CNN1

Summary

CNN1 (calponin 1, HGNC:2155) is a protein-coding gene on chromosome 19p13.2, encoding Calponin-1 (P51911). Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction.

Predicted to enable actin filament binding activity. Involved in negative regulation of vascular associated smooth muscle cell proliferation. Located in cytoskeleton.

Source: NCBI Gene 1264 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 63 total
• GTEx eGene: eQTL in 6 tissues, sQTL in 7 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.81 (unconstrained)
• MANE Select transcript: NM_001299
• Interaction hub: 2,151 STRING partners (top 6% of genes corpus-wide)
• Notable: 63 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2155
Approved symbol	CNN1
Name	calponin 1
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	SMCC, Sm-Calp
Ensembl gene	ENSG00000130176
Ensembl biotype	protein_coding
OMIM	600806
Entrez	1264

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000252456

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 2, TSL 4: 1, TSL 5: 4

ENST00000252456, ENST00000535659, ENST00000585869, ENST00000586059, ENST00000586577, ENST00000587087, ENST00000588468, ENST00000588935, ENST00000592338, ENST00000592923, ENST00000873889, ENST00000873890, ENST00000873891, ENST00000873892, ENST00000873893, ENST00000962387, ENST00001123701, ENST00001136651

RefSeq mRNA: 3 — MANE Select: NM_001299 NM_001299, NM_001308341, NM_001308342

CCDS: CCDS12263, CCDS77238

Canonical transcript exons

ENST00000252456 — 7 exons

Exon	Start	End
ENSE00000679861	11549323	11549469
ENSE00000679862	11547797	11547907
ENSE00000679863	11546832	11546969
ENSE00000679864	11546675	11546741
ENSE00002789578	11538851	11538990
ENSE00003590752	11541076	11541197
ENSE00004789186	11549550	11550323

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 99.92.

FANTOM5 (CAGE): breadth broad, TPM avg 36.6013 / max 4973.7087, expressed in 902 samples.

Highest expression (Bgee): saphenous vein, lower esophagus muscularis layer, popliteal artery, tibial artery, lower esophagus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CNN1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	1.3e-27	-1.42	19:11527181:G:T
Artery Tibial	sqtl	3.1e-04	-0.54	19:11499005:G:A
Artery Aorta	sqtl	6.3e-04	-0.63	19:11516815:T:C
Skin Sun Exposed Lower leg	eqtl	3.8e-03	-0.36	19:11977001:C:G
Cells Cultured fibroblasts	eqtl	4.6e-03	-0.20	19:11674358:A:G
Muscle Skeletal	eqtl	1.1e-02	-0.41	19:11271222:G:A
Esophagus Mucosa	eqtl	1.1e-02	-0.30	19:11639104:T:C
Thyroid	sqtl	1.3e-02	-1.21	19:11006895:G:A
Spleen	eqtl	2.1e-02	+0.51	19:10603382:G:T
Esophagus Mucosa	sqtl	2.6e-02	-0.82	19:11230786:C:T
Skin Not Sun Exposed Suprapubic	sqtl	3.3e-02	-0.49	19:11925751:G:C
Esophagus Gastroesophageal Junction	sqtl	3.6e-02	-0.64	19:11496196:A:G
Heart Atrial Appendage	eqtl	4.5e-02	+0.13	19:11123265:A:G

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
173931	33.7707	858
208692	2.0930	498
173934	0.3176	123
173933	0.2195	115
173935	0.0955	46
173932	0.0759	26
173936	0.0291	14

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	99.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.82	gold quality
popliteal artery	UBERON:0002250	99.81	gold quality
tibial artery	UBERON:0007610	99.81	gold quality
lower esophagus	UBERON:0013473	99.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.74	gold quality
right coronary artery	UBERON:0001625	99.73	gold quality
cauda epididymis	UBERON:0004360	99.73	gold quality
body of uterus	UBERON:0009853	99.73	gold quality
aorta	UBERON:0000947	99.72	gold quality
seminal vesicle	UBERON:0000998	99.72	gold quality
mucosa of stomach	UBERON:0001199	99.68	gold quality
urethra	UBERON:0000057	99.67	gold quality
myometrium	UBERON:0001296	99.67	gold quality
left uterine tube	UBERON:0001303	99.66	gold quality
ascending aorta	UBERON:0001496	99.61	gold quality
thoracic aorta	UBERON:0001515	99.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.60	gold quality
blood vessel layer	UBERON:0004797	99.59	gold quality
descending thoracic aorta	UBERON:0002345	99.52	gold quality
left coronary artery	UBERON:0001626	99.51	gold quality
vena cava	UBERON:0004087	99.51	gold quality
coronary artery	UBERON:0001621	99.50	gold quality
gall bladder	UBERON:0002110	99.21	gold quality
lower esophagus mucosa	UBERON:0035834	99.00	gold quality
endocervix	UBERON:0000458	98.87	gold quality
adult organism	UBERON:0007023	98.82	gold quality
fundus of stomach	UBERON:0001160	98.78	gold quality
superficial temporal artery	UBERON:0001614	98.73	gold quality
nipple	UBERON:0002030	98.70	gold quality
right atrium auricular region	UBERON:0006631	98.40	gold quality
vermiform appendix	UBERON:0001154	98.21	gold quality
caecum	UBERON:0001153	98.20	gold quality
right uterine tube	UBERON:0001302	98.16	gold quality
urinary bladder	UBERON:0001255	97.97	gold quality
cardiac atrium	UBERON:0002081	97.86	gold quality
prostate gland	UBERON:0002367	97.79	gold quality
esophagus	UBERON:0001043	97.31	gold quality
rectum	UBERON:0001052	97.26	gold quality
apex of heart	UBERON:0002098	96.95	gold quality
right testis	UBERON:0004534	96.95	gold quality
left testis	UBERON:0004533	96.94	gold quality
heart	UBERON:0000948	96.71	gold quality
sigmoid colon	UBERON:0001159	96.33	gold quality
heart left ventricle	UBERON:0002084	96.27	gold quality
cardiac ventricle	UBERON:0002082	96.09	gold quality
decidua	UBERON:0002450	96.07	gold quality
penis	UBERON:0000989	96.04	gold quality
stomach	UBERON:0000945	96.03	gold quality
mucosa of urinary bladder	UBERON:0001259	96.03	gold quality
stromal cell of endometrium	CL:0002255	95.93	gold quality
heart right ventricle	UBERON:0002080	95.79	gold quality
body of stomach	UBERON:0001161	95.77	gold quality
corpus epididymis	UBERON:0004359	95.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.49	gold quality
transverse colon	UBERON:0001157	95.28	gold quality
smooth muscle tissue	UBERON:0001135	95.14	gold quality
esophagus mucosa	UBERON:0002469	95.13	gold quality
mammary duct	UBERON:0001765	94.99	gold quality
caput epididymis	UBERON:0004358	94.96	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.85	gold quality
pylorus	UBERON:0001166	94.72	gold quality
colon	UBERON:0001155	94.68	gold quality
large intestine	UBERON:0000059	94.63	gold quality
intestine	UBERON:0000160	94.53	gold quality
trachea	UBERON:0003126	94.43	gold quality
testis	UBERON:0000473	94.14	gold quality
ectocervix	UBERON:0012249	94.06	gold quality
small intestine	UBERON:0002108	94.05	gold quality
upper lobe of left lung	UBERON:0008952	93.86	gold quality
right ovary	UBERON:0002118	93.83	gold quality
colonic epithelium	UBERON:0000397	93.75	gold quality
upper lobe of lung	UBERON:0008948	93.36	gold quality
myocardium	UBERON:0002349	92.75	gold quality
right lung	UBERON:0002167	92.74	gold quality
minor salivary gland	UBERON:0001830	92.18	gold quality
skin of leg	UBERON:0001511	92.12	gold quality
epithelium of mammary gland	UBERON:0003244	92.06	gold quality
cardia of stomach	UBERON:0001162	91.75	gold quality
tibial nerve	UBERON:0001323	91.52	gold quality
peritoneum	UBERON:0002358	91.48	gold quality
omental fat pad	UBERON:0010414	91.47	gold quality
pericardium	UBERON:0002407	91.39	gold quality
left ovary	UBERON:0002119	91.07	gold quality
saliva-secreting gland	UBERON:0001044	90.87	gold quality
left ventricle myocardium	UBERON:0006566	90.60	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.30	gold quality
mammary gland	UBERON:0001911	89.78	gold quality
thoracic mammary gland	UBERON:0005200	89.68	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.63	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.59	gold quality
zone of skin	UBERON:0000014	89.49	gold quality
vagina	UBERON:0000996	89.34	gold quality
upper arm skin	UBERON:0004263	89.21	silver quality
calcaneal tendon	UBERON:0003701	88.94	gold quality
skin of abdomen	UBERON:0001416	88.89	gold quality
metanephros cortex	UBERON:0010533	88.10	gold quality
lung	UBERON:0002048	87.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.43	gold quality
mouth mucosa	UBERON:0003729	87.39	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	2686.67
E-MTAB-10885	yes	1579.59
E-MTAB-8205	yes	136.97
E-HCAD-1	yes	37.29
E-MTAB-8410	yes	29.34
E-HCAD-11	yes	11.42
E-GEOD-124858	no	41.78
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Smooth muscle	tissue	2059.2	high
Seminal vesicle	tissue	1492.5	not detected
Endometrium 1	tissue	1003.1	not detected
Urinary bladder	tissue	754.9	not detected
Esophagus	tissue	635.7	not detected
Prostate	tissue	609.4	not detected
Colon	tissue	457.7	not detected
Rectum	tissue	306.8	not detected
Vagina	tissue	297.4	not detected
Gallbladder	tissue	219.6	not detected
Fallopian tube	tissue	207.2	not detected
Heart muscle	tissue	195.0	not detected
Epididymis	tissue	166.7	not detected
Cervix	tissue	156.0	not detected
Appendix	tissue	151.5	not detected
Duodenum	tissue	128.0	not detected
Small intestine	tissue	110.0	not detected
Adipose tissue	tissue	104.7	not detected
Breast	tissue	65.1	medium
Testis	tissue	64.2	not detected
Salivary gland	tissue	58.0	not detected
Adrenal gland	tissue	55.0	not detected
Stomach 1	tissue	47.8	not detected
Substantia nigra	tissue	40.6
Ovary	tissue	31.4	not detected
Lung	tissue	30.9	not detected
Placenta	tissue	26.6	not detected
Pancreas	tissue	22.8	not detected
Spleen	tissue	20.8	not detected
Superior colliculi	tissue	17.8
Kidney	tissue	17.1	not detected
Thalamus	tissue	15.0
Pons	tissue	13.8
Spinal cord	tissue	12.9
Hippocampal formation	tissue	11.8
Cerebral cortex	tissue	11.6	not detected
Retrosplenial and cingulate cortex	tissue	11.6
Septum	tissue	11.6
Prefrontal cortex	tissue	11.1
Tongue	tissue	10.9
Entorhinal cortex	tissue	10.8
Motor cortex	tissue	10.4
Midbrain	tissue	10.0
Medulla oblongata	tissue	9.6
Insular cortex	tissue	9.6
Somatosensory cortex	tissue	9.2
Temporal cortex	tissue	9.2
Retrosplenial cortex	tissue	9.1
Pituitary gland	tissue	9.0
Amygdala	tissue	8.4
Thyroid gland	tissue	8.3	not detected
Periaqueductal gray	tissue	8.0
Occipital cortex	tissue	7.5
Lymph node	tissue	6.8	not detected
Ventral forebrain	tissue	6.8
Hypothalamus	tissue	6.3
Basal ganglia	tissue	4.9	not detected
Choroid plexus	tissue	4.8
Skeletal muscle	tissue	4.6	not detected
Putamen	tissue	4.4

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (2087.4), Dorsal spinal cord (12.9), Ventral hippocampus (11.8), Subiculum (9.9), Anterior insular cortex, dorsal (9.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR2, HMGXB4, MYOCD, SRF, TCF21, TCF3

miRNA regulators (miRDB)

Targeting CNN1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 59 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-106A-5P	99.90	73.94	2683
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-17-5P	99.89	73.83	2665
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4498	99.47	67.42	2360

Functional genomics

gnomAD constraint: pLI 0.000388, LOEUF 0.811, missense Z 1.75 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000252456 — one region, missense o/e 0.78.

Literature-anchored findings (GeneRIF, showing 20)

• expression in tumor vessels is a new and useful means to predict prognosis of hepatocellular carcinoma after hepatic resection (PMID:11920541)
• results suggest that regulation of h1-calponin is involved in the regulation of differentiation of AR42J cells into insulin-producing cells (PMID:12606518)
• the calponin homology domain of Vav1 associates with calmodulin and is prerequisite to T cell antigen receptor-induced calcium release in Jurkat T lymphocytes (PMID:17550897)
• analysis of distinct sites of interaction that form the calponin: gelsolin complex and two calcium switches that control its activity (PMID:17556051)
• expression of vascular CNN1 in the peripheral region of colon cancer tissues was significantly reduced in association with tumor progression, lymphatic invasion, vascular invasion and recurrence. (PMID:17707120)
• Calponin and alpha-inhibin are the most useful positive markers for serous microcystic adenoma, and are negative in most entities in the differential diagnosis. (PMID:19391217)
• The point mutation S175T exhibited more resistance to actin rearrangement by cytochalasin D and PDBu than intact CNh1, suppressing cell motility induced by PDBu. (PMID:20530411)
• Inhibition of calponin-1 expression can inhibit uterine smooth muscle cell migration and cause the morphological change and rearrangement of F-actin without affecting its proliferation and apoptosis in vitro. (PMID:20584679)
• Calponin-1 expression in the uterine smooth muscle tissue of the body and the lower uterine segment of smooth muscle tissues was significantly different. (PMID:21051832)
• D2-40 immunohistochemistry reliably identifies the myoepithelial cells of breast in a variety of lesions in a pattern similar to that of calponin and p63. (PMID:21326813)
• A single intronic CArG element is necessary but insufficient for proper CNN1 expression in vivo. CNN1 overexpression antagonizes arterial injury-induced neointimal formation. (PMID:21817093)
• Expression of transforming growth factor-beta (4.3 +/- 1.4 vs 2.6 +/- 2.3, p = 0.01) and calponin (3.7 +/- 0.7 vs 0.6 +/- 1.1, p = 0.05) was lower from infants with vs without a PDA. (PMID:23731614)
• CNN1 immunohistochemical staining allows ready recognition of intracytoplasmic inclusions, aiding diagnosis of infantile digital fibromatosis. (PMID:24117680)
• Calponin knockdown inhibits autophosphorylation. (PMID:24350264)
• epsilonPKC/ERK/mTOR pathway activation induced by the rescued expression of CNN1 contributed to the improvement of cardiac dysfunction and pathological changes observed in transgenic mice. (PMID:24631115)
• Loss of myoepithelial calponin was specifically associated with gain of the basal marker p63 in adjacent tumor cells. (PMID:26343330)
• Loss of CNN1 expression is associated with Ovarian Cancer. (PMID:26504022)
• Studied maternal serum calponin 1 levels in the prediction of delivery within 7 days among pregnancies complicated with threatened preterm labor. Of 73 women included in the study, found the maternal serum calponin 1 level was significantly high in women who delivered within 7 days vs. those who delivered after 7 days. (PMID:28068849)
• Calponin and MUC6 complement inhibin as diagnostic immunomarkers of serous cystadenoma in endoscopic ultrasound-guided aspiration/biopsy specimens. (PMID:33657658)
• Long non-coding RNA MEG3 acts as a suppressor in breast cancer by regulating miR-330/CNN1. (PMID:38240701)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnn1a	ENSDARG00000017193
danio_rerio	cnn1b	ENSDARG00000102398
mus_musculus	Cnn1	ENSMUSG00000001349
rattus_norvegicus	Cnn1	ENSRNOG00000027736
drosophila_melanogaster	Mp20	FBGN0002789
drosophila_melanogaster	Chd64	FBGN0035499
caenorhabditis_elegans	cpn-1	WBGENE00000777
caenorhabditis_elegans		WBGENE00000778
caenorhabditis_elegans	cpn-3	WBGENE00000779
caenorhabditis_elegans	cpn-4	WBGENE00000780

Paralogs (5): CNN2 (ENSG00000064666), CNN3 (ENSG00000117519), TAGLN3 (ENSG00000144834), TAGLN (ENSG00000149591), TAGLN2 (ENSG00000158710)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104979) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning 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
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
ECSIT	protein-coding	51295
ELOF1	protein-coding	84337
ACP5	protein-coding	54
ZNF627	protein-coding	199692
MIR7974	ncRNA	102465856
ZNF653	protein-coding	115950
ELAVL3	protein-coding	1995

Protein

Protein identifiers

Calponin-1 — P51911 (reviewed: P51911)

Alternative names: Basic calponin, Calponin H1, smooth muscle

All UniProt accessions (9): B7Z7E1, P51911, K7ENC5, K7EQ72, K7ER02, K7ERK4, K7ERM8, K7ESJ2, V9HWA5

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.

Subunit / interactions. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1.

Tissue specificity. Smooth muscle, and tissues containing significant amounts of smooth muscle.

Similarity. Belongs to the calponin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P51911-1	1	yes
P51911-2	2

RefSeq proteins (3): NP_001290, NP_001295270, NP_001295271 (=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 (23 total): helix 7, modified residue 5, sequence conflict 4, repeat 3, chain 1, domain 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
1WYP	Solution structure of the CH domain of human Calponin 1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51911-F1	72.06	0.33

Human Protein Atlas

Protein class: Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): actin filaments

Antibody reliability (HPA): IH enhanced · IF approved

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 (5)

Type	Positions
Phosphothreonine	170, 180, 184, 259
Phosphoserine	175

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9927432	Developmental Lineage of Mammary Gland Myoepithelial Cells	curated
R-HSA-1266738	Developmental Biology	—
R-HSA-9734767	Developmental Cell Lineages	—
R-HSA-9734779	Developmental Cell Lineages of the Integumentary System	—
R-HSA-9924644	Developmental Lineages of the Mammary Gland	—

MSigDB gene sets: 188 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, WWTAAGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, MCBRYAN_TERMINAL_END_BUD_UP, KYNG_DNA_DAMAGE_DN, TGACCTY_ERR1_Q2, TOMLINS_PROSTATE_CANCER_DN, GOBP_MUSCLE_CELL_PROLIFERATION, LA_MEN1_TARGETS, SRF_Q5_01, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP

GO Biological Process (4): regulation of smooth muscle contraction (GO:0006940), actin filament organization (GO:0007015), actomyosin structure organization (GO:0031032), negative regulation of vascular associated smooth muscle cell proliferation (GO:1904706)

GO Molecular Function (4): calmodulin binding (GO:0005516), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (3): cytoskeleton (GO:0005856), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Developmental Lineages of the Mammary Gland	1
Developmental Biology	1
Developmental Cell Lineages	1
Developmental Cell Lineages of the Integumentary System	1

GO top-level categories

15 GO namespaces:

Category	Terms
actin cytoskeleton organization	2
regulation of muscle contraction	1
smooth muscle contraction	1
supramolecular fiber organization	1
negative regulation of smooth muscle cell proliferation	1
regulation of vascular associated smooth muscle cell proliferation	1
vascular associated smooth muscle cell proliferation	1
protein binding	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
binding	1
intracellular membraneless organelle	1
cell-substrate junction	1
cytoskeleton	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of vascular associated smooth muscle cell proliferation	BP	genetic interaction
cytoskeleton	CC	direct assay
focal adhesion	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 2,151 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNN1	MYH11	P35749	846
CNN1	ACTA2	P03996	832
CNN1	CALD1	Q05682	811
CNN1	MYOCD	Q8IZQ8	772
CNN1	SMTN	P53814	765
CNN1	SPEF1	Q9Y4P9	754
CNN1	MYH14	Q7Z406	673
CNN1	NAV2	Q8IVL1	671
CNN1	NAV3	Q8IVL0	659
CNN1	RGCC	Q9H4X1	653
CNN1	SRF	P11831	644
CNN1	ACTG2	P12718	644
CNN1	EHD2	Q9NZN4	638
CNN1	MAPRE3	Q9UPY8	604
CNN1	MYL9	P24844	602

IntAct

Human interaction partners of CNN1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
MYEOV	association	0.560	2
TFPT	physical association	0.490	4
CCHCR1	physical association	0.490	2
COG6	physical association	0.490	2
NCAPD2	physical association	0.490	2
PLRG1	physical association	0.490	2
SYCE1	physical association	0.490	2
RNF150	physical association	0.400	2
DOK6	physical association	0.400	1
SSUH2	physical association	0.400	1
MYBPC3	physical association	0.370	1
AK4	association	0.350	1
FAM3D	association	0.350	1

BioGRID (65 interactions; top human partners by supporting records): APOA2 (Cross-Linking-MS (XL-MS); 2 records), CALM1 (Reconstituted Complex; 2 records), MYEOV (Affinity Capture-MS; 2 records), PDLIM7 (Affinity Capture-Western; 2 records), RNF150 (Affinity Capture-MS; 2 records), TPM1 (Reconstituted Complex; 2 records), ACTA1 (Reconstituted Complex), ADRB2 (PCA), AK4 (Affinity Capture-MS), APOA1 (Cross-Linking-MS (XL-MS)), BAK1 (Positive Genetic), CBL (Negative Genetic), CCHCR1 (Two-hybrid), CEBPA (Positive Genetic), CIAPIN1 (Affinity Capture-MS)

SIGNOR signaling

showing 2 of 3 signaling interactions:

A	Effect	B	Mechanism
SRF	“up-regulates quantity by expression”	CNN1	“transcriptional regulation”
FYN	“down-regulates activity”	CNN1	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for CNN1: 63 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 444):

Position(s)	Effect	Δscore	Sites
19:11541068	acceptor_gain	1.0000
19:11546742–11546743	donor_loss	1.0000	5
19:11546831	acceptor_loss	1.0000
19:11547871	donor_gain	1.0000
19:11547875	donor_gain	1.0000
19:11547908–11547909	donor_loss	1.0000	5
19:11549312–11549313	acceptor_gain	1.0000	2
19:11549321	acceptor_loss	1.0000	3
19:11549470–11549471	donor_loss	1.0000	5
19:11549548–11549549	acceptor_loss	1.0000	4

AlphaMissense

1,044 missense substitutions predicted likely pathogenic (of 1,967 scored), across 219 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	0.974	0.997
M208	9	0.963	0.996
M168	9	0.962	0.996
M219	9	0.948	0.995
M247	9	0.902	0.982
M258	9	0.862	0.972
F106	8	0.988	0.998
D110	8	0.988	0.996
N87	8	0.987	0.997
N211	8	0.957	0.998
N171	8	0.950	0.997
F91	8	0.949	0.996
D104	8	0.945	0.981
D269	8	0.931	0.981
D200	8	0.926	0.972
D190	8	0.915	0.979
F50	8	0.907	0.993
H187	8	0.837	0.976
H83	8	0.791	0.987
W82	7	0.997	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Prostate Adenocarcinoma, Stomach Adenocarcinoma)

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	5.88e-07
Bladder Urothelial Carcinoma (TCGA)	favorable	0.000962

Disease associations

OMIM: gene MIM:600806 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST003563_3	Presence of antiphospholipid antibodies	5e-8
GCST003563_8	Presence of antiphospholipid antibodies	3e-6
GCST003563_9	Presence of antiphospholipid antibodies	4e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Cadmium	decreases expression, increases abundance, increases expression	2
Doxorubicin	increases expression, affects expression	2
Silicon Dioxide	affects expression, increases expression	2
Valproic Acid	affects expression, increases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	decreases expression	1
propionaldehyde	increases expression	1
trichostatin A	affects expression	1
trimellitic anhydride	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
butyraldehyde	increases expression	1
zinc chromate	increases abundance, decreases expression	1
nickel sulfate	decreases expression	1
triadimefon	decreases expression	1
pentanal	increases expression	1
brequinar	decreases expression	1
bisindolylmaleimide I	decreases expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
SB 203580	decreases reaction, increases expression	1
entinostat	increases expression	1
monomethylarsonous acid	increases expression	1
Roflumilast	increases expression, decreases reaction	1
2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1NP	Abcam HeLa CNN1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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