KCNH1

Protein identityUniProt · HPA

UniProt accession

O95259

Gene

KCNH1

Ensembl

ENSG00000143473

Chromosome

1

Canonical length

989 aa

Protein class

Disease related genes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters, Voltage-gated ion channels

Subcellular location

Vesicles

Quaternary structure

Homomultimer

OverviewNCBI Gene

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit of a voltage-gated non-inactivating delayed rectifier potassium channel. It is activated at the onset of myoblast differentiation. The gene is highly expressed in brain and in myoblasts. Overexpression of the gene may confer a growth advantage to cancer cells and favor tumor cell proliferation. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

989 residues, UniProt reviewed canonical sequence.

>O95259|KCNH1
     1  MTMAGGRRGL VAPQNTFLEN IVRRSNDTNF VLGNAQIVDW PIVYSNDGFC KLSGYHRAEV
    61  MQKSSTCSFM YGELTDKDTI EKVRQTFENY EMNSFEILMY KKNRTPVWFF VKIAPIRNEQ
   121  DKVVLFLCTF SDITAFKQPI EDDSCKGWGK FARLTRALTS SRGVLQQLAP SVQKGENVHK
   181  HSRLAEVLQL GSDILPQYKQ EAPKTPPHII LHYCVFKTTW DWIILILTFY TAILVPYNVS
   241  FKTRQNNVAW LVVDSIVDVI FLVDIVLNFH TTFVGPAGEV ISDPKLIRMN YLKTWFVIDL
   301  LSCLPYDVIN AFENVDEVSA FMGDPGKIGF ADQIPPPLEG RESQGISSLF SSLKVVRLLR
   361  LGRVARKLDH YIEYGAAVLV LLVCVFGLAA HWMACIWYSI GDYEIFDEDT KTIRNNSWLY
   421  QLAMDIGTPY QFNGSGSGKW EGGPSKNSVY ISSLYFTMTS LTSVGFGNIA PSTDIEKIFA
   481  VAIMMIGSLL YATIFGNVTT IFQQMYANTN RYHEMLNSVR DFLKLYQVPK GLSERVMDYI
   541  VSTWSMSRGI DTEKVLQICP KDMRADICVH LNRKVFKEHP AFRLASDGCL RALAMEFQTV
   601  HCAPGDLIYH AGESVDSLCF VVSGSLEVIQ DDEVVAILGK GDVFGDVFWK EATLAQSCAN
   661  VRALTYCDLH VIKRDALQKV LEFYTAFSHS FSRNLILTYN LRKRIVFRKI SDVKREEEER
   721  MKRKNEAPLI LPPDHPVRRL FQRFRQQKEA RLAAERGGRD LDDLDVEKGN VLTEHASANH
   781  SLVKASVVTV RESPATPVSF QAASTSGVPD HAKLQAPGSE CLGPKGGGGD CAKRKSWARF
   841  KDACGKSEDW NKVSKAESME TLPERTKASG EATLKKTDSC DSGITKSDLR LDNVGEARSP
   901  QDRSPILAEV KHSFYPIPEQ TLQATVLEVR HELKEDIKAL NAKMTNIEKQ LSEILRILTS
   961  RRSSQSPQEL FEISRPQSPE SERDIFGAS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KCNH1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

6

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

16 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KCNH1.

Disease | AllUniProt

Conditions KCNH1 is implicated in, by any mechanism.

• Temple-Baraitser syndrome (TMBTS) MIM:611816
• Zimmermann-Laband syndrome 1 (ZLS1) MIM:135500

Disease | GeneticClinVar

27 pathogenic / likely-pathogenic of 901 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Zimmermann-Laband syndrome 1
• Temple-Baraitser syndrome
• KCNH1-related disorder
• Inborn genetic diseases
• See cases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.39

gnomAD pLI

0.55

gnomAD missense Z

3.82

DepMap mean gene effect

0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to calcium ion
• myoblast fusion
• potassium ion transmembrane transport
• potassium ion transport
• regulation of cell population proliferation
• regulation of membrane potential

Molecular functions

• calmodulin binding
• delayed rectifier potassium channel activity
• phosphatidylinositol bisphosphate binding

Cellular components

• axon
• dendrite
• early endosome membrane
• nuclear inner membrane
• perikaryon
• plasma membrane
• postsynaptic density membrane
• presynaptic membrane
• voltage-gated potassium channel complex

Protein domainsUniProt · Pfam · InterPro

• PAS domain
• Cyclic nucleotide-binding domain
• PAS-associated, C-terminal
• PAC motif
• Potassium channel, voltage-dependent, EAG/ELK/ERG-like
• Potassium channel, voltage-dependent, EAG
• Ion transport domain
• RmlC-like jelly roll fold
• Cyclic nucleotide-binding domain superfamily
• PAS domain superfamily
• Potassium channel, voltage-dependent, EAG/ELK/ERG-like, animal-type
• Cyclic nucleotide-binding domain
• Ion transport protein
• PAS domain

KeywordsUniProt

• Calmodulin-binding
• Cell membrane
• Cell projection
• Endosome
• Epilepsy
• Glycoprotein
• Intellectual disability
• Ion channel
• Ion transport
• Lipid-binding
• Membrane
• Nucleus
• Phosphoprotein
• Postsynaptic cell membrane
• Potassium
• Potassium channel
• Potassium transport
• Synapse
• Transmembrane
• Transmembrane helix
• Transport
• Voltage-gated channel

InteractionsUniProt · HPA

Protein binding partners of KCNH1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ALG10B
• RABEP1
• CTTN