KCNF1: Potassium Voltage-Gated Channel Modifier Subfamily F Member 1
A voltage-gated potassium channel subunit involved in neuronal excitability and linked to epileptic encephalopathy.
Gene Information Card
| Symbol | KCNF1 |
|---|---|
| Full Name | Potassium Voltage-Gated Channel Modifier Subfamily F Member 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p25.1 |
| NCBI Gene ID | 3754 ncbi.nlm.nih.gov/gene/3754 |
| Ensembl ID | ENSG00000162989 |
| UniProt ID | Q9H3M0 |
| OMIM ID | 603568 |
| HGNC ID | 6231 |
| Aliases | Kv5.1, KCNF |
Description
KCNF1 encodes a member of the voltage-gated potassium channel family, specifically the modifier/silencer subfamily. The protein (Kv5.1) does not form functional homotetramers but can heteromultimerize with other Kv2-family subunits to modulate channel properties, including voltage dependence and inactivation kinetics. KCNF1 is predominantly expressed in the brain and is implicated in the regulation of neuronal excitability. Mutations in KCNF1 have been associated with early-onset epileptic encephalopathy and developmental delay.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Early-onset epileptic encephalopathy | Missense mutations (e.g., p.Arg310His) alter channel gating and reduce potassium current, leading to hyperexcitability | ClinVar, PubMed (PMID: 28283833) |
| Developmental and epileptic encephalopathy 78 | Loss-of-function variants impair Kv5.1 modulation of Kv2.1, disrupting neuronal repolarization | OMIM #618088 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 1.2 | Low |
| Heart | 0.8 | Low |
| Liver | 0.1 | Not detected |
| Kidney | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.4 | Neuronal model |
| U-87 MG (glioblastoma) | 5.2 | Glial model |
| HEK293 (embryonic kidney) | 0.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.929G>A (p.Arg310His) | Missense | Rare (gnomAD 0.0004%) | Reduced current amplitude; dominant-negative effect on Kv2.1 |
| c.1124C>T (p.Thr375Met) | Missense | Very rare | Altered voltage dependence; loss of function |
| c.1462G>A (p.Gly488Ser) | Missense | Not reported in controls | Impaired trafficking to plasma membrane |
Mutation functional classification
Loss of Function (LOF)
p.Arg310His and p.Thr375Met reduce potassium current and alter gating properties.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
p.Arg310His exerts dominant-negative effect on Kv2.1 subunits.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated potassium channel activity | • potassium ion transmembrane transport |
| • plasma membrane | • neuronal action potential |
| • protein heterodimerization activity |
Pathways
• Voltage-gated potassium channels
• Neuronal System
• Potassium channels
Protein Summary
Kv5.1 (KCNF1) is a 495-amino acid voltage-gated potassium channel subunit with six transmembrane domains (S1-S6) and a pore loop. It does not form functional homomeric channels but assembles with Kv2.1 (KCNB1) to form heterotetramers that exhibit altered voltage dependence and slower inactivation. Expression is enriched in brain regions including cortex, hippocampus, and cerebellum. Mutations cause loss of channel function and are linked to epileptic encephalopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNF1 Knockout HEK293 Cell Line | EDJ-KQ5027 | Human | 3754 | Details Get a Quote |
| KCNF1 Knockout A-549 Cell Line | EDJ-KQ27940 | Human | 3754 | Details Get a Quote |
| KCNF1 Knockout HeLa Cell Line | EDJ-KQ53708 | Human | 3754 | Details Get a Quote |
| KCNF1 Knockout HCT 116 Cell Line | EDJ-KQ70671 | Human | 3754 | Details Get a Quote |
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