CRACR2B

Summary

CRACR2B (calcium release activated channel regulator 2B, HGNC:28703) is a protein-coding gene on chromosome 11p15.5, encoding EF-hand calcium-binding domain-containing protein 4A (Q8N4Y2). Plays a role in store-operated Ca(2+) entry (SOCE).

Predicted to enable calcium ion binding activity. Involved in store-operated calcium entry.

Source: NCBI Gene 283229 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_001286606

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28703
Approved symbol	CRACR2B
Name	calcium release activated channel regulator 2B
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	MGC45840
Ensembl gene	ENSG00000177685
Ensembl biotype	protein_coding
OMIM	614177
Entrez	283229

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 7 retained_intron

ENST00000450448, ENST00000525077, ENST00000526531, ENST00000527089, ENST00000527763, ENST00000528315, ENST00000528542, ENST00000528694, ENST00000530183, ENST00000530688, ENST00000530737, ENST00000533803, ENST00000534191, ENST00000534606, ENST00000865120, ENST00000865121, ENST00000865122, ENST00000948430, ENST00000948431, ENST00000948432, ENST00000948433, ENST00000948434

RefSeq mRNA: 2 — MANE Select: NM_001286606 NM_001286606, NM_173584

CCDS: CCDS41588, CCDS65995

Canonical transcript exons

ENST00000525077 — 9 exons

Exon	Start	End
ENSE00001362207	830621	830713
ENSE00001667883	828852	828963
ENSE00001732230	829360	829540
ENSE00002197732	827919	828772
ENSE00003497538	831224	831295
ENSE00003577996	831535	831986
ENSE00003663997	830866	831032
ENSE00003684145	830250	830337
ENSE00003692969	829986	830132

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 98.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1640 / max 1405.7544, expressed in 1179 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112304	2.3372	640
112291	1.2619	481
112290	1.1769	111
112292	0.6927	215
112293	0.2336	110
112298	0.1589	94
112303	0.1167	48
112295	0.0557	9
112297	0.0431	12
112299	0.0399	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.20	gold quality
mucosa of transverse colon	UBERON:0004991	97.29	gold quality
saliva-secreting gland	UBERON:0001044	96.13	gold quality
minor salivary gland	UBERON:0001830	96.02	gold quality
trachea	UBERON:0003126	95.97	gold quality
apex of heart	UBERON:0002098	95.47	gold quality
pancreatic ductal cell	CL:0002079	93.96	gold quality
parotid gland	UBERON:0001831	93.28	gold quality
body of stomach	UBERON:0001161	93.17	gold quality
mouth mucosa	UBERON:0003729	92.86	gold quality
transverse colon	UBERON:0001157	92.70	gold quality
nasal cavity epithelium	UBERON:0005384	92.68	gold quality
pylorus	UBERON:0001166	92.29	gold quality
nasal cavity mucosa	UBERON:0001826	92.05	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.20	gold quality
stomach	UBERON:0000945	91.08	gold quality
right uterine tube	UBERON:0001302	91.05	gold quality
fundus of stomach	UBERON:0001160	90.54	gold quality
small intestine	UBERON:0002108	89.37	gold quality
pancreas	UBERON:0001264	88.51	gold quality
bone marrow cell	CL:0002092	88.45	gold quality
skin of leg	UBERON:0001511	88.19	gold quality
heart left ventricle	UBERON:0002084	87.84	gold quality
skin of abdomen	UBERON:0001416	87.74	gold quality
right atrium auricular region	UBERON:0006631	87.71	gold quality
pituitary gland	UBERON:0000007	87.70	gold quality
prostate gland	UBERON:0002367	87.37	gold quality
adenohypophysis	UBERON:0002196	87.30	gold quality
cardiac ventricle	UBERON:0002082	87.29	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	107.23
E-ANND-3	yes	15.10
E-HCAD-1	yes	13.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting CRACR2B, 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-6793-5P	99.97	65.95	758
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-596	97.48	63.13	469
HSA-MIR-937-5P	97.43	68.39	667
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-6828-3P	96.06	67.61	1155

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cracr2b	ENSDARG00000053636
mus_musculus	Cracr2b	ENSMUSG00000048200
rattus_norvegicus	Cracr2b	ENSRNOG00000019199

Paralogs (1): CRACR2A (ENSG00000130038)

Protein

Protein identifiers

EF-hand calcium-binding domain-containing protein 4A — Q8N4Y2 (reviewed: Q8N4Y2)

Alternative names: Calcium release-activated calcium channel regulator 2B, Calcium release-activated channel regulator 2B

All UniProt accessions (5): E9PHZ8, E9PK04, E9PPF3, E9PRE5, Q8N4Y2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in store-operated Ca(2+) entry (SOCE).

