CNN3

Summary

CNN3 (calponin 3, HGNC:2157) is a protein-coding gene on chromosome 1p21.3, encoding Calponin-3 (Q15417). Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction.

This gene encodes a protein with a markedly acidic C terminus; the basic N-terminus is highly homologous to the N-terminus of a related gene, CNN1. Members of the CNN gene family all contain similar tandemly repeated motifs. This encoded protein is associated with the cytoskeleton but is not involved in contraction.

Source: NCBI Gene 1266 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 33 total — 1 pathogenic
• MANE Select transcript: NM_001839

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2157
Approved symbol	CNN3
Name	calponin 3
Location	1p21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000117519
Ensembl biotype	protein_coding
OMIM	602374
Entrez	1266

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000370206, ENST00000394202, ENST00000415017, ENST00000461018, ENST00000474409, ENST00000487539, ENST00000545882, ENST00000885995, ENST00000885996, ENST00000939684, ENST00000939685

RefSeq mRNA: 3 — MANE Select: NM_001839 NM_001286055, NM_001286056, NM_001839

CCDS: CCDS30775, CCDS65592, CCDS65593

Canonical transcript exons

ENST00000370206 — 7 exons

Exon	Start	End
ENSE00001887536	94896957	94898083
ENSE00001928046	94926838	94927110
ENSE00003477154	94899371	94899517
ENSE00003523278	94902121	94902258
ENSE00003527145	94901669	94901785
ENSE00003643594	94903122	94903188
ENSE00003661769	94903403	94903524

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 238.6389 / max 1615.8375, expressed in 1474 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13424	221.4853	1469
13423	15.8935	1343
13422	0.9221	347
13421	0.2203	87
13425	0.1178	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.68	gold quality
calcaneal tendon	UBERON:0003701	99.50	gold quality
ganglionic eminence	UBERON:0004023	99.39	gold quality
left adrenal gland	UBERON:0001234	99.28	gold quality
right adrenal gland	UBERON:0001233	99.26	gold quality
tibial nerve	UBERON:0001323	99.25	gold quality
body of uterus	UBERON:0009853	99.23	gold quality
left adrenal gland cortex	UBERON:0035825	99.22	gold quality
right adrenal gland cortex	UBERON:0035827	99.19	gold quality
left uterine tube	UBERON:0001303	99.12	gold quality
right lung	UBERON:0002167	99.07	gold quality
metanephros cortex	UBERON:0010533	99.07	gold quality
ectocervix	UBERON:0012249	99.03	gold quality
adrenal gland	UBERON:0002369	99.01	gold quality
colonic epithelium	UBERON:0000397	99.00	gold quality
adrenal tissue	UBERON:0018303	99.00	gold quality
upper lobe of left lung	UBERON:0008952	98.98	gold quality
gall bladder	UBERON:0002110	98.94	gold quality
right coronary artery	UBERON:0001625	98.93	gold quality
left ovary	UBERON:0002119	98.93	gold quality
left coronary artery	UBERON:0001626	98.91	gold quality
right ovary	UBERON:0002118	98.88	gold quality
stromal cell of endometrium	CL:0002255	98.87	gold quality
oocyte	CL:0000023	98.86	gold quality
adrenal cortex	UBERON:0001235	98.78	gold quality
ascending aorta	UBERON:0001496	98.77	gold quality
thoracic aorta	UBERON:0001515	98.77	gold quality
upper lobe of lung	UBERON:0008948	98.76	gold quality
left lobe of thyroid gland	UBERON:0001120	98.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.67	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 30.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1749.93
E-GEOD-84465	yes	1516.07
E-MTAB-9154	yes	1367.08
E-MTAB-8142	yes	1333.38
E-MTAB-9435	yes	1308.70
E-MTAB-11121	yes	1000.38
E-HCAD-10	yes	907.43
E-HCAD-1	yes	78.42
E-MTAB-6701	yes	64.60
E-MTAB-8410	yes	56.77
E-MTAB-10553	yes	51.91
E-HCAD-5	yes	37.25
E-HCAD-11	yes	35.91
E-MTAB-7316	yes	33.09
E-GEOD-137537	yes	32.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting CNN3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-5700	99.64	69.88	2280

Literature-anchored findings (GeneRIF, showing 12)

• These results suggest a role of calponin 3 in the regulation of Bone morphogenetic proteins -dependent cellular responses. (PMID:17825283)
• Gene rearrangements of CNN3 is associated with mucosa-associated lymphoid tissue lymphoma. (PMID:18927281)
• Results indicate that CNN3 regulates actin cytoskeleton rearrangement which is required for the plasma membranes of trophoblasts to become fusion competent. (PMID:20861310)
• The mRNA and protein level of calponin-3 were increase expression in brain in patiens with epilepsy. (PMID:22119193)
• Participates in actin stress fiber remodeling (PMID:23545751)
• CNN3 as a new pro-invasive protein in trophoblast cells that is induced under low oxygen conditions. (PMID:25050546)
• overexpressed CNN3 during sonic vibration increases expression of glutamate receptors and promotes functional neural differentiation of human umbilical cords-mesenchymal stem cells. (PMID:26175098)
• These results reveal the importance of the MEKK1-calponin-3 signaling pathway to cell contractility. (PMID:27528401)
• Cnn3 depletion resulted in increased and uncoordinated contractility of stress fibers that often led to breakage of individual actomyosin bundles within the stress fiber network. (PMID:30518778)
• CNN3 acts as a potential oncogene in cervical cancer by affecting RPLP1 mRNA expression. (PMID:32051425)
• Calponin 3 is associated with poor prognosis and regulates proliferation and metastasis in osteosarcoma. (PMID:32667904)
• Calponin 3 Acts as a Potential Diagnostic and Prognostic Marker and Promotes Glioma Cell Proliferation, Migration, and Invasion. (PMID:35792226)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnn3b	ENSDARG00000029856
danio_rerio	cnn3a	ENSDARG00000099510
mus_musculus	Cnn3	ENSMUSG00000053931
rattus_norvegicus	Cnn3	ENSRNOG00000011559
caenorhabditis_elegans		WBGENE00000778
caenorhabditis_elegans	cpn-3	WBGENE00000779
caenorhabditis_elegans	cpn-4	WBGENE00000780

Paralogs (5): CNN2 (ENSG00000064666), CNN1 (ENSG00000130176), TAGLN3 (ENSG00000144834), TAGLN (ENSG00000149591), TAGLN2 (ENSG00000158710)

Protein

Protein identifiers

Calponin-3 — Q15417 (reviewed: Q15417)

Alternative names: Calponin, acidic isoform

All UniProt accessions (2): E9PDU6, Q15417

UniProt curated annotations — full annotation on UniProt →

Function. Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity.

Tissue specificity. Expressed in both non-smooth muscle tissues as well as smooth muscle tissues.

Similarity. Belongs to the calponin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15417-1	1	yes
Q15417-2	2
Q15417-3	3

RefSeq proteins (3): NP_001272984, NP_001272985, NP_001830* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000557	Calponin_repeat	Repeat
IPR001715	CH_dom	Domain
IPR001997	Calponin/LIMCH1	Family
IPR003096	SM22_calponin	Family
IPR036872	CH_dom_sf	Homologous_superfamily
IPR050606	Calponin-like	Family

Pfam: PF00307, PF00402

UniProt features (13 total): repeat 3, modified residue 3, splice variant 2, chain 1, domain 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15417-F1	67.78	0.33

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 (3): 23, 158, 323

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 332 (showing top): MODULE_52, GOBP_EPITHELIUM_DEVELOPMENT, BOYLAN_MULTIPLE_MYELOMA_PCA1_DN, KAAB_FAILED_HEART_ATRIUM_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, CTATGCA_MIR153, CHX10_01, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_CELL_CELL_ADHESION, MODULE_118, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN

GO Biological Process (4): actin filament organization (GO:0007015), epithelial cell differentiation (GO:0030855), actomyosin structure organization (GO:0031032), cell-cell adhesion (GO:0098609)

GO Molecular Function (5): calmodulin binding (GO:0005516), actin filament binding (GO:0051015), cadherin binding involved in cell-cell adhesion (GO:0098641), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (4): cytosol (GO:0005829), adherens junction (GO:0005912), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
actin cytoskeleton organization	2
supramolecular fiber organization	1
cell differentiation	1
epithelium development	1
cell adhesion	1
protein binding	1
actin binding	1
protein-containing complex binding	1
cadherin binding	1
cell-cell adhesion	1
cell-cell adhesion mediator activity	1
cytoskeletal protein binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1
cell-cell junction	1
cell-substrate junction	1
cytoskeleton	1

Protein interactions and networks

STRING

3314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNN3	VCL	P18206	637
CNN3	CALML4	Q96GE6	559
CNN3	CALM1	P02593	509
CNN3	CALML3	P27482	509
CNN3	CALML5	Q9NZT1	509
CNN3	CALML6	Q8TD86	483
CNN3	DSTN	P18282	456
CNN3	TMOD3	Q9NYL9	454
CNN3	EGFR	P00533	427
CNN3	PDLIM4	P50479	425
CNN3	PLEC	Q15149	410
CNN3	PBXIP1	Q96AQ6	407
CNN3	SMTN	P53814	404
CNN3	MYH11	P35749	391
CNN3	RSPH1	Q8WYR4	389

IntAct

59 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CNN2	ATE1	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
CNN3	CARM1	psi-mi:“MI:0915”(physical association)	0.400
CNN3	CRMP1	psi-mi:“MI:0915”(physical association)	0.400
CNN3	F2RL1	psi-mi:“MI:0915”(physical association)	0.370
CNN3	rep	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
HSPA8	PPP6C	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
SLX4	SMAP	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
HDAC1	ZBTB43	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
TEC	SEC16A	psi-mi:“MI:0914”(association)	0.350
SCYL3	PPIH	psi-mi:“MI:0914”(association)	0.350
ATG5	IGKV1-5	psi-mi:“MI:0914”(association)	0.350
GABARAPL1	GABARAP	psi-mi:“MI:0914”(association)	0.350

BioGRID (104): CNN3 (Affinity Capture-MS), CARM1 (Affinity Capture-MS), CNN3 (Co-fractionation), MTHFD1L (Co-fractionation), CNN3 (Affinity Capture-MS), CNN3 (Affinity Capture-MS), CNN3 (Proximity Label-MS), CNN3 (Affinity Capture-MS), CNN3 (Affinity Capture-MS), CARM1 (Affinity Capture-MS), CNN3 (Affinity Capture-MS), CNN3 (Affinity Capture-MS), CNN3 (Affinity Capture-MS), CNN3 (Affinity Capture-MS), CNN3 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0G2UGT2, A0A0P0E482, A0A2Z6UD27, A0A646QV53, A7EWX9, A7XUK7, B3EWR1, B8WI85, C0HK25, C0HL90, H2FH31, O18423, O18424, O61064, O74703, O77009, P08696, P09334, P09335, P09336, P09338, P19616, P26932, P40483, P49714, P51911, P55296, P80708, P84331, Q00801, Q00802, Q05097, Q08091, Q08092, Q08290, Q15417, Q27084, Q2HJ38, Q32L92, Q3LX99

Diamond homologs: B9EUM5, O14185, O14188, P14318, P19966, P26932, P31232, P37397, P37802, P37803, P37804, P37805, P46940, P51911, Q01995, Q08091, Q08092, Q08093, Q08094, Q08290, Q08873, Q12280, Q15052, Q15417, Q24799, Q2HJ38, Q32L92, Q3SYU6, Q3ZBY2, Q4R5J4, Q54TK8, Q55E26, Q55GV9, Q5AH02, Q5E9F5, Q5R6R2, Q5RFN6, Q5XFX0, Q5XXR3, Q5ZLR6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
BTK	“up-regulates quantity”	CNN3	phosphorylation
FYN	“down-regulates activity”	CNN3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1073069	NC_000001.10:g.(?94458793)(95538454_?)del	Pathogenic

SpliceAI

1010 predictions. Top by Δscore:

Variant	Effect	Δscore
1:94899365:GCTTA:G	donor_loss	1.0000
1:94899366:CTTAC:C	donor_loss	1.0000
1:94899367:TTAC:T	donor_loss	1.0000
1:94899368:TA:T	donor_loss	1.0000
1:94899369:A:AG	donor_loss	1.0000
1:94899370:CCTGG:C	donor_gain	1.0000
1:94899513:CCCAT:C	acceptor_gain	1.0000
1:94899514:CCAT:C	acceptor_gain	1.0000
1:94899514:CCATC:C	acceptor_gain	1.0000
1:94899515:CAT:C	acceptor_gain	1.0000
1:94899515:CATCT:C	acceptor_gain	1.0000
1:94899519:T:C	acceptor_gain	1.0000
1:94899519:T:TC	acceptor_gain	1.0000
1:94899521:T:C	acceptor_gain	1.0000
1:94899521:T:TC	acceptor_gain	1.0000
1:94899525:G:GC	acceptor_gain	1.0000
1:94899526:T:C	acceptor_gain	1.0000
1:94899526:T:TC	acceptor_gain	1.0000
1:94901665:TTAC:T	donor_loss	1.0000
1:94901666:TA:T	donor_loss	1.0000
1:94901667:A:AC	donor_gain	1.0000
1:94901668:C:CC	donor_gain	1.0000
1:94901668:CCT:C	donor_gain	1.0000
1:94901668:CCTG:C	donor_gain	1.0000
1:94901781:TTAGC:T	acceptor_gain	1.0000
1:94901784:GCCTA:G	acceptor_loss	1.0000
1:94901786:C:CC	acceptor_gain	1.0000
1:94901787:T:C	acceptor_loss	1.0000
1:94902115:ACGT:A	donor_loss	1.0000
1:94902116:CGT:C	donor_loss	1.0000

AlphaMissense

2188 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:94897947:C:T	G262E	1.000
1:94897990:C:G	G248R	1.000
1:94898054:T:A	R226S	1.000
1:94898054:T:G	R226S	1.000
1:94898055:C:A	R226I	1.000
1:94898055:C:G	R226T	1.000
1:94898064:C:T	G223D	1.000
1:94899393:C:T	G209D	1.000
1:94899394:C:G	G209R	1.000
1:94899398:C:A	Q207H	1.000
1:94899398:C:G	Q207H	1.000
1:94899461:C:A	R186S	1.000
1:94899461:C:G	R186S	1.000
1:94899462:C:A	R186M	1.000
1:94899462:C:G	R186T	1.000
1:94899471:C:A	G183V	1.000
1:94899471:C:T	G183E	1.000
1:94899472:C:A	G183W	1.000
1:94899472:C:G	G183R	1.000
1:94899472:C:T	G183R	1.000
1:94899491:C:A	Q176H	1.000
1:94899491:C:G	Q176H	1.000
1:94899494:G:C	S175R	1.000
1:94899494:G:T	S175R	1.000
1:94899496:T:G	S175R	1.000
1:94899513:C:A	G169V	1.000
1:94899513:C:T	G169E	1.000
1:94899514:C:G	G169R	1.000
1:94899514:C:T	G169R	1.000
1:94901669:C:A	Q167H	1.000

dbSNP variants (sampled 300 via entrez): RS1000079613 (1:94922757 A>G,T), RS1000142140 (1:94925419 C>T), RS1000274083 (1:94897685 C>T), RS1000420728 (1:94904847 G>C), RS1000455963 (1:94927451 G>T), RS1000539113 (1:94927352 C>T), RS1000611269 (1:94927556 G>A), RS1000742598 (1:94926745 G>A,T), RS1000858999 (1:94913732 T>C), RS1001030650 (1:94914659 C>A), RS1001060285 (1:94915144 T>C), RS1001152486 (1:94915765 G>A), RS1001183553 (1:94916072 T>G), RS1001602531 (1:94904557 C>A,T), RS1001686420 (1:94914313 C>T)

Disease associations

OMIM: gene MIM:602374 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001838_4	Palmitic acid (16:0) levels	3.000000e-11
GCST001840_2	Stearic acid (18:0) levels	2.000000e-14
GCST008103_84	Bipolar disorder	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases methylation, increases expression	3
Cyclosporine	decreases expression	3
Particulate Matter	increases methylation, decreases expression, increases abundance, affects cotreatment	3
bisphenol F	increases expression, affects cotreatment	2
bisphenol S	increases expression, affects cotreatment	2
Cadmium	increases expression, decreases reaction, increases abundance, increases palmitoylation	2
Cadmium Chloride	increases palmitoylation, increases expression, decreases reaction, increases abundance	2
trichostatin A	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
perfluorooctanoic acid	decreases expression	1
cupric oxide	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
candoxin	increases expression	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
MRK 003	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	decreases expression	1
Antimycin A	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression, decreases reaction	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C8FJ	HAP1 CNN3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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