CATSPER2

Summary

CATSPER2 (cation channel sperm associated 2, HGNC:18810) is a protein-coding gene on chromosome 15q15.3, encoding Cation channel sperm-associated protein 2 (Q96P56). Pore-forming subunit of the CatSper complex, a sperm-specific voltage-gated calcium channel, that plays a central role in calcium-dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acrosome reaction and chemotaxis towards the….

This gene encodes a member of a family of cation channel proteins that localize to the flagellum of spermatozoa. Defects at this locus causes male infertility. Alternatively spliced transcript variants have been observed at this locus. Readthrough transcription originates upstream of this locus in diphosphoinositol pentakisphosphate kinase 1 pseudogene 1 and is represented by GeneID:110006325. Related pseudogenes are found next to this locus on chromosome 15 and on chromosome 5.

Source: NCBI Gene 117155 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 192 total — 8 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 14
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_172095

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18810
Approved symbol	CATSPER2
Name	cation channel sperm associated 2
Location	15q15.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166762
Ensembl biotype	protein_coding
OMIM	607249
Entrez	117155

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000321596, ENST00000381761, ENST00000396879, ENST00000409481, ENST00000415968, ENST00000419262, ENST00000432420, ENST00000433380, ENST00000450810, ENST00000464721, ENST00000469461, ENST00000472960

RefSeq mRNA: 3 — MANE Select: NM_172095 NM_001282309, NM_001282310, NM_172095

CCDS: CCDS10099, CCDS32216, CCDS73714

Canonical transcript exons

ENST00000396879 — 13 exons

Exon	Start	End
ENSE00001146137	43635360	43635416
ENSE00001526572	43628503	43630732
ENSE00001715471	43635727	43635826
ENSE00003492387	43648629	43648844
ENSE00003500886	43640324	43640496
ENSE00003503149	43632717	43632934
ENSE00003520967	43647050	43647118
ENSE00003527303	43647917	43648063
ENSE00003547458	43632199	43632363
ENSE00003612180	43638904	43639028
ENSE00003674924	43636041	43636219
ENSE00003675339	43639643	43639798
ENSE00003694462	43647294	43647467

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 96.55.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0281 / max 30.6738, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149618	0.0281	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	96.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.84	gold quality
cerebellar cortex	UBERON:0002129	94.79	gold quality
cerebellar hemisphere	UBERON:0002245	94.77	gold quality
cerebellum	UBERON:0002037	94.71	gold quality
right testis	UBERON:0004534	93.71	gold quality
left testis	UBERON:0004533	93.66	gold quality
buccal mucosa cell	CL:0002336	90.64	gold quality
testis	UBERON:0000473	89.95	gold quality
adenohypophysis	UBERON:0002196	88.98	gold quality
pituitary gland	UBERON:0000007	88.16	gold quality
right uterine tube	UBERON:0001302	85.20	gold quality
nipple	UBERON:0002030	85.05	gold quality
right frontal lobe	UBERON:0002810	84.11	gold quality
right lobe of thyroid gland	UBERON:0001119	83.62	gold quality
colonic epithelium	UBERON:0000397	83.50	gold quality
mucosa of transverse colon	UBERON:0004991	82.84	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.66	gold quality
parietal lobe	UBERON:0001872	82.54	gold quality
nucleus accumbens	UBERON:0001882	82.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.96	gold quality
hypothalamus	UBERON:0001898	81.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.88	gold quality
postcentral gyrus	UBERON:0002581	81.78	gold quality
anterior cingulate cortex	UBERON:0009835	81.76	gold quality
left lobe of thyroid gland	UBERON:0001120	81.60	gold quality
left ovary	UBERON:0002119	81.56	gold quality
spinal cord	UBERON:0002240	81.20	gold quality
sural nerve	UBERON:0015488	81.01	gold quality
brain	UBERON:0000955	81.00	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting CATSPER2, 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-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-7843-3P	98.31	67.94	803
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-6724-5P	96.41	63.11	507

