RCN3

protein-coding

reticulocalbin 3, the group of CREC family

Gene summary

Enables calcium ion binding activity. Involved in several processes, including collagen biosynthetic process; positive regulation of peptidase activity; and regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_020650.3

Inheritance

—

ClinVar variants

U:60B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.13

Max pathogenic AF

—

Genomic locus

chr19:49,528,003-49,546,962

External References & Databases

Ensembl (ENSG00000142552)

Transcript & Mutation Effects

hg38 • Region Span ~19.0 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 RCN3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 54

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020650.3. 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 clinvar		4
missense			56 clinvar			56
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	60	2	0	62

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020650.3	RefSeq	NP_065701.2	6	MANE Select
ENST00000270645.8	Ensembl	ENSP00000270645.2	6	MANE Select
ENST00000593483.1	Ensembl	ENSP00000470771.1	2	Standard
ENST00000597801.1	Ensembl	ENSP00000469727.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein secretion
positive regulation of peptidase activity
protein transport
collagen biosynthetic process
ERAD pathway

Molecular Function

calcium ion binding
protein binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000270645
Coding exons: 6
Length: 19345
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 71
Defined: 125748
p: 0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.215	173	181	0.955	0.0000108	2089
Missense (PolyPhen)		55	54.7	1.0055		605
Synonymous	0.457	70	75.0	0.933	0.00000469	615
Loss of Function	-0.443	15	13.3	1.13	6.94e-7	151

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00025	rare
Latino/Admixed American	0.00035	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00012	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00037	0.00035	rare
South Asian	0.00029	0.00026	rare
Other	0.00092	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable molecular chaperone assisting protein biosynthesis and transport in the endoplasmic reticulum (PubMed:16433634, PubMed:28939891). Required for the proper biosynthesis and transport of pulmonary surfactant-associated protein A/SP-A, pulmonary surfactant-associated protein D/SP-D and the lipid transporter ABCA3 (By similarity). By regulating both the proper expression and the degradation through the endoplasmic reticulum-associated protein degradation pathway of these proteins plays a crucial role in pulmonary surfactant homeostasis (By similarity). Has an anti-fibrotic activity by negatively regulating the secretion of type I and type III collagens (PubMed:28939891). This calcium-binding protein also transiently associates with immature PCSK6 and regulates its secretion (PubMed:16433634). {ECO:0000250|UniProtKB:Q8BH97, ECO:0000269|PubMed:16433634, ECO:0000269|PubMed:28939891}.;

Intolerance Scores

LoFtool: 0.908
RVIS EVS: 0.86
RVIS percentile EVS: 88.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.792

Gene Damage Prediction

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