KCNG4
gene geneOn this page
Also known as Kv6.4
Summary
KCNG4 (potassium voltage-gated channel modifier subfamily G member 4, HGNC:19697) is a protein-coding gene on chromosome 16q24.1, encoding Voltage-gated potassium channel regulatory subunit KCNG4 (Q8TDN1). Regulatory subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1, modulates the kinetics parameters of the heterotetrameric channel namely the time course of activation, deactivation and inactivation and on the voltage-dependence of activation.
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 G. This member functions as a modulatory subunit. The gene has strong expression in brain. Multiple alternatively spliced variants have been found in normal and cancerous tissues.
Source: NCBI Gene 93107 — RefSeq curated summary.
At a glance
- GWAS associations: 3
- Clinical variants (ClinVar): 134 total
- Druggable target: yes
- MANE Select transcript:
NM_172347
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:19697 |
| Approved symbol | KCNG4 |
| Name | potassium voltage-gated channel modifier subfamily G member 4 |
| Location | 16q24.1 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | Kv6.4 |
| Ensembl gene | ENSG00000168418 |
| Ensembl biotype | protein_coding |
| OMIM | 607603 |
| Entrez | 93107 |
Gene structure
Transcript identifiers
Ensembl transcripts: 2 — 2 protein_coding
ENST00000308251, ENST00000568181
RefSeq mRNA: 1 — MANE Select: NM_172347
NM_172347
CCDS: CCDS10945
Canonical transcript exons
ENST00000308251 — 3 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001190857 | 84236730 | 84237525 |
| ENSE00001190862 | 84218657 | 84223020 |
| ENSE00001860611 | 84239670 | 84240012 |
Expression profiles
Bgee: expression breadth broad, 40 present calls, max score 68.81.
FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0170 / max 5.1472, expressed in 8 samples.
FANTOM5 promoters (1 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 158343 | 0.0170 | 8 |
Top tissues by expression
244 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 68.81 | silver quality |
| endothelial cell | CL:0000115 | 59.89 | gold quality |
| epithelium of nasopharynx | UBERON:0001951 | 59.67 | gold quality |
| secondary oocyte | CL:0000655 | 58.28 | gold quality |
| sperm | CL:0000019 | 54.97 | gold quality |
| skin of hip | UBERON:0001554 | 54.37 | silver quality |
| amygdala | UBERON:0001876 | 50.97 | gold quality |
| substantia nigra | UBERON:0002038 | 49.76 | gold quality |
| midbrain | UBERON:0001891 | 48.92 | gold quality |
| hypothalamus | UBERON:0001898 | 48.17 | gold quality |
| lateral globus pallidus | UBERON:0002476 | 47.79 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 47.18 | gold quality |
| oocyte | CL:0000023 | 46.59 | gold quality |
| spinal cord | UBERON:0002240 | 46.51 | gold quality |
| temporal lobe | UBERON:0001871 | 46.26 | gold quality |
| buccal mucosa cell | CL:0002336 | 46.12 | gold quality |
| prefrontal cortex | UBERON:0000451 | 46.04 | gold quality |
| saphenous vein | UBERON:0007318 | 45.76 | gold quality |
| Ammon’s horn | UBERON:0001954 | 45.73 | gold quality |
| upper leg skin | UBERON:0004262 | 44.77 | silver quality |
| putamen | UBERON:0001874 | 44.34 | gold quality |
| bone marrow cell | CL:0002092 | 44.12 | gold quality |
| amniotic fluid | UBERON:0000173 | 43.90 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 43.56 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 43.37 | gold quality |
| nipple | UBERON:0002030 | 43.01 | gold quality |
| trigeminal ganglion | UBERON:0001675 | 42.99 | gold quality |
| sural nerve | UBERON:0015488 | 42.80 | gold quality |
| trachea | UBERON:0003126 | 42.77 | gold quality |
| neocortex | UBERON:0001950 | 42.42 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 3.59 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): E2F1
miRNA regulators (miRDB)
67 targeting KCNG4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-4747-5P | 100.00 | 67.90 | 2681 |
| HSA-MIR-5196-5P | 100.00 | 67.98 | 2761 |
| HSA-MIR-4533 | 100.00 | 69.48 | 2758 |
| HSA-MIR-4692 | 100.00 | 67.32 | 2066 |
| HSA-MIR-574-5P | 100.00 | 66.01 | 989 |
| HSA-MIR-6758-5P | 100.00 | 66.21 | 1470 |
| HSA-MIR-6856-5P | 100.00 | 65.47 | 1298 |
| HSA-MIR-4514 | 99.99 | 67.10 | 1870 |
| HSA-MIR-6825-5P | 99.96 | 69.81 | 3431 |
| HSA-MIR-6721-5P | 99.93 | 68.92 | 2981 |
| HSA-MIR-497-5P | 99.92 | 71.83 | 2674 |
| HSA-MIR-195-5P | 99.90 | 72.81 | 2805 |
| HSA-MIR-15A-5P | 99.90 | 72.80 | 2787 |
| HSA-MIR-15B-5P | 99.90 | 72.78 | 2798 |
| HSA-MIR-16-5P | 99.90 | 72.80 | 2780 |
| HSA-MIR-424-5P | 99.89 | 71.90 | 2641 |
| HSA-MIR-6838-5P | 99.89 | 71.94 | 2690 |
| HSA-MIR-7845-5P | 99.88 | 64.88 | 771 |
| HSA-MIR-6124 | 99.87 | 69.78 | 3551 |
| HSA-MIR-3934-3P | 99.76 | 65.51 | 1351 |
| HSA-MIR-3150A-3P | 99.76 | 64.44 | 1640 |
| HSA-MIR-6763-5P | 99.76 | 64.68 | 1767 |
| HSA-MIR-6764-5P | 99.75 | 67.89 | 2304 |
| HSA-MIR-4530 | 99.69 | 66.47 | 1509 |
| HSA-MIR-6766-5P | 99.68 | 67.70 | 2325 |
| HSA-MIR-7157-5P | 99.66 | 69.33 | 1829 |
| HSA-MIR-3175 | 99.65 | 66.30 | 2031 |
| HSA-MIR-7150 | 99.62 | 66.80 | 1322 |
| HSA-MIR-4310 | 99.59 | 68.84 | 2527 |
| HSA-MIR-4524A-5P | 99.57 | 71.73 | 1193 |
Literature-anchored findings (GeneRIF, showing 7)
- Obligatory heterotetramerization of three previously uncharacterized Kv channel subunits identified in human genome (Kv6.3)(Kv10.1) (Kv11.1) (PMID:12060745)
- This study suggests that the silent behaviour of Kv6.3 is largely caused by the C-terminal part of its sixth transmembrane domain that causes ER retention of the subunit. (PMID:16096342)
- Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4. (PMID:19074135)
- KCNE5 subunits may affect Kv2.1 homotetramers and Kv2.1/Kv6.4 heterotetramers in vivo, resulting in more tissue-specific fine-tuning mechanisms. (PMID:26242757)
- KvS subunits modify the pharmacological response of Kv2 subunits when assembled in heterotetramers and illustrate the potential of KvS subunits to provide unique properties to the heterotetramers, as is the case for 4-AP on Kv2.1/Kv6.4 channels. (PMID:26505474)
- Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit. (PMID:32697988)
- KCNG4 Genetic Variant Linked to Migraine Prevents Expression of KCNB1. (PMID:39201645)
Cross-species orthologs
4 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | kcng4b | ENSDARG00000051892 |
| danio_rerio | kcng4a | ENSDARG00000062967 |
| mus_musculus | Kcng4 | ENSMUSG00000045246 |
| rattus_norvegicus | Kcng4 | ENSRNOG00000015746 |
Paralogs (31): KCNG1 (ENSG00000026559), KCNQ1 (ENSG00000053918), KCNQ2 (ENSG00000075043), KCND1 (ENSG00000102057), KCNA7 (ENSG00000104848), KCNA1 (ENSG00000111262), KCNC4 (ENSG00000116396), KCNQ4 (ENSG00000117013), KCNS1 (ENSG00000124134), KCNC1 (ENSG00000129159), KCNA5 (ENSG00000130037), KCNC3 (ENSG00000131398), KCNA10 (ENSG00000143105), KCNA6 (ENSG00000151079), KCNS2 (ENSG00000156486), KCNB1 (ENSG00000158445), KCNF1 (ENSG00000162975), KCNV1 (ENSG00000164794), KCNC2 (ENSG00000166006), KCNV2 (ENSG00000168263), KCNS3 (ENSG00000170745), KCNG3 (ENSG00000171126), KCND3 (ENSG00000171385), KCNA3 (ENSG00000177272), KCNA2 (ENSG00000177301), KCNG2 (ENSG00000178342), KCNA4 (ENSG00000182255), KCNB2 (ENSG00000182674), KCNQ3 (ENSG00000184156), KCND2 (ENSG00000184408), KCNQ5 (ENSG00000185760)
Protein
Protein identifiers
Voltage-gated potassium channel regulatory subunit KCNG4 — Q8TDN1 (reviewed: Q8TDN1)
Alternative names: Potassium voltage-gated channel subfamily G member 4, Voltage-gated potassium channel subunit Kv6.3, Voltage-gated potassium channel subunit Kv6.4
All UniProt accessions (2): Q8TDN1, Q547S7
UniProt curated annotations — full annotation on UniProt →
Function. Regulatory subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1, modulates the kinetics parameters of the heterotetrameric channel namely the time course of activation, deactivation and inactivation and on the voltage-dependence of activation. Potassium channel subunit that does not form functional channels by itself. Reduces the deactivation rate. Modulates the threshold for activation by shifting by approximately 20 mV in hyperpolarizing direction. Markedly changes the inactivation by shifting the voltage dependence of inactivation by approximately 40 mV in hyperpolarizing direction. Acceleratee activation and enhances the time course of activation.
Subunit / interactions. Heterotetramer with KCNB1. Does not form homomultimer.
Subcellular location. Cell membrane.
Tissue specificity. Highly expressed in brain, and at lower levels in liver, small intestine and colon.
Domain organisation. The transmembrane segment S4 functions as a voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.
Similarity. Belongs to the potassium channel family. G (TC 1.A.1.2) subfamily. Kv6.4/KCNG4 sub-subfamily.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q8TDN1-1 | 1 | yes |
| Q8TDN1-2 | 2 |
RefSeq proteins (1): NP_758857* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR003131 | T1-type_BTB | Domain |
| IPR003968 | K_chnl_volt-dep_Kv | Family |
| IPR003971 | K_chnl_volt-dep_Kv5/Kv9 | Family |
| IPR005821 | Ion_trans_dom | Domain |
| IPR011333 | SKP1/BTB/POZ_sf | Homologous_superfamily |
| IPR027359 | Volt_channel_dom_sf | Homologous_superfamily |
| IPR028325 | VG_K_chnl | Family |
Pfam: PF00520, PF02214
UniProt features (27 total): topological domain 8, transmembrane region 6, sequence variant 6, intramembrane region 2, splice variant 2, chain 1, region of interest 1, short sequence motif 1
Structure
Experimental structures (PDB)
0 structures.
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q8TDN1-F1 | 78.07 | 0.33 |
Function
Pathways and Gene Ontology
Reactome pathways
3 pathways
| ID | Pathway |
|---|---|
| R-HSA-1296072 | Voltage gated Potassium channels |
| R-HSA-112316 | Neuronal System |
| R-HSA-1296071 | Potassium Channels |
MSigDB gene sets: 84 (showing top):
GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, TGACCTY_ERR1_Q2, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, TGACCTTG_SF1_Q6, GOBP_REGULATION_OF_POTASSIUM_ION_TRANSPORT, AP4_01, GOBP_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, LEIN_PONS_MARKERS, LEIN_MEDULLA_MARKERS
GO Biological Process (9): action potential (GO:0001508), regulation of potassium ion transport (GO:0043266), protein homooligomerization (GO:0051260), potassium ion transmembrane transport (GO:0071805), regulation of potassium ion transmembrane transport (GO:1901379), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)
GO Molecular Function (5): voltage-gated potassium channel activity (GO:0005249), potassium channel regulator activity (GO:0015459), transmembrane transporter binding (GO:0044325), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267)
GO Cellular Component (5): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)
Reactome top-level categories
Rollup of top-2 pathways:
| Category | Pathways |
|---|---|
| Potassium Channels | 1 |
| Neuronal System | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| potassium ion transport | 2 |
| transport | 2 |
| potassium channel activity | 2 |
| cellular anatomical structure | 2 |
| regulation of membrane potential | 1 |
| regulation of metal ion transport | 1 |
| protein complex oligomerization | 1 |
| monoatomic cation transmembrane transport | 1 |
| regulation of potassium ion transport | 1 |
| potassium ion transmembrane transport | 1 |
| regulation of monoatomic cation transmembrane transport | 1 |
| metal ion transport | 1 |
| monoatomic ion transport | 1 |
| transmembrane transport | 1 |
| cellular process | 1 |
| voltage-gated monoatomic cation channel activity | 1 |
| ion channel regulator activity | 1 |
| protein binding | 1 |
| monoatomic ion transmembrane transporter activity | 1 |
| channel activity | 1 |
| monoatomic cation channel activity | 1 |
| potassium ion transmembrane transporter activity | 1 |
| nuclear lumen | 1 |
| membrane | 1 |
| cell periphery | 1 |
| potassium channel complex | 1 |
| plasma membrane protein complex | 1 |
| transmembrane transporter complex | 1 |
Protein interactions and networks
STRING
1778 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| KCNG4 | KCNB1 | Q14721 | 860 |
| KCNG4 | CACNA1S | Q13698 | 487 |
| KCNG4 | KCNAB1 | Q14722 | 485 |
| KCNG4 | KCNAB2 | Q13303 | 462 |
| KCNG4 | KCNB2 | Q92953 | 447 |
| KCNG4 | OPN4 | Q9UHM6 | 443 |
| KCNG4 | NETO1 | Q8TDF5 | 421 |
| KCNG4 | NXPH4 | O95158 | 407 |
| KCNG4 | TMC8 | Q8IU68 | 406 |
| KCNG4 | KCNH8 | Q96L42 | 404 |
| KCNG4 | CNTN5 | O94779 | 403 |
| KCNG4 | SDK2 | Q58EX2 | 401 |
| KCNG4 | ZNF799 | Q96GE5 | 395 |
| KCNG4 | LRRTM1 | Q86UE6 | 388 |
| KCNG4 | KCNH7 | Q9NS40 | 386 |
IntAct
3 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| KCNG4 | KCNB2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| KCNG4 | CA1 | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (25): CST4 (Affinity Capture-MS), CST1 (Affinity Capture-MS), CST2 (Affinity Capture-MS), KCNB1 (FRET), KCNG4 (FRET), CST2 (Affinity Capture-MS), CST4 (Affinity Capture-MS), CST1 (Affinity Capture-MS), KCNG4 (Affinity Capture-MS), KCNB2 (Affinity Capture-MS), PPP1R15B (Affinity Capture-MS), AXL (Affinity Capture-MS), DCAKD (Affinity Capture-MS), ATF6 (Affinity Capture-MS), SREBF1 (Affinity Capture-MS)
ESM2 similar proteins: A2BDX4, A4K2T1, A4K2Y2, D4AD53, O15554, O73606, O88454, O89109, P15388, P17971, P17972, P35739, P48547, P59053, P59994, P59995, P97557, Q03719, Q0P583, Q17ST2, Q52PG9, Q5RC10, Q60565, Q63881, Q6IVV8, Q6PIU1, Q7TN37, Q80XM3, Q8BZN2, Q8CFS6, Q8HYZ1, Q8IV77, Q8R1P5, Q8R523, Q8TAE7, Q8TD43, Q8TDN1, Q8TDN2, Q96RP8, Q9ERS0
Diamond homologs: A2BDX4, A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, A6H8H5, D4AD53, D4ADX7, G5EFC3, O18868, O35173, O35174, O73606, O88758, O88759, P10499, P15384, P15385, P15387, P15388, P16388, P16390, P17970, P17971, P17972, P22001, P22459, P22739, P25122, P48547, P59053, P59994, P59995
SIGNOR signaling
0 interactions.
Disease & clinical
Clinical variants and AI predictions
ClinVar
134 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 123 |
| Likely benign | 5 |
| Benign | 5 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
518 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 16:84237534:C:T | acceptor_gain | 1.0000 |
| 16:84237534:C:CT | acceptor_gain | 0.9900 |
| 16:84237535:A:T | acceptor_gain | 0.9900 |
| 16:84239665:CTCA:C | donor_loss | 0.9900 |
| 16:84239667:CA:C | donor_loss | 0.9900 |
| 16:84239668:ACCT:A | donor_loss | 0.9900 |
| 16:84239669:C:G | donor_loss | 0.9900 |
| 16:84239669:CCTT:C | donor_gain | 0.9900 |
| 16:84239668:A:AC | donor_gain | 0.9800 |
| 16:84239669:C:CC | donor_gain | 0.9800 |
| 16:84239668:ACCTT:A | donor_gain | 0.9600 |
| 16:84239669:CCTTC:C | donor_gain | 0.9600 |
| 16:84239668:AC:A | donor_gain | 0.9500 |
| 16:84239669:CC:C | donor_gain | 0.9500 |
| 16:84237533:C:CT | acceptor_gain | 0.9400 |
| 16:84239669:CCT:C | donor_gain | 0.9400 |
| 16:84237521:CCAGT:C | acceptor_gain | 0.9100 |
| 16:84237522:CAGTC:C | acceptor_gain | 0.9100 |
| 16:84236724:GCTCA:G | donor_loss | 0.8900 |
| 16:84236725:CTCAC:C | donor_loss | 0.8900 |
| 16:84236726:TCACC:T | donor_loss | 0.8900 |
| 16:84236727:CACCT:C | donor_loss | 0.8900 |
| 16:84236729:C:T | donor_loss | 0.8900 |
| 16:84236722:CCGCT:C | donor_loss | 0.8800 |
| 16:84236723:CGCTC:C | donor_loss | 0.8800 |
| 16:84222216:G:C | donor_gain | 0.8700 |
| 16:84222221:A:C | donor_gain | 0.8700 |
| 16:84239145:T:TA | donor_gain | 0.8700 |
| 16:84229747:CAGTG:C | donor_gain | 0.8600 |
| 16:84236730:C:G | donor_loss | 0.8500 |
AlphaMissense
3393 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 16:84222454:G:C | S441R | 0.998 |
| 16:84222454:G:T | S441R | 0.998 |
| 16:84222456:T:G | S441R | 0.998 |
| 16:84222463:G:C | S438R | 0.998 |
| 16:84222463:G:T | S438R | 0.998 |
| 16:84222465:T:G | S438R | 0.998 |
| 16:84222546:A:G | W411R | 0.998 |
| 16:84222546:A:T | W411R | 0.998 |
| 16:84222565:G:C | S404R | 0.998 |
| 16:84222565:G:T | S404R | 0.998 |
| 16:84222567:T:G | S404R | 0.998 |
| 16:84222958:G:C | F273L | 0.998 |
| 16:84222958:G:T | F273L | 0.998 |
| 16:84222960:A:G | F273L | 0.998 |
| 16:84222406:G:C | F457L | 0.997 |
| 16:84222406:G:T | F457L | 0.997 |
| 16:84222408:A:G | F457L | 0.997 |
| 16:84222466:G:C | S437R | 0.997 |
| 16:84222466:G:T | S437R | 0.997 |
| 16:84222468:T:G | S437R | 0.997 |
| 16:84222500:G:T | P426H | 0.997 |
| 16:84222571:G:C | F402L | 0.997 |
| 16:84222571:G:T | F402L | 0.997 |
| 16:84222573:A:G | F402L | 0.997 |
| 16:84222881:T:A | D299V | 0.997 |
| 16:84222963:A:G | W272R | 0.997 |
| 16:84222963:A:T | W272R | 0.997 |
| 16:84222452:C:T | G442E | 0.996 |
| 16:84222485:C:T | G431D | 0.996 |
| 16:84222544:C:A | W411C | 0.996 |
dbSNP variants (sampled 300 via entrez): RS1000012795 (16:84238881 C>A), RS1000016728 (16:84226772 G>A,C), RS1000106886 (16:84228495 C>G,T), RS1000118187 (16:84228591 C>A,T), RS1000206938 (16:84240863 T>A), RS1000263508 (16:84218339 C>A,G,T), RS1000293169 (16:84218173 G>A,T), RS1000308309 (16:84236869 C>A,T), RS1000382902 (16:84236709 A>G), RS1000400929 (16:84241897 C>G,T), RS1000464475 (16:84220941 A>G), RS1000540181 (16:84238211 G>A,C), RS1000600242 (16:84240682 A>G), RS1000725331 (16:84221207 C>G), RS1000907255 (16:84225649 T>C)
Disease associations
OMIM: gene MIM:607603 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
3 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST001523_23 | Visceral adipose tissue adjusted for BMI | 6.000000e-06 |
| GCST003830_11 | Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1) | 7.000000e-07 |
| GCST011891_4 | Systolic blood pressure (baseline) | 2.000000e-08 |
EFO canonical traits (3, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004340 | body mass index |
| EFO:0005921 | FEV change measurement |
| EFO:0006335 | systolic blood pressure |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL2362996 (PROTEIN FAMILY)
PharmGKB: 1 entry (VIP=true, CPIC=false)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: vgic — Voltage-gated potassium channels (Kv)
ChEMBL bioactivities
2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 9.82 | Ki | 0.15 | nM | CHEMBL5722941 |
| 9.74 | IC50 | 0.18 | nM | CHEMBL5722941 |
PubChem BioAssay actives
2 with measured affinity, of 34 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 3-[(1R,2aS,4S,5aS,8aS,10S,11aR,14aS,16S,17aS,19S,20aS,22S,23aS,25S,26aS,28S,29aS,31R,32aS,35aS,36R,38aS,39S,41aS,42S,44aS,45S,48R,50aS,51S,53aS,54S,56aS,57S,59aS,60S,63S,66S,69S,72S,75S,78S,87R,93S,96S,99S)-17a,20a,23a,53a,63-pentakis(4-aminobutyl)-31-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-16,29a,72,78-tetrakis(2-amino-2-oxoethyl)-14a,26a-bis(3-amino-3-oxopropyl)-2a,38a,66-tribenzyl-28,50a,57-tris[(2S)-butan-2-yl]-4,5a,19,42,45,69-hexakis(3-carbamimidamidopropyl)-51,54-bis(2-carboxyethyl)-56a,99-bis(carboxymethyl)-36-[[(2S,3S)-1-(carboxymethylamino)-3-methyl-1-oxopentan-2-yl]carbamoyl]-39,60-bis[(1R)-1-hydroxyethyl]-75,93-bis(hydroxymethyl)-32a,35a,59a-tris[(4-hydroxyphenyl)methyl]-22-(1H-imidazol-4-ylmethyl)-96-(1H-indol-3-ylmethyl)-41a-methyl-25-(2-methylpropyl)-1a,3,4a,6,7a,9,10a,13a,15,16a,18,19a,21,22a,24,25a,27,28a,30,31a,34a,37a,38,40a,41,43a,44,47,49a,50,52a,53,55a,56,58a,59,61a,62,65,68,71,74,77,80,83,86,89,92,95,98-pentacontaoxo-33,34,63a,64a,67a,68a-hexathia-a,2,3a,5,6a,8,9a,12a,14,15a,17,18a,20,21a,23,24a,26,27a,29,30a,33a,36a,37,39a,40,42a,43,46,48a,49,51a,52,54a,55,57a,58,60a,61,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazapentacyclo[85.74.4.448,111.010,14.0144,148]nonahexacontahectan-8a-yl]propanoic acid | 2198828: Binding affinity to KV channel (unknown origin) assessed as inhibition constant | ki | 0.0001 | uM |
CTD chemical–gene interactions
10 total (human), top 10 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Resveratrol | affects cotreatment, decreases expression | 2 |
| bisphenol A | decreases methylation | 1 |
| S-(1,2-dichlorovinyl)cysteine | increases expression, affects response to substance | 1 |
| bisphenol S | decreases methylation | 1 |
| Acetaminophen | increases expression | 1 |
| Benzo(a)pyrene | affects methylation, increases methylation | 1 |
| Copper | affects cotreatment, decreases expression | 1 |
| Lipopolysaccharides | decreases expression, affects response to substance, increases expression | 1 |
| Plant Extracts | affects cotreatment, decreases expression | 1 |
| Valproic Acid | increases methylation | 1 |
ChEMBL screening assays
21 unique, capped per target: 20 binding, 1 toxicity
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1787442 | Binding | Inhibition of human recombinant Kv channel at 10 uM by radioligand binding assay | Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. — Bioorg Med Chem Lett |
| CHEMBL5522525 | Toxicity | Inhibition of human K+ channel by automated electrophysiology | Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure. — J Med Chem |
Cellosaurus cell lines
1 cell lines: 1 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_YA61 | IDG-HEK293T-KCNG4-V5-OE | Transformed cell line | Female |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.