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• CatSper1 and CatSper2 can associate with and modulate the function of the Ca(v)3.3 channel, which might be important in the regulation of sperm function. (PMID:16740636)
• Levels of Tektin 2 and CatSper 2 proteins are positively associated with sperm motility parameters. Measurements of Tektin 2 levels can be correlated with the clinical outcome of ICSI. (PMID:23519396)
• disruption of CATSPER2 current is a significant factor causing idiopathic male infertility; the specific copy number variation disrupts one gene copy in the region 43894500-43950000 in chromosome 15 (PMID:30629171)
• Frequency of the STRC-CATSPER2 deletion in STRC-associated hearing loss patients. (PMID:35022556)
• Dispersed DNA variants underlie hearing loss in South Florida’s minority population. (PMID:37996878)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Catsper2	ENSMUSG00000033486
rattus_norvegicus	Catsper2	ENSRNOG00000023064

Paralogs (26): CACNA1G (ENSG00000006283), SCN4A (ENSG00000007314), CACNA1S (ENSG00000081248), CACNA1I (ENSG00000100346), CACNA1F (ENSG00000102001), NALCN (ENSG00000102452), SCN2A (ENSG00000136531), SCN7A (ENSG00000136546), CACNA1A (ENSG00000141837), SCN1A (ENSG00000144285), CACNA1B (ENSG00000148408), CACNA1C (ENSG00000151067), CATSPER3 (ENSG00000152705), SCN3A (ENSG00000153253), CACNA1D (ENSG00000157388), TPCN2 (ENSG00000162341), SCN11A (ENSG00000168356), SCN9A (ENSG00000169432), CATSPER1 (ENSG00000175294), SCN5A (ENSG00000183873), SCN10A (ENSG00000185313), TPCN1 (ENSG00000186815), CATSPER4 (ENSG00000188782), CACNA1H (ENSG00000196557), SCN8A (ENSG00000196876), CACNA1E (ENSG00000198216)

Protein

Protein identifiers

Cation channel sperm-associated protein 2 — Q96P56 (reviewed: Q96P56)

All UniProt accessions (6): Q96P56, B8ZZQ9, E7EX46, F8W9H2, H7BZ89, H7C2X6

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming subunit of the CatSper complex, a sperm-specific voltage-gated calcium channel, that plays a central role in calcium-dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acrosome reaction and chemotaxis towards the oocyte.

Subunit / interactions. Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG, CATSPERD, CATSPERE, CATSPERZ, CATSPERT, CATSPERQ, CATSPERH and EFCAB9. HSPA1 may be an additional auxiliary complex member. The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel. The auxiliary CATSPERB, CATSPERG, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively. CATSPERH interacts with CATSPERB, further stabilizing the complex. CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane. Interacts with Ca(v)3.3/CACNA1I, leading to suppression of T-type calcium channel activity.

Subcellular location. Cell projection. Cilium. Flagellum membrane.

Tissue specificity. Testis-specific.

Disease relevance. Deafness-infertility syndrome (DIS) [MIM:611102] Characterized by deafness and infertility and is caused by large contiguous gene deletions at 15q15.3 that removes both STRC and CATSPER2 genes. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The CatSper calcium channel is indirectly activated by extracellular progesterone and prostaglandins following the sequence: progesterone > PGF1-alpha = PGE1 > PGA1 > PGE2 » PGD2. The CatSper calcium channel is directly inhibited by endocannabinoid 2-arachidonoylglycerol (2AG). Indirect activation by progesterone takes place via the following mechanism: progesterone binds and activates the acylglycerol lipase ABHD2, which in turn mediates hydrolysis of 2AG inhibitor, relieving inhibition of the CatSper channel. The primary effect of progesterone activation is to shift voltage dependence towards more physiological, negative membrane potentials; it is not mediated by metabotropic receptors and second messengers. Sperm capacitation enhances the effect of progesterone by providing additional negative shift. Also activated by the elevation of intracellular pH.

Similarity. Belongs to the cation channel sperm-associated (TC 1.A.1.19) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96P56-1	1, Variant 2	yes
Q96P56-2	2, Variant 1
Q96P56-3	3, Variant 3
Q96P56-4	4

RefSeq proteins (3): NP_001269238, NP_001269239, NP_742093* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005821	Ion_trans_dom	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR028747	CatSper2	Family

Pfam: PF00520

Catalyzed reactions (Rhea), 1 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)

UniProt features (27 total): topological domain 8, transmembrane region 6, splice variant 5, compositionally biased region 2, sequence variant 2, chain 1, intramembrane region 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96P56-F1	69.83	0.17

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1300642	Sperm Motility And Taxes

MSigDB gene sets: 132 (showing top): RNGTGGGC_UNKNOWN, TGACCTY_ERR1_Q2, GOBP_MALE_GAMETE_GENERATION, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_CELL_MATURATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, TGACATY_UNKNOWN, ATAACCT_MIR154, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, WEBER_METHYLATED_HCP_IN_SPERM_UP

GO Biological Process (11): calcium ion transport (GO:0006816), fertilization (GO:0009566), flagellated sperm motility (GO:0030317), sperm capacitation (GO:0048240), monoatomic ion transport (GO:0006811), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), calcium ion transmembrane transport (GO:0070588), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (5): calcium-activated cation channel activity (GO:0005227), voltage-gated calcium channel activity (GO:0005245), monoatomic ion channel activity (GO:0005216), calcium channel activity (GO:0005262), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), CatSper complex (GO:0036128), cilium (GO:0005929), membrane (GO:0016020), motile cilium (GO:0031514), monoatomic ion channel complex (GO:0034702), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Fertilization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
transport	2
cellular anatomical structure	2
metal ion transport	1
sexual reproduction	1
reproductive process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
male gamete generation	1
cellular developmental process	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
monoatomic ion-gated channel activity	1
ligand-gated monoatomic cation channel activity	1
calcium channel activity	1
voltage-gated monoatomic cation channel activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1
voltage-gated calcium channel complex	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

1186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CATSPER2	STRC	Q7RTU9	989
CATSPER2	CKMT1B	P12532	948
CATSPER2	PPIP5K1	Q6PFW1	927
CATSPER2	CATSPERB	Q9H7T0	796
CATSPER2	CDAN1	Q8IWY9	789
CATSPER2	CATSPER4	Q7RTX7	767
CATSPER2	CATSPERD	Q86XM0	748
CATSPER2	CATSPER3	Q86XQ3	727
CATSPER2	EFCAB9	A8MZ26	705
CATSPER2	CATSPERE	Q5SY80	664
CATSPER2	CATSPERZ	Q9NTU4	643
CATSPER2	CATSPER1	Q8NEC5	563
CATSPER2	CATSPERG	Q6ZRH7	545
CATSPER2	DNAH1	Q9P2D7	495
CATSPER2	TEKT2	Q9UIF3	478

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CACNA1I	CATSPER2	psi-mi:“MI:0915”(physical association)	0.520
CATSPER2	CACNA1I	psi-mi:“MI:0915”(physical association)	0.520
rep	CATSPER2	psi-mi:“MI:0915”(physical association)	0.490
CATSPER2	RCAN1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (4): CATSPER2 (Synthetic Lethality), RCAN1 (Affinity Capture-MS), CATSPER2 (Two-hybrid), CATSPER2 (Affinity Capture-MS)

ESM2 similar proteins: A2ARP9, A2ASI5, B1AWN6, B1AYL1, F1LQQ7, O08562, O46669, O70344, O73925, O88420, O88457, O88944, O97531, P02719, P04775, P08104, P0DMA5, P15389, P15390, P35499, P51787, P59111, P97414, Q01118, Q14524, Q28371, Q28644, Q2XVR7, Q62205, Q62968, Q6AXP6, Q6QIY3, Q7RTX7, Q8K3F6, Q96L42, Q96P56, Q99250, Q9ER60, Q9JJV9, Q9JK45

Diamond homologs: A2ARP9, Q6AXP6, Q96P56, A2APX8, A2ASI5, B1AWN6, B1AYL1, D0E0C2, F1LQQ7, O08562, O42398, O46669, O73705, O73706, O73707, O88420, O88457, P02719, P04774, P04775, P08104, P0DMA5, P15389, P15390, P35498, P35499, P35500, Q01118, Q05973, Q07652, Q14524, Q15858, Q15878, Q20JQ7, Q28371, Q28644, Q2XVR3, Q2XVR4, Q2XVR5, Q2XVR6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CATSPER2	“form complex”	“CatSpermasome complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	1
Uncertain significance	120
Likely benign	21
Benign	25

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1175705	NC_000015.9:g.(43851199_43890333)_(43897676_43924279)del	Pathogenic
1175707	NC_000015.9:g.(43851199_43890391)_(?_44038820)del	Pathogenic
148737	GRCh38/hg38 15q15.3(chr15:43596729-43659103)x0	Pathogenic
162825	NM_172095.1(CATSPER2):c.(?718-34)(843-857_?)del	Pathogenic
3024592	GRCh37/hg19 15q15.3(chr15:43888054-43941032)x0	Pathogenic
443647	GRCh37/hg19 15q15.3(chr15:43868571-44014518)x0	Pathogenic
562140	NC_000015.9:g.(43886857_43888004)_(43984930_43992627)del	Pathogenic
625827	GRCh37/hg19 15q15.3(chr15:43891364-43939659)	Pathogenic
148856	GRCh38/hg38 15q15.2-15.3(chr15:42566761-43847106)x1	Likely pathogenic

SpliceAI

1953 predictions. Top by Δscore:

Variant	Effect	Δscore
15:43636039:AC:A	donor_gain	1.0000
15:43636040:CC:C	donor_gain	1.0000
15:43636040:CCCAT:C	donor_gain	1.0000
15:43636054:TATGA:T	donor_gain	1.0000
15:43636063:T:TA	donor_gain	1.0000
15:43636174:C:CT	acceptor_gain	1.0000
15:43640365:T:TA	donor_gain	1.0000
15:43647922:AACTC:A	donor_gain	1.0000
15:43647926:C:CA	donor_gain	1.0000
15:43647958:AAG:A	donor_gain	1.0000
15:43630728:CTGCA:C	acceptor_gain	0.9900
15:43630733:C:CC	acceptor_gain	0.9900
15:43632936:T:C	acceptor_gain	0.9900
15:43635351:A:AC	donor_gain	0.9900
15:43635352:C:CC	donor_gain	0.9900
15:43636035:GCTT:G	donor_loss	0.9900
15:43636036:CTT:C	donor_loss	0.9900
15:43636037:TTA:T	donor_loss	0.9900
15:43636038:TA:T	donor_loss	0.9900
15:43636039:A:AC	donor_gain	0.9900
15:43636039:A:C	donor_loss	0.9900
15:43636040:C:CC	donor_gain	0.9900
15:43636088:A:AT	donor_gain	0.9900
15:43636167:A:T	acceptor_gain	0.9900
15:43636174:C:T	acceptor_gain	0.9900
15:43636175:A:T	acceptor_gain	0.9900
15:43636218:CC:C	acceptor_gain	0.9900
15:43636219:CC:C	acceptor_gain	0.9900
15:43636219:CCTA:C	acceptor_loss	0.9900
15:43636220:C:CC	acceptor_gain	0.9900

AlphaMissense

3484 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:43632350:C:A	W470C	0.997
15:43632350:C:G	W470C	0.997
15:43632352:A:G	W470R	0.997
15:43632352:A:T	W470R	0.997
15:43632222:C:G	R513P	0.996
15:43632243:A:G	L506P	0.996
15:43632289:A:G	W491R	0.996
15:43632289:A:T	W491R	0.996
15:43630727:C:G	A523P	0.992
15:43632287:C:A	W491C	0.992
15:43632287:C:G	W491C	0.992
15:43630723:A:G	L524P	0.991
15:43632252:A:G	L503P	0.991
15:43647984:G:C	F26L	0.987
15:43647984:G:T	F26L	0.987
15:43647986:A:G	F26L	0.987
15:43647997:A:G	L22P	0.987
15:43632202:C:G	A520P	0.986
15:43632213:A:G	L516S	0.986
15:43632273:A:G	L496P	0.985
15:43632265:A:C	Y499D	0.983
15:43632351:C:G	W470S	0.983
15:43647979:A:G	L28P	0.980
15:43632267:C:G	R498P	0.977
15:43632327:A:G	L478P	0.977
15:43648006:C:G	R19P	0.976
15:43632248:T:A	E504D	0.975
15:43632248:T:G	E504D	0.975
15:43632249:T:A	E504V	0.973
15:43632288:C:G	W491S	0.972

dbSNP variants (sampled 300 via entrez): RS1000388056 (15:43648136 C>T), RS1000420486 (15:43648384 A>G), RS1000751758 (15:43649076 CAGCCG>C), RS1000772111 (15:43648996 C>A,T), RS1000899631 (15:43637731 G>A), RS1001025573 (15:43632485 A>G), RS1001268988 (15:43650559 T>C), RS1001420342 (15:43646857 A>G), RS1001458069 (15:43632193 C>G,T), RS1001691335 (15:43629974 G>A), RS1001698670 (15:43650817 C>G), RS1001866196 (15:43636676 C>T), RS1001898683 (15:43636390 T>C), RS1001966399 (15:43642371 A>G), RS1002120807 (15:43629806 C>T)

Disease associations

OMIM: gene MIM:607249 | disease phenotypes: MIM:603720, MIM:189800

GenCC curated gene-disease

Mondo (5): autosomal recessive nonsyndromic hearing loss 16 (MONDO:0011364), preeclampsia (MONDO:0005081), infertility disorder (MONDO:0005047), male infertility (MONDO:0005372), hearing loss disorder (MONDO:0005365)

Orphanet (3): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Preeclampsia (Orphanet:275555), Rare genetic deafness (Orphanet:96210)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000407	Sensorineural hearing impairment
HP:0000798	Oligozoospermia
HP:0001751	Abnormal vestibular function
HP:0003251	Male infertility
HP:0003577	Congenital onset
HP:0008619	Bilateral sensorineural hearing impairment
HP:0008669	Abnormal spermatogenesis
HP:0011462	Young adult onset
HP:0012207	Reduced sperm motility
HP:0012208	Immotile sperm
HP:0012865	Abnormal sperm head morphology
HP:0012868	Abnormal sperm tail morphology

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004748_30	Lung cancer	2.000000e-06
GCST004750_6	Squamous cell lung carcinoma	2.000000e-06
GCST006611_11	HDL cholesterol	9.000000e-26
GCST012232_22	Lipoprotein (a) levels	4.000000e-28
GCST90013406_53	Liver enzyme levels (alkaline phosphatase)	7.000000e-34
GCST90013407_37	Liver enzyme levels (gamma-glutamyl transferase)	9.000000e-22

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006925	lipoprotein A measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D007246	Infertility	C12.100.750
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
D011225	Pre-Eclampsia	C12.050.703.395.249
C566339	Deafness, Autosomal Recessive 16 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — CatSper and Two-Pore channels (TPC)

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
progesterone	Full agonist	8.11	pEC50
PGE1	Full agonist	6.3	pEC50
PGE2	Full agonist	6.3	pEC50
PGF1α	Full agonist	6.3	pEC50
NNC55-0396	Inhibition	5.7	pIC50
ruthenium red	Antagonist	5.0	pIC50
mibefradil	Inhibition	4.5	pIC50
Cd2+	Inhibition	3.7	pIC50
Ni2+	Antagonist	3.5	pIC50

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
beta-methylcholine	affects expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Hydrogen Peroxide	affects expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Asbestos, Crocidolite	decreases expression	1
Thapsigargin	decreases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	increases expression	1
Acrylamide	decreases expression	1
S-Nitrosoglutathione	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_YA33	IDG-HEK293T-CATSPER2-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	PHASE4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	PHASE4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	PHASE4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	PHASE4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665	PHASE4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial