CATSPER1

Summary

CATSPER1 (cation channel sperm associated 1, HGNC:17116) is a protein-coding gene on chromosome 11q13.1, encoding Cation channel sperm-associated protein 1 (Q8NEC5). 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….

Calcium ions play a primary role in the regulation of sperm motility. This gene belongs to a family of putative cation channels that are specific to spermatozoa and localize to the flagellum. The protein family features a single repeat with six membrane-spanning segments and a predicted calcium-selective pore region.

Source: NCBI Gene 117144 — RefSeq curated summary.

At a glance

• Gene–disease (curated): non-syndromic male infertility due to sperm motility disorder (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 222 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 6
• Druggable target: yes
• MANE Select transcript: NM_053054

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17116
Approved symbol	CATSPER1
Name	cation channel sperm associated 1
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	CATSPER
Ensembl gene	ENSG00000175294
Ensembl biotype	protein_coding
OMIM	606389
Entrez	117144

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000312106, ENST00000529244

RefSeq mRNA: 1 — MANE Select: NM_053054 NM_053054

CCDS: CCDS8127

Canonical transcript exons

ENST00000312106 — 12 exons

Exon	Start	End
ENSE00001189859	66018827	66018902
ENSE00001189870	66020317	66020389
ENSE00001189876	66020564	66020627
ENSE00001189890	66021094	66021185
ENSE00001189899	66021496	66021643
ENSE00001189907	66021766	66021879
ENSE00001189909	66022849	66023061
ENSE00001189918	66025164	66026479
ENSE00002162650	66016752	66016916
ENSE00003544461	66020811	66020954
ENSE00003544781	66020140	66020200
ENSE00003650821	66017060	66017174

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 86.42.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1680 / max 67.7072, expressed in 731 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120750	1.8670	663
120751	0.2500	126
120752	0.0443	3
206343	0.0067	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.42	gold quality
monocyte	CL:0000576	84.60	gold quality
leukocyte	CL:0000738	84.38	gold quality
granulocyte	CL:0000094	84.17	gold quality
left testis	UBERON:0004533	82.83	gold quality
right testis	UBERON:0004534	82.41	gold quality
testis	UBERON:0000473	80.38	gold quality
descending thoracic aorta	UBERON:0002345	76.20	gold quality
thoracic aorta	UBERON:0001515	76.06	gold quality
ascending aorta	UBERON:0001496	76.05	gold quality
blood	UBERON:0000178	72.44	gold quality
aorta	UBERON:0000947	69.53	gold quality
popliteal artery	UBERON:0002250	64.76	gold quality
tibial artery	UBERON:0007610	64.75	gold quality
right coronary artery	UBERON:0001625	64.32	gold quality
left coronary artery	UBERON:0001626	64.10	gold quality
coronary artery	UBERON:0001621	63.59	gold quality
bone marrow	UBERON:0002371	63.11	gold quality
upper lobe of left lung	UBERON:0008952	63.02	gold quality
apex of heart	UBERON:0002098	62.09	gold quality
vermiform appendix	UBERON:0001154	61.45	gold quality
upper lobe of lung	UBERON:0008948	60.94	gold quality
right lung	UBERON:0002167	60.56	gold quality
vena cava	UBERON:0004087	60.26	gold quality
caecum	UBERON:0001153	59.81	gold quality
mammary duct	UBERON:0001765	59.52	gold quality
bone marrow cell	CL:0002092	58.82	silver quality
epithelium of nasopharynx	UBERON:0001951	58.48	gold quality
saphenous vein	UBERON:0007318	58.06	gold quality
spleen	UBERON:0002106	57.96	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-10	no	64.93
E-ANND-3	no	1.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SOX5, SOX9

miRNA regulators (miRDB)

9 targeting CATSPER1, 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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4530	99.69	66.47	1509

Literature-anchored findings (GeneRIF, showing 29)

• Potential role for CatSper in sperm motility and fertility in mouse and human. CatSper is therefore implicated as a potential target to explore the molecular mechanisms of male infertility. (PMID:14688170)
• CATSPER1 is meiotically and post-meiotically expressed in human testis tissue. (PMID:16625279)
• 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)
• CatSper1 may be a potential target for immunocontraception, and the antibody may be a tool to study the function of ion channels in sperm. (PMID:18976756)
• sequence analysis of CATSPER1 in heritable forms of nonsyndromic male infertility revealed two separate insertion mutations (c.539-540insT and c.948-949insATGGC) that are predicted to lead to frameshifts and premature stop codons (PMID:19344877)
• Studies indicate that CATSPER channel represents a novel human male fertility factor. (PMID:20648059)
• The decreased or abnormal expression of the CatSper1 protein may be a factor involved in the pathogenesis of idiopathic asthenozoospermia. (PMID:21404705)
• progesterone activates the sperm-specific, pH-sensitive CatSper Ca(2+) channel (PMID:21412338)
• human CatSper is synergistically activated by elevation of intracellular pH and extracellular progesterone (PMID:21412339)
• It was shown that odorants directly activate CatSper without involving G protein-coupled receptors and cAMP. Membrane-permeable analogues of cyclic nucleotides activated CatSper directly via an extracellular site. (PMID:22354039)
• The immediate upstream region and the first exon in the human CATSPER1 gene negatively regulate transcriptional activity. (PMID:23313885)
• This work reports the cloning and characterization of the promoter regions in the human and murine Catsper1 genes. The immediate upstream region and the first exon in the human CATSPER1 gene negatively regulate transcriptional activity. The mouse Catsper1 promoter exhibited transcriptional activity in both orientations and displayed significant expression levels in mouse testis in vivo. (PMID:23313885)
• CatSper activation can elicit functionally different behaviors according to the sensitivity of the Ca(2+) store, which may be regulated by capacitation and NO from the cumulus. (PMID:23344959)
• CatSper is indeed the principal Ca2+ channel of human spermatozoa, and that it is strongly potentiated by progesterone. (PMID:23530196)
• Progesterone via CatSper activates the PI3K-AKT pathway required for motility and hyperactivation but not for acrosome reaction. (PMID:23623968)
• Sox5 and Sox9 cause a significant increase in transactivation of the Catsper1 promoter. (PMID:25101494)
• The role of CATSPER1 in idiopathic asthenospermia pathogenesis: exonal SNP rs1893316 in CATSPER1 significantly correlated with idiopathic asthenospermia risk (PMID:26354096)
• Sperm with a near absence of CatSper current failed to respond to activation of CatSper by progesterone and there was fertilization failure at IVF. (PMID:26453676)
• Electrophysiological studies showed a significant increase in Cd(2+) and manganese (Mn(2+)) currents through the CaV3.1 mutants as well as a reduction in the inhibitory effect of Cd(2+) on the Ca(2+) current. (PMID:27134080)
• explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2 (PMID:28507119)
• The human CATSPER1 promoter is positively regulated in vitro by CREB-A in HEK293 and GC1-spg cells. Both lines showed differential transcriptional regulation, which was defined by the factors and coactivators present in each cell line as well as the context in which the CRE sites were found in the promoter. (PMID:30017233)
• Catsper1 tyrosine phosphorylation functions as an intracellular sensor for Ca (2+) entry in human sperm through regulation of cytoplasmic pH. (PMID:30203545)
• results show that the transcriptional factor SRY specifically binds to different sites in the promoter sequence and has the ability to control CATSPER1 gene transcription. (PMID:30379860)
• CatSper: The complex main gate of calcium entry in mammalian spermatozoa. (PMID:32712386)
• Roles of CatSper channels in the pathogenesis of asthenozoospermia and the therapeutic effects of acupuncture-like treatment on asthenozoospermia. (PMID:33456575)
• CRISP2, CATSPER1 and PATE1 Expression in Human Asthenozoospermic Semen. (PMID:34440724)
• Overview of the complications of diabetes. (PMID:3530540)
• Both protein and non-protein components in extracellular vesicles of human seminal plasma improve human sperm function via CatSper-mediated calcium signaling. (PMID:38335261)
• Flagellar pH homeostasis mediated by Na+/H+ exchangers regulates human sperm functions through coupling with CatSper and KSper activation. (PMID:38366201)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Catsper1	ENSMUSG00000038498

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), CATSPER2 (ENSG00000166762), SCN11A (ENSG00000168356), SCN9A (ENSG00000169432), SCN5A (ENSG00000183873), SCN10A (ENSG00000185313), TPCN1 (ENSG00000186815), CATSPER4 (ENSG00000188782), CACNA1H (ENSG00000196557), SCN8A (ENSG00000196876), CACNA1E (ENSG00000198216)

Protein

Protein identifiers

Cation channel sperm-associated protein 1 — Q8NEC5 (reviewed: Q8NEC5)

All UniProt accessions (1): Q8NEC5

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. Spermatogenic failure 7 (SPGF7) [MIM:612997] An infertility disorder characterized by non-motile sperm or sperm motility below the normal threshold, low sperm count, increased abnormally structured spermatozoa, and reduced semen volume. 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.

Induction. Down-regulated in patients lacking sperm motility.

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

RefSeq proteins (1): NP_444282* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005821	Ion_trans_dom	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR028746	CatSper1	Family

Pfam: PF00520

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (29 total): topological domain 8, transmembrane region 6, compositionally biased region 6, region of interest 3, sequence variant 3, chain 1, intramembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEC5-F1	56.10	0.07

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1300642	Sperm Motility And Taxes

MSigDB gene sets: 119 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_MALE_GAMETE_GENERATION, chr11q13, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_CELL_MATURATION, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, WEBER_METHYLATED_LCP_IN_SPERM_UP, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_REGULATION_OF_CILIUM_MOVEMENT

GO Biological Process (9): calcium ion transport (GO:0006816), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), flagellated sperm motility (GO:0030317), regulation of cilium beat frequency involved in ciliary motility (GO:0060296), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), calcium ion transmembrane transport (GO:0070588)

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 (9): plasma membrane (GO:0005886), sperm flagellum (GO:0036126), CatSper complex (GO:0036128), sperm principal piece (GO:0097228), 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
cellular anatomical structure	3
transport	2
metal ion transport	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
regulation of cilium beat frequency	1
regulation of cilium movement involved in cell motility	1
regulation of biological quality	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
calcium ion transport	1
monoatomic cation 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
9+2 motile cilium	1
voltage-gated calcium channel complex	1
sperm flagellum	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

1024 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CATSPER1	CATSPERB	Q9H7T0	999
CATSPER1	CATSPERG	Q6ZRH7	972
CATSPER1	CATSPERD	Q86XM0	930
CATSPER1	EFCAB9	A8MZ26	922
CATSPER1	CRISP2	P16562	751
CATSPER1	HSPA2	P54652	742
CATSPER1	KCNU1	A8MYU2	717
CATSPER1	CATSPERZ	Q9NTU4	710
CATSPER1	CATSPERE	Q5SY80	668
CATSPER1	TRPC1	P48995	651
CATSPER1	CATSPER3	Q86XQ3	635
CATSPER1	SPATA16	Q9BXB7	593
CATSPER1	CATSPER4	Q7RTX7	592
CATSPER1	ABHD2	P08910	589
CATSPER1	SLC9C1	Q4G0N8	582

IntAct

447 interactions, top by confidence:

A	B	Type	Score
EMD	CATSPER1	psi-mi:“MI:0915”(physical association)	0.810
CATSPER1	EMD	psi-mi:“MI:0915”(physical association)	0.810
CATSPER1	APOA2	psi-mi:“MI:0915”(physical association)	0.780
CATSPER1	TRIP6	psi-mi:“MI:0915”(physical association)	0.780
CATSPER1	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.780
APOA2	CATSPER1	psi-mi:“MI:0915”(physical association)	0.780
CATSPER1	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
CATSPER1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
CATSPER1	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
CATSPER1	KRTAP10-11	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-6	CATSPER1	psi-mi:“MI:0915”(physical association)	0.720
CATSPER1	AGR2	psi-mi:“MI:0915”(physical association)	0.720
KHDRBS2	CATSPER1	psi-mi:“MI:0915”(physical association)	0.720
RFX6	CATSPER1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP9-2	CATSPER1	psi-mi:“MI:0915”(physical association)	0.720
PLSCR3	CATSPER1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (150): CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid), CATSPER1 (Two-hybrid)

ESM2 similar proteins: A1YEX3, A2A3V1, A2ARP9, A6H8H5, A6H8Z2, A6X8Z9, A8MVX0, F6QRE9, O43526, O43734, O88944, P23499, P24278, P26436, P56696, P86174, Q03717, Q0P6D6, Q14721, Q32NZ6, Q4ZHA6, Q5M7W4, Q5XI03, Q63099, Q68CR7, Q6AXP6, Q6PCP7, Q6UXY8, Q6ZU67, Q76N89, Q7TQI8, Q8BVV7, Q8BW86, Q8K3F6, Q8K451, Q8N7N6, Q8NEC5, Q8NFN8, Q91ZR5, Q92953

Diamond homologs: A2APX8, A2ASI5, B1AWN6, B1AYL1, D0E0C2, F1LQQ7, O08562, O42398, O46669, O73705, O88420, O88457, P02719, P04774, P04775, P08104, P0DMA5, P15389, P15390, P35498, P35499, P35500, Q00975, Q01118, Q02294, Q05973, Q14524, Q15858, Q20JQ7, Q28371, Q28644, Q2XVR3, Q2XVR4, Q2XVR5, Q2XVR6, Q2XVR7, Q62205, Q62968, Q6QIY3, Q8NEC5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CATSPER1	“form complex”	“CatSpermasome complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
Keratinization	30	32.8×	6e-38

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	101.8×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	161
Likely benign	24
Benign	17

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
4400	NM_053054.4(CATSPER1):c.539dup (p.His182fs)	Pathogenic
4401	NM_053054.4(CATSPER1):c.944_948dup (p.Asp317fs)	Pathogenic
2627058	NM_053054.4(CATSPER1):c.889C>T (p.Arg297Ter)	Likely pathogenic

SpliceAI

1998 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66018786:AC:A	donor_gain	1.0000
11:66018787:CC:C	donor_gain	1.0000
11:66018809:C:CA	donor_gain	1.0000
11:66018813:T:A	donor_gain	1.0000
11:66018825:A:AC	donor_gain	1.0000
11:66018826:C:CC	donor_gain	1.0000
11:66018826:CTT:C	donor_gain	1.0000
11:66018826:CTTCT:C	donor_gain	1.0000
11:66018828:T:TA	donor_gain	1.0000
11:66018901:CT:C	acceptor_gain	1.0000
11:66018903:C:CA	acceptor_loss	1.0000
11:66018903:C:CC	acceptor_gain	1.0000
11:66018904:T:A	acceptor_loss	1.0000
11:66018907:A:AC	acceptor_gain	1.0000
11:66018907:A:C	acceptor_gain	1.0000
11:66018909:G:GC	acceptor_gain	1.0000
11:66020134:CCATA:C	donor_loss	1.0000
11:66020135:CATAC:C	donor_loss	1.0000
11:66020136:ATAC:A	donor_loss	1.0000
11:66020137:TACC:T	donor_loss	1.0000
11:66020138:A:AT	donor_loss	1.0000
11:66020318:T:TA	donor_gain	1.0000
11:66020562:A:AC	donor_gain	1.0000
11:66020563:C:CC	donor_gain	1.0000
11:66020806:CCTA:C	donor_loss	1.0000
11:66020807:CTAC:C	donor_loss	1.0000
11:66020808:TACCC:T	donor_loss	1.0000
11:66020809:A:AC	donor_gain	1.0000
11:66020809:AC:A	donor_gain	1.0000
11:66020809:ACCCT:A	donor_loss	1.0000

