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CATSPER3

gene
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Also known as CACRC

Summary

CATSPER3 (cation channel sperm associated 3, HGNC:20819) is a protein-coding gene on chromosome 5q31.1, encoding Cation channel sperm-associated protein 3 (Q86XQ3). 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….

Predicted to enable voltage-gated calcium channel activity. Predicted to be involved in flagellated sperm motility; sodium ion transport; and sperm capacitation. Predicted to act upstream of or within establishment of localization in cell. Predicted to be located in plasma membrane. Predicted to be part of CatSper complex. Predicted to be active in acrosomal vesicle.

Source: NCBI Gene 347732 — RefSeq curated summary.

At a glance

  • GWAS associations: 12
  • Clinical variants (ClinVar): 67 total
  • MANE Select transcript: NM_178019

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:20819
Approved symbolCATSPER3
Namecation channel sperm associated 3
Location5q31.1
Locus typegene with protein product
StatusApproved
AliasesCACRC
Ensembl geneENSG00000152705
Ensembl biotypeprotein_coding
OMIM609120
Entrez347732

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000282611, ENST00000511235

RefSeq mRNA: 1 — MANE Select: NM_178019 NM_178019

CCDS: CCDS4181

Canonical transcript exons

ENST00000282611 — 8 exons

ExonStartEnd
ENSE00001085869135009371135009490
ENSE00001085870135008841135008981
ENSE00001293518135010373135010530
ENSE00001298298134967907134968089
ENSE00001310489135011521135011696
ENSE00001317445135007957135008139
ENSE00003520969134969939134970092
ENSE00003659626134996273134996512

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 90.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0314 / max 28.8694, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
586350.02154
586340.00983

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
spermCL:000001990.30gold quality
right testisUBERON:000453487.79gold quality
left testisUBERON:000453387.72gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047386.62gold quality
testisUBERON:000047385.72gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099175.90gold quality
adult organismUBERON:000702373.11gold quality
gastrocnemiusUBERON:000138870.47gold quality
muscle of legUBERON:000138370.19gold quality
hindlimb stylopod muscleUBERON:000425269.99gold quality
lower esophagus mucosaUBERON:003583468.84gold quality
right uterine tubeUBERON:000130267.64gold quality
mucosa of transverse colonUBERON:000499167.43gold quality
mucosa of stomachUBERON:000119967.32gold quality
right lobe of liverUBERON:000111467.17gold quality
tibialis anteriorUBERON:000138564.85silver quality
body of pancreasUBERON:000115063.28gold quality
tibial arteryUBERON:000761062.21gold quality
popliteal arteryUBERON:000225062.20gold quality
esophagogastric junction muscularis propriaUBERON:003584161.87gold quality
granulocyteCL:000009461.79gold quality
ventricular zoneUBERON:000305361.54gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450261.51gold quality
minor salivary glandUBERON:000183061.39gold quality
adenohypophysisUBERON:000219661.27gold quality
pancreasUBERON:000126461.14gold quality
body of stomachUBERON:000116160.71gold quality
esophagus mucosaUBERON:000246960.63gold quality
deltoidUBERON:000147660.50gold quality
right adrenal glandUBERON:000123360.25gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3no1.25

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

  • PMID: 12646162 concludes Alu repeats interfere with splicing of DCOHM and CAVL such that transcripts containing exons of both genes exist. (PMID:12646162)
  • Catsper3 has a single channel-forming domain, a pore-loop with the consensus sequence TxDxW, & a coiled-coil protein-protein interaction domain in the C-terminal tail. CatSpers 1,2,3 & 4 may interact directly or indirectly to form a functional tetramer. (PMID:12932298)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusCatsper3ENSMUSG00000021499
rattus_norvegicusCatsper3ENSRNOG00000011374

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), SCN3A (ENSG00000153253), CACNA1D (ENSG00000157388), TPCN2 (ENSG00000162341), CATSPER2 (ENSG00000166762), 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 3 — Q86XQ3 (reviewed: Q86XQ3)

Alternative names: Ca(v)-like protein, One-repeat calcium channel-like protein

All UniProt accessions (1): Q86XQ3

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.

Subcellular location. Cell projection. Cilium. Flagellum membrane.

Tissue specificity. Testis-specific.

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.

