RCAN1

Chr 21

regulator of calcineurin 1

Also known as: ADAPT78, CSP1, DSCR1, MCIP1

NCBI Gene: 1827 ENSG00000159200 UniProt: P53805 OMIM: 602917

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.07

Clinical Summary— RCAN1

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

17 VUS of 22 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.017

Z-score 1.44

OE 0.47 (0.23–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.02Z-score

OE missense 0.74 (0.62–0.88)

88 obs / 119.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.23–1.07)

0≤0.351.4

Missense OE?0.74 (0.62–0.88)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 4 / 8.5Missense obs/exp: 88 / 119.3Syn Z: 1.04

This gene — mechanism propensity

0.7133th %ile

GOF

0.6247th %ile

LOF

0.3941th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

22 submitted variants in ClinVar

ClinVar

Classification Summary

VUS17

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	17	17
Likely Benign	1	1
Benign	0	0
Total	18	18

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

62 pathogenic / likely-pathogenic (of 81) ClinVar copy-number / structural variants overlap RCAN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →