Table II.

Transcription factor mutations reported to be associated with human infertility.

Disease	Associated transcription factors	Description	References
Disorders of sex development
Swyer syndrome	SRY	Mutations in the SRY gene are the cause of 15% to 20% of cases of Swyer syndrome.	Arboleda et al. (2014); Baxter and Vilain (2013)
Sex reversal	SOX9 SOX3	Copy number variants or mutations in the regulatory regions of the genes lead to human sex reversal.	Croft et al. (2018a); Croft et al. (2018b); Gonen et al. (2018); Vetro et al. (2015); Laumonnier et al. (2002)
Denys-Drash syndrome	WT1	Heterozygous mutations in the zinc finger domain of WT1 gene cause Denys-Drash syndrome.	Pelletier et al. (1991)
Frasier syndrome	WT1	A mutation in a splice donor site in WT1 leads to Frasier syndrome.	Klamt et al. (1998);
Gonadal dysgenesis	NR5A1 GATA4 FOG2 CBX2 DMRT1/2	Mutations in these transcription factors are associated with gonadal dysgenesis.	El-Khairi and Achermann (2012)
Cryptorchidism	HOXD13, SOX2, ESR1, NR5A1, ZNF214, ZNF215, ARX	Single gene mutations are associated with cryptorchidism.	Tannour-Louet et al. (2010)
Male infertility
NOA	DMRT1, PRDM9, ESR2, AR, KDM5D, NR0B1, NR5A1, SOX9, NPAS2, PGR	The paper screened OMIM database and identified genes related to human male infertility- and NOA -	Wang et al. (2018)
NOA	SOHLH1	SOHLH1 mutations are associated with loss of testicular reproductive capacity.	Nakamura et al. (2017)
NOA	SOX8	SOX8 mutations were found at increased frequency in oligozoospermic men as compared with fertile/normospermic control populations.	Portnoi et al. (2018) Choi et al. (2010)
SCOS, MA	YBX1, YBX2	YBX1 and YBX2 protein was markedly downregulated in SCOS and MA samples.	Alikhani et al. (2017)
Female infertility
POI*	FOXL2	Foxl2 appears predominantly in the ovary and was first identified as mutated in a syndrome involving risk of POI.	Schlessinger et al. (2010) Crisponi et al. (2001) De Baere et al. (2005) Lakhal et al. (2008) Gersak et al. (2004) Harris et al. (2002)
POI*	LHX8	Preferentially expressed in germ cells and critical for mammalian oogenesis.	Qin et al. (2007)
POI*	FOXO3A, FOXO1A	Potentially causal mutations for POI.	Watkins et al. (2006) Lakhal et al. (2008)
POI*	FIGLA	Two plausible mutations in the FIGLA gene were identified among 100 POI cases (2%), whereas none were present among 304 ethnically matched controls.	Zhao et al. (2008)
POI*	AIRE	Mutations in AIRE gene are likely cause polyglandular syndrome, which is associated with POI.	McLaren et al. (2003)
POI*	NOBOX	Homeobox mutation causes POI.	Qin et al. (2007)
POI*	SALL4	Two novel variants (c.541G>A (p. Val181Met) and c. 2449A>G (p. Thr817Ala)) might be POI-associated gene variants.	Wang et al. (2009)
POI*	WT1	Two novel heterozygous mutations p. P126S and p. R370H were identified to be involved in POI.	Wang et al. (2015)
POI*	ESR1	ESR1 gene variants are associated with both age at natural menopause and premature ovarian failure.	Qin et al., (2012) Weel (1999)
POI	TP63	The combination of TP63 and BMP15 alterations contributes to the ovarian dysgenesis and early onset POI.	Bestetti et al. (2021)
POI	LHX8, NOBOX, FOXL2, SOHLH1, FIGLA	Combined functional and bibliographic analyses identified several novel or recurrent deleterious heterozygous mutations in POI patients.	Bouilly et al. (2016)

^*MA, maturation arrest; NOA, non-obstructive azoospermia; POI, premature ovarian insufficiency (also known as premature ovarian failure); SCOS, Sertoli cell-only syndrome.