfamily H member 2
Gene: KCNH2
Variant information

Variant position:  65
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 Threonine (T) to Proline (P) at position 65 (T65P, p.Thr65Pro).
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 polar (T) to medium size and hydrophobic (P)
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 LQT2; decreased protein stability.
Any additional useful information about the variant.

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



Sequence information

Variant position:  65
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1159
The length of the canonical sequence.

Location on the sequence:   NDGFCELCGYSRAEVMQRPC  T CDFLHGPRTQRRAAAQIAQA
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                         NDGFCELCGYSRAEVMQRPCTCDFLHGPRTQRRAAAQIAQA

Mouse                         NDGFCELCGYSRAEVMQRPCTCDFLHGPRTQRRAAAQIAQA

Rat                           NDGFCELCGYSRAEVMQRPCTCDFLHGPRTQRRAAAQIAQA

Rabbit                        NDGFCELCGYSRAEVMQRPCTCDFLHGPRTQRRAAAQIAQA

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 – 1159 Potassium voltage-gated channel subfamily H member 2
Topological domain 1 – 403 Cytoplasmic
Domain 41 – 70 PAS
Alternative sequence 1 – 376 MPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARVENCAVIYCNDGFCELCGYSRAEVMQRPCTCDFLHGPRTQRRAAAQIAQALLGAEERKVEIAFYRKDGSCFLCLVDVVPVKNEDGAVIMFILNFEVVMEKDMVGSPAHDTNHRGPPTSWLAPGRAKTFRLKLPALLALTARESSVRSGGAGGAGAPGAVVVDVDLTPAAPSSESLALDEVTAMDNHVAGLGPAEERRALVGPGSPPRSAPGQLPSPRAHSLNPDASGSSCSLARTRSRESCASVRRASSADDIEAMRAGVLPPPPRHASTGAMHPLRSGLLNSTSDSDLVRYRTISKIPQITLNFVDLKGDPFLASPTSDREIIAPKIKERTHNVTEKVTQ -> MAAPAGKASRTGALRPRAQKGRVRRAVRISSLVAQE. In isoform B.
Alternative sequence 1 – 102 MPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARVENCAVIYCNDGFCELCGYSRAEVMQRPCTCDFLHGPRTQRRAAAQIAQALLGAEERKVEIAFYRKD -> MSSHSA. In isoform 3.1.
Alternative sequence 37 – 376 Missing. In isoform B-USO.


Literature citations

Tetrameric assembly of K(+) channels requires ER-located chaperone proteins.
Li K.; Jiang Q.; Bai X.; Yang Y.F.; Ruan M.Y.; Cai S.Q.;
Mol. Cell 65:52-65(2017)
Cited for: FUNCTION; SUBUNIT; INTERACTION WITH DNAJB12 AND DNAJB14; VARIANT LQT2 TYR-64; CHARACTERIZATION OF VARIANTS LQT2 TYR-64 AND PRO-65;

A novel mutation (T65P) in the PAS domain of the human potassium channel HERG results in the long QT syndrome by trafficking deficiency.
Paulussen A.; Raes A.; Matthijs G.; Snyders D.J.; Cohen N.; Aerssens J.;
J. Biol. Chem. 277:48610-48616(2002)
Cited for: VARIANT LQT2 PRO-65;

Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.
Tester D.J.; Will M.L.; Haglund C.M.; Ackerman M.J.;
Heart Rhythm 2:507-517(2005)
Cited for: VARIANTS LQT2 ILE-26; LEU-29; SER-31; ARG-53; LEU-55; PRO-65; ARG-70; PRO-78; VAL-85; GLN-100; SER-238; TRP-306; LEU-320; CYS-328; CYS-420; MET-421; THR-422; SER-427; TYR-456; TYR-475 DEL; CYS-534; SER-552; THR-561; VAL-561; PRO-562; LEU-571; SER-572; CYS-582; SER-584; ASP-588; ARG-596; SER-604; MET-613; VAL-614; PHE-622; ILE-623; SER-628; VAL-628; ALA-630; SER-633; ILE-635; VAL-640; PHE-641; 671-ALA--THR-675 DEL; LEU-721; TYR-774; TRP-784; ASP-788; CYS-805; ARG-820; MET-822; GLY-837; HIS-887; VAL-913; ARG-925; ILE-983; ILE-996 AND ASP-1036;

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.