CATSPERZ

Summary

CATSPERZ (catsper channel auxiliary subunit zeta, HGNC:19231) is a protein-coding gene on chromosome 11q13.1, encoding Cation channel sperm-associated auxiliary subunit zeta (Q9NTU4). Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation.

Predicted to be involved in flagellated sperm motility; male meiotic nuclear division; and sperm capacitation. Located in cytoplasm and sperm principal piece.

Source: NCBI Gene 25858 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_001039496

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19231
Approved symbol	CATSPERZ
Name	catsper channel auxiliary subunit zeta
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP566E164
Ensembl gene	ENSG00000219435
Ensembl biotype	protein_coding
OMIM	617511
Entrez	25858

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000328404, ENST00000535981, ENST00000539943

RefSeq mRNA: 1 — MANE Select: NM_001039496 NM_001039496

Canonical transcript exons

ENST00000328404 — 5 exons

Exon	Start	End
ENSE00001556272	64300358	64300431
ENSE00002311212	64304543	64304770
ENSE00003465712	64303773	64303839
ENSE00003472136	64303482	64303561
ENSE00003805360	64300657	64300987

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 99.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8977 / max 778.1216, expressed in 52 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114940	0.8857	47
114944	0.0119	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.18	gold quality
right testis	UBERON:0004534	99.12	gold quality
testis	UBERON:0000473	98.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.71	gold quality
cerebellar hemisphere	UBERON:0002245	79.06	gold quality
cerebellar cortex	UBERON:0002129	78.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.86	gold quality
cerebellum	UBERON:0002037	78.84	gold quality
temporal lobe	UBERON:0001871	74.72	gold quality
amygdala	UBERON:0001876	74.67	gold quality
right frontal lobe	UBERON:0002810	74.51	gold quality
Ammon’s horn	UBERON:0001954	74.02	gold quality
anterior cingulate cortex	UBERON:0009835	73.82	gold quality
caudate nucleus	UBERON:0001873	73.45	gold quality
primary visual cortex	UBERON:0002436	73.30	gold quality
nucleus accumbens	UBERON:0001882	73.22	gold quality
superior frontal gyrus	UBERON:0002661	72.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.39	gold quality
putamen	UBERON:0001874	72.37	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	72.26	gold quality
cerebral cortex	UBERON:0000956	71.83	gold quality
frontal cortex	UBERON:0001870	71.03	gold quality
brain	UBERON:0000955	70.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.21	gold quality
prefrontal cortex	UBERON:0000451	68.83	gold quality
hypothalamus	UBERON:0001898	68.73	gold quality
placenta	UBERON:0001987	66.85	gold quality
skin of leg	UBERON:0001511	63.44	gold quality
cortical plate	UBERON:0005343	63.15	gold quality
zone of skin	UBERON:0000014	62.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	2582.34
E-ANND-3	no	0.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting CATSPERZ, 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-4492	99.87	68.25	3611
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-4431	90.07	69.53	39

Literature-anchored findings (GeneRIF, showing 3)

• ESRRA-C11orf20, a gene fusion between ESRRA and C11orf20 (TEX40) is recurrent serous ovarian carcinoma. (PMID:21949640)
• The frequency of the ESRRA/C11orf20 gene fusion in serous ovarian carcinomas of stages III and IV must be very low. (PMID:24504521)
• Low TEX40 expression is associated with asthenozoospermia. (PMID:30550884)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Catsperz	ENSMUSG00000050623
rattus_norvegicus		ENSRNOG00000089798

Protein

Protein identifiers

Cation channel sperm-associated auxiliary subunit zeta — Q9NTU4 (reviewed: Q9NTU4)

Alternative names: Testis-expressed protein 40

All UniProt accessions (2): Q9NTU4, F5H186

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. Required for a distribution of the CatSper complex in linear quadrilateral nanodomains along the flagellum, maximizing fertilization inside the mammalian female reproductive tract. Together with EFCAB9, associates with the CatSper channel pore and is required for the two-row structure of each single CatSper channel.

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 EFCAB9; the interaction is direct, Ca(2+)-dependent and connects EFCAB9 with the CatSper complex. Dissociates from EFCAB9 at elevated pH.

Subcellular location. Cell projection. Cilium. Flagellum membrane.

RefSeq proteins (1): NP_001034585* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039019	CATSPERZ	Family

UniProt features (5 total): region of interest 2, chain 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NTU4-F1	63.15	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): GOBP_MALE_GAMETE_GENERATION, chr11q13, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_ORGANELLE_FISSION, 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, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, SHEN_SMARCA2_TARGETS_DN, GOCC_VOLTAGE_GATED_CALCIUM_CHANNEL_COMPLEX, GOBP_MEIOTIC_CELL_CYCLE, GOCC_MOTILE_CILIUM

GO Biological Process (5): male meiotic nuclear division (GO:0007140), spermatogenesis (GO:0007283), flagellated sperm motility (GO:0030317), sperm capacitation (GO:0048240), cell differentiation (GO:0030154)

GO Molecular Function (0):

GO Cellular Component (8): cytoplasm (GO:0005737), 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	4
male gamete generation	2
developmental process involved in reproduction	2
meiotic cell cycle	1
meiotic nuclear division	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
cellular developmental process	1
intracellular anatomical structure	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

