Table 1.

Pathogenic variants in genes encoding ion channels or transporters and associated with asthenozoospermia and male infertility in humans, AST, asthenozoospermia; OAT, oligo-astheno-teratozoospermia; AZOO, azoospermia; HET: heterozygous; HOM: Homozygous; ICSI, intracytoplasmic sperm injection; IVF, In vitro fertilization; N/A: not applicable; PGD, preimplantation genetic diagnosis.

Ion Channel	Mutation(s)		Patients	Phenotype	ART Outcome	Reference
CATSPER1	c.539–540insT (p.Lys180LysfsX8) c.948–949insATGGC (p.Asp317MetfsX18)	HOM	3 patients from 2 consanguineous Iranian families	OAT Low semen volume	-	Avenarius et al., 2009 [34]
CATSPER2	~70-kb deletion in chr 15q15 (last 2 exons of CATSPER2)	HOM	3 brothers from a French family	Congenital dyserythropoietic anemia type I (CDAI) Astheno-teratozoospermia (91% sperm with short, coiled flagella)	-	Avidan et al., 2003 [35]
			1 patient	Severe asthenoteratozoospermia Disruption of progesterone-sensitive Ca2+ current Absence of Catsperβ	-	Avidan et al., 2003 [35]; Smith et al., 2013 [36]
	~100-kb deletion in chr 15q15.3 (integral loss of CATSPER2)	HOM	7 patients from 3 Iranian families (one of which is consanguineous)	Deafness infertility syndrome (DIS) Astheno-teratozoospermia (thin heads, macrocephaly, irregular acrosome, short or coiled flagella)	-	Zhang et al., 2007 [37]
				Quadrilateral CatSper domains, sperm rolling (rotation around the longitudinal axis), and rheotaxis (navigation in fluid flow) are not affected	-	Schiffer et al., 2020 [38]
	CNV (one copy lost in the region of 43,894,500 to 43,950,000 on chr 15q15.3, containing the entire CATSPER2) deletion of CATSPER2	HET	1 Chinese patient	Normal semen parameters Impaired sperm hyperactivation, no response to progesterone	Failure of IVF cycle (6 oocytes) ICSI positive outcome with singleton pregnancy	Luo et al., 2019 [39]
CATSPERε	In-frame 6-bp deletion in exon 18 (c.2393_2398delCTATGG, p.Met799_Ala800del)	HOM	1 European patient	Normal motility and concentration Loss of CATSPER function	Failure of IVF	Brown et al., 2018 [40]
SLC26A3	V317del	HOM (7) HET (1)	8 Finnish patients	Congenital chloride diarrhea (CLD) with male subfertility (OAT) Spermatoceles	-	Höglund et al., 2006 [41]
	c.2062 G > C (p.Asp688His) (9) c.949_951delGTG (p.Val318del) (3)	HET	12 Finnish patients	11/12: severe or moderate oligo-astheno-zoospermia 1/12: azoospzermia (patient also carrying a CFTR 5T heterozygous allele)	-	Wedenoja et al., 2017 [42]
SLC26A8 (TAT1)	Patient 1: c.260G > A (p.Arg87Gln) (1) Patient 2: c.2434G > A (p.Glu812Lys) (1) Patient 3: c.2860C > T (p.Arg954Cys) (1).	HET	3 patients Patient 1: Caucasian Patient 2: North African Patient 3: Caucasian	Astheno-teratozoospermia (Patient 3 has OAT) Reduced amount of SLC26A8-mutated protein and associated CFTR channel	Patient 1: ART attempt, natural pregnancy after 2.5 years without proof of paternity Patient 2: ART attempt, natural pregnancy with a new partner Patient 3: ART attempt, 4 ICSI failures	Dirami et al., 2013 [43]
SLC9C1 (sNHE)	c.2748 + 2T > C (p.Glu884_Lys916del)	HOM	1 African patient	Asthenozoospermia	ICSI failure	Cavarocchi et al., 2021 [44]
VDAC2	CpGs hypermethylation in the promoter		25 Chinese patients	Idiopathic asthenozoospermia	-	Xu et al., 2016 [45]
VDAC3	Missense variants in exon 6 (Ile131Leu, Lys171Glu)		-	Asthenozoospermia	-	Asmarinah et al., 2005 [46]
	3 patients: deletion in exon 5 1 patient: deletion in exon 7 1 patient: deletions in exons 5 and 7 1 patient: missense mutation (Asp228Asn) in exon 7 1 patient: deletions in exons 5, 7, and 8		7 Chinese patients	Asthenozoospermia	-	Asmarinah et al., 2011 [47]
SLO3	Missense variant c.1237A > T, p.Ile413Phe	HOM	1 Chinese patient	Asthenoteratozoospermia	ICSI positive outcome with singleton pregnancy	Lv et al., 2022 [48]
PKD1-2	Several PKD1 or PKD2 mutations	N/A	46 Chinese patients	Autosomal dominant polycystic kidney disease (ADPKD) 37/46 patients with abnormal semen parameters (AST, OAT, AZOO)	2 natural pregnancies 2 ICSI 31 ICSI + PGD	He et al., 2018 [49]