KCNH2 Paralogue Annotation
This page details the annotation of KCNH2 with disease causing variants in the following paralogues: CNGA3, CNGB3, HCN4, CNGB1, HCN1, CNGA1, HCN2, KCNH6, KCNH5, KCNH7, KCNH1, CNGA4. Click here to see the multiple sequence alignment of KCNH2 with all paralogues.
The paralogue variant mappings to KCNH2 are based on the Locus Reference Genomic entry for KCNH2 - LRG_288. This is based on the transcript ENST00000262186 and protein ENSP00000262186 (1159 amino acids) for the Ensembl gene ENSG00000055118.
- Paralogue Annotations
- Known KCNH2 Variants
- All Variants and Paralogue Annotations
Amino acid residues of KCNH2 with mapped disease-causing missense variants from paralogues are shown below, along with details about the KCNH2 protein domain and known missense variant status for these residues (the number of published reports for the residue is in parentheses), the consensus from the M-Coffee multiple sequence alignment at this mapping and the disease(s) associated with the paralogue variant(s). Click on the residue to see further details about the known KCNH2 variants and the mapped paralogue variants.
| Residue | Domain | Known Variant Status | Consensus | Mapped Paralogues and Variant Disease |
|---|---|---|---|---|
| 99-Y | N-terminus | Arrhythmia (5) | 4 | HCN2 - Febrile seizures |
| 141-P | N-terminus | Arrhythmia (3) | 2 | CNGA3 - Progressive cone dystrophy ? |
| 161-K | N-terminus | None | 1 | HCN4 - Sudden infant death syndrome |
| 164-R | N-terminus | Arrhythmia (3) | 1 | CNGB1 - Retinitis pigmentosa, autosomal recessive |
| 290-A | N-terminus | Prob. Benign (0) | 1 | CNGB1 - Retinitis pigmentosa |
| 296-L | N-terminus | None | 1 | CNGB1 - Retinitis pigmentosa, autosomal recessive |
| 334-P | N-terminus | Arrhythmia (1) | 1 | CNGB3 - Achromatopsia |
| 342-D | N-terminus | Other Cardiac (1) | 1 | CNGB3 - Achromatopsia |
| 363-I | N-terminus | None | 2 | CNGA3 - Cone dystrophy HCN1 - Epileptic encephalopathy, early infantile |
| 394-R | N-terminus | Prob. Benign (0) | 5 | KCNH7 - Bipolar spectrum disorder |
| 401-L | N-terminus | None | 9 | CNGA3 - Colour-blindness, total |
| 402-H | N-terminus | Arrhythmia (2) | 9 | CNGA1 - Usher syndrome CNGA3 - Colour-blindness, total HCN4 - Atrial fibrillation |
| 407-K | Transmembrane/Linker/Pore | None | 6 | KCNH1 - Temple-Baraister syndrome |
| 410-W | Transmembrane/Linker/Pore | Arrhythmia (1) | 7 | CNGA3 - Cone dystrophy |
| 416-L | Transmembrane/Linker/Pore | None | 7 | CNGB3 - Cone-rod dystrophy |
| 418-V | Transmembrane/Linker/Pore | None | 9 | CNGA3 - Achromatopsia |
| 420-Y | Transmembrane/Linker/Pore | Arrhythmia (3) | 9 | CNGA3 - Colour-blindness, total |
| 421-T | Transmembrane/Linker/Pore | Arrhythmia (5) | 9 | CNGA3 - Colour-blindness, total |
| 425-T | Transmembrane/Linker/Pore | None | 8 | CNGA3 - Colour-blindness, total |
| 430-A | Transmembrane/Linker/Pore | None | 7 | CNGA3 - Colour-blindness, total |
| 433-L | Transmembrane/Linker/Pore | None | 6 | CNGA3 - Colour-blindness, total |
| 460-D | Transmembrane/Linker/Pore | Arrhythmia (1) | 9 | CNGA3 - Achromatopsia |
