TABLE 1.

Genes that represent potential hot spots for genitourinary birth defects.

Gene	Location	Function	Associated phenotypes
PIK3R1	5q13	Encodes a phosphorylating kinase involved in molecular signaling (96)	SHORT syndrome cryptorchidism, decreased testicular size, ocular changes, respiratory anomalies, intellectual disability, seizures, and abnormal facial features (40, 97)
EYA1	8q13	Protein required for the development of the kidney, branchial arches, eye, and ear (98)	Branchio-oto-renal syndrome, hypospadias, facial dysmorphisms, intellectual disability, developmental delay, hearing impairment, short stature, cranial nerve anomalies, ocular changes, and renal agenesis (40, 98)
HNF1B	17q12	Encodes a homeodomain-containing transcription factor (99)	Renal hypoplasia, renal cysts, hydronephrosis, duplex and horseshoe kidneys, cryptorchidism, vasal agenesis, epididymal cysts, hypospadias, asthenospermia, diabetes mellitus, pancreatic problems, abnormal liver enzyme levels, neurodevelopmental issues, and psychiatric conditions (99, 100)
PAX2	10q24	Encodes a transcription factor that plays a role in embryogenesis (101)	Renal hypoplasia, renal-coloboma syndrome, papillorenal syndrome, vesicoureteral reflux, and cryptorchidism (101–104)
CREBBP	16p13	Involved in transcriptional coactivation (105)	Rubinstein-Taybi Syndrome and bilateral cryptorchidism (105, 106)
MECP2	Xq28	Protein involved in transcription modulation by binding of methylated CpG in DNA (107)	Cryptorchidism, hypospadias, hydronephrosis, urethral abnormalities, speech problems, hypotonia, recurrent infections, neurologic abnormalities, facial dysmorphisms, and brain abnormalities (108)
RBFOX2	22q12	Encodes an RNA binding protein involved in RNA splicing in numerous cell types (muscle, brain, and heart) (109)	Cardiac problems, development delay, facial dysmorphisms, renal development, hypospadias, scrotal development, finger abnormalities, and short stature (40)
DYRKA1	21q3	Protein kinase family (110)	Intellectual problems, failure to thrive, microcephaly, seizures, facial abnormalities, developmental delay, intrauterine growth restriction, feeding difficulties, micropenis, chordee, hypospadias, CAKUT (renal agenesis and hydronephrosis) (111)
FGFR2	10q26	Family of growth factors involved in numerous pathways and expressed in numerous cell types throughout the body (112)	Urethral formation, hypospadias, cryptorchidism, reduced testicular size, intellectual disability, facial abnormalities, renal hypoplasia, vesicoureteral reflux, ocular problems, microcephaly, seizures, developmental delay, dental problems, cardiac problems, altered stature, hand problems, altered chest, and small size for gestational age (40, 113, 114)
INSL3	19p13	Member of relaxin protein family and specific roles in male testicular descent (115, 116)	Bone metabolism, female infertility, developmental delay, facial abnormalities, intellectual disability, renal anomalies (multicystic kidney dysplasia, hypoplasia, agenesis, and hydronephrosis), skin changes, short stature, microcephaly, cardiac problems, and gastrointestinal abnormalities (40, 115, 117)
RXFP2	13q13	Encodes a member of a G-protein coupled transmembrane receptor and receptor for INSL3 (118, 119)	Cryptorchidism, bone metabolism, osteoporosis, cardiovascular disease (120, 121)

Note: CAKUT = congenital anomalies of the kidney and urinary tract; CREBBP = cAMP-response element binding protein; DYRKA1 = dual specificity tyrosine-phosphorylation-regulated kinase 1A; EYA1 = EYA transcriptional coactivator and phosphatase 1; FGFR2 = fibroblast growth factor receptor 2; HNF1B = hepatocyte nuclear factor 1β; INSL3 = insulin-like peptide3; MECP2 = methyl CpG binding protein 2; PAX2 = paired box gene 2; PIK3R1 = phosphoinositide-3-kinase regulatory subunit 1; RBFOX2 = RNA binding fox-1 homolog2; RXFP2 = relaxin family peptide receptor 2; SHORT = short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay.