RCN2

Chr 15

reticulocalbin 2

Also known as: E6BP, ERC-55, ERC55, TCBP49

NCBI Gene: 5955 ENSG00000117906 UniProt: Q14257

The protein encoded by this gene is a calcium-binding protein located in the lumen of the ER. The protein contains six conserved regions with similarity to a high affinity Ca(+2)-binding motif, the EF-hand. This gene maps to the same region as type 4 Bardet-Biedl syndrome, suggesting a possible causative role for this gene in the disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.74

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.029

Z-score 2.27

OE 0.35 (0.18–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.84Z-score

OE missense 0.80 (0.69–0.94)

112 obs / 140.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.18–0.74)

0≤0.351.4

Missense OE?0.80 (0.69–0.94)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 5 / 14.3Missense obs/exp: 112 / 140.0Syn Z: 0.69

Background carrier burden — how many people carry a rare variant somewhere in RCN2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

444 rare PASS variants

Rare truncating (LoF)

1 in 2,600

67 rare PASS variants

Rare synonymous (reference)

1 in 420

157 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RCN2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 240	1 in 3,000
South Asian	~43k	1 in 81	1 in 1,900
Remaining (unassigned)	~30k	1 in 140	≈ 1 in 9,800
European (Finnish)	~27k	1 in 260	≈ 1 in 12,000
Admixed American	~22k	1 in 170	1 in 3,900
African / African American	~21k	1 in 210	1 in 870
East Asian	~20k	1 in 180	1 in 1,800
Ashkenazi Jewish	~13k	none seen	≈ 1 in 3,400
Middle Eastern	~2,884	1 in 170	≈ 1 in 2,700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 7 coding exons well covered in gnomAD exomes; exons 1, 4, 5 marginal. Genomes: all 7.? see exons ↓