Table 3. Current List of Genes Associated with Both Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome.
| Gene and protein (alternative names) |
OMIM | Known biological activity | Reversible | Oligogenicity | Inheritance |
|---|---|---|---|---|---|
|
AXL (AXL receptor tyrosine kinase) |
109135 | Receptor tyrosine kinase containing fibronectin type III domain with oncogenic activity. Required for GnRH neuron migration. | ND | ND | ND |
|
CHD7 (chromodomain helicase DNA-binding protein 7) |
612370 | Transcriptional regulator essential for the formation of neural crest and the development of forebrain, craniofacial bones and heart. | Yes | ND | Autosomal dominant |
|
FGF8 (fibroblast growth factor 8) |
612702 | Ligand for FGFR1. Essential morphogen for development of forebrain, olfactory GnRH system, skeletal structure and heart. | ND | Yes | Autosomal dominant |
|
FGF17 (fibroblast growth factor 17) |
603725 | Similar to FGF8 as a ligand for FGFR1, but more in patterning the dorsal frontal cortex. | ND | Yes | ND |
|
FGFR1 (fibroblast growth factor receptor 1) |
147950 | Receptor tyrosine kinase essential for development of forebrain, craniofacial niche, and stimulation and secretion of GnRH neurons and gonadotrophs. | Yes | Yes | Autosomal dominant |
|
HS6ST1 (heparan-sulphate 6O-sulphotransferase 1) |
614880 | Catalyzes the transfer of sulphate to position 6 of the N-sulfoglucosamine residue of heparan sulphate, essential for FGFR1 signaling activity. | Yes | Yes | Autosomal dominant |
|
NSMF (nasal embryonic luteinizing hormone-releasing hormone factor; NELF) |
614838 | Guidance molecule for olfactory axon projections required for the axonophilic migration of GnRH neurons. | Yes | Yes | ND |
|
PROK2 (prokineticin 2) |
610628 | Secreted by the hypothalamic neurons of suprachiasmatic nucleus that regulate circadian clock. Chemoattractant for subventricular zone neuronal progenitors. Involved in olfactory bulb morphogenesis and the migration and stimulation of GnRH neurons. | ND | Yes | A utosomal recessive/dominant |
|
PROKR2 (prokineticin receptor-2; GPR73L 1) |
607123 | G-protein-coupled receptor for PROK2. Regulate the formation of olfactory bulb, GnRH neuron and reproductive organs. | Yes | Yes | A utosomal recessive/dominant |
|
SEMA7A (semaphorin 7A) |
607961 | Membrane-anchored guidance molecule of the semaphorin family. Enhances axon outgrowth and interacts with integrin receptors. | ND | Yes | ND |
|
WDR11 (WD repeat protein 11) |
614858 | Member of the WD repeat-containing protein family. Expressed in the forebrain and HPG axis. | ND | Yes | Autosomal dominant |
OMIM, Online Mendelian Inheritance in Man; GnRH, gonadotrophin-releasing hormone; ND, not determined; HPG, hypothalamic-pituitary-gonadal.