Similarity. Belongs to the EFCAB4 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N4Y2-1	1	yes
Q8N4Y2-2	2
Q8N4Y2-3	3

RefSeq proteins (2): NP_001273535, NP_775855 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR051111	Ca-binding_regulatory	Family

UniProt features (17 total): splice variant 5, sequence variant 4, domain 2, region of interest 2, chain 1, coiled-coil region 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4Y2-F1	78.45	0.40

Functional residue map

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

Post-translational modifications (1): 3

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, RYTTCCTG_ETS2_B, DBP_Q6, OCT1_B, ISRE_01, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MCBRYAN_PUBERTAL_BREAST_4_5WK_UP, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, CHYLA_CBFA2T3_TARGETS_UP, OCT_Q6

GO Biological Process (1): store-operated calcium entry (GO:0002115)

GO Molecular Function (2): calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium ion transport	1
metal ion binding	1
binding	1

Protein interactions and networks

STRING

614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRACR2B	OR5H2	Q8NGV7	525
CRACR2B	STIM1	Q13586	505
CRACR2B	CFDP1	Q9UEE9	437
CRACR2B	ORAI2	Q96SN7	412
CRACR2B	NADK	O95544	410
CRACR2B	CMIP	Q8IY22	342
CRACR2B	NRIP2	Q9BQI9	340
CRACR2B	SARAF	Q96BY9	326
CRACR2B	STIMATE	Q86TL2	324
CRACR2B	CPEB4	Q17RY0	323
CRACR2B	RHOV	Q96L33	310
CRACR2B	NUDCD2	Q8WVJ2	310
CRACR2B	RERG	Q96A58	307
CRACR2B	ATP2B1	P20020	306
CRACR2B	MAN1A2	O60476	305

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TCEANC	CRACR2B	psi-mi:“MI:0915”(physical association)	0.560
CRACR2B	TCEANC	psi-mi:“MI:0915”(physical association)	0.560
IDH1	CRACR2B	psi-mi:“MI:0915”(physical association)	0.370
CRACR2B	CFTR	psi-mi:“MI:0915”(physical association)	0.370
CRACR2B	CARD19	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): CRACR2B (Two-hybrid), GHITM (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), CRACR2B (Two-hybrid), CRACR2B (Two-hybrid), CRACR2B (Two-hybrid), CRACR2B (Two-hybrid), CRACR2B (Two-hybrid), CRACR2B (Two-hybrid), CRACR2B (Two-hybrid), CRACR2B (Two-hybrid), CRACR2B (Two-hybrid), CRACR2B (Two-hybrid)

ESM2 similar proteins: A0A8I5KY20, A2A9T0, A2IDD5, B0BNK9, B8ZZ34, C9JI98, C9JLR9, F5GYI3, O18734, P0CG25, P84157, Q0IIA6, Q0PHV7, Q0X0E2, Q13387, Q1RMK9, Q2M3D2, Q2TAM9, Q3ZCQ3, Q4VA45, Q673H1, Q69YZ2, Q6NS60, Q6P6N5, Q6PJ61, Q7Z6J2, Q80ZJ8, Q810I0, Q86SX3, Q86UD0, Q86XT2, Q8BNN1, Q8IUW3, Q8N4Y2, Q8N6N2, Q8QZV0, Q8R4T5, Q8TF61, Q8VCR9, Q8WXF8

Diamond homologs: A0JP75, A1A600, B0BNK9, Q3UP38, Q7Z6P3, Q80ZJ8, Q8CB87, Q8N4Y2, Q9BSW2, Q619T5, A4FV54, C4YL11, F1PTE3, O00194, O23561, O24466, O42819, O95716, P07560, P0CY30, P0CY31, P10948, P11023, P16976, P17609, P20336, P20337, P20790, P20791, P22127, P22128, P24409, P28186, P28188, P35276, P35280, P35281, P35286, P35289, P36861

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1402 predictions. Top by Δscore:

Variant	Effect	Δscore
11:828769:GCAG:G	donor_gain	1.0000
11:828771:AGG:A	donor_loss	1.0000
11:828772:GGT:G	donor_loss	1.0000
11:828773:G:GG	donor_gain	1.0000
11:828774:T:A	donor_loss	1.0000
11:828944:G:GT	donor_gain	1.0000
11:829359:GGGAT:G	acceptor_gain	1.0000
11:829537:GCAA:G	donor_gain	1.0000
11:829541:G:GG	donor_gain	1.0000
11:830130:G:GT	donor_gain	1.0000
11:830130:GAGGT:G	donor_loss	1.0000
11:830132:GGTGA:G	donor_loss	1.0000
11:830133:GTGAG:G	donor_loss	1.0000
11:830134:T:G	donor_loss	1.0000
11:830710:GGAG:G	donor_gain	1.0000
11:830711:G:GT	donor_gain	1.0000
11:830711:GAG:G	donor_gain	1.0000
11:830711:GAGGT:G	donor_loss	1.0000
11:830712:AGGT:A	donor_loss	1.0000
11:830713:GGT:G	donor_loss	1.0000
11:830714:G:GG	donor_gain	1.0000
11:830714:GT:G	donor_loss	1.0000
11:830715:T:G	donor_loss	1.0000
11:831019:G:GT	donor_gain	1.0000
11:831222:A:AG	acceptor_gain	1.0000
11:831223:G:GG	acceptor_gain	1.0000
11:831223:GA:G	acceptor_gain	1.0000
11:831223:GAGAC:G	acceptor_gain	1.0000
11:831292:TCAG:T	donor_loss	1.0000
11:831293:CAGG:C	donor_loss	1.0000

AlphaMissense

2550 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:828900:T:C	F72L	0.994
11:828902:T:A	F72L	0.994
11:828902:T:G	F72L	0.994
11:828948:T:C	F88L	0.989
11:828950:C:A	F88L	0.989
11:828950:C:G	F88L	0.989
11:828719:T:C	F38L	0.988
11:828721:T:A	F38L	0.988
11:828721:T:G	F38L	0.988
11:828749:T:C	F48L	0.988
11:828751:C:A	F48L	0.988
11:828751:C:G	F48L	0.988
11:828949:T:C	F88S	0.984
11:828753:T:A	I49N	0.983
11:828720:T:G	F38C	0.980
11:828901:T:G	F72C	0.979
11:828720:T:C	F38S	0.977
11:828930:T:C	F82L	0.973
11:828932:C:A	F82L	0.973
11:828932:C:G	F82L	0.973
11:828901:T:C	F72S	0.972
11:828934:T:A	L83H	0.971
11:828949:T:G	F88C	0.971
11:828753:T:C	I49T	0.970
11:828753:T:G	I49S	0.968
11:828900:T:A	F72I	0.954
11:828768:T:C	L54P	0.951
11:831271:T:C	L334P	0.950
11:828937:C:T	T84I	0.946
11:831292:T:C	L341P	0.944

dbSNP variants (sampled 300 via entrez): RS1000058934 (11:824186 C>A,T), RS1000059149 (11:827974 C>A,T), RS1000118368 (11:827702 C>T), RS1000219575 (11:832081 GAATACAGGGA>G), RS1000889128 (11:828163 G>C), RS1001376421 (11:824412 A>G), RS1002262116 (11:832032 G>A), RS1002325221 (11:825485 G>T), RS1002657506 (11:832264 C>A,T), RS1003288336 (11:830309 G>A,C,T), RS1003672704 (11:831128 T>A,C), RS1003818589 (11:827048 T>C), RS1004020020 (11:829609 T>C), RS1004201438 (11:829626 T>A,C,G), RS1004308613 (11:825359 A>G)

Disease associations

OMIM: gene MIM:614177 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001762_163	Obesity-related traits	3.000000e-06
GCST002625_2	Chronic bronchitis and chronic obstructive pulmonary disease	5.000000e-08
GCST002625_9	Chronic bronchitis and chronic obstructive pulmonary disease	3.000000e-07
GCST008129_22	Body mass index	1.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Nickel	decreases expression	2
GSK-J4	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	increases expression	1
maleic acid	increases expression	1
ICG 001	increases expression	1
jinfukang	affects cotreatment, increases expression	1
trametinib	increases expression, affects cotreatment	1
NVP-BKM120	increases expression, affects cotreatment	1
Resveratrol	decreases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Arsenic	increases methylation	1
Aspirin	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Triiodothyronine	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression, increases methylation	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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