RefSeq proteins (1): NP_821138* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR005821Ion_trans_domDomain
IPR027359Volt_channel_dom_sfHomologous_superfamily

Pfam: PF00520

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (17 total): topological domain 8, transmembrane region 6, chain 1, intramembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q86XQ3-F180.010.27

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-1300642Sperm Motility And Taxes

MSigDB gene sets: 72 (showing top): GOCC_SECRETORY_GRANULE, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_MALE_GAMETE_GENERATION, 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, WEBER_METHYLATED_LCP_IN_SPERM_UP, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT

GO Biological Process (11): sodium ion transport (GO:0006814), flagellated sperm motility (GO:0030317), sperm capacitation (GO:0048240), establishment of localization in cell (GO:0051649), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (3): voltage-gated calcium channel activity (GO:0005245), monoatomic ion channel activity (GO:0005216), calcium channel activity (GO:0005262)

GO Cellular Component (11): acrosomal vesicle (GO:0001669), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), CatSper complex (GO:0036128), sperm midpiece (GO:0097225), 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:

CategoryPathways
Fertilization1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
metal ion transport2
developmental process involved in reproduction2
transport2
sperm flagellum2
cilium-dependent cell motility1
cilium movement involved in cell motility1
sperm motility1
spermatid development1
cellular process involved in reproduction in multicellular organism1
cell maturation1
establishment of localization1
cellular localization1
male gamete generation1
cellular developmental process1
monoatomic ion transport1
transmembrane transport1
cellular process1
calcium ion transport1
monoatomic cation transmembrane transport1
calcium channel activity1
voltage-gated monoatomic cation channel activity1
monoatomic ion transmembrane transporter activity1
channel activity1
monoatomic cation channel activity1
calcium ion transmembrane transporter activity1
secretory granule1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
membrane1
cell periphery1
voltage-gated calcium channel complex1
intraciliary transport particle1
membrane-bounded organelle1
plasma membrane bounded cell projection1
cilium1
transmembrane transporter complex1

Protein interactions and networks

STRING

922 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CATSPER3PCBD2Q9H0N5935
CATSPER3CATSPERBQ9H7T0795
CATSPER3CATSPERDQ86XM0781
CATSPER3EFCAB9A8MZ26740
CATSPER3CATSPER2Q96P56727
CATSPER3CATSPER4Q7RTX7705
CATSPER3CATSPEREQ5SY80673
CATSPER3CATSPER1Q8NEC5635
CATSPER3CATSPERZQ9NTU4623
CATSPER3OR52W1Q6IF63573
CATSPER3CCDC185Q8N715568
CATSPER3TXNDC15Q96J42564
CATSPER3CATSPERGQ6ZRH7548
CATSPER3MSANTD1Q6ZTZ1532
CATSPER3SLC9C1Q4G0N8525

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2ARP9, B1AYL1, D0E0C2, F1LQQ7, O08562, O14234, O35505, O43497, O46669, O54898, O55017, O73700, O88457, P02719, P0DMA5, P15381, P15390, P22002, P27732, P50077, P56698, P56699, P59111, Q01118, Q02294, Q02343, Q07652, Q13936, Q15858, Q15878, Q28371, Q28644, Q61290, Q62205, Q62968, Q6AXP6, Q6QIY3, Q7RTX7, Q80W99, Q86XQ3

Diamond homologs: O95180, Q80W99, Q86XQ3, O57483

SIGNOR signaling

1 interactions.

AEffectBMechanism
CATSPER3“form complex”“CatSpermasome complex”binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance53
Likely benign8
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

963 predictions. Top by Δscore:

VariantEffectΔscore
5:134968086:T:Gdonor_gain1.0000
5:134968086:T:TGdonor_gain1.0000
5:134968090:G:GGdonor_gain1.0000
5:134996271:A:AGacceptor_gain1.0000
5:134996272:G:GGacceptor_gain1.0000
5:135008838:CAGG:Cacceptor_loss1.0000
5:135008839:AGGTT:Aacceptor_gain1.0000
5:135008840:GGTTG:Gacceptor_gain1.0000
5:135008978:AGAG:Adonor_loss1.0000
5:135008979:GAG:Gdonor_gain1.0000
5:135008980:AGG:Adonor_loss1.0000
5:135008981:GGTGA:Gdonor_loss1.0000
5:135008982:G:Tdonor_loss1.0000
5:135008983:T:Adonor_loss1.0000
5:135009366:TCTA:Tacceptor_loss1.0000
5:135009367:CTAG:Cacceptor_loss1.0000
5:135009369:A:AGacceptor_gain1.0000
5:135009369:AG:Aacceptor_gain1.0000
5:135009370:G:GAacceptor_gain1.0000
5:135009370:GG:Gacceptor_gain1.0000
5:135009370:GGA:Gacceptor_gain1.0000
5:135009370:GGAC:Gacceptor_gain1.0000
5:135009370:GGACT:Gacceptor_gain1.0000
5:135009486:TACAG:Tdonor_gain1.0000
5:135009490:GGTG:Gdonor_loss1.0000
5:135009491:G:GAdonor_loss1.0000
5:135009491:G:GGdonor_gain1.0000
5:135009492:T:Adonor_loss1.0000
5:135010367:CTCTA:Cacceptor_loss1.0000
5:135010369:CTAGA:Cacceptor_loss1.0000

