RCN2

Summary

RCN2 (reticulocalbin 2, HGNC:9935) is a protein-coding gene on chromosome 15q24.3, encoding Reticulocalbin-2 (Q14257). Not known.

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.

Source: NCBI Gene 5955 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_002902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9935
Approved symbol	RCN2
Name	reticulocalbin 2
Location	15q24.3
Locus type	gene with protein product
Status	Approved
Aliases	ERC-55, E6BP, ERC55, TCBP49
Ensembl gene	ENSG00000117906
Ensembl biotype	protein_coding
OMIM	602584
Entrez	5955

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000320963, ENST00000394883, ENST00000394885, ENST00000557805, ENST00000558598, ENST00000560833, ENST00000880270, ENST00000880271, ENST00000971424, ENST00000971425

RefSeq mRNA: 2 — MANE Select: NM_002902 NM_001271837, NM_002902

CCDS: CCDS10291, CCDS61719

Canonical transcript exons

ENST00000394885 — 7 exons

Exon	Start	End
ENSE00000942765	76935526	76935722
ENSE00001161315	76948410	76948552
ENSE00001323150	76932361	76932466
ENSE00001872833	76931749	76931985
ENSE00001904194	76949070	76954393
ENSE00003558050	76943758	76943871
ENSE00003651958	76947421	76947517

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 99.3907 / max 1028.0247, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147846	99.2928	1823
147845	0.0979	27

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.64	gold quality
tibia	UBERON:0000979	99.02	gold quality
caput epididymis	UBERON:0004358	98.80	gold quality
embryo	UBERON:0000922	98.68	gold quality
ventricular zone	UBERON:0003053	98.67	gold quality
ganglionic eminence	UBERON:0004023	98.39	gold quality
adult organism	UBERON:0007023	98.06	gold quality
cartilage tissue	UBERON:0002418	97.53	gold quality
pigmented layer of retina	UBERON:0001782	97.48	gold quality
endometrium	UBERON:0001295	97.47	gold quality
cauda epididymis	UBERON:0004360	97.27	gold quality
pons	UBERON:0000988	97.21	gold quality
superior vestibular nucleus	UBERON:0007227	97.10	gold quality
bronchial epithelial cell	CL:0002328	96.91	gold quality
biceps brachii	UBERON:0001507	96.87	gold quality
substantia nigra pars compacta	UBERON:0001965	96.82	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.78	gold quality
palpebral conjunctiva	UBERON:0001812	96.76	gold quality
orbitofrontal cortex	UBERON:0004167	96.70	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.62	gold quality
subthalamic nucleus	UBERON:0001906	96.52	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.52	gold quality
epithelium of nasopharynx	UBERON:0001951	96.47	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.44	gold quality
placenta	UBERON:0001987	96.43	gold quality
choroid plexus epithelium	UBERON:0003911	96.31	gold quality
seminal vesicle	UBERON:0000998	96.29	gold quality
hypothalamus	UBERON:0001898	96.19	gold quality
stromal cell of endometrium	CL:0002255	96.18	gold quality
cortical plate	UBERON:0005343	96.00	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	584.64
E-MTAB-3929	yes	226.53
E-HCAD-10	yes	19.80
E-HCAD-13	yes	12.42
E-CURD-114	yes	9.37
E-HCAD-11	yes	7.82
E-MTAB-8271	yes	7.52
E-CURD-112	yes	6.51
E-MTAB-6142	no	220.13
E-HCAD-5	no	21.33
E-MTAB-9388	no	9.34
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting RCN2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-3529-3P	99.90	73.55	3045

Literature-anchored findings (GeneRIF, showing 7)

• RCN2 is implicated in idiopathic absence epilepsy. (PMID:18435749)
• Confirmed is the existence of several ERC-55 splicing variants including ERC-55-C localized in the cytosol in association with the cytoskeleton. (PMID:19927312)
• RCN2 plays a pivotal role in hepatocellular carcinoma cell proliferation and tumor growth presumably through regulating activation of the EGFR-ERK pathway. (PMID:28745317)
• High expression of RCN2 is associated with vascular calcification in diabetes. (PMID:31401313)
• Long non-coding RNA DUXAP8 elevates RCN2 expression and facilitates cell malignant behaviors and angiogenesis in cervical cancer via sponging miR-1297. (PMID:34774078)
• Reticulocalbin 2 as a Potential Biomarker and Therapeutic Target for Atherosclerosis. (PMID:35406670)
• RCN2 promotes Nasopharyngeal carcinoma progression by curbing Calcium flow and Mitochondrial apoptosis. (PMID:36952101)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rcn2	ENSDARG00000039378
mus_musculus	Rcn2	ENSMUSG00000032320
rattus_norvegicus	Rcn2	ENSRNOG00000015780
caenorhabditis_elegans		WBGENE00023407

Paralogs (4): RCN1 (ENSG00000049449), SDF4 (ENSG00000078808), CALU (ENSG00000128595), RCN3 (ENSG00000142552)

Protein

Protein identifiers

Reticulocalbin-2 — Q14257 (reviewed: Q14257)

Alternative names: Calcium-binding protein ERC-55, E6-binding protein

All UniProt accessions (3): Q14257, A8MXP8, H0YL43

UniProt curated annotations — full annotation on UniProt →

Function. Not known. Binds calcium.

Subcellular location. Endoplasmic reticulum lumen.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the CREC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14257-1	1	yes
Q14257-2	2

RefSeq proteins (2): NP_001258766, NP_002893* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site

Pfam: PF13202, PF13499

UniProt features (36 total): binding site 25, domain 6, signal peptide 1, chain 1, modified residue 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14257-F1	78.86	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (25): 76; 78; 85; 110; 112; 114; 116; 121; 164; 173; 199; 201 …

Post-translational modifications (1): 137

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 225 (showing top): MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, PAL_PRMT5_TARGETS_UP, MODULE_151, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, RIZKI_TUMOR_INVASIVENESS_3D_DN, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, MODULE_118, AGTCTTA_MIR499, GATA1_01, DAZARD_RESPONSE_TO_UV_SCC_UP, SCHLOSSER_SERUM_RESPONSE_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (0):

GO Molecular Function (3): calcium ion binding (GO:0005509), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleolus (GO:0005730), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	1
binding	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RCN2	NPTXR	O95502	926
RCN2	KDELR1	P24390	819
RCN2	NPTX2	P47972	753
RCN2	NPTX1	Q15818	716
RCN2	SIPA1L1	O43166	582
RCN2	SCAPER	Q9BY12	540
RCN2	PXN	P49023	538
RCN2	UBE3A	P78355	519
RCN2	TSPAN3	O60637	506
RCN2	PPT1	P50897	496
RCN2	CYP27B1	O15528	494
RCN2	FBLN1	P23142	475
RCN2	STK40	Q8N2I9	464
RCN2	CALM1	P02593	452
RCN2	TADA3	O75528	449

IntAct

387 interactions, top by confidence:

A	B	Type	Score
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
GABARAPL2	RCN2	psi-mi:“MI:0915”(physical association)	0.740
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
PRELID3B	TRIAP1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GABARAPL2	IPO5	psi-mi:“MI:0914”(association)	0.690
RCN2	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.670
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
RCN2	UNG	psi-mi:“MI:0915”(physical association)	0.560
RCN2	STUB1	psi-mi:“MI:0915”(physical association)	0.560
RCN2		psi-mi:“MI:0915”(physical association)	0.550
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
COQ2	SLC25A5	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530

BioGRID (360): RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RCN2 (Proximity Label-MS), RCN2 (Proximity Label-MS), RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RCN2 (Affinity Capture-MS)

ESM2 similar proteins: A0A6I8RMG7, A0AVX7, A2VEI2, A4IG32, A5D7A0, B5X186, B5X4E0, I6L9G5, J3S9D9, O35783, O35887, O93390, O93434, P07214, P09486, P13213, P16975, P20112, P22676, P36377, P36378, P41044, P49257, P61022, P61023, P79881, Q05186, Q14257, Q15293, Q28BT4, Q2KJ39, Q3T0K1, Q4U471, Q5R767, Q5R7F0, Q5ZM44, Q62703, Q62902, Q6IP82, Q6IQP3

Diamond homologs: B5X186, B5X4E0, I6L9G5, J3S9D9, O35783, O35887, O43852, O93434, P02597, P04464, Q05186, Q14257, Q15293, Q28BT4, Q2KJ39, Q3T0K1, Q4U471, Q5RDD8, Q62703, Q66JA6, Q6IP82, Q6IQP3, Q6XLQ7, Q7SXV9, Q8BH97, Q8BP92, Q96D15, Q9FKW4, P42529, Q5ZKE5, Q03975, Q9M7R0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 181 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial protein import	9	12.4×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
ubiquinone biosynthetic process	5	31.2×	3e-04
tumor necrosis factor-mediated signaling pathway	7	15.4×	3e-04
negative regulation of apoptotic process	15	3.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

