HVCN1

hydrogen voltage gated channel 1, the group of Hydrogen voltage gated channels

Basic information

Region (hg38): 12:110627840-110704950

Links

ENSG00000122986 ∙ NCBI:84329 ∙ OMIM:611227 ∙ HGNC:28240 ∙ Uniprot:Q96D96 ∙ 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 HVCN1 gene.

• Inborn genetic diseases (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HVCN1 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			4			4
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	4	0	0

Variants in HVCN1

This is a list of pathogenic ClinVar variants found in the HVCN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-110628746-ACT-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Conflicting classifications of pathogenicity (Jul 12, 2022)
12-110628749-GT-G		Familial aplasia of the vermis;Meckel-Gruber syndrome • TCTN1-related disorder	Benign/Likely benign (Mar 31, 2023)
12-110628749-G-GT		Meckel-Gruber syndrome;Familial aplasia of the vermis	Benign/Likely benign (Jul 28, 2023)
12-110628757-T-A		not specified • Joubert syndrome 13 • Familial aplasia of the vermis;Meckel-Gruber syndrome	Benign (Jan 30, 2024)
12-110628757-TAAA-T		not specified • Familial aplasia of the vermis	Benign/Likely benign (Feb 21, 2019)
12-110628757-T-TA		Familial aplasia of the vermis;Meckel-Gruber syndrome	Benign (Nov 05, 2023)
12-110628758-A-T		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Aug 23, 2022)
12-110628777-A-T		TCTN1-related disorder	Likely benign (Oct 05, 2022)
12-110628782-C-A		not specified • Familial aplasia of the vermis;Meckel-Gruber syndrome • Joubert syndrome 13	Benign/Likely benign (Jan 26, 2024)
12-110628790-A-C		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Apr 29, 2022)
12-110628793-C-A		Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Oct 13, 2022)
12-110628806-A-G		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Dec 31, 2023)
12-110628821-A-G		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Sep 01, 2022)
12-110628826-T-C		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Oct 22, 2023)
12-110628837-A-T		Joubert syndrome 13	Uncertain significance (Jan 13, 2018)
12-110628853-T-C		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Oct 01, 2023)
12-110628854-T-C		Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Apr 06, 2021)
12-110628862-G-T			Likely pathogenic (Jul 12, 2022)
12-110628864-A-G		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Oct 24, 2023)
12-110628868-T-A		Joubert syndrome 13 • Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Oct 17, 2022)
12-110628871-GT-G		Joubert syndrome 13	Likely pathogenic (Dec 16, 2021)
12-110628879-C-T		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Nov 08, 2022)
12-110628880-A-G		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (May 26, 2022)
12-110628891-G-T		Familial aplasia of the vermis;Meckel-Gruber syndrome	Likely benign (Jul 19, 2022)
12-110628898-C-T		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Oct 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HVCN1	protein_coding	protein_coding	ENST00000356742	6	77110

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.627	0.371	125741	0	3	125744	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.34	113	161	0.703	0.00000919	1799
Missense in Polyphen		25	49.154	0.50861		553
Synonymous	0.613	59	65.3	0.904	0.00000389	526
Loss of Function	2.64	2	11.8	0.170	4.99e-7	145

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000887	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates the voltage-dependent proton permeability of excitable membranes. Forms a proton-selective channel through which protons may pass in accordance with their electrochemical gradient. Proton efflux, accompanied by membrane depolarization, facilitates acute production of reactive oxygen species in phagocytosis. {ECO:0000269|PubMed:16554753, ECO:0000269|PubMed:20037153, ECO:0000269|PubMed:22020278}.
• Pathway: Neutrophil degranulation;Fertilization;Reproduction;Innate Immune System;Immune System;Sperm Motility And Taxes (Consensus)

Recessive Scores

• pRec: 0.0854

Intolerance Scores

• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.23

Haploinsufficiency Scores

• pHI: 0.0627
• hipred: Y
• hipred_score: 0.535
• ghis: 0.486

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hvcn1
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: response to pH;response to zinc ion;regulation of ion transmembrane transport;sperm-egg recognition;neutrophil degranulation;cellular response to zinc ion;cellular response to pH;proton transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;secretory granule membrane;specific granule membrane
• Molecular function: voltage-gated cation channel activity;voltage-gated proton channel activity;identical protein binding