CACNB1

protein-coding

calcium voltage-gated channel auxiliary subunit beta 1, the group of Membrane associated guanylate kinases|Calcium voltage-gated channel auxiliary beta subunits

Gene summary

The protein encoded by this gene belongs to the calcium channel beta subunit family. It plays an important role in the calcium channel by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Alternative splicing occurs at this locus and three transcript variants encoding three distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

Previous symbols:

CACNLB1

MANE transcript

NM_000723.5

Inheritance

—

ClinVar variants

P:2U:73B:6

Top phenotype

Congenital muscular disorder

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr17:39,173,453-39,197,702

External References & Databases

Ensembl (ENSG00000067191)

Transcript & Mutation Effects

hg38 • Region Span ~24.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CACNB1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 69

not providedTotal: 7

Congenital muscular disorderTotal: 1

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000723.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar	2 clinvar	7
missense			69 clinvar	1 clinvar		70
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar		2 clinvar			3
Total	2	0	73	4	2	81

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000723.5	RefSeq	NP_000714.3	14	MANE Select
ENST00000394303.8	Ensembl	ENSP00000377840.3	14	MANE Select
NM_199247.3	RefSeq	NP_954855.1	13	Standard
NM_199248.3	RefSeq	NP_954856.1	13	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cacnb1	Danio rerio	Structure: slow muscle cell Quality: undulate abnormal

Gene / Model

Organism

Observed Phenotype

cacnb1

Danio rerio

Structure: slow muscle cell

Quality: undulate

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oxytocin signaling pathway - Homo sapiens (human)
Cardiac muscle contraction - Homo sapiens (human)
Dilated cardiomyopathy (DCM) - Homo sapiens (human)
Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human)
Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human)

Biological Process

chemical synaptic transmission
neuromuscular junction development
calcium ion transmembrane transport
regulation of voltage-gated calcium channel activity
regulation of calcium ion transmembrane transport via high voltage-gated calcium channel

Molecular Function

voltage-gated calcium channel activity
high voltage-gated calcium channel activity

Cellular Component

plasma membrane
voltage-gated calcium channel complex
sarcolemma

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394303
Coding exons: 14
Length: 24248
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125746
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.14	260	377	0.690	0.0000244	3839
Missense (PolyPhen)		138	217.67	0.63399		2169
Synonymous	1.97	123	154	0.798	0.00000984	1228
Loss of Function	4.21	6	31.5	0.190	0.00000174	345

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of L-type calcium channels (PubMed:1309651, PubMed:8107964, PubMed:15615847). Regulates the activity of L-type calcium channels that contain CACNA1A as pore- forming subunit (By similarity). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane (PubMed:15615847). Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit (PubMed:1309651). Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit (PubMed:8107964). {ECO:0000250|UniProtKB:P19517, ECO:0000269|PubMed:1309651, ECO:0000269|PubMed:15615847, ECO:0000269|PubMed:8107964}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.121
RVIS EVS: -0.56
RVIS percentile EVS: 19.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.322

Gene Damage Prediction

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