44 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1365 predictions. Top by Δscore:

Variant	Effect	Δscore
15:76931983:CAGGT:C	donor_loss	1.0000
15:76931984:AGG:A	donor_loss	1.0000
15:76931985:GGTGA:G	donor_loss	1.0000
15:76931986:G:GG	donor_gain	1.0000
15:76931986:G:T	donor_loss	1.0000
15:76931987:T:G	donor_loss	1.0000
15:76932357:A:AG	acceptor_gain	1.0000
15:76932463:GAAA:G	donor_gain	1.0000
15:76932464:A:T	donor_gain	1.0000
15:76932467:G:GG	donor_gain	1.0000
15:76943754:A:AG	acceptor_gain	1.0000
15:76943755:A:AG	acceptor_gain	1.0000
15:76943756:A:G	acceptor_gain	1.0000
15:76943757:G:GG	acceptor_gain	1.0000
15:76943868:GACG:G	donor_gain	1.0000
15:76943870:CGG:C	donor_loss	1.0000
15:76943872:G:GC	donor_loss	1.0000
15:76943872:G:GG	donor_gain	1.0000
15:76943873:T:A	donor_loss	1.0000
15:76947405:A:AG	acceptor_gain	1.0000
15:76947405:AAT:A	acceptor_gain	1.0000
15:76947406:A:G	acceptor_gain	1.0000
15:76947407:T:G	acceptor_gain	1.0000
15:76947407:T:TA	acceptor_gain	1.0000
15:76947518:G:GG	donor_gain	1.0000
15:76947609:A:T	donor_gain	1.0000
15:76948402:A:AG	acceptor_gain	1.0000
15:76948403:T:G	acceptor_gain	1.0000
15:76948404:A:AG	acceptor_gain	1.0000
15:76948405:T:G	acceptor_gain	1.0000

AlphaMissense

2141 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:76935632:G:C	W119C	0.997
15:76935632:G:T	W119C	0.997
15:76943791:G:C	A161P	0.996
15:76943816:T:C	L169S	0.996
15:76935532:T:C	L86P	0.995
15:76935630:T:A	W119R	0.995
15:76935630:T:C	W119R	0.995
15:76943782:T:C	F158L	0.995
15:76943784:T:A	F158L	0.995
15:76943784:T:G	F158L	0.995
15:76947476:T:A	V206D	0.995
15:76947490:T:C	F211L	0.995
15:76947492:T:A	F211L	0.995
15:76947492:T:G	F211L	0.995
15:76949080:T:C	L271P	0.995
15:76949152:T:C	F295S	0.995
15:76949152:T:G	F295C	0.995
15:76943839:T:C	F177L	0.994
15:76943841:T:A	F177L	0.994
15:76943841:T:G	F177L	0.994
15:76948432:G:C	W227C	0.994
15:76948432:G:T	W227C	0.994
15:76943816:T:G	L169W	0.993
15:76949160:A:C	S298R	0.993
15:76949162:T:A	S298R	0.993
15:76949162:T:G	S298R	0.993
15:76935625:T:A	V117E	0.992
15:76943840:T:C	F177S	0.992
15:76948516:G:C	W255C	0.992
15:76948516:G:T	W255C	0.992

dbSNP variants (sampled 300 via entrez): RS1000020974 (15:76932947 A>G), RS1000240867 (15:76952583 C>T), RS1000253604 (15:76951713 T>C), RS1000370122 (15:76951411 A>G), RS1000403069 (15:76939246 ATAAATAAATAAATAAAT>A), RS1000473764 (15:76954764 G>A), RS1000696212 (15:76938166 G>A,C), RS1000871514 (15:76934869 T>G), RS1000904655 (15:76931615 G>A), RS1001175701 (15:76947239 T>G), RS1001441239 (15:76931872 G>A,C,T), RS1001837905 (15:76947614 T>C,G), RS1001909121 (15:76936257 GATTT>G), RS1001987737 (15:76944045 T>C,G), RS1002019116 (15:76944260 C>G,T)

Disease associations

OMIM: gene MIM:602584 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

54 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
trichostatin A	affects cotreatment, decreases expression, affects expression	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	2
Air Pollutants	increases abundance, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
quinoline	decreases expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	affects expression	1
LDN 193189	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3FW	Abcam HEK293T RCN2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.