CATSPERG

Summary

CATSPERG (catsper channel auxiliary subunit gamma, HGNC:25243) is a protein-coding gene on chromosome 19q13.2, encoding Cation channel sperm-associated auxiliary subunit gamma (Q6ZRH7). Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation.

CATSPERG is a subunit of the CATSPER (see CATSPER1; MIM 606389) sperm calcium channel, which is required for sperm hyperactivated motility and male fertility (Wang et al., 2009 [PubMed 19516020]).

Source: NCBI Gene 57828 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 188 total
• MANE Select transcript: NM_021185

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25243
Approved symbol	CATSPERG
Name	catsper channel auxiliary subunit gamma
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434A1022, FLJ46353
Ensembl gene	ENSG00000099338
Ensembl biotype	protein_coding
OMIM	613452
Entrez	57828

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 6 retained_intron, 4 nonsense_mediated_decay, 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000312265, ENST00000409235, ENST00000409410, ENST00000410018, ENST00000412458, ENST00000466060, ENST00000467739, ENST00000470292, ENST00000471517, ENST00000475343, ENST00000475646, ENST00000477793, ENST00000488473, ENST00000489693, ENST00000492088, ENST00000585424

RefSeq mRNA: 2 — MANE Select: NM_021185 NM_001330496, NM_021185

CCDS: CCDS12514, CCDS82346

Canonical transcript exons

ENST00000409235 — 29 exons

Exon	Start	End
ENSE00002238094	38352261	38352432
ENSE00002784011	38337221	38337504
ENSE00003461864	38362210	38362272
ENSE00003473319	38364891	38364971
ENSE00003480569	38367509	38367572
ENSE00003499487	38359470	38359581
ENSE00003501343	38354710	38354847
ENSE00003532967	38344296	38344368
ENSE00003535751	38367156	38367312
ENSE00003536133	38365061	38365117
ENSE00003537580	38362714	38362832
ENSE00003538986	38361648	38361861
ENSE00003553834	38362376	38362574
ENSE00003581960	38356484	38356543
ENSE00003585663	38369972	38370064
ENSE00003588692	38356742	38356861
ENSE00003589313	38367681	38367776
ENSE00003592439	38358432	38358561
ENSE00003598303	38358278	38358328
ENSE00003619754	38360731	38360843
ENSE00003631144	38360489	38360647
ENSE00003631329	38346450	38346605
ENSE00003654975	38370526	38370943
ENSE00003661445	38370159	38370258
ENSE00003665020	38337593	38337646
ENSE00003670613	38343580	38343724
ENSE00003676776	38368048	38368137
ENSE00003677548	38343993	38344119
ENSE00003847996	38335830	38335875

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 96.48.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1658 / max 217.0966, expressed in 723 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175616	1.4094	592
175618	0.4236	159
175615	0.1929	54
175614	0.0792	30
175617	0.0607	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.48	gold quality
right testis	UBERON:0004534	96.26	gold quality
sperm	CL:0000019	92.62	gold quality
testis	UBERON:0000473	92.62	gold quality
male germ cell	CL:0000015	90.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.93	gold quality
cerebellar cortex	UBERON:0002129	84.40	gold quality
cerebellar hemisphere	UBERON:0002245	84.38	gold quality
sural nerve	UBERON:0015488	82.72	gold quality
cerebellum	UBERON:0002037	82.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.94	gold quality
right lobe of thyroid gland	UBERON:0001119	77.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.75	silver quality
granulocyte	CL:0000094	76.61	gold quality
cortical plate	UBERON:0005343	76.41	gold quality
left lobe of thyroid gland	UBERON:0001120	75.92	gold quality
monocyte	CL:0000576	75.15	gold quality
leukocyte	CL:0000738	75.00	gold quality
mononuclear cell	CL:0000842	74.91	gold quality
thyroid gland	UBERON:0002046	74.61	gold quality
skin of leg	UBERON:0001511	74.26	gold quality
skin of abdomen	UBERON:0001416	73.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.12	gold quality
colonic epithelium	UBERON:0000397	72.85	gold quality
mucosa of transverse colon	UBERON:0004991	72.41	gold quality
ganglionic eminence	UBERON:0004023	71.83	gold quality
endocervix	UBERON:0000458	71.70	gold quality
ascending aorta	UBERON:0001496	71.05	gold quality
apex of heart	UBERON:0002098	71.02	gold quality
thoracic aorta	UBERON:0001515	70.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-70580	yes	51.74
E-ANND-3	yes	5.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting CATSPERG, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-8081	96.42	67.75	738
HSA-MIR-627-5P	95.51	66.80	509
HSA-MIR-2861	95.24	65.47	1056

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Catsperg2	ENSMUSG00000049123
mus_musculus	Catsperg1	ENSMUSG00000049676
rattus_norvegicus	Catsperg	ENSRNOG00000060693

Protein

Protein identifiers

Cation channel sperm-associated auxiliary subunit gamma — Q6ZRH7 (reviewed: Q6ZRH7)

All UniProt accessions (8): Q6ZRH7, B8ZZI7, F8WDD6, H9KV36, K7EQR6, K7EQY4, M0QZ16, X1WI24

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 CATSPERG family.

RefSeq proteins (2): NP_001317425, NP_067008* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028246	CATSPERG	Family
IPR053871	CATSPERG_beta-prop	Domain
IPR053872	CATSPERG_N	Domain
IPR053873	CATSPERG_C	Domain
IPR053874	CATSPERG_Ig-like	Domain

Pfam: PF15064, PF22840, PF22846, PF22851

UniProt features (25 total): disulfide bond 9, glycosylation site 4, sequence variant 3, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZRH7-F1	83.99	0.50

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 (9): 44–105, 159–165, 288–343, 394–402, 638–860, 806–834, 882–1046, 909–918, 1010–1016

Glycosylation sites (4): 574, 102, 355, 426

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1300642	Sperm Motility And Taxes

MSigDB gene sets: 92 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, 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, GOCC_VOLTAGE_GATED_CALCIUM_CHANNEL_COMPLEX, GOCC_MOTILE_CILIUM, GOCC_CATION_CHANNEL_COMPLEX, GOCC_SPERM_PRINCIPAL_PIECE, GOCC_TRANSPORTER_COMPLEX

GO Biological Process (2): spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (0):

GO Cellular Component (7): plasma membrane (GO:0005886), motile cilium (GO:0031514), CatSper complex (GO:0036128), sperm principal piece (GO:0097228), cilium (GO:0005929), membrane (GO:0016020), 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
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
membrane	1
cell periphery	1
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

Protein interactions and networks

STRING

732 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CATSPERG	CATSPER1	Q8NEC5	972
CATSPERG	CATSPERB	Q9H7T0	847
CATSPERG	CATSPERD	Q86XM0	806
CATSPERG	CATSPERE	Q5SY80	627
CATSPERG	TSACC	Q96A04	587
CATSPERG	CYLC2	Q14093	565
CATSPERG	CATSPER3	Q86XQ3	548
CATSPERG	CATSPER2	Q96P56	545
CATSPERG	CATSPER4	Q7RTX7	538
CATSPERG	ANKZF1	Q9H8Y5	474
CATSPERG	SPATA16	Q9BXB7	472
CATSPERG	CATSPERZ	Q9NTU4	432
CATSPERG	TXNDC8	Q6A555	420
CATSPERG	CLEC4A	Q9UMR7	418
CATSPERG	WFIKKN1	Q96NZ8	410

IntAct

0 interactions, top by confidence:

BioGRID (5): CATSPERG (Affinity Capture-RNA), CATSPERG (Affinity Capture-RNA), CATSPERG (Affinity Capture-MS), CATSPERG (Affinity Capture-MS), CATSPERG (Two-hybrid)

ESM2 similar proteins: A0A0A6YXX9, A0A1Z2R986, A2RTF1, C6KI89, E9Q355, F5HFJ7, O36400, P03425, P04853, P09258, P09728, P0DP43, P12554, P12556, P16772, P19758, P21526, P22229, P28907, P35740, P35771, Q04547, Q2TAV2, Q2YDM0, Q3TBN1, Q499E0, Q4R6B2, Q5BKX0, Q5E9L2, Q5RDR5, Q66000, Q66001, Q68FB2, Q6AY76, Q6DFY8, Q6ZRH7, Q76B58, Q77MP7, Q77NN4, Q783Y1

Diamond homologs: C6KI89, E9Q355, Q4R6B2, Q6ZRH7

SIGNOR signaling

1 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	159
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5491 predictions. Top by Δscore:

Variant	Effect	Δscore
19:38344366:G:GT	donor_gain	1.0000
19:38358420:T:A	acceptor_gain	1.0000
19:38358425:C:CA	acceptor_gain	1.0000
19:38358426:G:A	acceptor_gain	1.0000
19:38358427:GTCAG:G	acceptor_loss	1.0000
19:38358430:A:AG	acceptor_gain	1.0000
19:38358430:A:T	acceptor_loss	1.0000
19:38358431:G:GA	acceptor_gain	1.0000
19:38358513:ACCC:A	donor_gain	1.0000
19:38358557:CAGAG:C	donor_loss	1.0000
19:38358558:AGAGG:A	donor_loss	1.0000
19:38358559:GAG:G	donor_gain	1.0000
19:38358560:AGG:A	donor_loss	1.0000
19:38358561:GG:G	donor_loss	1.0000
19:38359468:A:AG	acceptor_gain	1.0000
19:38359469:G:GA	acceptor_gain	1.0000
19:38359469:GCTCT:G	acceptor_gain	1.0000
19:38359579:G:GT	donor_gain	1.0000
19:38360727:GCA:G	acceptor_loss	1.0000
19:38360729:A:AG	acceptor_gain	1.0000
19:38360729:AGCT:A	acceptor_gain	1.0000
19:38360729:AGCTG:A	acceptor_gain	1.0000
19:38360730:G:A	acceptor_loss	1.0000
19:38360730:G:GA	acceptor_gain	1.0000
19:38360730:GC:G	acceptor_gain	1.0000
19:38360730:GCT:G	acceptor_gain	1.0000
19:38360730:GCTG:G	acceptor_gain	1.0000
19:38360730:GCTGG:G	acceptor_gain	1.0000
19:38360842:GG:G	donor_gain	1.0000
19:38360842:GGGT:G	donor_loss	1.0000

AlphaMissense

7692 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:38369973:T:A	W1008R	0.999
19:38369973:T:C	W1008R	0.999
19:38352364:G:C	R310P	0.998
19:38368064:T:A	W983R	0.998
19:38368064:T:C	W983R	0.998
19:38369975:G:C	W1008C	0.998
19:38369975:G:T	W1008C	0.998
19:38367267:T:A	C909S	0.997
19:38367267:T:C	C909R	0.997
19:38367268:G:C	C909S	0.997
19:38367294:T:C	C918R	0.997
19:38367296:C:G	C918W	0.997
19:38368066:G:C	W983C	0.997
19:38368066:G:T	W983C	0.997
19:38352281:G:C	W282C	0.996
19:38352281:G:T	W282C	0.996
19:38358543:G:T	G493V	0.996
19:38367268:G:A	C909Y	0.996
19:38367269:C:G	C909W	0.996
19:38367295:G:A	C918Y	0.996
19:38369997:T:C	C1016R	0.996
19:38337370:T:A	W46R	0.995
19:38337370:T:C	W46R	0.995
19:38337372:G:C	W46C	0.995
19:38337372:G:T	W46C	0.995
19:38354715:T:A	W335R	0.995
19:38354715:T:C	W335R	0.995
19:38367202:G:C	R887P	0.995
19:38367294:T:A	C918S	0.995
19:38367295:G:C	C918S	0.995

dbSNP variants (sampled 300 via entrez): RS1000060846 (19:38352453 C>A), RS1000138922 (19:38340897 G>C,T), RS1000171924 (19:38355368 A>C), RS1000203160 (19:38355779 C>T), RS1000409973 (19:38361470 G>A), RS1000493332 (19:38365042 C>T), RS1000505936 (19:38348636 G>C), RS1000558233 (19:38348289 G>A), RS1000602309 (19:38338118 G>A), RS1000685282 (19:38349926 A>G), RS1000702775 (19:38336694 A>C,G), RS1000753708 (19:38336502 C>G), RS1000937974 (19:38360774 G>A), RS1001029932 (19:38341927 A>C), RS1001067964 (19:38371041 T>C)

Disease associations

OMIM: gene MIM:613452 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST012139_5	D-dimer levels in HIV infection	4.000000e-12
GCST90002395_410	Mean platelet volume	3.000000e-18

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004507	D dimer measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	4
bisphenol A	decreases expression, increases methylation	2
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
licochalcone B	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases expression	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Methapyrilene	decreases methylation	1
Smoke	decreases expression	1
Toluene	decreases methylation, increases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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