CALD1

Summary

CALD1 (caldesmon 1, HGNC:1441) is a protein-coding gene on chromosome 7q33, encoding Caldesmon (Q05682). Actin- and myosin-binding protein implicated in the regulation of actomyosin interactions in smooth muscle and nonmuscle cells (could act as a bridge between myosin and actin filaments).

This gene encodes a calmodulin- and actin-binding protein that plays an essential role in the regulation of smooth muscle and nonmuscle contraction. The conserved domain of this protein possesses the binding activities to Ca(2+)-calmodulin, actin, tropomyosin, myosin, and phospholipids. This protein is a potent inhibitor of the actin-tropomyosin activated myosin MgATPase, and serves as a mediating factor for Ca(2+)-dependent inhibition of smooth muscle contraction. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 800 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 130 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_033138

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1441
Approved symbol	CALD1
Name	caldesmon 1
Location	7q33
Locus type	gene with protein product
Status	Approved
Aliases	CDM, H-CAD, L-CAD, h-CD
Ensembl gene	ENSG00000122786
Ensembl biotype	protein_coding
OMIM	114213
Entrez	800

Gene structure

Transcript identifiers

Ensembl transcripts: 60 — 48 protein_coding, 6 retained_intron, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000361675, ENST00000361901, ENST00000393118, ENST00000417172, ENST00000422748, ENST00000424922, ENST00000430085, ENST00000435928, ENST00000436461, ENST00000443197, ENST00000445569, ENST00000454108, ENST00000462181, ENST00000466704, ENST00000472096, ENST00000473714, ENST00000475772, ENST00000478075, ENST00000480638, ENST00000482470, ENST00000489019, ENST00000495522, ENST00000496024, ENST00000498254, ENST00000866419, ENST00000866420, ENST00000866421, ENST00000866422, ENST00000866423, ENST00000866424, ENST00000866425, ENST00000866426, ENST00000866427, ENST00000866428, ENST00000927566, ENST00000927567, ENST00000927568, ENST00000927569, ENST00000927570, ENST00000927571, ENST00000927572, ENST00000927573, ENST00000972406, ENST00000972407, ENST00000972408, ENST00000972409, ENST00000972410, ENST00000972411, ENST00000972412, ENST00000972413, ENST00000972414, ENST00000972415, ENST00000972416, ENST00000972417, ENST00000972418, ENST00000972419, ENST00000972420, ENST00000972421, ENST00000972422, ENST00000972423

RefSeq mRNA: 5 — MANE Select: NM_033138 NM_004342, NM_033138, NM_033139, NM_033140, NM_033157

CCDS: CCDS47716, CCDS47717, CCDS5834, CCDS5835, CCDS5836

Canonical transcript exons

ENST00000361675 — 15 exons

Exon	Start	End
ENSE00001086615	134932988	134934077
ENSE00001141359	134843884	134843971
ENSE00001860248	134779634	134779749
ENSE00001931783	134968340	134970729
ENSE00002532576	134935688	134935765
ENSE00003460906	134947508	134947769
ENSE00003462172	134960533	134960628
ENSE00003465251	134959974	134960111
ENSE00003522806	134965306	134965386
ENSE00003538609	134958209	134958290
ENSE00003542681	134958069	134958112
ENSE00003605793	134867693	134867804
ENSE00003649233	134941092	134941237
ENSE00003655852	134950374	134950514
ENSE00003789113	134928754	134928900

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 330.6494 / max 13577.7498, expressed in 1376 samples.

FANTOM5 promoters (49 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81280	226.2152	1330
81289	16.4773	1211
81300	12.7552	1180
81292	11.0212	1151
81281	8.2314	1091
81290	7.6235	1140
81299	6.4595	1058
81282	6.2536	920
81298	3.6235	910
81291	2.9538	949

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	99.90	gold quality
saphenous vein	UBERON:0007318	99.89	gold quality
cauda epididymis	UBERON:0004360	99.88	gold quality
seminal vesicle	UBERON:0000998	99.87	gold quality
tendon of biceps brachii	UBERON:0008188	99.84	gold quality
urethra	UBERON:0000057	99.79	gold quality
superficial temporal artery	UBERON:0001614	99.77	gold quality
visceral pleura	UBERON:0002401	99.72	gold quality
pleura	UBERON:0000977	99.71	gold quality
parietal pleura	UBERON:0002400	99.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.70	gold quality
stromal cell of endometrium	CL:0002255	99.69	gold quality
right coronary artery	UBERON:0001625	99.69	gold quality
germinal epithelium of ovary	UBERON:0001304	99.68	gold quality
lower esophagus	UBERON:0013473	99.68	gold quality
myometrium	UBERON:0001296	99.65	gold quality
aorta	UBERON:0000947	99.64	gold quality
thoracic aorta	UBERON:0001515	99.64	gold quality
popliteal artery	UBERON:0002250	99.64	gold quality
descending thoracic aorta	UBERON:0002345	99.64	gold quality
tibial artery	UBERON:0007610	99.64	gold quality
ascending aorta	UBERON:0001496	99.63	gold quality
vena cava	UBERON:0004087	99.63	gold quality
smooth muscle tissue	UBERON:0001135	99.62	gold quality
pericardium	UBERON:0002407	99.58	gold quality
colonic epithelium	UBERON:0000397	99.57	gold quality
coronary artery	UBERON:0001621	99.56	gold quality
penis	UBERON:0000989	99.54	gold quality
mucosa of stomach	UBERON:0001199	99.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.54	gold quality

Single-cell (SCXA)

Detected in 68 experiment(s), a significant marker in 59.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	6406.91
E-MTAB-9841	yes	5213.43
E-MTAB-10885	yes	5118.65
E-MTAB-8410	yes	4832.31
E-MTAB-10287	yes	4821.85
E-HCAD-31	yes	4744.06
E-CURD-46	yes	4637.72
E-CURD-126	yes	4584.70
E-MTAB-8495	yes	4088.12
E-MTAB-6653	yes	4025.47
E-MTAB-8894	yes	3905.54
E-MTAB-10855	yes	3899.19
E-HCAD-11	yes	3721.07
E-CURD-119	yes	3699.69
E-MTAB-6308	yes	3670.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MSX1, MSX2, NR3C1, SOX4, SRF, TP53

miRNA regulators (miRDB)

129 targeting CALD1, 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-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 36)

• Specific but variable expression of h-caldesmon in leiomyosarcomas (PMID:11759055)
• Motifs of the caldesmon family. (PMID:11996092)
• results suggest a role for the caldesmon gene in susceptibility to diabetic nephropathy in type 1 diabetes (PMID:15047636)
• Alternative splicing contributes to dysfunctionality of glioma neovascularization. (PMID:15161654)
• plays a crucial role in mediating the effects of Ca(2+)-calmodulin on the dynamics of the actin cytoskeleton (PMID:15226374)
• unphosphorylated, but not ERK-phosphorylated, caldesmon could stabilize actin filaments and resist F-actin severing or depolymerization in both smooth muscle and nonmuscle cells (PMID:15456752)
• These results suggest that CaD is critically involved in the regulation of the actin cytoskeleton and migration in EC, and that p38 MAPK-mediated CaD phosphorylation may be involved in endothelial cytoskeletal remodeling. (PMID:15521070)
• Serum l-CaD level as determined by ELISA is a good discriminator between glioma patients versus patients with other intracranial tumor. (PMID:15958622)
• K-cyclin expression modulates the activity of caldesmon and through this the microfilament functions in cells (PMID:16115893)
• Phosphorylation of caldesmon by PAK is a dynamic process required to regulate actin dynamics and membrane protrusions in wound-induced cell migration. (PMID:16800003)
• low molecular weight isoform CaD undergoes a DNA replication-associated switch in localization from the cytoplasm to the nuclei of endothelial cells/endothelial progenitor cells in human tumor vasculature (PMID:17582218)
• Caldesmon suppresses cancer cell invasion by regulating podosome/invadopodium formation. (PMID:17631293)
• A subset of the tumor-specific splicing alterations (ACTN1, CALD1, and VCL) was found in all three organs and may represent general cancer-related splicing events. (PMID:18353764)
• GR directly bound to the two glucocorticoid-response element-like sequences in the human CALD1 promoter and transactivated the CALD1 gene, thereby up-regulating the CaD protein. (PMID:18772142)
• Vaginal caldesmon expression is significantly decreased in women with anterior vaginal wall prolapse compared to normal subjects (PMID:19582387)
• Results describe the mechanisms of PC6 action in decidualization and identify caldesmon as one of its physiological substrates. (PMID:19764806)
• Stretch activates myometrium via ERK, caldesmon and focal adhesion signaling (PMID:19834610)
• The effect of a C-terminal fragment of CaD (H32K) on the kinetics of the in vitro actin polymerization by monitoring the fluorescence of pyrene-labeled actin, was studied. (PMID:19889635)
• An involvement of caldesmon in the susceptibility to diabetic nephropathy in type 1 diabetes, independently from environmental glucose levels. (PMID:20801058)
• h-caldesmon is useful in distinguishing atypical polypoid adenomyoma from myoinvasive endometrioid carcinoma (PMID:21131830)
• Novel biological cascade that involved the phosphorylation activation of CaD by PFTK1 kinase in promoting formation of actin stress fibers. (PMID:21184254)
• Our results show a differential behavior of h- and l-caldesmon isoforms in epithelium and stroma of colon adenocarcinoma and lymph node metastases. (PMID:21626272)
• Data found phasic phosphorylation of caldesmon and ERK 1/2 during contractions in human myometrium. (PMID:21738699)
• Disruption of the normal inhibitory function of human caldesmon 1 enhances intestinal peristalsis in both wild-type zebrafish larvae and mutant larvae that lack enteric nerves (PMID:22316291)
• caldesmon is not useful in distinguishing between peritoneal epithelioid mesotheliomas and papillary serous carcinomas involving the peritoneum (PMID:23196794)
• Caldesmon expression inhibits cancer cell migration and invasiveness. (PMID:23265641)
• The data suggest that PKGIbeta enhances breast cancer cell motility and invasive capacity, at least in part, by phosphorylating CaD. (PMID:23418348)
• Caldesmon is a possible predictor of endometrial dysregulation in patients with endometriosis. (PMID:23575144)
• Caldesmon and smoothelin staining allows better delineation of the muscularis propria from the desmoplastic stromal reaction which provides a critical aide for proper staging of colonic adenocarcinomas. (PMID:24551305)
• Data indicate that low-molecular-weight caldesmon isoforms (L-CAD) promotes migration and invasiveness of urothelial bladder carcinoma (BC) cells. (PMID:26430961)
• ANXA1 and CALD1 proteins are independent markers for tamoxifen therapy outcome and are associated to fast tumor progression. (PMID:26657294)
• rs 3807337 polymorphism of CALD1 gene is associated with diabetic nephropathy occurrence in type 1 diabetes. (PMID:28255976)
• Proteomic analysis revealed a group of molecules associated with cytoskeleton organization, including caldesmon, were differentially expressed between fibroblasts isolated from bone destruction non-functioning pituitary adenomas (BD-NFPAs) and fibroblasts isolated from non-bone destruction NFPAs (NBD-NFPAs). The secreted proteins analysis found that osteopontin was significantly upregulated in BD-NFPAs fibroblasts. (PMID:29235490)
• METTL14 Promotes Oral Squamous Cell Carcinoma Progression by Regulating the mRNA and m6A Levels of CALD1. (PMID:37017680)
• Upregulation of CALD1 predicted a poor prognosis for platinum-treated ovarian cancer and revealed it as a potential therapeutic resistance target. (PMID:38365611)
• The gene expression of CALD1, CDH2, and POSTN in fibroblast are related to idiopathic pulmonary fibrosis. (PMID:38370408)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cald1b	ENSDARG00000086391
mus_musculus	Cald1	ENSMUSG00000029761
rattus_norvegicus	Cald1	ENSRNOG00000010233

Paralogs (1): LSP1 (ENSG00000130592)

Protein

Protein identifiers

Caldesmon — Q05682 (reviewed: Q05682)

All UniProt accessions (9): A0A140VKA0, A0A6Q8PGI1, C9J813, C9JE79, C9JEK3, E7EX44, E9PGZ1, Q05682, F8WE61

UniProt curated annotations — full annotation on UniProt →

Function. Actin- and myosin-binding protein implicated in the regulation of actomyosin interactions in smooth muscle and nonmuscle cells (could act as a bridge between myosin and actin filaments). Stimulates actin binding of tropomyosin which increases the stabilization of actin filament structure. In muscle tissues, inhibits the actomyosin ATPase by binding to F-actin. This inhibition is attenuated by calcium-calmodulin and is potentiated by tropomyosin. Interacts with actin, myosin, two molecules of tropomyosin and with calmodulin. Also plays an essential role during cellular mitosis and receptor capping. Involved in Schwann cell migration during peripheral nerve regeneration.

Subcellular location. Cytoplasm. Cytoskeleton. Myofibril. Stress fiber.

Tissue specificity. High-molecular-weight caldesmon (isoform 1) is predominantly expressed in smooth muscles, whereas low-molecular-weight caldesmon (isoforms 2, 3, 4 and 5) are widely distributed in non-muscle tissues and cells. Not expressed in skeletal muscle or heart.

Post-translational modifications. In non-muscle cells, phosphorylation by CDK1 during mitosis causes caldesmon to dissociate from microfilaments. Phosphorylation reduces caldesmon binding to actin, myosin, and calmodulin as well as its inhibition of actomyosin ATPase activity. Phosphorylation also occurs in both quiescent and dividing smooth muscle cells with similar effects on the interaction with actin and calmodulin and on microfilaments reorganization. CDK1-mediated phosphorylation promotes Schwann cell migration during peripheral nerve regeneration.

Domain organisation. The N-terminal part seems to be a myosin/calmodulin-binding domain, and the C-terminal a tropomyosin/actin/calmodulin-binding domain. These two domains are separated by a central helical region in the smooth-muscle form.

Similarity. Belongs to the caldesmon family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q05682-1	1, H-CAD	yes
Q05682-2	2, WI-38 L-CAD I
Q05682-3	3, HELA L-CAD I
Q05682-4	4, WI-38 L-CAD II, 1-CAD
Q05682-5	5, HELA L-CAD II
Q05682-6	6

RefSeq proteins (5): NP_004333, NP_149129, NP_149130, NP_149131, NP_149347 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006017	Caldesmon	Family
IPR006018	Caldesmon_LSP	Family

Pfam: PF02029

UniProt features (56 total): modified residue 17, region of interest 14, compositionally biased region 11, cross-link 4, splice variant 4, repeat 3, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05682-F1	65.68	0.27

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 (21): 129, 643, 656, 724, 730, 753, 759, 789, 459, 645, 202, 12, 21, 196, 202, 209, 12, 21, 196, 203 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-445355	Smooth Muscle Contraction
R-HSA-397014	Muscle contraction

MSigDB gene sets: 0 (showing top):

GO Biological Process (2): muscle contraction (GO:0006936), actin filament bundle assembly (GO:0051017)

GO Molecular Function (6): actin binding (GO:0003779), calmodulin binding (GO:0005516), tropomyosin binding (GO:0005523), myosin binding (GO:0017022), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (9): stress fiber (GO:0001725), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), myofibril (GO:0030016), actin cap (GO:0030478), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoskeletal protein binding	3
muscle system process	1
cellular component assembly	1
actin filament bundle organization	1
protein binding	1
cell adhesion molecule binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
cytoplasm	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
cytoskeleton	1
contractile muscle fiber	1
cortical actin cytoskeleton	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1862 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CALD1	CALM1	P02593	996
CALD1	CALML6	Q8TD86	996
CALD1	CALML3	P27482	996
CALD1	CALML4	Q96GE6	996
CALD1	CALML5	Q9NZT1	996
CALD1	CNN1	P51911	826
CALD1	BCL7C	Q8WUZ0	779
CALD1	TAGLN	Q01995	727
CALD1	CD34	P28906	722
CALD1	ANO1	Q5XXA6	720
CALD1	BCL7B	Q9BQE9	690
CALD1	BCL7A	Q4VC05	689
CALD1	MYH11	P35749	686
CALD1	NIPBL	Q6KC79	678
CALD1	CD99L2	Q8TCZ2	669

IntAct

84 interactions, top by confidence:

A	B	Type	Score
HSP90AA1	HSP90AB1	psi-mi:“MI:0914”(association)	0.840
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HSP90AA1	CHUK	psi-mi:“MI:0914”(association)	0.670
CALD1	SPTAN1	psi-mi:“MI:0915”(physical association)	0.560
ATF3	MYL6B	psi-mi:“MI:0914”(association)	0.530
CALD1	TINF2	psi-mi:“MI:0915”(physical association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
CALD1	DLD	psi-mi:“MI:0915”(physical association)	0.400
CALD1	AXIN1	psi-mi:“MI:0915”(physical association)	0.400
ARHGAP28	CALD1	psi-mi:“MI:0915”(physical association)	0.400
TPTE2	CALD1	psi-mi:“MI:0915”(physical association)	0.400
BCL7A	CALD1	psi-mi:“MI:0915”(physical association)	0.400
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
TERF1	CALD1	psi-mi:“MI:0915”(physical association)	0.370
CALD1	POT1	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
BCAR1	CEP290	psi-mi:“MI:0914”(association)	0.350
ARRB1		psi-mi:“MI:0914”(association)	0.350
PDHA1		psi-mi:“MI:0914”(association)	0.350

BioGRID (313): CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CALD1 (Affinity Capture-MS)

ESM2 similar proteins: A2AG50, A2AUY4, D4A4L4, E7F5E1, O13024, O60237, O60293, O75167, O88735, O94885, P12957, P53352, P62025, Q05682, Q0IHP2, Q14244, Q2MJV9, Q2YDJ0, Q32N93, Q3KQW7, Q3MHH7, Q3UH68, Q4G0F8, Q501J7, Q5R7F9, Q5RG44, Q5U236, Q5ZIA2, Q62736, Q6Y7W6, Q6Y7W8, Q80ST9, Q80TN7, Q80Z38, Q86VQ0, Q8BG95, Q8IVL0, Q8IVL1, Q8IWC1, Q8K298

Diamond homologs: P12957, P13505, Q05682, Q62736, P19973, P33241, Q27976

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
MYLK	down-regulates	CALD1	phosphorylation
PAK3	down-regulates	CALD1	phosphorylation
CAMK2A	down-regulates	CALD1	phosphorylation
Gbeta	down-regulates	CALD1	phosphorylation
ERK1/2	down-regulates	CALD1	phosphorylation
CDK5	“down-regulates quantity by destabilization”	CALD1	phosphorylation
PRKCA	down-regulates	CALD1	phosphorylation
MAPK1	down-regulates	CALD1	phosphorylation
MAPK3	down-regulates	CALD1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
ESR-mediated signaling	8	13.7×	8e-05
Extra-nuclear estrogen signaling	5	11.4×	8e-03
Apoptosis	5	11.2×	8e-03
Programmed Cell Death	5	9.8×	1e-02
Estrogen-dependent gene expression	7	7.1×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	5	19.5×	2e-03
G1/S transition of mitotic cell cycle	6	13.1×	2e-03
negative regulation of gene expression	8	6.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	103
Likely benign	10
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2660 predictions. Top by Δscore:

Variant	Effect	Δscore
7:134779746:CAAGG:C	donor_loss	1.0000
7:134779748:AGG:A	donor_loss	1.0000
7:134779749:GGT:G	donor_loss	1.0000
7:134779750:GTAAG:G	donor_loss	1.0000
7:134843877:A:AG	acceptor_gain	1.0000
7:134843878:TTCCA:T	acceptor_loss	1.0000
7:134843879:TCCAG:T	acceptor_loss	1.0000
7:134843880:CCAG:C	acceptor_loss	1.0000
7:134843881:CAG:C	acceptor_loss	1.0000
7:134843882:A:T	acceptor_loss	1.0000
7:134843883:GGT:G	acceptor_gain	1.0000
7:134843967:GACCT:G	donor_gain	1.0000
7:134843968:ACCT:A	donor_gain	1.0000
7:134843969:CCT:C	donor_gain	1.0000
7:134843970:CT:C	donor_gain	1.0000
7:134843971:TG:T	donor_loss	1.0000
7:134843972:G:C	donor_loss	1.0000
7:134843972:G:GG	donor_gain	1.0000
7:134843973:TGA:T	donor_loss	1.0000
7:134843974:GAG:G	donor_loss	1.0000
7:134843976:G:GG	donor_gain	1.0000
7:134867691:A:AG	acceptor_gain	1.0000
7:134867691:AGGT:A	acceptor_loss	1.0000
7:134867692:G:GG	acceptor_gain	1.0000
7:134867692:GGTCC:G	acceptor_gain	1.0000
7:134867800:GAAAG:G	donor_gain	1.0000
7:134867802:AAG:A	donor_gain	1.0000
7:134867803:AG:A	donor_gain	1.0000
7:134867803:AGGTA:A	donor_loss	1.0000
7:134867804:GG:G	donor_gain	1.0000

AlphaMissense

5292 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:134928806:C:A	R42S	1.000
7:134928810:G:C	R43P	1.000
7:134960058:T:A	W716R	1.000
7:134960058:T:C	W716R	1.000
7:134960060:G:C	W716C	1.000
7:134960060:G:T	W716C	1.000
7:134960578:T:A	W749R	1.000
7:134960578:T:C	W749R	1.000
7:134867762:T:C	L10P	0.999
7:134867765:G:C	R11T	0.999
7:134867766:A:C	R11S	0.999
7:134867766:A:T	R11S	0.999
7:134867778:G:C	R15S	0.999
7:134867778:G:T	R15S	0.999
7:134928798:G:C	R39P	0.999
7:134928804:G:C	R41P	0.999
7:134928807:G:C	R42P	0.999
7:134928809:C:A	R43S	0.999
7:134928813:G:C	R44P	0.999
7:134928815:G:C	A45P	0.999
7:134928819:G:C	R46P	0.999
7:134947678:T:C	L568P	0.999
7:134950411:G:C	R611P	0.999
7:134950415:A:C	R612S	0.999
7:134950415:A:T	R612S	0.999
7:134950416:G:C	A613P	0.999
7:134958091:T:C	L653S	0.999
7:134960049:A:G	K713E	0.999
7:134960051:G:C	K713N	0.999
7:134960051:G:T	K713N	0.999

dbSNP variants (sampled 300 via entrez): RS1000003157 (7:134880512 G>A), RS1000012759 (7:134821816 C>T), RS1000090731 (7:134780300 A>T), RS1000098496 (7:134825764 T>C,G), RS1000103430 (7:134969375 C>T), RS1000149398 (7:134916448 A>T), RS1000149778 (7:134760196 T>G), RS1000152673 (7:134803905 A>G), RS1000158064 (7:134961537 A>G), RS1000172838 (7:134914911 C>A), RS1000194847 (7:134863762 T>A), RS1000198510 (7:134773997 C>T), RS1000214255 (7:134811382 A>G), RS1000228722 (7:134759866 C>T), RS1000232488 (7:134779176 C>A)

Disease associations

OMIM: gene MIM:114213 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002366_3	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 1 peripheral neuropathy)	6.000000e-06
GCST003657_3	Attention deficit hyperactivity disorder symptom score	2.000000e-06
GCST004862_123	Itch intensity from mosquito bite adjusted by bite size	4.000000e-06
GCST90002383_439	Hematocrit	2.000000e-12
GCST90002384_164	Hemoglobin	2.000000e-10
GCST90002403_592	Red blood cell count	1.000000e-09
GCST90011770_14	Glaucoma (primary open-angle)	2.000000e-06
GCST90011900_193	Serum alkaline phosphatase levels	3.000000e-13
GCST90013406_41	Liver enzyme levels (alkaline phosphatase)	8.000000e-12
GCST90013407_44	Liver enzyme levels (gamma-glutamyl transferase)	8.000000e-19

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0007860	ADHD symptom measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count
EFO:0004533	alkaline phosphatase measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724794 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.48	IC50	3340	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178722: Inhibition of CAD (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	3.3400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	7
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance, increases expression (+2 more)	6
methylmercuric chloride	increases expression, affects cotreatment	4
Air Pollutants	affects cotreatment, decreases expression, increases abundance	3
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression, decreases expression	3
Benzo(a)pyrene	increases methylation, decreases methylation, increases expression	3
Smoke	decreases expression, increases abundance, increases expression	3
trichostatin A	increases expression	2
mono-(2-ethylhexyl)phthalate	decreases expression, decreases methylation, increases abundance	2
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
perfluorooctane sulfonic acid	decreases expression	2
Acetaminophen	decreases expression	2
Acrolein	increases abundance, affects cotreatment, decreases expression, increases oxidation	2
Diethylhexyl Phthalate	decreases methylation, increases abundance, increases expression	2
Doxorubicin	affects response to substance, affects expression	2
Estradiol	increases expression, affects cotreatment	2
Formaldehyde	decreases expression, increases expression	2
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression, increases expression, affects expression	2
Potassium Dichromate	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
geldanamycin	increases expression	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697452	Binding	Inhibition of CAD (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1LZ	Abcam HeLa CALD1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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