Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed August 2013

What is the official name of the HCN4 gene?

The official name of this gene is “hyperpolarization activated cyclic nucleotide gated potassium channel 4.”

HCN4 is the gene's official symbol. The HCN4 gene is also known by other names, listed below.

What is the normal function of the HCN4 gene?

The HCN4 gene provides instructions for making a channel that transports positively charged atoms (ions) into heart muscle cells. This channel is located primarily in the sino-atrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The HCN4 channel allows potassium and sodium ions to flow into cells of the SA node. This ion flow is often called the "pacemaker current" because it generates electrical impulses that start each heartbeat and is involved in maintaining a regular heart rhythm.

Does the HCN4 gene share characteristics with other genes?

The HCN4 gene belongs to a family of genes called CNG (cyclic nucleotide-regulated channels).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? ( in the Handbook.

How are changes in the HCN4 gene related to health conditions?

sick sinus syndrome - caused by mutations in the HCN4 gene

At least five mutations in the HCN4 gene have been identified in people with sick sinus syndrome, a heart condition that affects the function of the SA node. Most of these mutations change single protein building blocks (amino acids) in the HCN4 channel. In some cases, fewer of the altered channels reach the cell membrane, where they are needed to transport ions. In other cases, the channel is in the right place but has an abnormal structure that changes how ions flow through it. All of the mutations reduce the overall flow of ions into cells of the SA node, preventing it from creating the electrical signals that control the heartbeat. These changes increase the risk of an abnormally slow heartbeat (bradycardia), which can cause dizziness, light-headedness, fainting (syncope), and related symptoms. HCN4 gene mutations have also been found in people who have a slow heartbeat without any other symptoms (asymptomatic bradycardia).

Where is the HCN4 gene located?

Cytogenetic Location: 15q24.1

Molecular Location on chromosome 15: base pairs 73,319,859 to 73,369,264

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The HCN4 gene is located on the long (q) arm of chromosome 15 at position 24.1.

The HCN4 gene is located on the long (q) arm of chromosome 15 at position 24.1.

More precisely, the HCN4 gene is located from base pair 73,319,859 to base pair 73,369,264 on chromosome 15.

See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about HCN4?

You and your healthcare professional may find the following resources about HCN4 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the HCN4 gene or gene products?

  • hyperpolarization activated cyclic nucleotide-gated cation channel 4
  • hyperpolarization activated cyclic nucleotide-gated potassium channel 4
  • potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
  • SSS2

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding HCN4?

acids ; asymptomatic ; atrial ; bradycardia ; cation ; cell ; cell membrane ; channel ; fainting ; gene ; ions ; muscle cells ; nucleotide ; pacemaker ; potassium ; protein ; SA node ; sinus ; sodium ; syncope ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Baruscotti M, Bottelli G, Milanesi R, DiFrancesco JC, DiFrancesco D. HCN-related channelopathies. Pflugers Arch. 2010 Jul;460(2):405-15. doi: 10.1007/s00424-010-0810-8. Epub 2010 Mar 8. Review. (
  • Milanesi R, Baruscotti M, Gnecchi-Ruscone T, DiFrancesco D. Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel. N Engl J Med. 2006 Jan 12;354(2):151-7. Erratum in: N Engl J Med. 2006 Jun 8;354(23):2520. (
  • NCBI Gene (
  • Netter MF, Zuzarte M, Schlichthörl G, Klöcker N, Decher N. The HCN4 channel mutation D553N associated with bradycardia has a C-linker mediated gating defect. Cell Physiol Biochem. 2012;30(5):1227-40. doi: 10.1159/000343314. Epub 2012 Oct 15. (
  • Nof E, Luria D, Brass D, Marek D, Lahat H, Reznik-Wolf H, Pras E, Dascal N, Eldar M, Glikson M. Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia. Circulation. 2007 Jul 31;116(5):463-70. Epub 2007 Jul 23. (
  • Ueda K, Hirano Y, Higashiuesato Y, Aizawa Y, Hayashi T, Inagaki N, Tana T, Ohya Y, Takishita S, Muratani H, Hiraoka M, Kimura A. Role of HCN4 channel in preventing ventricular arrhythmia. J Hum Genet. 2009 Feb;54(2):115-21. doi: 10.1038/jhg.2008.16. Epub 2009 Jan 23. (
  • Ueda K, Nakamura K, Hayashi T, Inagaki N, Takahashi M, Arimura T, Morita H, Higashiuesato Y, Hirano Y, Yasunami M, Takishita S, Yamashina A, Ohe T, Sunamori M, Hiraoka M, Kimura A. Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. J Biol Chem. 2004 Jun 25;279(26):27194-8. Epub 2004 Apr 30. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: August 2013
Published: February 8, 2016