CATSPERE

Summary

CATSPERE (catsper channel auxiliary subunit epsilon, HGNC:28491) is a protein-coding gene on chromosome 1q44, encoding Cation channel sperm-associated auxiliary subunit epsilon (Q5SY80). Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation.

Predicted to be involved in flagellated sperm motility and sperm capacitation. Located in sperm principal piece.

Source: NCBI Gene 257044 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_001130957

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28491
Approved symbol	CATSPERE
Name	catsper channel auxiliary subunit epsilon
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	MGC33370
Ensembl gene	ENSG00000179397
Ensembl biotype	protein_coding
OMIM	617510
Entrez	257044

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding_CDS_not_defined, 4 protein_coding

ENST00000366531, ENST00000366533, ENST00000366534, ENST00000428042, ENST00000460986, ENST00000464170, ENST00000473875, ENST00000478554, ENST00000485888, ENST00000487449

RefSeq mRNA: 3 — MANE Select: NM_001130957 NM_001130957, NM_001242340, NM_173807

CCDS: CCDS1625, CCDS44340, CCDS55693

Canonical transcript exons

ENST00000366534 — 22 exons

Exon	Start	End
ENSE00001292719	244552322	244552814
ENSE00001296059	244610240	244610326
ENSE00001441952	244617529	244617686
ENSE00001873662	244639928	244640504
ENSE00003458848	244461273	244461494
ENSE00003480871	244635489	244635542
ENSE00003524258	244560668	244561145
ENSE00003525543	244593395	244593428
ENSE00003528690	244591681	244591731
ENSE00003529701	244605695	244605794
ENSE00003553447	244490447	244490471
ENSE00003560001	244583864	244583939
ENSE00003574896	244477906	244477975
ENSE00003580581	244581796	244581854
ENSE00003581122	244593499	244593578
ENSE00003581821	244479717	244479784
ENSE00003589090	244572330	244572772
ENSE00003589158	244463908	244463956
ENSE00003590779	244499002	244499079
ENSE00003652220	244477541	244477614
ENSE00003655992	244518592	244518698
ENSE00003664710	244588482	244588534

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 85.31.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6635 / max 54.2742, expressed in 304 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9477	0.2527	105
9476	0.2290	88
9475	0.1678	82
202029	0.0140	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.31	gold quality
left testis	UBERON:0004533	85.00	gold quality
right testis	UBERON:0004534	84.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.03	gold quality
testis	UBERON:0000473	83.73	gold quality
sperm	CL:0000019	82.16	gold quality
oviduct epithelium	UBERON:0004804	73.57	silver quality
bronchial epithelial cell	CL:0002328	73.35	gold quality
bronchus	UBERON:0002185	71.87	gold quality
calcaneal tendon	UBERON:0003701	70.94	gold quality
right uterine tube	UBERON:0001302	70.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	69.23	gold quality
stromal cell of endometrium	CL:0002255	67.00	gold quality
fallopian tube	UBERON:0003889	65.31	gold quality
tibialis anterior	UBERON:0001385	65.08	silver quality
left lobe of thyroid gland	UBERON:0001120	65.04	gold quality
thyroid gland	UBERON:0002046	64.46	gold quality
right lobe of thyroid gland	UBERON:0001119	64.36	gold quality
right adrenal gland cortex	UBERON:0035827	64.22	gold quality
metanephros cortex	UBERON:0010533	64.13	gold quality
adenohypophysis	UBERON:0002196	64.10	gold quality
ventricular zone	UBERON:0003053	64.08	gold quality
right adrenal gland	UBERON:0001233	63.76	gold quality
adrenal tissue	UBERON:0018303	63.67	gold quality
muscle of leg	UBERON:0001383	63.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	63.31	gold quality
right lobe of liver	UBERON:0001114	63.24	gold quality
left ovary	UBERON:0002119	63.21	gold quality
gastrocnemius	UBERON:0001388	63.16	gold quality
left adrenal gland	UBERON:0001234	63.10	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.45
E-MTAB-6379	no	546.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting CATSPERE, 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-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-4711-5P	98.89	68.00	965

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Catspere2	ENSMUSG00000091476
mus_musculus	Catspere1	ENSMUSG00000102483
rattus_norvegicus	Catspere	ENSRNOG00000056537

Protein

Protein identifiers

Cation channel sperm-associated auxiliary subunit epsilon — Q5SY80 (reviewed: Q5SY80)

All UniProt accessions (2): Q5SY80, B1AQM6

UniProt curated annotations — full annotation on UniProt →

Function. Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation. Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization.

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.

Similarity. Belongs to the CATSPERD family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5SY80-1	1	yes
Q5SY80-2	2
Q5SY80-3	3

RefSeq proteins (3): NP_001124429, NP_001229269, NP_776168 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028751	CATSPERD/E	Family
IPR053814	CATSPERD/E_C	Domain
IPR053815	CATSPERE_Ig-like	Domain
IPR053816	CATSPERE_beta-prop	Domain
IPR053817	CATSPERE_NTD2	Domain
IPR053818	CATSPERE_NTD1	Domain

Pfam: PF22841, PF22843, PF22844, PF22849, PF22850

UniProt features (30 total): glycosylation site 11, disulfide bond 8, splice variant 3, sequence variant 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SY80-F1	89.01	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (8): 57–71, 101–206, 246–336, 410–413, 583–690, 703–885, 719–752, 804–835

Glycosylation sites (11): 493, 535, 796, 854, 881, 886, 61, 114, 414, 472, 487

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): GOBP_MALE_GAMETE_GENERATION, 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, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, chr1q44, GOCC_VOLTAGE_GATED_CALCIUM_CHANNEL_COMPLEX, GOCC_MOTILE_CILIUM, GOCC_CATION_CHANNEL_COMPLEX, GOCC_SPERM_PRINCIPAL_PIECE, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX

GO Biological Process (2): flagellated sperm motility (GO:0030317), sperm capacitation (GO:0048240)

GO Molecular Function (0):

GO Cellular Component (7): CatSper complex (GO:0036128), sperm principal piece (GO:0097228), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
voltage-gated calcium channel complex	1
sperm flagellum	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CATSPERE	CATSPERZ	Q9NTU4	720
CATSPERE	CATSPERB	Q9H7T0	718
CATSPERE	CATSPER3	Q86XQ3	673
CATSPERE	CATSPER1	Q8NEC5	668
CATSPERE	CATSPER2	Q96P56	664
CATSPERE	CATSPER4	Q7RTX7	648
CATSPERE	CATSPERG	Q6ZRH7	627
CATSPERE	EFCAB9	A8MZ26	626
CATSPERE	SPMIP3	Q5SVJ3	446
CATSPERE	ZSWIM3	Q96MP5	428
CATSPERE	DESI2	Q9BSY9	397
CATSPERE	COX20	Q5RI15	391
CATSPERE	CCDC60	Q8IWA6	370
CATSPERE	ANKS4B	Q8N8V4	354
CATSPERE	CATSPERD	Q86XM0	354

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CATSPERE	PYGB	psi-mi:“MI:0914”(association)	0.350
CATSPERE		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): C1orf101 (Affinity Capture-MS), OGDHL (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), PYGB (Affinity Capture-MS), GNPTG (Affinity Capture-MS), FKBP14 (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), C1orf101 (Positive Genetic)

ESM2 similar proteins: A0A2R8Y4Y8, A0A2R8YFL7, A0A2R8YFM6, A0A8J1K1A4, A5D791, E7FKV8, O77726, O88393, P20239, P20783, P26342, P35054, P40200, P47984, Q03167, Q05996, Q08DT3, Q17R60, Q2Q0J1, Q3MHP9, Q3U0X8, Q3V1M1, Q4FZG8, Q4V7E2, Q5BK49, Q5SY80, Q5XI99, Q6DFV8, Q6WRH9, Q6WRI0, Q6X784, Q7TST5, Q80VH0, Q86WS3, Q8JIR8, Q8R1W8, Q925U0, Q95KG7, Q9D9J7, Q9ET62

Diamond homologs: A0A0A6YXX9, P0DP43, Q5SY80, E9Q9F6, Q86XM0, Q95JI2

SIGNOR signaling

1 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3762 predictions. Top by Δscore:

Variant	Effect	Δscore
1:244477971:GCCCA:G	donor_gain	1.0000
1:244477976:G:GG	donor_gain	1.0000
1:244479711:TTTTA:T	acceptor_loss	1.0000
1:244479712:TTTAG:T	acceptor_loss	1.0000
1:244479713:TTAGG:T	acceptor_loss	1.0000
1:244479714:TAGG:T	acceptor_loss	1.0000
1:244479716:G:GT	acceptor_loss	1.0000
1:244479780:GTTAG:G	donor_gain	1.0000
1:244518696:G:GT	donor_gain	1.0000
1:244560817:GGT:G	donor_gain	1.0000
1:244560819:T:G	donor_gain	1.0000
1:244591679:A:AG	acceptor_gain	1.0000
1:244591680:G:GG	acceptor_gain	1.0000
1:244591732:G:GG	donor_gain	1.0000
1:244639919:T:TA	acceptor_gain	1.0000
1:244639926:A:AG	acceptor_gain	1.0000
1:244639927:G:GG	acceptor_gain	1.0000
1:244639927:GT:G	acceptor_gain	1.0000
1:244639927:GTC:G	acceptor_gain	1.0000
1:244639927:GTCCA:G	acceptor_gain	1.0000
1:244461442:G:T	donor_gain	0.9900
1:244461492:G:GT	donor_gain	0.9900
1:244477897:A:AG	acceptor_gain	0.9900
1:244477898:A:G	acceptor_gain	0.9900
1:244477901:A:AG	acceptor_gain	0.9900
1:244477904:A:AG	acceptor_gain	0.9900
1:244477905:G:GA	acceptor_gain	0.9900
1:244479715:A:AG	acceptor_gain	0.9900
1:244479715:AG:A	acceptor_gain	0.9900
1:244479716:G:GA	acceptor_gain	0.9900

AlphaMissense

6274 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:244477577:T:A	W51R	0.997
1:244477577:T:C	W51R	0.997
1:244477579:G:C	W51C	0.997
1:244477579:G:T	W51C	0.997
1:244479768:T:A	W104R	0.997
1:244479768:T:C	W104R	0.997
1:244499014:T:A	W122R	0.996
1:244499014:T:C	W122R	0.996
1:244499016:G:C	W122C	0.996
1:244499016:G:T	W122C	0.996
1:244518607:A:C	S149R	0.996
1:244518609:C:A	S149R	0.996
1:244518609:C:G	S149R	0.996
1:244610246:T:A	C804S	0.996
1:244610247:G:C	C804S	0.996
1:244610315:T:A	W827R	0.996
1:244610315:T:C	W827R	0.996
1:244610317:G:C	W827C	0.995
1:244610317:G:T	W827C	0.995
1:244617543:T:G	C835W	0.995
1:244479770:G:C	W104C	0.994
1:244479770:G:T	W104C	0.994
1:244610246:T:C	C804R	0.994
1:244617541:T:C	C835R	0.994
1:244617541:T:A	C835S	0.993
1:244617542:G:A	C835Y	0.993
1:244617542:G:C	C835S	0.993
1:244518644:T:A	I161K	0.991
1:244617625:T:A	W863R	0.991
1:244617625:T:C	W863R	0.991

dbSNP variants (sampled 300 via entrez): RS1000016398 (1:244504629 G>C), RS1000101778 (1:244559615 G>C), RS1000104572 (1:244566399 G>A), RS1000104984 (1:244601836 C>A), RS1000151277 (1:244558714 G>A), RS1000192181 (1:244531272 T>C,G), RS1000227293 (1:244557114 G>C), RS1000228259 (1:244619859 C>A,T), RS1000246055 (1:244626799 T>C), RS1000325092 (1:244469425 C>T), RS1000351178 (1:244503138 A>G,T), RS1000355650 (1:244462500 TC>T), RS1000369672 (1:244546484 A>C,G), RS1000393444 (1:244581609 A>G), RS1000405992 (1:244496559 T>C)

Disease associations

OMIM: gene MIM:617510 | disease phenotypes: MIM:613615, MIM:615993

GenCC curated gene-disease

Mondo (2): Senior-Loken syndrome 7 (MONDO:0013326), Bardet-Biedl syndrome 16 (MONDO:0014444)

Orphanet (2): Bardet-Biedl syndrome (Orphanet:110), Senior-Loken syndrome (Orphanet:3156)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008161_9	Waist circumference adjusted for body mass index	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sotorasib	affects cotreatment, increases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	increases methylation	1
Estradiol	affects binding, increases reaction	1
Phthalic Acids	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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