| 472-R | Transmembrane/Linker/Pore | Prob. Benign (0) | 9 | CNGA3 - Achromatopsia, Colour-blindness, total |
| 473-T | Transmembrane/Linker/Pore | Arrhythmia (3) | 9 | CNGA3 - Colour-blindness, total, Cone dystrophy |
| 477-N | Transmembrane/Linker/Pore | None | 5 | CNGA3 - Achromatopsia |
| 497-W | Transmembrane/Linker/Pore | Arrhythmia (1) | 7 | CNGA3 - Cone dystrophy |
| 498-F | Transmembrane/Linker/Pore | None | 9 | CNGA3 - Achromatopsia |
| 501-D | Transmembrane/Linker/Pore | Arrhythmia (8) | 9 | CNGA3 - Achromatopsia |
| 507-P | Transmembrane/Linker/Pore | Arrhythmia (1) | 9 | CNGA3 - Cone dystrophy CNGB3 - Achromatopsia |
| 509-D | Transmembrane/Linker/Pore | Arrhythmia (1) | 9 | CNGA3 - Colour-blindness, total |
| 512-I | Transmembrane/Linker/Pore | Benign (0) | 9 | CNGA3 - Achromatopsia |
| 516-G | Transmembrane/Linker/Pore | None | 7 | CNGA3 - Colour-blindness, total |
| 522-G | Transmembrane/Linker/Pore | Arrhythmia (1) | 6 | CNGA3 - Achromatopsia, Cone dystrophy CNGB1 - Retinitis pigmentosa |
| 523-L | Transmembrane/Linker/Pore | None | 6 | HCN4 - Atrial fibrillation KCNH1 - Zimmermann-Laband syndrome |
| 524-L | Transmembrane/Linker/Pore | None | 6 | CNGA3 - Achromatopsia |
| 525-K | Transmembrane/Linker/Pore | Arrhythmia (1) | 6 | CNGA3 - Achromatopsia, Colour-blindness, total CNGB1 - Retinitis pigmentosa, Retinitis pigmentosa & rod cone dystrophy |
| 526-T | Transmembrane/Linker/Pore | None | 6 | CNGA3 - Cone dystrophy |
| 528-R | Transmembrane/Linker/Pore | Arrhythmia (1) | 6 | CNGA1 - Retinitis pigmentosa, autosomal recessive KCNH1 - Hypotonia, seizures and developmental delay, Intellectual disability KCNH5 - Epileptic encephalopathy |
| 530-L | Transmembrane/Linker/Pore | None | 6 | HCN1 - Epileptic encephalopathy, early infantile |
| 531-R | Transmembrane/Linker/Pore | Arrhythmia (4) | 6 | CNGA3 - Colour-blindness, total |
| 537-R | Transmembrane/Linker/Pore | Arrhythmia (1) | 6 | HCN1 - Epileptic encephalopathy, early infantile |
| 539-L | Transmembrane/Linker/Pore | None | 6 | CNGA3 - Colour-blindness, total |
| 546-G | Transmembrane/Linker/Pore | None | 6 | KCNH1 - Zimmermann-Laband syndrome |
| 547-A | Transmembrane/Linker/Pore | Prob. Benign (0) | 6 | HCN4 - Bradycardia & left ventricular noncompaction cardi |
| 550-L | Transmembrane/Linker/Pore | None | 6 | KCNH1 - Zimmermann-Laband syndrome |
| 554-M | Transmembrane/Linker/Pore | None | 9 | KCNH1 - Zimmermann-Laband syndrome |
| 566-C | Transmembrane/Linker/Pore | Arrhythmia (5) | 9 | CNGA3 - Cone-rod dystrophy |
| 569-Y | Transmembrane/Linker/Pore | Arrhythmia (4) | 9 | CNGA3 - Cone dystrophy |
| 570-A | Transmembrane/Linker/Pore | None | 9 | CNGA1 - Retinitis pigmentosa CNGA3 - Achromatopsia |
| 576-Q | Transmembrane/Linker/Pore | Prob. Benign (0) | 9 | CNGA3 - Achromatopsia |
| 577-P | Transmembrane/Linker/Pore | None | 9 | CNGA3 - Cone dystrophy |
| 578-H | Transmembrane/Linker/Pore | None | 9 | CNGA3 - Achromatopsia CNGA4 - Amyotrophic lateral sclerosis |
| 584-G | Transmembrane/Linker/Pore | Arrhythmia (12) | 8 | CNGA3 - Cone dystrophy |
| 586-L | Transmembrane/Linker/Pore | Arrhythmia (1) | 8 | CNGA3 - Achromatopsia |
| 594-G | Transmembrane/Linker/Pore | Arrhythmia (4) | 5 | CNGA3 - Colour-blindness, total |
| 612-V | Transmembrane/Linker/Pore | Arrhythmia (3) | 8 | CNGA3 - Achromatopsia |
| 616-Y | Transmembrane/Linker/Pore | Arrhythmia (2) | 9 | CNGA3 - Oligocone trichromacy |
| 620-S | Transmembrane/Linker/Pore | Arrhythmia (2) | 9 | CNGB3 - Progressive cone dystrophy |
| 622-L | Transmembrane/Linker/Pore | Arrhythmia (1) | 9 | CNGA3 - Achromatopsia |
| 625-V | Transmembrane/Linker/Pore | Arrhythmia (5) | 9 | CNGA4 - Amyotrophic lateral sclerosis |
| 626-G | Transmembrane/Linker/Pore | Arrhythmia (9) | 9 | CNGA1 - Retinitis pigmentosa CNGA3 - Achromatopsia |
| 627-F | Transmembrane/Linker/Pore | Arrhythmia (7) | 7 | HCN4 - Bradycardia & left ventricular noncompaction cardi |
| 628-G | Transmembrane/Linker/Pore | Arrhythmia (24) | 8 | HCN4 - Bradycardia & left ventricular noncompaction cardi, Sinus bradycardia & myocardial noncompaction |
| 629-N | Transmembrane/Linker/Pore | Arrhythmia (20) | 9 | CNGA3 - Colour-blindness, total |
| 631-S | Transmembrane/Linker/Pore | Arrhythmia (2) | 9 | HCN4 - Sinus bradycardia |
| 632-P | Transmembrane/Linker/Pore | Arrhythmia (3) | 9 | CNGA3 - Colour-blindness, total |
| 636-S | Transmembrane/Linker/Pore | None | 9 | CNGA3 - Achromatopsia |
| 640-F | Transmembrane/Linker/Pore | Arrhythmia (10) | 9 | CNGA3 - Colour-blindness, total |
| 642-I | Transmembrane/Linker/Pore | Arrhythmia (1) | 9 | CNGB3 - Cone-rod dystrophy |
| 647-I | Transmembrane/Linker/Pore | None | 9 | CNGA1 - Retinitis pigmentosa ? |
| 650-L | Transmembrane/Linker/Pore | None | 9 | KCNH1 - Temple-Baraister syndrome |
| 653-A | Transmembrane/Linker/Pore | None | 9 | CNGB3 - Achromatopsia |
| 655-I | Transmembrane/Linker/Pore | None | 9 | KCNH1 - Temple-Baraister syndrome |
| 657-G | Transmembrane/Linker/Pore | Arrhythmia (6) | 9 | CNGA3 - Achromatopsia KCNH1 - Hypotonia, seizures and developmental delay, Zimmermann-Laband syndrome |
| 661-A | C-terminus | Prob. Benign (0) | 9 | CNGA3 - Achromatopsia |
| 664-Q | C-terminus | None | 9 | KCNH1 - Temple-Baraister syndrome |
| 666-L | C-terminus | None | 9 | CNGA3 - Colour-blindness, total |
| 667-Y | C-terminus | None | 9 | HCN1 - Epileptic encephalopathy, early infantile |
| 670-T | C-terminus | None | 9 | CNGA3 - Colour-blindness, total HCN4 - Inappropriate sinus tachycardia |
| 676-Q | C-terminus | None | 9 | HCN4 - Tachycardia-bradycardia syndrome and atrial fibril |
| 680-V | C-terminus | None | 9 | KCNH6 - Hyperinsulism |
| 684-I | C-terminus | None | 9 | CNGA3 - Achromatopsia CNGB3 - Cone dystrophy |
| 687-H | C-terminus | Arrhythmia (2) | 9 | CNGA1 - Retinitis pigmentosa CNGA3 - Colour-blindness, total CNGB3 - Macular degeneration, juvenile |
| 693-L | C-terminus | Arrhythmia (3) | 9 | CNGA3 - Achromatopsia |
| 696-R | C-terminus | Arrhythmia (5) | 9 | CNGA3 - Colour-blindness, total, Cone dystrophy CNGB1 - Retinitis pigmentosa |
| 699-E | C-terminus | Prob. Benign (0) | 9 | CNGA3 - Achromatopsia HCN4 - Sinus node disease |
| 704-A | C-terminus | Prob. Benign (0) | 9 | KCNH6 - Schizophrenia |
| 713-M | C-terminus | Prob. Benign (0) | 9 | HCN2 - Epilepsy, idiopathic generalised |
| 724-L | C-terminus | None | 9 | CNGA3 - Achromatopsia |
| 729-C | C-terminus | None | 9 | CNGA3 - Achromatopsia |
| 731-H | C-terminus | Arrhythmia (1) | 9 | CNGA3 - Colour-blindness, total |
| 745-G | C-terminus | None | 9 | CNGA3 - Colour-blindness, total |
| 765-P | C-terminus | Prob. Benign (0) | 9 | CNGA3 - Cone-rod dystrophy |
| 766-G | C-terminus | None | 9 | CNGB1 - Retinitis pigmentosa |
| 770-V | C-terminus | Arrhythmia (2) | 9 | CNGA3 - Colour-blindness, total |
| 773-G | C-terminus | None | 9 | CNGA3 - Colour-blindness, total, Cone-rod dystrophy CNGB1 - Retinitis pigmentosa? |
| 774-D | C-terminus | Arrhythmia (5) | 9 | CNGA3 - Achromatopsia |
| 776-L | C-terminus | Arrhythmia (1) | 9 | CNGA1 - Retinitis pigmentosa, autosomal recessive CNGA3 - Colour-blindness, total CNGB3 - Achromatopsia |
| 779-L | C-terminus | None | 9 | CNGA3 - Cone-rod dystrophy |
| 782-I | C-terminus | None | 9 | CNGA3 - Colour-blindness, total |
| 785-G | C-terminus | Arrhythmia (4) | 9 | CNGA3 - Colour-blindness, total, Leber congenital amaurosis |
| 787-I | C-terminus | None | 9 | CNGA3 - Achromatopsia, Leber congenital amaurosis |
| 789-I | C-terminus | Arrhythmia (1) | 9 | CNGA3 - Colour-blindness, total |
| 793-D | C-terminus | Prob. Benign (0) | 7 | CNGA3 - Cone dystrophy |
| 798-I | C-terminus | None | 7 | CNGA3 - Progressive cone dystrophy ? |
| 799-L | C-terminus | None | 7 | CNGA3 - Achromatopsia |
| 805-F | C-terminus | Arrhythmia (9) | 9 | CNGA3 - Achromatopsia, Colour-blindness, total |
| 806-G | C-terminus | Arrhythmia (2) | 9 | CNGA3 - Achromatopsia |
| 810-N | C-terminus | None | 8 | CNGB3 - Achromatopsia |
| 817-K | C-terminus | None | 9 | CNGA3 - Achromatopsia, Colour-blindness, total |
| 819-N | C-terminus | None | 9 | CNGA3 - Colour-blindness, total |
| 821-D | C-terminus | None | 9 | HCN4 - Sinus bradycardia |
| 823-R | C-terminus | Arrhythmia (8) | 9 | CNGA3 - Colour-blindness, total |
| 824-A | C-terminus | None | 9 | CNGA3 - Achromatopsia ?, Cone dystrophy |
| 827-Y | C-terminus | None | 9 | CNGA3 - Colour-blindness, total |
| 844-M | C-terminus | None | 9 | CNGA3 - Achromatopsia |
| 847-E | C-terminus | None | 9 | CNGA3 - Colour-blindness, total CNGB3 - Achromatopsia |
| 857-E | C-terminus | None | 5 | CNGB1 - Retinitis pigmentosa, autosomal dominant |
| 864-D | C-terminus | Arrhythmia (1) | 3 | CNGB3 - Cone-rod dystrophy |
| 871-S | C-terminus | None | 2 | CNGA3 - Achromatopsia |
| 876-E | C-terminus | None | 2 | CNGA3 - Cone-rod dystrophy |
| 886-K | C-terminus | None | 2 | CNGA3 - Achromatopsia |
| 908-L | C-terminus | None | 2 | HCN4 - Sudden infant death syndrome |
| 914-G | C-terminus | None | 1 | CNGA3 - Achromatopsia |
| 919-S | C-terminus | None | 2 | CNGA1 - Retinitis pigmentosa, autosomal recessive |
| 998-F | C-terminus | None | 2 | HCN4 - Sudden unexpected death in epilepsy |
| 1069-R | C-terminus | Prob. Benign (0) | 1 | HCN4 - Bradycardia, postpartum |
| 1150-L | C-terminus | Prob. Benign (0) | 2 | CNGB3 - Cone-rod dystrophy |
| 1152-R | C-terminus | None | 2 | HCN4 - Brugada syndrome |
| 1153-H | C-terminus | Arrhythmia (2) | 2 | HCN1 - Idiopathic epilepsy, generalised ? |