AlphaMissense

2681 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
5:135008094:G:CW210C0.982
5:135008094:G:TW210C0.982
5:135008850:T:AW229R0.977
5:135008850:T:CW229R0.977
5:135008092:T:AW210R0.974
5:135008092:T:CW210R0.974
5:135008059:T:CF199L0.969
5:135008061:T:AF199L0.969
5:135008061:T:GF199L0.969
5:135008852:G:CW229C0.967
5:135008852:G:TW229C0.967
5:135008916:T:CF251L0.967
5:135008918:C:AF251L0.967
5:135008918:C:GF251L0.967
5:135008125:T:CF221L0.957
5:135008127:C:AF221L0.957
5:135008127:C:GF221L0.957
5:135008035:T:CF191L0.956
5:135008037:C:AF191L0.956
5:135008037:C:GF191L0.956
5:135008895:A:CS244R0.953
5:135008897:C:AS244R0.953
5:135008897:C:GS244R0.953
5:135008934:T:CF257L0.952
5:135008936:C:AF257L0.952
5:135008936:C:GF257L0.952
5:135008047:G:CG195R0.951
5:135008050:T:CF196L0.948
5:135008052:C:AF196L0.948
5:135008052:C:GF196L0.948

dbSNP variants (sampled 300 via entrez): RS1000004533 (5:134997016 G>A), RS1000114835 (5:135007710 A>G), RS1000217408 (5:135011678 T>C), RS1000300586 (5:134987441 T>A), RS1000327603 (5:134970562 T>C), RS1000410622 (5:134967004 T>C), RS1000449905 (5:135006661 T>C), RS1000584158 (5:134985594 A>G), RS1000584968 (5:134993148 G>A), RS1000603863 (5:134998136 T>A), RS1000755325 (5:135006488 T>C), RS1000963952 (5:134980853 A>T), RS1000975385 (5:134968836 A>G), RS1001060708 (5:134981026 C>T), RS1001143629 (5:134985936 C>A)

Disease associations

OMIM: gene MIM:609120 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

StudyTraitp-value
GCST000175_35Height8.000000e-06
GCST001792_5Colorectal cancer4.000000e-10
GCST001792_7Colorectal cancer1.000000e-10
GCST001958_2Bulimia nervosa3.000000e-06
GCST002022_4Testicular germ cell tumor2.000000e-08
GCST002702_118Height9.000000e-09
GCST004713_21Testicular germ cell tumor9.000000e-06
GCST006979_122Heel bone mineral density1.000000e-16
GCST008156_139Hip circumference adjusted for BMI8.000000e-06
GCST008163_526Height9.000000e-11
GCST008839_492Height8.000000e-18
GCST90020028_993Hip circumference adjusted for BMI2.000000e-08

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0009270heel bone mineral density
EFO:0008039BMI-adjusted hip circumference

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:

LigandActionAffinityParameter
progesteroneFull agonist8.11pEC50
PGE1Full agonist6.3pEC50
PGE2Full agonist6.3pEC50
PGF1αFull agonist6.3pEC50
NNC55-0396Inhibition5.7pIC50
ruthenium redAntagonist5.0pIC50
mibefradilInhibition4.5pIC50
Cd2+Antagonist3.7pIC50
Ni2+Antagonist3.5pIC50

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

ChemicalActions (top 5)PubMed papers
Tobacco Smoke Pollutiondecreases expression, increases expression2
methyleugenoldecreases expression1
tris(1,3-dichloro-2-propyl)phosphateincreases expression1
sodium arsenitedecreases expression1
CGP 52608affects binding, increases reaction1
Sunitinibdecreases expression1
Quercetinincreases expression1

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 76

This page pulls from 76 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot