GENE REFERENCE / HGNC:16882

HCN4

hyperpolarization activated cyclic nucleotide gated potassium channel 4

protein-coding gene15q24.1Gene information

What does this gene do?

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.

Source: MedlinePlus, National Library of Medicine. Source publication: 2020-08-18. Source review: 2013-08.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
Brugada syndrome 1MONDO:0011001 · Evaluated 2017-11-21	Autosomal dominant	DisputedBrugada Syndrome Gene Curation Expert Panel
sick sinus syndrome 2, autosomal dominantMONDO:0008102 · Evaluated 2025-06-24	Autosomal dominant	DefinitiveHereditary Cardiovascular Disease Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 2,353
Submissions for variants in or overlapping this gene: 4,372
Submissions explicitly reporting this gene: 4,293
Alleles reported pathogenic / likely pathogenic: 21
VariationIDs with uncertain significance: 1,272
VariationIDs with conflicting classifications: 97

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about HCN4?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 21 alleles in HCN4 reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in HCN4.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

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