HCN3

hyperpolarization activated cyclic nucleotide gated potassium channel 3, the group of Cyclic nucleotide gated channels

Basic information

Region (hg38): 1:155277462-155289848

Links

ENSG00000143630 ∙ NCBI:57657 ∙ OMIM:609973 ∙ HGNC:19183 ∙ Uniprot:Q9P1Z3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HCN3 gene.

• Inborn genetic diseases (27 variants)
• Pyruvate kinase deficiency of red cells (10 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HCN3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			27	1		28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			9		1	10
Total	0	0	36	1	1

Variants in HCN3

This is a list of pathogenic ClinVar variants found in the HCN3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-155277626-C-A		not specified	Uncertain significance (Jun 06, 2023)
1-155277675-C-T		not specified	Uncertain significance (Oct 25, 2022)
1-155277697-C-G		not specified	Uncertain significance (Dec 20, 2023)
1-155277792-C-T		not specified	Uncertain significance (Nov 12, 2021)
1-155282448-G-A		not specified	Uncertain significance (Apr 12, 2022)
1-155282497-A-C		not specified	Uncertain significance (Apr 20, 2023)
1-155282514-G-A		not specified	Uncertain significance (Mar 15, 2023)
1-155282563-A-G		not specified	Uncertain significance (Dec 14, 2023)
1-155283987-C-A		not specified	Uncertain significance (Jan 03, 2024)
1-155284023-A-C		not specified	Uncertain significance (Jun 21, 2023)
1-155284025-C-A		not specified	Uncertain significance (Oct 05, 2023)
1-155284122-T-C		not specified	Uncertain significance (Jun 13, 2022)
1-155284641-G-C		not specified	Uncertain significance (Oct 06, 2021)
1-155284646-G-T		not specified	Uncertain significance (Apr 13, 2023)
1-155285231-G-A		not specified	Uncertain significance (Feb 05, 2024)
1-155285246-C-T		not specified	Uncertain significance (Aug 15, 2023)
1-155285263-G-A		not specified	Uncertain significance (Jan 23, 2024)
1-155285301-C-T		not specified	Uncertain significance (Sep 22, 2023)
1-155285307-G-A		not specified	Uncertain significance (Jun 18, 2021)
1-155285745-C-T		not specified	Uncertain significance (Aug 22, 2023)
1-155285748-G-A		not specified	Uncertain significance (May 18, 2022)
1-155285806-T-C		not specified	Uncertain significance (Aug 02, 2022)
1-155285850-G-A		not specified	Uncertain significance (Dec 13, 2022)
1-155285882-G-A		not specified	Uncertain significance (Jul 06, 2021)
1-155285910-G-A		not specified	Uncertain significance (Dec 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HCN3	protein_coding	protein_coding	ENST00000368358	8	12266

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000257	0.997	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.52	424	522	0.813	0.0000353	4917
Missense in Polyphen		92	111.29	0.82666		1068
Synonymous	1.13	190	211	0.901	0.0000129	1748
Loss of Function	2.57	12	26.2	0.458	0.00000138	273

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000345	0.000337
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000616	0.0000462
European (Non-Finnish)	0.000196	0.000193
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions. {ECO:0000269|PubMed:16043489}.
• Pathway: Neuronal System;HCN channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.132

Intolerance Scores

• loftool: 0.101
• rvis_EVS: 0.07
• rvis_percentile_EVS: 59.11

Haploinsufficiency Scores

• pHI: 0.130
• hipred: Y
• hipred_score: 0.740
• ghis: 0.554

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.964

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hcn3
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of ion transmembrane transport;sodium ion transmembrane transport;regulation of membrane potential;cellular response to cAMP;potassium ion transmembrane transport;response to cisplatin;cellular response to dopamine
• Cellular component: plasma membrane;integral component of plasma membrane;dendrite;neuronal cell body;cone cell pedicle
• Molecular function: voltage-gated sodium channel activity;voltage-gated potassium channel activity;protein binding;cAMP binding