CALCA

protein-coding

calcitonin related polypeptide alpha, the group of Neuropeptides

Gene summary

This gene encodes the peptide hormones calcitonin, calcitonin gene-related peptide and katacalcin by tissue-specific alternative RNA splicing of the gene transcripts and cleavage of inactive precursor proteins. Calcitonin is involved in calcium regulation and acts to regulate phosphorus metabolism. Calcitonin gene-related peptide functions as a vasodilator and as an antimicrobial peptide while katacalcin is a calcium-lowering peptide. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2014]

Previous symbols:

CALC1

MANE transcript

NM_001741.3

Inheritance

—

ClinVar variants

U:21B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr11:14,966,622-14,972,354

External References & Databases

Ensembl (ENSG00000110680)

UniProt (P01258, P06881)

Transcript & Mutation Effects

hg38 • Region Span ~5.7 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 CALCA variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 22

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001741.3. 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	2
missense			21 clinvar	1 clinvar		22
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	21	1	2	24

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001741.3	RefSeq	NP_001732.1	3	MANE Select
ENST00000331587.9	Ensembl	ENSP00000331746.4	3	MANE Select
NM_001033952.3	RefSeq	NP_001029124.1	3	Standard
NM_001033953.3	RefSeq	NP_001029125.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
calca	Danio rerio	Structure: integument Quality: has extra parts of type abnormal

Gene / Model

Organism

Observed Phenotype

calca

Danio rerio

Structure: integument

Quality: has extra parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endothelin Pathways
Myometrial Relaxation and Contraction Pathways
Lung fibrosis
Signaling by GPCR
Signal Transduction

Biological Process

artery vasodilation involved in baroreceptor response to increased systemic arterial blood pressure
monocyte chemotaxis
inflammatory response
G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway

Molecular Function

hormone activity
protein binding
calcitonin receptor binding
identical protein binding

Cellular Component

extracellular region
extracellular space
nucleus
cytoplasm
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000331587
Coding exons: 3
Length: 5687
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125748
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.598	94	79.0	1.19	0.00000417	930
Missense (PolyPhen)		20	20.609	0.97046		277
Synonymous	-1.28	42	32.7	1.28	0.00000183	277
Loss of Function	0.676	3	4.56	0.658	1.94e-7	52

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcitonin causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones.;

Recessive Scores

pRec: 0.616

Intolerance Scores

LoFtool: 0.899
RVIS EVS: 0.91
RVIS percentile EVS: 89.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00787

Gene Damage Prediction

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