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
• GTEx eGene: eQTL in 26 tissues, sQTL in 4 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.43 (moderately constrained)
• MANE Select transcript: NM_001839
• Interaction hub: 1,725 STRING partners (top 10% of genes corpus-wide)

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: 18 — 12 protein_coding, 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

MANE Select: ENST00000370206

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 3: 1

ENST00000370206, ENST00000394202, ENST00000415017, ENST00000461018, ENST00000474409, ENST00000487539, ENST00000545882, ENST00000885995, ENST00000885996, ENST00000939684, ENST00000939685, ENST00000998672, ENST00001022727, ENST00001022733, ENST00001121661, ENST00001123633, ENST00001123634, ENST00001144648

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.

Highest expression (Bgee): ventricular zone, calcaneal tendon, ganglionic eminence, adrenal gland, tibial nerve.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CNN3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellar Hemisphere	eqtl	9.6e-30	+0.71	1:94855162:T:C
Brain Cerebellum	eqtl	1.6e-19	+0.48	1:94855162:T:C
Nerve Tibial	eqtl	3.1e-09	-0.15	1:94909143:T:C
Esophagus Muscularis	eqtl	6.7e-09	-0.20	1:94899861:A:G
Colon Sigmoid	eqtl	7.6e-07	+0.15	1:94887366:ATC:A
Artery Aorta	eqtl	2.4e-06	-0.19	1:94919559:C:G
Adipose Subcutaneous	eqtl	7.8e-06	+0.13	1:94892540:A:G
Brain Caudate basal ganglia	eqtl	2.5e-05	+0.13	1:94887607:A:G
Colon Transverse	eqtl	5.6e-05	-0.12	1:94960809:A:G
Skin Sun Exposed Lower leg	eqtl	1.2e-04	+0.16	1:95142839:G:C
Artery Coronary	eqtl	1.6e-04	-0.26	1:94899861:A:G
Esophagus Gastroesophageal Junction	eqtl	1.8e-04	-0.17	1:94899861:A:G
Skin Not Sun Exposed Suprapubic	eqtl	2.4e-04	+0.09	1:94945045:C:A
Artery Tibial	eqtl	2.6e-04	+0.10	1:94887145:T:A
Breast Mammary Tissue	eqtl	4.0e-04	+0.13	1:94906171:C:T
Brain Cortex	eqtl	7.0e-04	+0.11	1:94887607:A:G
Brain Nucleus accumbens basal ganglia	eqtl	8.8e-04	+0.13	1:94887607:A:G
Brain Frontal Cortex BA9	eqtl	1.0e-03	+0.11	1:94887607:A:G
Heart Left Ventricle	eqtl	1.4e-03	+0.18	1:94932483:G:T
Cells Cultured fibroblasts	eqtl	1.5e-03	+0.12	1:94887650:G:T

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

showing 100 of 295 tissues 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
endocervix	UBERON:0000458	98.65	gold quality
aorta	UBERON:0000947	98.65	gold quality
omental fat pad	UBERON:0010414	98.63	gold quality
peritoneum	UBERON:0002358	98.62	gold quality
tibial artery	UBERON:0007610	98.61	gold quality
popliteal artery	UBERON:0002250	98.60	gold quality
descending thoracic aorta	UBERON:0002345	98.58	gold quality
right lobe of thyroid gland	UBERON:0001119	98.57	gold quality
pericardium	UBERON:0002407	98.55	gold quality
lower esophagus	UBERON:0013473	98.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.53	gold quality
minor salivary gland	UBERON:0001830	98.44	gold quality
lower esophagus mucosa	UBERON:0035834	98.36	gold quality
adenohypophysis	UBERON:0002196	98.32	gold quality
embryo	UBERON:0000922	98.31	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.29	gold quality
esophagus	UBERON:0001043	98.28	gold quality
secondary oocyte	CL:0000655	98.18	gold quality
mucosa of stomach	UBERON:0001199	98.17	gold quality
coronary artery	UBERON:0001621	98.09	gold quality
esophagus mucosa	UBERON:0002469	98.06	gold quality
right atrium auricular region	UBERON:0006631	97.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.78	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.77	gold quality
rectum	UBERON:0001052	97.74	gold quality
thyroid gland	UBERON:0002046	97.71	gold quality
amygdala	UBERON:0001876	97.67	gold quality
seminal vesicle	UBERON:0000998	97.64	gold quality
spinal cord	UBERON:0002240	97.55	gold quality
body of stomach	UBERON:0001161	97.53	gold quality
transverse colon	UBERON:0001157	97.49	gold quality
sigmoid colon	UBERON:0001159	97.47	gold quality
cortical plate	UBERON:0005343	97.39	gold quality
caudate nucleus	UBERON:0001873	97.33	gold quality
cardiac atrium	UBERON:0002081	97.31	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.27	gold quality
adipose tissue	UBERON:0001013	97.19	gold quality
islet of Langerhans	UBERON:0000006	97.11	gold quality
nucleus accumbens	UBERON:0001882	97.08	gold quality
body of pancreas	UBERON:0001150	97.07	gold quality
adult mammalian kidney	UBERON:0000082	97.04	gold quality
small intestine	UBERON:0002108	97.04	gold quality
smooth muscle tissue	UBERON:0001135	97.00	gold quality
right frontal lobe	UBERON:0002810	97.00	gold quality
myometrium	UBERON:0001296	96.96	gold quality
hypothalamus	UBERON:0001898	96.96	gold quality
right uterine tube	UBERON:0001302	96.92	gold quality
anterior cingulate cortex	UBERON:0009835	96.83	gold quality
duodenum	UBERON:0002114	96.82	gold quality
cingulate cortex	UBERON:0003027	96.82	gold quality
colon	UBERON:0001155	96.80	gold quality
stomach	UBERON:0000945	96.75	gold quality
cartilage tissue	UBERON:0002418	96.73	gold quality
putamen	UBERON:0001874	96.68	gold quality
vena cava	UBERON:0004087	96.65	gold quality
cauda epididymis	UBERON:0004360	96.65	gold quality
pituitary gland	UBERON:0000007	96.64	gold quality
intestine	UBERON:0000160	96.64	gold quality
connective tissue	UBERON:0002384	96.54	gold quality
saliva-secreting gland	UBERON:0001044	96.51	gold quality
pancreas	UBERON:0001264	96.46	gold quality
large intestine	UBERON:0000059	96.45	gold quality
right lobe of liver	UBERON:0001114	96.45	gold quality
lung	UBERON:0002048	96.45	gold quality
skin of leg	UBERON:0001511	96.41	gold quality
mouth mucosa	UBERON:0003729	96.40	gold quality
corpus callosum	UBERON:0002336	96.35	gold quality
mucosa of transverse colon	UBERON:0004991	96.30	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	407.8
Medulla oblongata	tissue	294.9
Corpus callosum	tissue	291.8
Midbrain	tissue	290.0
Substantia nigra	tissue	286.2
Olfactory bulb	tissue	283.9
Periaqueductal gray	tissue	268.4
Placenta	tissue	240.5	medium
Hypothalamus	tissue	230.7
Thalamus	tissue	229.7
Pons	tissue	227.0
Hippocampal formation	tissue	225.4
Superior colliculi	tissue	213.1
Adrenal gland	tissue	202.8	medium
Amygdala	tissue	192.1
Endometrium 1	tissue	191.9	medium
Septum	tissue	184.1
Smooth muscle	tissue	183.0	medium
Kidney	tissue	180.9	medium
Vagina	tissue	175.3	low
Ventral forebrain	tissue	158.6
Basal ganglia	tissue	158.3	medium
Putamen	tissue	154.3
Ovary	tissue	152.6	medium
Urinary bladder	tissue	146.1	medium
Hippocampus	tissue	145.1	medium
Gallbladder	tissue	142.7	medium
Entorhinal cortex	tissue	142.4
Cerebral cortex	tissue	140.7	medium
Motor cortex	tissue	140.7
Esophagus	tissue	140.6	low
Temporal cortex	tissue	138.8
Adipose tissue	tissue	138.7	not detected
Choroid plexus	tissue	138.3
Liver	tissue	134.4	low
Cervix	tissue	134.2	low
Prefrontal cortex	tissue	132.8
Retrosplenial cortex	tissue	132.2
Insular cortex	tissue	128.2
Duodenum	tissue	127.9	high
Seminal vesicle	tissue	125.9	medium
Occipital cortex	tissue	124.3
Somatosensory cortex	tissue	120.8
Nucleus accumbens	tissue	119.2
Retrosplenial and cingulate cortex	tissue	117.7
Retina	tissue	115.9
Locus coeruleus	tissue	114.5
Lung	tissue	111.6	medium
Postcentral gyrus	tissue	110.7
Pituitary gland	tissue	105.8
Breast	tissue	99.8	medium
Prostate	tissue	98.0	medium
Small intestine	tissue	94.2	high
Cerebellum	tissue	90.3	medium
Spleen	tissue	88.6	low
Caudate putamen	tissue	87.3
Heart muscle	tissue	83.9	low
Fallopian tube	tissue	83.0	medium
Thyroid gland	tissue	82.4	medium
Pancreas	tissue	78.6	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (407.8), Dorsal spinal cord (379.8), White matter (291.8), Area postrema (246.0), Supraoptic nucleus (231.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CNN3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 64 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.999, LOEUF 0.43, missense Z 2.77 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000370206 — one region, missense o/e 0.66.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919244) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
exencephaly	1
abnormal nervous system development	1
neonatal lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q4R5J4	100.0%	Diamond
Pongo abelii	Q5RFN6	100.0%	Diamond
Sus scrofa	Q08092	99.7%	Diamond
Bos taurus	Q2HJ38	99.7%	Diamond
Ovis aries	Q7YRL2	99.7%	Diamond
Mustela putorius furo	Q9GK38	99.0%	Diamond
Gallus gallus	P26932	98.9%	Diamond
Meleagris gallopavo	P37803	98.9%	Diamond
Xenopus laevis	Q3KQW7	57.5%	Diamond
Drosophila melanogaster	P14318	51.7%	Diamond
Echinococcus granulosus	Q24799	51.1%	Diamond
Dictyostelium discoideum	Q55GV9	47.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SLC44A3-AS1	ncRNA	101928079
SLC44A3	protein-coding	126969
CNN3-DT	ncRNA	729970
MIR378G	ncRNA	100616321
MIR12133	ncRNA	113219466
F3	protein-coding	2152
TLCD4-RWDD3	protein-coding	100527978
ALG14-AS1	ncRNA	101928098
RWDD3-DT	ncRNA	101928118
TLCD4	protein-coding	148534
ALG14	protein-coding	199857
RWDD3	protein-coding	25950

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): actin filaments; cytosol

Antibody reliability (HPA): IH enhanced · IF enhanced

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)

Type	Positions
N6-acetyllysine	23
N6-methyllysine	158
Phosphoserine	323

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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

18 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
epithelial cell differentiation	BP	expression pattern
actin cytoskeleton	CC	direct assay
adherens junction	CC	high-throughput assay
cytosol	CC	direct assay
focal adhesion	CC	high-throughput assay
cadherin binding involved in cell-cell adhesion	MF	high-throughput assay

Protein interactions and networks

STRING

showing 17 of 1,725 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNN3	VCL	P18206	603
CNN3	CALML4	Q96GE6	485
CNN3	DSTN	P18282	473
CNN3	CALML3	P27482	472
CNN3	CALML5	Q9NZT1	472
CNN3	CALM1	P02593	471
CNN3	CALD1	Q05682	447
CNN3	PDLIM4	P50479	446
CNN3	CALML6	Q8TD86	443
CNN3	SMTN	P53814	426
CNN3	MYH14	Q7Z406	410
CNN3	TMOD3	Q9NYL9	390
CNN3	DOCK7	Q96N67	383
CNN3	RSPH1	Q8WYR4	370
CNN3	CALB2	P22676	370
CNN3	DST	Q03001	370
CNN3	MACF1	Q9UPN3	370

IntAct

Human interaction partners of CNN3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
CARM1	physical association	0.400	1
CRMP1	physical association	0.400	1
F2RL1	physical association	0.370	1
ATE1	association	0.350	1

BioGRID (111 interactions; top human partners by supporting records): ACTB (Proximity Label-MS; 3 records), CNN2 (Affinity Capture-MS; 3 records), PARK2 (Affinity Capture-MS; 3 records), ACTC1 (Proximity Label-MS; 2 records), CARM1 (Affinity Capture-MS; 2 records), HSPA1A (Affinity Capture-MS; 2 records), KCNA3 (Proximity Label-MS; 2 records), MAPT (Proximity Label-MS; 2 records), PARP1 (Proximity Label-MS; 2 records), SNCA (Proximity Label-MS; 2 records), YAP1 (Proximity Label-MS; 2 records), ACTA1 (Cross-Linking-MS (XL-MS)), ACTA2 (Cross-Linking-MS (XL-MS)), ACTG2 (Cross-Linking-MS (XL-MS)), BAP1 (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
Emerin complex 1	8	ACTB, CNN3, EMD, LMO7, MYH9, MYO1E, SIKE1, SPTAN1

Disease & clinical

Genetic variants

Variant evidence for CNN3: 33 ClinVar records (1 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

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)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1073069	NC_000001.10:g.(?94458793)(95538454_?)del	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CNN3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 533):

Position(s)	Effect	Δscore	Sites
1:94899369–94899370	donor_loss	1.0000	5
1:94899519–94899521	acceptor_gain	1.0000	2
1:94899526	acceptor_gain	1.0000
1:94901667–94901668	donor_loss	1.0000	5
1:94901786–94901787	acceptor_loss	1.0000	6
1:94902119–94902120	donor_loss	1.0000	5
1:94902259	acceptor_loss	1.0000
1:94903120–94903121	donor_loss	1.0000	5
1:94903189–94903190	acceptor_loss	1.0000	6
1:94903397	donor_gain	1.0000

AlphaMissense

1,236 missense substitutions predicted likely pathogenic (of 2,188 scored), across 254 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M179	9	0.990	0.999
M168	9	0.981	0.999
M208	9	0.981	0.999
M247	9	0.956	0.996
M219	9	0.949	0.996
M258	9	0.883	0.987
D108	8	0.997	0.999
F104	8	0.996	1.000
N85	8	0.992	0.997
N171	8	0.983	0.999
F152	8	0.979	1.000
F89	8	0.978	0.999
D102	8	0.978	0.995
D200	8	0.978	0.994
N211	8	0.973	0.999
N114	8	0.969	0.999
F48	8	0.953	0.999
D269	8	0.951	0.992
D190	8	0.945	0.990
F4	8	0.934	0.996

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.94e-08

Disease associations

OMIM: gene MIM:602374 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST001840_3	Stearic acid (18:0) levels	2e-14
GCST001838_1	Palmitic acid (16:0) levels	3e-11
GCST008103_67	Bipolar disorder	1e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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 abundance, increases palmitoylation, increases expression, decreases reaction	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
trichostatin A	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	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)

Via MONDO — disease-level, not drug-specific.