292 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CATSPERZ	EFCAB9	A8MZ26	951
CATSPERZ	CATSPERE	Q5SY80	720
CATSPERZ	CATSPER1	Q8NEC5	710
CATSPERZ	CATSPERB	Q9H7T0	687
CATSPERZ	CATSPERD	Q86XM0	682
CATSPERZ	CATSPER2	Q96P56	643
CATSPERZ	CATSPER3	Q86XQ3	623
CATSPERZ	CATSPER4	Q7RTX7	617
CATSPERZ	WDFY2	Q96P53	526
CATSPERZ	CATSPERG	Q6ZRH7	432
CATSPERZ	KCNU1	A8MYU2	401
CATSPERZ	SPACA7	Q96KW9	400
CATSPERZ	ESRRA	P11474	379
CATSPERZ	SLC9C1	Q4G0N8	369
CATSPERZ	LRRC52	Q8N7C0	358
CATSPERZ	CCDC89	Q8N998	358

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CATSPERZ	HSPA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): SELO (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), AMD1 (Affinity Capture-MS)

ESM2 similar proteins: A0JP43, A2AHC3, A2RRS8, A2VCV0, A4FU69, A4IG55, A5WUN7, A8T6P4, D3Z6S9, D3Z8E6, D4AEC2, E7F7X0, F7EC58, G3UZ78, Q06190, Q08AD1, Q2MJV9, Q3KQW7, Q3UH68, Q3UMB5, Q3V036, Q5SUV2, Q5T5Y3, Q5ZM60, Q640L3, Q640U0, Q66H73, Q69CM7, Q6AYC8, Q6IRN6, Q6PG04, Q6Q759, Q76LL6, Q76N89, Q7L0X2, Q80VH0, Q8C1B1, Q8C627, Q8CCG4, Q8CDN1

Diamond homologs: Q9CQP8, Q9NTU4

SIGNOR signaling

1 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

697 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64300942:G:GT	donor_gain	1.0000
11:64300984:GCCG:G	donor_gain	1.0000
11:64301024:GGCAA:G	donor_gain	1.0000
11:64303562:G:T	donor_gain	1.0000
11:64303837:GGA:G	donor_gain	1.0000
11:64303838:GA:G	donor_gain	1.0000
11:64303838:GAG:G	donor_gain	1.0000
11:64303840:G:GG	donor_gain	1.0000
11:64300956:G:T	donor_gain	0.9900
11:64300963:G:GT	donor_gain	0.9900
11:64300986:CG:C	donor_loss	0.9900
11:64300987:GG:G	donor_loss	0.9900
11:64300988:G:GG	donor_gain	0.9900
11:64300988:GT:G	donor_loss	0.9900
11:64300989:T:C	donor_loss	0.9900
11:64300991:A:AG	donor_gain	0.9900
11:64300992:G:GG	donor_gain	0.9900
11:64301025:GCAA:G	donor_gain	0.9900
11:64302013:T:G	donor_gain	0.9900
11:64303560:GG:G	donor_gain	0.9900
11:64303561:GG:G	donor_gain	0.9900
11:64303767:CTCCA:C	acceptor_loss	0.9900
11:64303768:TCCA:T	acceptor_loss	0.9900
11:64303769:CCA:C	acceptor_loss	0.9900
11:64303770:CAGCT:C	acceptor_loss	0.9900
11:64303771:A:AG	acceptor_gain	0.9900
11:64303771:A:C	acceptor_loss	0.9900
11:64303772:G:GG	acceptor_gain	0.9900
11:64303772:GCT:G	acceptor_gain	0.9900
11:64303772:GCTGC:G	acceptor_gain	0.9900

AlphaMissense

1307 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64304588:T:C	L182P	0.971
11:64303799:G:A	M153I	0.957
11:64303799:G:C	M153I	0.957
11:64303799:G:T	M153I	0.957
11:64303543:G:C	W138C	0.952
11:64303543:G:T	W138C	0.952
11:64304571:C:A	H176Q	0.952
11:64304571:C:G	H176Q	0.952
11:64303830:G:C	A164P	0.951
11:64304579:C:T	T179I	0.950
11:64303819:T:C	I160T	0.943
11:64303834:T:C	L165P	0.943
11:64303807:A:T	E156V	0.939
11:64303822:T:C	L161P	0.935
11:64304545:T:G	Y168D	0.932
11:64303819:T:G	I160S	0.919
11:64303552:G:C	Q141H	0.917
11:64303552:G:T	Q141H	0.917
11:64303795:T:C	L152P	0.917
11:64303774:T:C	L145P	0.915
11:64303813:T:C	L158P	0.912
11:64304588:T:A	L182Q	0.905
11:64303786:T:C	L149P	0.904
11:64304561:G:T	G173V	0.904
11:64303807:A:G	E156G	0.898
11:64303809:G:C	A157P	0.897
11:64304609:T:C	L189P	0.893
11:64300728:G:C	W31C	0.889
11:64300728:G:T	W31C	0.889
11:64304570:A:G	H176R	0.887

dbSNP variants (sampled 300 via entrez): RS1001840955 (11:64304310 C>T), RS1001907775 (11:64299628 C>G,T), RS1002963449 (11:64299254 G>A,T), RS1003444081 (11:64302908 G>A,T), RS1003496263 (11:64299053 A>G), RS1003590279 (11:64303733 T>A), RS1003706301 (11:64303463 C>A,G,T), RS1004141398 (11:64302579 C>T), RS1004516850 (11:64304602 G>C), RS1004654094 (11:64304362 C>T), RS1005556027 (11:64304079 T>C), RS1006030999 (11:64298956 G>A), RS1006613072 (11:64304904 C>T), RS1006666197 (11:64305268 A>G), RS1006765769 (11:64299882 C>T)

Disease associations

OMIM: gene MIM:617511 | 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
GCST004132_98	Crohn’s disease	5.000000e-06
GCST004785_38	Vitiligo	5.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Smoke	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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