Table 3.
Genes associated with hypogonadotropic hypogonadism
| Gene | Inheritance | OMIM gene | OMIM phenotype | OMIM or HGMD phenotype ID | Gene function |
| KISS1 | AR | 603286 | HH13 | 614842 | Stimulation of GnRH-induced gonadotropin secretion, activation of GnRH neurons |
| HS6ST1 | AD | 604846 | HH15 | 614880 | Neuron development, neuron branching |
| IL17RD | AD, AR | 606807 | HH18 | 615267 | Fate-specification of GnRH-secreting neurons |
| PROK2 | AD | 607002 | HH4 | 610628 | Chemoattractant for neuronal precursor cells in olfactory bulb |
| GNRHR | AR | 138850 | HH7 | 146110 | Receptor for GnRH. Stimulation of LH and FSH secretion |
| TACR3 | AR | 162332 | HH11 | 614840 | Receptor for neurokinin B. Expressed in hippocampus, hypothalamus, substantia nigra |
| SPRY4 | AD | 607984 | HH17 | 615266 | Regulation of neurite outgrowth in hippocampal neurons |
| SEMA3A | AD | 603961 | HH16 | 614897 | Inhibition of axonal outgrowth, stimulation of apical dendrite growth |
| FEZF1 | AR | 613301 | HH22 | 616030 | Embryonic migration of GnRH-releasing neurons into brain |
| FGF17 | AD | 603725 | HH20 | 615270 | Induction and patterning of embryonic brain |
| GNRH1 | AR | 152760 | HH12 | 614841 | Stimulation of LH and FSH secretion |
| FGFR1 | AD | 136350 | HH2 | 147950 | Mesoderm patterning, correct axial organization during embryo development, skeletogenesis, development of GnRH neuronal system |
| CHD7 | AD | 608892 | HH5 | 612370 | Formation of neural crest |
| NSMF | AD | 608137 | HH9 | 614838 | Guidance of olfactory axon projections, migration of LHRH neurons |
| FGF8 | AD | 600483 | HH6 | 612702 | Regulation of embryo development, cell proliferation, differentiation, migration. Brain, eye, ear, limb, GnRH neuronal system, hippocampal neuron development |
| WDR11 | AD | 606417 | HH14 | 614858 | Regulation of GnRH production |
| FSHB | AR | 136530 | HH24 | 229070 | Beta subunit of FSH. Induction of egg and sperm production |
| TAC3 | AR | 162330 | HH10 | 614839 | Central regulator of gonad function |
| DUSP6 | AD | 602748 | HH19 | 615269 | Expression regulated by GnRH |
| KISS1R | AR | 604161 | HH8 | 614837 | Neuroendocrine control of gonadotropin axis |
| LHB | AR | 152780 | HH23 | 228300 | Promotion of spermatogenesis and ovulation by stimulating gonads to synthesize steroids |
| PROKR2 | AD | 607123 | HH3 | 244200 | Induction of tangential and radial migration of olfactory bulb interneurons |
| FLRT3 | AD | 604808 | HH21 | 615271 | Spatial organization of brain neurons. |
| ANOS1 | XLR | 300836 | HH1 (KS) | 308700 | Neural cell adhesion, axonal migration, patterning of mitral and tufted cell collaterals to olfactory cortex |
| SOX10 | AD | 602229 | WS2E | 611584 | Development of neural crest, peripheral nervous system, glia |
| AXL | AD | 109135 | HH | 1734393901 | GnRH neuron survival and migration |
| CCDC141 | AR | 616031 | KS | 817012261 | Neural radial migration |
| SEMA3E | AD | 608166 | KS | 817012261 | Ensuring synapse formation specificity |
| SRA1 | AR | 603819 | HH | 1734393901 | Mediation of transcriptional co-activation of steroid receptors |
GnRH = gonadotropin-releasing hormone; HH = hypogonadotropic hypogonadism; KS = Kallmann syndrome; WS = Waardenburg syndrome; AD = autosomal dominant; AR = autosomal recessive; XLR = X-linked recessive; HGMD = Human Gene Mutation Database (https://portal.biobase-international.com/hgmd/pro/)