AlphaMissense

5227 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66020899:G:C	F613L	0.995
11:66020899:G:T	F613L	0.995
11:66020901:A:G	F613L	0.995
11:66020844:A:G	W632R	0.994
11:66020844:A:T	W632R	0.994
11:66020387:A:G	L665P	0.992
11:66020900:A:G	F613S	0.992
11:66020842:C:A	W632C	0.989
11:66020842:C:G	W632C	0.989
11:66021100:A:G	C593R	0.988
11:66020923:G:C	F605L	0.986
11:66020923:G:T	F605L	0.986
11:66020925:A:G	F605L	0.986
11:66020900:A:C	F613C	0.985
11:66021537:G:C	S550R	0.985
11:66021537:G:T	S550R	0.985
11:66021539:T:G	S550R	0.985
11:66017142:A:G	L745P	0.984
11:66021844:A:G	C489R	0.984
11:66022871:G:C	F469L	0.984
11:66022871:G:T	F469L	0.984
11:66022873:A:G	F469L	0.984
11:66017148:A:G	L743P	0.983
11:66020870:A:G	L623P	0.982
11:66022906:A:G	C458R	0.982
11:66020901:A:T	F613I	0.980
11:66021643:T:A	D515V	0.978
11:66020901:A:C	F613V	0.977
11:66021766:C:G	D515H	0.977
11:66020389:G:C	N664K	0.976

dbSNP variants (sampled 300 via entrez): RS1000902696 (11:66018427 A>C,G), RS1000918365 (11:66024870 A>G), RS1001245813 (11:66021263 C>A,T), RS1002429167 (11:66025253 T>G), RS1002584118 (11:66020938 G>A,C), RS1003103963 (11:66028018 C>G,T), RS1003511637 (11:66022212 C>T), RS1003641187 (11:66016497 C>T), RS1004134821 (11:66025505 T>C,G), RS1004187831 (11:66016265 G>A), RS1004422544 (11:66025746 C>G), RS1004865327 (11:66020215 C>A), RS1004872413 (11:66027125 C>T), RS1004959976 (11:66020010 C>T), RS1005330146 (11:66027522 C>A,T)

Disease associations

OMIM: gene MIM:606389 | disease phenotypes: MIM:612997

GenCC curated gene-disease

Disease	Classification	Inheritance
non-syndromic male infertility due to sperm motility disorder	Supportive	Autosomal recessive
spermatogenic failure 7	Limited	Unknown

Mondo (2): spermatogenic failure 7 (MONDO:0013070), (MONDO:0017173)

Orphanet (1): Non-syndromic male infertility due to sperm motility disorder (Orphanet:276234)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000798	Oligozoospermia
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012207	Reduced sperm motility
HP:0012208	Immotile sperm

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002481_8	Acne (severe)	3.000000e-11
GCST007294_7	Body fat distribution (trunk fat ratio)	8.000000e-12
GCST007294_75	Body fat distribution (trunk fat ratio)	1.000000e-07
GCST007295_158	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_48	Body fat distribution (leg fat ratio)	3.000000e-09
GCST008103_21	Bipolar disorder	2.000000e-08
GCST008839_459	Height	2.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567832	Spermatogenic Failure 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1628462 (SINGLE PROTEIN)

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 (10 total), top 10:

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	Inhibition	5.0	pIC50
HC-056456	Channel blocker	4.7	pIC50
mibefradil	Inhibition	4.5	pIC50
Cd2+	Inhibition	3.7	pIC50
Ni2+	Inhibition	3.5	pIC50

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
GSK-J4	decreases expression	1
afuresertib	increases expression	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, decreases expression	1
Endosulfan	increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	increases expression	1
Testosterone	decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases expression	1
Asbestos, Crocidolite	decreases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3880972	Binding	Inhibition of CatSper1 channel in human sperm assessed as sperm hyperactivity at 1 uM after 5 mins by computer-assisted sperm analysis (Rvb = 10.5%)	Modulators of sperm hypermobility and uses thereof

Clinical trials (associated diseases)

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