RCAN1

protein-coding

regulator of calcineurin 1

Gene summary

The protein encoded by this gene interacts with calcineurin A and inhibits calcineurin-dependent signaling pathways, possibly affecting central nervous system development. This gene is located in the minimal candidate region for the Down syndrome phenotype, and is overexpressed in the brain of Down syndrome fetuses. Chronic overexpression of this gene may lead to neurofibrillary tangles such as those associated with Alzheimer disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

Previous symbols:

DSCR1

MANE transcript

NM_004414.7

Inheritance

ClinVar variants

U:20B:1

Top phenotype

RCAN1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr21:34,513,142-34,615,113

External References & Databases

Ensembl (ENSG00000159200)

Transcript & Mutation Effects

hg38 • Region Span ~102.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

focal segmental glomerulosclerosisMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0100313

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RCAN1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 17

not providedTotal: 1

RCAN1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004414.7. 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			1 clinvar			1
missense			19 clinvar	1 clinvar		20
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	20	1	0	21

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004414.7	RefSeq	NP_004405.3	4	MANE Select
ENST00000313806.9	Ensembl	ENSP00000320768.4	4	MANE Select
NM_001285389.2	RefSeq	NP_001272318.1	4	Standard
NM_001285391.2	RefSeq	NP_001272320.2	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rcan1a	Danio rerio	Structure: dorsal longitudinal anastomotic vessel Quality: arrested abnormal

Gene / Model

Organism

Observed Phenotype

rcan1a

Danio rerio

Structure: dorsal longitudinal anastomotic vessel

Quality: arrested

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oxytocin signaling pathway - Homo sapiens (human)
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Thyroid hormone signaling pathway - Homo sapiens (human)
MicroRNAs in cardiomyocyte hypertrophy
VEGFA-VEGFR2 Signaling Pathway

Biological Process

regulation of transcription, DNA-templated
signal transduction
central nervous system development
blood circulation
calcineurin-NFAT signaling cascade

Molecular Function

DNA binding
DNA-binding transcription factor activity
protein binding
calcium-dependent protein serine/threonine phosphatase regulator activity

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313806
Coding exons: 4
Length: 102002
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125746
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.02	88	119	0.738	0.00000629	1635
Missense (PolyPhen)		33	63.599	0.51888		778
Synonymous	1.04	41	50.4	0.813	0.00000317	481
Loss of Function	1.44	4	8.54	0.469	4.58e-7	115

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A (PubMed:12809556). Could play a role during central nervous system development (By similarity). {ECO:0000250|UniProtKB:Q9JHG6, ECO:0000269|PubMed:12809556}.;

Recessive Scores

pRec: 0.234

Intolerance Scores

LoFtool: 0.214
RVIS EVS: -0.05
RVIS percentile EVS: 49.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.663

Gene Damage Prediction

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