CANX

Summary

CANX (calnexin, HGNC:1473) is a protein-coding gene on chromosome 5q35.3, encoding Calnexin (P27824). Calcium-binding protein that interacts with newly synthesized monoglucosylated glycoproteins in the endoplasmic reticulum.

This gene encodes a member of the calnexin family of molecular chaperones. The encoded protein is a calcium-binding, endoplasmic reticulum (ER)-associated protein that interacts transiently with newly synthesized N-linked glycoproteins, facilitating protein folding and assembly. It may also play a central role in the quality control of protein folding by retaining incorrectly folded protein subunits within the ER for degradation. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 821 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 123 total — 2 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001746

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1473
Approved symbol	CANX
Name	calnexin
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	CNX, IP90, P90
Ensembl gene	ENSG00000127022
Ensembl biotype	protein_coding
OMIM	114217
Entrez	821

Gene structure

Transcript identifiers

Ensembl transcripts: 92 — 75 protein_coding, 11 nonsense_mediated_decay, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000247461, ENST00000452673, ENST00000502296, ENST00000502498, ENST00000502673, ENST00000503303, ENST00000504734, ENST00000506654, ENST00000509563, ENST00000513246, ENST00000514032, ENST00000679395, ENST00000679471, ENST00000679523, ENST00000679527, ENST00000679642, ENST00000679719, ENST00000680006, ENST00000680013, ENST00000680042, ENST00000680092, ENST00000680406, ENST00000680504, ENST00000680614, ENST00000680618, ENST00000680812, ENST00000680827, ENST00000680837, ENST00000680894, ENST00000680984, ENST00000680985, ENST00000681072, ENST00000681076, ENST00000681168, ENST00000681265, ENST00000681342, ENST00000681398, ENST00000681431, ENST00000681476, ENST00000681504, ENST00000681576, ENST00000681674, ENST00000681712, ENST00000681733, ENST00000681762, ENST00000681894, ENST00000681903, ENST00000903537, ENST00000903538, ENST00000903539, ENST00000903540, ENST00000903541, ENST00000903542, ENST00000903543, ENST00000903544, ENST00000903545, ENST00000903546, ENST00000903547, ENST00000903548, ENST00000903549, ENST00000938057, ENST00000938058, ENST00000938059, ENST00000938060, ENST00000938061, ENST00000938062, ENST00000938063, ENST00000938064, ENST00000938065, ENST00000938066, ENST00000938067, ENST00000938068, ENST00000938069, ENST00000938070, ENST00000938071, ENST00000938072, ENST00000938073, ENST00000938074, ENST00000938075, ENST00000938076, ENST00000938077, ENST00000949187, ENST00000949188, ENST00000949189, ENST00000949190, ENST00000949191, ENST00000949192, ENST00000949193, ENST00000949194, ENST00000949195, ENST00000949196, ENST00000949197

RefSeq mRNA: 11 — MANE Select: NM_001746 NM_001024649, NM_001363993, NM_001363994, NM_001363995, NM_001363996, NM_001363997, NM_001363998, NM_001363999, NM_001364000, NM_001364001, NM_001746

CCDS: CCDS4447, CCDS93837, CCDS93838, CCDS93839, CCDS93840

Canonical transcript exons

ENST00000247461 — 15 exons

Exon	Start	End
ENSE00002034845	179698967	179699102
ENSE00003480781	179720404	179720560
ENSE00003481218	179708978	179709059
ENSE00003483534	179708239	179708380
ENSE00003497532	179709873	179710065
ENSE00003504858	179722804	179723019
ENSE00003527186	179723660	179723779
ENSE00003561323	179726680	179726759
ENSE00003622798	179716105	179716294
ENSE00003647365	179706258	179706331
ENSE00003651503	179705679	179705852
ENSE00003654563	179719668	179719781
ENSE00003676231	179724657	179724783
ENSE00003692269	179707132	179707190
ENSE00003847647	179728591	179731641

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 410.8302 / max 2350.7294, expressed in 1828 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60554	401.8368	1828
60557	3.5389	1564
60555	1.9464	1227
60553	1.6208	886
60552	1.1180	579
60566	0.7692	358

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.68	gold quality
islet of Langerhans	UBERON:0000006	99.55	gold quality
calcaneal tendon	UBERON:0003701	99.54	gold quality
colonic epithelium	UBERON:0000397	99.51	gold quality
endometrium	UBERON:0001295	99.49	gold quality
adrenal tissue	UBERON:0018303	99.41	gold quality
bone marrow cell	CL:0002092	99.38	gold quality
ventricular zone	UBERON:0003053	99.35	gold quality
tonsil	UBERON:0002372	99.33	gold quality
smooth muscle tissue	UBERON:0001135	99.28	gold quality
corpus callosum	UBERON:0002336	99.28	gold quality
placenta	UBERON:0001987	99.26	gold quality
sural nerve	UBERON:0015488	99.26	gold quality
pancreas	UBERON:0001264	99.25	gold quality
body of pancreas	UBERON:0001150	99.08	gold quality
right lobe of thyroid gland	UBERON:0001119	99.04	gold quality
vermiform appendix	UBERON:0001154	99.04	gold quality
rectum	UBERON:0001052	99.01	gold quality
thyroid gland	UBERON:0002046	98.99	gold quality
left lobe of thyroid gland	UBERON:0001120	98.97	gold quality
monocyte	CL:0000576	98.94	gold quality
superior frontal gyrus	UBERON:0002661	98.94	gold quality
duodenum	UBERON:0002114	98.93	gold quality
bone marrow	UBERON:0002371	98.93	gold quality
bone element	UBERON:0001474	98.92	gold quality
embryo	UBERON:0000922	98.91	gold quality
uterus	UBERON:0000995	98.91	gold quality
ganglionic eminence	UBERON:0004023	98.91	gold quality
gall bladder	UBERON:0002110	98.88	gold quality
leukocyte	CL:0000738	98.83	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	14.13
E-CURD-11	no	1546.53
E-HCAD-31	no	19.49
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

200 targeting CANX, 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-190A-3P	100.00	80.35	5520
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-144-3P	99.94	73.98	2698

Literature-anchored findings (GeneRIF, showing 40)

• Data show that CD1d associates in the ER with both calnexin and calreticulin and with the thiol oxidoreductase ERp57 in a manner dependent on glucose trimming of its N-linked glycans. (PMID:12239218)
• EDEM appeared to function in the ERAD (endoplasmic reticulum-associated degradation)pathway by accepting substrates from calnexin. (PMID:12610305)
• EDEM was shown to extract misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle (PMID:12610306)
• Data show that calnexin associates with newly synthesized proteolipid protein (PLP) molecules, binding stably to misfolded PLP. (PMID:12805210)
• calnexin-downregulation may contribute to the metastatic phenotype of melanoma cells in vivo (PMID:14732231)
• Calnexin provides long-term protection of wild-type Shaker protein from ER-associated degradation. (PMID:15161937)
• the contribution of both the b and b’ domains to the binding with CNX and calreticulin was revealed (PMID:15236594)
• results support emerging models for a glycan-independent chaperone role for calnexin and for the mechanism of retention of misfolded membrane proteins in the endoplasmic reticulum (PMID:15537650)
• Calnexin decreases with aging and might contribute to a cytoprotection in a variety of human age-related diseases. (PMID:15557823)
• Data show that the major degradation pathway of the cystic fibrosis transmembrane conductance regulator with F508 deletion from the endoplasmic reticulum is independent of calnexin. (PMID:15923638)
• Calnexin associates with the neonatal Fc receptor for IgG (FcRn) heavy chain before it associates noncovalently with beta 2-microglobulin. (PMID:16002696)
• Polypeptide substrate recognition by CANX requires specific conformations of the CANX protein. (PMID:16061483)
• alphaIIb interacts with calnexin via its N15-linked glycan, and alphaIIbbeta3 biogenesis is partially controlled by engagement of alphaIIb in the calnexin cycle. (PMID:16304048)
• We characterized a molecular mechanism by which calnexin regulates ER-stress-mediated apoptosis in a manner independent of its chaperone functions but dependent of its binding to Bap31. (PMID:16858427)
• Here, we have observed that NCT N-linked oligosaccharides mediated specific interactions with the secretory pathway lectins calnexin and ERGIC-53 (PMID:16938437)
• proportion of the human and the rat WT gonadotropin-releasing hormone receptor appears to be retained in the endoplasmic reticulum by calnexin, an effect that decreases GnRHR signaling capacity (PMID:17170088)
• These results suggest that MCF-7 resistance to endoplasmic reticulum stress-induced apoptosis is partially mediated by the expression level of calnexin which in turn controls its sub-cellular localization, and its association with Bap31. (PMID:17203246)
• D1 and D2 dopamine receptor expression is regulated by direct interaction with the chaperone protein calnexin (PMID:17395585)
• Endoplasmic reticulum chaperones stabilize nicotinic receptor subunits and regulate receptor assembly. (PMID:17728248)
• Interaction with calnexin led to accumulation of GAT1 in concentric bodies corresponding to previously described multilamellar ER-derived structures. (PMID:18367207)
• the phosphorylation state of the calnexin cytosolic domain and its interaction with PACS-2 sort the chaperone between domains of the ER and the plasma membrane (PMID:18417615)
• A dependence on calnexin for proper assembly of CFTR’s membrane spanning domains, was identified. (PMID:18716059)
• The uncleaved 12-kDa form of p12(I) resides in the ER and interacts with the beta and gamma(c) chains of the interleukin-2 receptor (IL-2R), the heavy chain of the major histocompatibility complex (MHC) class I, as well as calreticulin and calnexin. (PMID:18791162)
• ERp57 must be physically associated with the calnexin cycle to catalyze isomerization reactions with most of its substrates (PMID:19054761)
• Data show that The cell surface expression levels of (ICAM)-2 and -3 on the apoptotic cells were markedly lower, while those of calnexin, calreticulin, and (LAMP)-1 and -2 were significantly higher compared to non-apoptotic cells. (PMID:19524015)
• Data show that demonstrate that Cnx preferentially associates with misfolded mutant opsins associated with retinitis pigmentosa. (PMID:19801547)
• Results show that the phosphorylation of calnexin is linked to the efficiency of secretion of the cargo glycoprotein, in this case, alpha1-antitrypsin. (PMID:19815548)
• Env interacts with intracellular CNX and extracellular PDI via discrete, largely nonoverlapping, regions. (PMID:20202930)
• calnexin could bind PrP both in vitro and in vivo; calnexin prevents caspase-3-mediated cytotoxicity induced by PrP (PMID:20506117)
• human delta opioid receptor (hdeltaOR) exists in a ternary complex with SERCA2b and the ER molecular chaperone calnexin (PMID:20528919)
• Transmembrane segments prevent surface expression of sodium channel Nav1.8 and promote calnexin-dependent channel degradation (PMID:20720009)
• Results reveal the P-domain functions as a unique protein-protein interaction domain and implicate a peptidyl prolyl isomerase as a new element in the calnexin cycle. (PMID:20801878)
• Nixin/ZNRF4 to be central for the regulation of calnexin turnover. (PMID:21205830)
• HLA-I, TAP1, CNX, LMP7, Erp57, Tapasin and ERAP1 were down-regulated in 68%, 44%, 48%, 40%, 52%, 32% and 20% of esophageal squamous cell carcinoma lesions then, respectively. (PMID:21362330)
• cysteine residues within calnexin are important for the structure and function of calnexin. (PMID:21842374)
• The data suggest that patients with low or defective TAP1 or calnexin in primary breast cancers may be at higher risks for developing brain metastasis due to the defects in T cell-based immunosurveillance. (PMID:22065046)
• The findings showed that calnexin is a stable component of the ribosome-translocon complex in a manner that is exquisitely dependent on calnexin’s palmitoylation status. (PMID:22314232)
• These findings demonstrated that calnexin strictly monitors the maturation of S protein by its direct binding, resulting in conferring infectivity on severe acute respiratory syndrome coronavirus. (PMID:22915798)
• calnexin tunes the cellular responses to epidermal growth factor receptor in a manner that depends on the health status of the endoplasmic reticulum (PMID:23932718)
• Soluble calnexin may fulfill functions similar to calreticulin. (PMID:24056258)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	canx	ENSDARG00000037488
mus_musculus	Canx	ENSMUSG00000020368
rattus_norvegicus	Canx	ENSRNOG00000003343
drosophila_melanogaster	Cnx99A	FBGN0015622
drosophila_melanogaster	CG1924	FBGN0030377
caenorhabditis_elegans		WBGENE00000567

Paralogs (3): CLGN (ENSG00000153132), CALR (ENSG00000179218), CALR3 (ENSG00000269058)

Protein

Protein identifiers

Calnexin — P27824 (reviewed: P27824)

Alternative names: IP90, Major histocompatibility complex class I antigen-binding protein p88, p90

All UniProt accessions (22): P27824, A0A7P0T840, A0A7P0T8G1, A0A7P0T8N1, A0A7P0T937, A0A7P0T9L0, A0A7P0T9S1, A0A7P0T9S4, A0A7P0TA04, A0A7P0TAE9, A0A7P0TAN9, A0A7P0TAR9, A0A7P0TB65, A0A7P0Z484, A0A7P0Z4D6, A0A7P0Z4H2, D6RAQ8, D6RAU8, D6RD16, D6RFL1, D6RFW4, D6RGY2

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-binding protein that interacts with newly synthesized monoglucosylated glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins. Associated with partial T-cell antigen receptor complexes that escape the ER of immature thymocytes, it may function as a signaling complex regulating thymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at the synapse.

Subunit / interactions. Interacts with MAPK3/ERK1. Interacts with KCNH2. Associates with ribosomes. Interacts with SGIP1; involved in negative regulation of endocytosis. The palmitoylated form interacts with the ribosome-translocon complex component SSR1, promoting efficient folding of glycoproteins. Interacts with SERPINA2P/SERPINA2 and with the S and Z variants of SERPINA1. Interacts with PPIB. Interacts with ZNRF4. Interacts with SMIM22. Interacts with TMX2. Interacts with TMEM35A/NACHO. Interacts with CHRNA7. Interacts with reticulophagy regulators RETREG2 and RETREG3. Interacts with DNM1L; may form part of a larger protein complex at the ER-mitochondrial interface during mitochondrial fission. Interacts with ADAM7. (Microbial infection) Interacts with HBV large envelope protein, isoform L. (Microbial infection) Interacts with HBV large envelope protein, isoform M; this association may be essential for isoform M proper secretion.

Subcellular location. Endoplasmic reticulum membrane. Mitochondrion membrane. Melanosome membrane.

Post-translational modifications. Phosphorylated at Ser-564 by MAPK3/ERK1. Phosphorylation by MAPK3/ERK1 increases its association with ribosomes. Palmitoylation by DHHC6 leads to the preferential localization to the perinuclear rough ER. It mediates the association of calnexin with the ribosome-translocon complex (RTC) which is required for efficient folding of glycosylated proteins. Ubiquitinated, leading to proteasomal degradation. Probably ubiquitinated by ZNRF4.

Similarity. Belongs to the calreticulin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P27824-1	1	yes
P27824-2	2
P27824-3	3

RefSeq proteins (11): NP_001019820, NP_001350922, NP_001350923, NP_001350924, NP_001350925, NP_001350926, NP_001350927, NP_001350928, NP_001350929, NP_001350930, NP_001737* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001580	Calret/calnex	Family
IPR009033	Calreticulin/calnexin_P_dom_sf	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR018124	Calret/calnex_CS	Conserved_site

Pfam: PF00262

UniProt features (45 total): repeat 8, binding site 8, region of interest 7, modified residue 5, compositionally biased region 3, sequence conflict 3, topological domain 2, lipid moiety-binding region 2, disulfide bond 2, splice variant 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P27824-F1	77.15	0.39

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 (8): 74; 117; 164; 166; 185; 192; 425; 436

Post-translational modifications (7): 137, 554, 562, 564, 583, 502, 503

Disulfide bonds (2): 160–194, 360–366

Function

Pathways and Gene Ontology

Reactome pathways

31 pathways

ID	Pathway
R-HSA-168316	Assembly of Viral Components at the Budding Site
R-HSA-2132295	MHC class II antigen presentation
R-HSA-8984722	Interleukin-35 Signalling
R-HSA-901042	Calnexin/calreticulin cycle
R-HSA-9020956	Interleukin-27 signaling
R-HSA-9683686	Maturation of spike protein
R-HSA-9694548	Maturation of spike protein
R-HSA-9768727	Regulation of CDH1 posttranslational processing and trafficking to plasma membrane
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC
R-HSA-9918432	Maturation of DENV proteins
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-1643685	Disease
R-HSA-168255	Influenza Infection
R-HSA-168256	Immune System
R-HSA-168268	Virus Assembly and Release
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-532668	N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-9678108	SARS-CoV-1 Infection
R-HSA-9679506	SARS-CoV Infections
R-HSA-9683701	Translation of Structural Proteins
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9694635	Translation of Structural Proteins
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 436 (showing top): MORF_MTA1, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, HORIUCHI_WTAP_TARGETS_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, MORF_MBD4, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, MODULE_151, CMYB_01, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS

GO Biological Process (7): protein folding (GO:0006457), protein secretion (GO:0009306), viral protein processing (GO:0019082), protein folding in endoplasmic reticulum (GO:0034975), ERAD pathway (GO:0036503), synaptic vesicle endocytosis (GO:0048488), clathrin-dependent endocytosis (GO:0072583)

GO Molecular Function (6): RNA binding (GO:0003723), calcium ion binding (GO:0005509), carbohydrate binding (GO:0030246), obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (13): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), nuclear membrane (GO:0031965), mitochondrial membrane (GO:0031966), melanosome membrane (GO:0033162), mitochondria-associated endoplasmic reticulum membrane contact site (GO:0044233), endoplasmic reticulum quality control compartment (GO:0044322), extracellular exosome (GO:0070062), lumenal side of endoplasmic reticulum membrane (GO:0098553), presynapse (GO:0098793), mitochondrion (GO:0005739)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Interleukin-12 family signaling	2
Immune System	2
Virus Assembly and Release	1
Adaptive Immune System	1
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1
Translation of Structural Proteins	1
Regulation of CDH1 Expression and Function	1
Class I MHC mediated antigen processing & presentation	1
Dengue Virus Genome Translation and Replication	1
Viral Infection Pathways	1
Influenza Infection	1
Post-translational protein modification	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle membrane	3
cellular anatomical structure	3
binding	2
cytoplasm	2
intracellular membrane-bounded organelle	2
endoplasmic reticulum	2
cellular process	1
protein maturation	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
viral process	1
viral gene expression	1
protein folding	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
receptor-mediated endocytosis	1
nucleic acid binding	1
metal ion binding	1
cation binding	1
endomembrane system	1
intracellular organelle lumen	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
nucleus	1
nuclear envelope	1
mitochondrion	1
mitochondrial envelope	1
melanosome	1
chitosome	1
pigment granule membrane	1
organelle membrane contact site	1
extracellular vesicle	1
endoplasmic reticulum membrane	1
lumenal side of membrane	1
synapse	1

Protein interactions and networks

STRING

5544 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CANX	PDIA3	P30101	998
CANX	TAPBP	O15533	993
CANX	CALR	P27797	988
CANX	HSPA5	P11021	982
CANX	OS9	Q13438	949
CANX	PACS2	Q86VP3	948
CANX	P4HB	P07237	945
CANX	ERLEC1	Q96DZ1	942
CANX	HSP90B1	P14625	936
CANX	EDEM1	Q92611	932
CANX	PPIB	P23284	926
CANX	FUNDC1	Q8IVP5	916
CANX	SEL1L	Q9UBV2	904
CANX	VCP	P55072	902
CANX	UGGT1	Q9NYU2	898

IntAct

635 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DNASE2	CANX	psi-mi:“MI:0915”(physical association)	0.690
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
CHST15	CANX	psi-mi:“MI:0915”(physical association)	0.670
LNPEP	CANX	psi-mi:“MI:0914”(association)	0.640
CHST14	CANX	psi-mi:“MI:0914”(association)	0.640
EMC1	EMC8	psi-mi:“MI:0914”(association)	0.640
CANX	env	psi-mi:“MI:0915”(physical association)	0.620
ABCA1	CANX	psi-mi:“MI:0915”(physical association)	0.580
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
CANX	CYB5R3	psi-mi:“MI:0915”(physical association)	0.560
Tor1aip1	CANX	psi-mi:“MI:0915”(physical association)	0.560
CLU	CANX	psi-mi:“MI:0914”(association)	0.530
MTNR1A	PGRMC1	psi-mi:“MI:0914”(association)	0.530
MTNR1B	IRS4	psi-mi:“MI:0914”(association)	0.530
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
ST8SIA3	KLRG2	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
CCNJL	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
UST	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CD1B	TOR1B	psi-mi:“MI:0914”(association)	0.530

BioGRID (1840): CANX (Affinity Capture-MS), CANX (Affinity Capture-MS), CANX (Co-fractionation), CANX (Affinity Capture-Western), CANX (Affinity Capture-MS), CANX (Affinity Capture-MS), CANX (Affinity Capture-MS), CANX (Affinity Capture-MS), CANX (Affinity Capture-MS), CANX (Affinity Capture-MS), CANX (Affinity Capture-MS), CANX (Affinity Capture-MS), CANX (Affinity Capture-MS), CANX (Affinity Capture-MS), CANX (Affinity Capture-MS)

ESM2 similar proteins: A0A0D1C6P2, A8XA40, D4AVD4, E2RA18, J9VLH0, O04151, O04153, O14967, O18750, O81919, O82709, P08110, P11012, P14625, P24643, P27798, P27824, P29402, P29413, P34652, P35564, P35565, P36581, P41148, P52194, P83003, P93508, Q06814, Q23858, Q29092, Q2TBR8, Q38798, Q38858, Q39817, Q39994, Q3SYT6, Q40401, Q4R520, Q5R440, Q5R6F7

Diamond homologs: A0A0D1C6P2, A8XA40, D4AVD4, E2RA18, J9VLH0, O04151, O04153, O14967, O81919, O82709, P11012, P14211, P15253, P18418, P24643, P27797, P27798, P27824, P27825, P28491, P29402, P29413, P34652, P35564, P35565, P36581, P52193, P52194, P83003, P93508, Q06814, Q23858, Q2HWU3, Q2TBR8, Q38798, Q38858, Q39817, Q39994, Q3SYT6, Q40401

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	87
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
146233	GRCh38/hg38 5q34-35.3(chr5:164386701-181269805)x3	Pathogenic
686512	GRCh37/hg19 5q35.3(chr5:176848982-180719789)x3	Pathogenic
145959	GRCh38/hg38 5q35.3(chr5:179669736-180897169)x1	Likely pathogenic

SpliceAI

2067 predictions. Top by Δscore:

Variant	Effect	Δscore
5:179702364:T:G	donor_gain	1.0000
5:179702364:T:TG	donor_gain	1.0000
5:179705672:T:G	acceptor_gain	1.0000
5:179705675:GTAG:G	acceptor_loss	1.0000
5:179705676:TA:T	acceptor_loss	1.0000
5:179705677:A:AG	acceptor_gain	1.0000
5:179705677:AG:A	acceptor_loss	1.0000
5:179705678:G:A	acceptor_loss	1.0000
5:179705678:G:GT	acceptor_gain	1.0000
5:179705678:GA:G	acceptor_gain	1.0000
5:179705678:GAT:G	acceptor_gain	1.0000
5:179705678:GATC:G	acceptor_gain	1.0000
5:179705849:CAAGG:C	donor_loss	1.0000
5:179705851:AGG:A	donor_loss	1.0000
5:179705852:GGT:G	donor_loss	1.0000
5:179705853:G:A	donor_loss	1.0000
5:179706330:GG:G	donor_gain	1.0000
5:179706331:GG:G	donor_gain	1.0000
5:179707126:TTACA:T	acceptor_loss	1.0000
5:179707127:TACAG:T	acceptor_loss	1.0000
5:179707129:CAG:C	acceptor_loss	1.0000
5:179707130:A:AG	acceptor_gain	1.0000
5:179707130:A:C	acceptor_loss	1.0000
5:179707130:AGGT:A	acceptor_gain	1.0000
5:179707130:AGGTG:A	acceptor_gain	1.0000
5:179707131:G:GT	acceptor_gain	1.0000
5:179707131:GGT:G	acceptor_gain	1.0000
5:179707131:GGTG:G	acceptor_gain	1.0000
5:179707131:GGTGG:G	acceptor_gain	1.0000
5:179707187:GATG:G	donor_gain	1.0000

AlphaMissense

3959 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:179708239:G:A	G102E	1.000
5:179708244:T:A	W104R	1.000
5:179708244:T:C	W104R	1.000
5:179708316:C:G	H128D	1.000
5:179709009:T:A	C160S	1.000
5:179709009:T:C	C160R	1.000
5:179709010:G:A	C160Y	1.000
5:179709010:G:C	C160S	1.000
5:179709011:T:G	C160W	1.000
5:179709912:G:C	G190R	1.000
5:179709913:G:A	G190D	1.000
5:179709918:G:C	D192H	1.000
5:179709924:T:A	C194S	1.000
5:179709924:T:C	C194R	1.000
5:179709925:G:A	C194Y	1.000
5:179709925:G:C	C194S	1.000
5:179709945:C:G	H201D	1.000
5:179710063:T:C	L240P	1.000
5:179719780:T:A	W342R	1.000
5:179719780:T:C	W342R	1.000
5:179720404:G:C	W342C	1.000
5:179720404:G:T	W342C	1.000
5:179720426:T:A	W350R	1.000
5:179720426:T:C	W350R	1.000
5:179720428:G:C	W350C	1.000
5:179720428:G:T	W350C	1.000
5:179722900:T:A	W427R	1.000
5:179722900:T:C	W427R	1.000
5:179722902:G:C	W427C	1.000
5:179722902:G:T	W427C	1.000

dbSNP variants (sampled 300 via entrez): RS1000076858 (5:179715725 T>A), RS1000126546 (5:179709614 C>T), RS1000132233 (5:179680792 G>A), RS1000146980 (5:179714499 CTTT>C,CT,CTT), RS1000202930 (5:179684941 T>A,G), RS1000222779 (5:179685821 T>A,C,G), RS1000264105 (5:179719980 C>T), RS1000361202 (5:179703683 T>G), RS1000402588 (5:179698414 A>G), RS1000422582 (5:179685368 C>G,T), RS1000457199 (5:179692326 C>G,T), RS1000484415 (5:179714245 C>G), RS1000504706 (5:179725077 C>A,T), RS1000538720 (5:179686314 T>A,G), RS1000555317 (5:179684267 G>C)

Disease associations

OMIM: gene MIM:114217 | disease phenotypes: MIM:105550, MIM:602080

GenCC curated gene-disease

Mondo (2): frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (MONDO:0007105), Paget disease of bone 2, early-onset (MONDO:0011183)

Orphanet (1): Frontotemporal dementia with motor neuron disease (Orphanet:275872)

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002398_1	Resting heart rate	9.000000e-09
GCST003518_46	Daytime sleep phenotypes	1.000000e-06
GCST003518_7	Daytime sleep phenotypes	7.000000e-07
GCST004610_6	White blood cell count	2.000000e-10
GCST004626_86	Myeloid white cell count	6.000000e-10
GCST90002388_336	Lymphocyte count	9.000000e-11
GCST90002398_12	Neutrophil count	4.000000e-18
GCST90002407_227	White blood cell count	1.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0004587	lymphocyte count
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2719 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.25	Kd	5637	nM	CHEMBL3752910
5.25	ED50	5637	nM	CHEMBL3752910
5.02	Kd	9625	nM	CHEMBL5653589
5.02	ED50	9625	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147988: Binding affinity to human CANX incubated for 45 mins by Kinobead based pull down assay	kd	5.6367	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147988: Binding affinity to human CANX incubated for 45 mins by Kinobead based pull down assay	kd	9.6251	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	4
Valproic Acid	increases expression, affects expression, affects cotreatment	4
Thapsigargin	affects localization, increases expression	4
Arsenic Trioxide	decreases reaction, decreases expression, increases expression	3
Tunicamycin	decreases reaction, increases expression	3
sodium arsenite	decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	decreases expression, affects cotreatment, increases expression	2
Doxorubicin	affects expression, decreases expression	2
Fluorouracil	affects cotreatment, decreases response to substance, affects reaction, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
NMS-873	increases expression	1
beta-N-methylamino-L-alanine	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
uranyl acetate	affects expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	increases expression	1
nickel sulfate	decreases expression	1
ursodoxicoltaurine	decreases reaction, increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
dinophysistoxin 1	increases expression	1
miglustat	affects binding, decreases reaction	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651030	Binding	Binding affinity to human CANX incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TF	Abcam HEK293T CANX KO	Transformed cell line	Female
CVCL_SG75	HAP1 CANX (-) 1	Cancer cell line	Male
CVCL_SG76	HAP1 CANX (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02964637	Not specified	RECRUITING	Diagnosing Frontotemporal Lobar Degeneration
NCT06051123	Not specified	RECRUITING	Effects of Probiotics in Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Spectrum Disorder (ALS-FTDSD) Patients