Table 1 List of genes, related phenotype, inheritance and coverage in the DSD panel.

From: Diagnostic Application of Targeted Next-Generation Sequencing of 80 Genes Associated with Disorders of Sexual Development

No. Gene (O) OMIM phenotype/(L)Literature Inheritance * Coverage
1 AKAP2 (L) Role in the pathways regulating ovarian development22 100%
2 AKR1C1 (L)Role in metabolism of steroid hormone23 100%
3 AKR1C2 (O)46XY sex reversal 8, 614279 (3) AR 100%
4 AKR1C4 (O)46XY sex reversal 8, modifier, 614279 (3) AR 100%
5 AR (O)Androgen insensitivity, 300068 (3); Hypospadias 1, X-linked, 300633 (3) X-LR 100%
6 ATF3 (L)A hormone responsive gene in hypospadias24 100%
7 ATRX (O)ATR-X syndrome with gonadal abnormalities, 301040 (3) X-LD/X-LR 100%
8 BMP15 (O)Ovarian dysgenesis 2, 300510 (3); Premature ovarian failure 4, 300510 (3) X-linked 99%
9 BMP4 (L)Mutations reported in hypospadias18 AD 92%
10 BMP7 (L)Downstream of androgen signaling25 100%
11 BNC2 (L)Required for ovary development and fertility in zebrafish26 100%
12 CBX2 (O)46XY sex reversal 5, 613080 (3) AR 99%
13 CHD7 (O)CHARGE syndrome, 214800 (3); Hypogonadotropic hypogonadism 5 with or without anosmia, 612370 (3) AD 100%
14 CUL4B (L)Essential for spermatogenesis and male fertility in mouse model27 X-LR 100%
15 CYB5A (L)Contribute to steroid hormone synthesis28 AR 100%
16 CYP11A1 (O)Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, 613743 (3) 100%
17 DHH (O)46XY partial gonadal dysgenesis, 607080 (3); 46XY sex reversal 7, 233420 (3) AR/hetero 100%
18 DMRT1 (L)Role in human sex determination with male-specific expression14 93%
19 DUSP6 (O)Hypogonadotropic hypogonadism 19 with or without anosmia, 615269 (3) AD 95%
20 ESR2 (L)Hormone receptor in gonadal development29 98%
21 FGF17 (O)Hypogonadotropic hypogonadism 20 with or without anosmia, 615270 (3) AD 94%
22 FGF8 (O)Hypogonadotropic hypogonadism 6 with or without anosmia, 612702 (3) 94%
23 FGFR1 (O)Hypogonadotropic hypogonadism 2 with or without anosmia, 147950 (3) AD 98%
24 FGFR2 (L)Downstream of SOX9 in sex determination30 AR/AD 100%
25 FLRT3 (O)Hypogonadotropic hypogonadism 21 with anosmia, 615271 (3) AD 100%
26 FSHR (O)Ovarian dysgenesis 1, 233300 (3); Ovarian hyperstimulation syndrome, 608115 (3) AR/AD 100%
27 GATA4 (O)Testicular anomalies with or without congenital heart disease, 615542 (3); AD 63%
28 GNRH1 (O)Hypogonadotropic hypogonadism 12 with or without anosmia, 614841 (3) AR 100%
29 GNRHR (O)Hypogonadotropic hypogonadism 7 without anosmia, 146110 (3) AR 100%
30 HDAC8 (O) Wilson-Turner syndrome, 309585 (3) X-LD 100%
31 HESX1 (O)Pituitary hormone deficiency, combined, 5, 182230 (3) AD/AR 88%
32 HOXA4 (L)Associated with hypospadias based on GWAS study31 58%
33 HOXB6 (L)Mutations found in Chinese patients with hypospadias18 98%
34 HS6ST1 (O)Hypogonadotropic hypogonadism 15 with or without anosmia, 614880 (3) AD 78%
35 HSD17B3 (O)Pseudohermaphroditism, male, with gynecomastia, 264300 (3) AR 100%
36 HSD17B4 (O)Perrault syndrome 1 (with ovarian dysfunction), 233400 (3) AR 100%
37 HSD3B2 (O)3-beta-hydroxysteroid dehydrogenase, type II, deficiency, 201810 (3) AR 99%
38 IL17RD (O)Hypogonadotropic hypogonadism 18 with or without anosmia, 615267 (3) AD 94%
39 KAL1 (O)Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1), 308700 (3) X-linked 92%
40 KISS1 (O)Hypogonadotropic hypogonadism 13 with or without anosmia, 614842 (3) AR 100%
41 KISS1R (O)Hypogonadotropic hypogonadism 8 with or without anosmia, 614837 (3);Precocious puberty, central, 1, 176400 (3) AD/AR 66%
42 LEP (O)Obesity, morbid, due to leptin deficiency, 614962 (3) AR 100%
43 LHB (O)Hypogonadotropic hypogonadism 23 with or without anosmia, 228300 (3) AR 42%
44 LHCGR (O)Leydig cell hypoplasia with pseudohermaphroditism, 238320 (3) Sex-limited AD/AR 99%
45 LHFPL5 (L) Variants reported in patients of hypospadias32 AR 99%
46 LHX3 (O)Pituitary hormone deficiency, combined, 3, 221750 (3) AR 92%
47 LHX9 (L)Essential gene for gonadal formation in mouse model33 96%
48 MAMLD1 (O)Hypospadias 2, X-linked, 300758 (3) X-LR 100%
49 MAP3K1 (O)46XY sex reversal 6, 613762 (3) AD 91%
50 MID1 (O)Opitz GBBB syndrome, type I, 300000 (3) X-LR 100%
51 NELF (O)Hypogonadotropic hypogonadism 9 with or without anosmia, 614838 (3) 75%
52 NLGN4X (L)Deletion identified in infants with atypical sexual development34 X-linked 100%
53 NMT2 (L)Disruption of gene structure found in hypogonadism35 99%
54 NR0B1 (O)Adrenal hypoplasia, congenital, with hypogonadotropic hypogonadism, 300200 (3); 46XY sex reversal 2, dosage-sensitive, 300018 (3) X-LR 97%
55 NR5A1 (O)46XY sex reversal 3, 612965 (3); Premature ovarian failure 7, 612964 (3); Adrenocortical insufficiency (3); Spermatogenic failure 8, 613957 (3) AR/AD 99%
56 PAX2 (L)Involved in initial formation of genital tracts36 AD/AR 100%
57 POLR3A (O)Leukodystrophy (with hypogonadotropic hypogonadism), 607694 (3) AR 100%
58 POR (O)Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, 201750 (3); Disordered steroidogenesis due to cytochrome P450 oxidoreductase, 613571 (3) AR 86%
59 PROK2 (O)Hypogonadotropic hypogonadism 4 with or without anosmia, 610628 (3) AD 75%
60 PROKR2 (O)Hypogonadotropic hypogonadism 3 with or without anosmia, 244200 (3) AD 99%
61 PROP1 (O)Pituitary hormone deficiency, combined, 2, 262600 (3) AR 100%
62 PSMC3IP (O)Ovarian dysgenesis 3, 614324 (3) AR 100%
63 RSPO1 (O)Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal, 610644 (3) 100%
64 SEMA3A (O)Hypogonadotropic hypogonadism 16 with or without anosmia, 614897 (3) AD 100%
65 SOX10 (L)Implicated in human 22q-linked disorders of sex development37 AD 98%
66 SOX2 (L)Role in Hypogonadotropic Hypogonadism38 AD 99%
67 SOX3 (O)Panhypopituitarism, X-linked, 312000 (3) X-linked 97%
68 SOX9 (O)Campomelic dysplasia with autosomal sex reversal, 114290 (3) AD 89%
69 SPRY4 (O)Hypogonadotropic hypogonadism 17 with or without anosmia, 615266 (3) AD 100%
70 SRD5A2 (O)Pseudovaginalperineoscrotal hypospadias, 264600 (3) AR 96%
71 SRY (O)46XY sex reversal 1, 400044 (3); 46XX sex reversal 1, 400045 (3) Y-Linked 100%
72 STAR (O)Lipoid adrenal hyperplasia, 201710 (3) AR 100%
73 TAC3 (O)Hypogonadotropic hypogonadism 10 with or without anosmia, 614839 (3) AR 100%
74 TACR3 (O)Hypogonadotropic hypogonadism 11 with or without anosmia, 614840 (3) AR 100%
75 TDRD7 (L)Involved in male germline development in mouse model39 100%
76 TUBB3 (L)TUBB3 syndrome (with hypogonadotropic hypogonadism)40 AD 71%
77 WDR11 (O)Hypogonadotropic hypogonadism 14 with or without anosmia, 614858 (3) AD 100%
78 WNT4 (O)Mullerian aplasia and hyperandrogenism, 158330 (3) AD 95%
79 WT1 (O) Wilms tumor 1, associated with urogenital abnormality, 194070 (3) AD/AR 87%
80 WWOX (L)Exonic deletion associated with 46 XY,DSD41 AR/AD 100%
  1. *Abbreviations for inheritance mode – AR: autosomal recessive; AD: autosomal dominant; X-LD: X-linked dominant; X-LR: X-linked recessive.