Table 1: Genetic causes of Kallmann’s syndrome (KS) and normosmic isolated hypogonadotropic hypogonadism (IHH).

GeneGene productFunctionInheritanceClinical phenotypeAssociated clinical phenotype

KAL1Anosmin-1Cell adhesionX-linkedKSAnosmia, bimanual synkinesis, renal agenesis
FGFR1Fibroblast-growth-factor receptor 1Tyrosine kinase receptorADKS or IHHAnosmia, cleft lip or palate, ear anomalies, tooth agenesis
FGF8Fibroblast growth factor 8Ligand of FGFR1ADKS or IHH
NELFNasal embryonic LHRH factorNeuronal migrationADKSAnosmia
CHD7Chromodomain- helicase-DNA-binding protein 7DNA-binding protein, neural crest developmentADKS or IHHCHARGE syndrome: anosmia, coloboma, heart anomaly, choanal atresia, retardation, ear abnormalities
PROKR2Prokineticin receptor 2GPCRAD
AR
KS or IHHAnosmia
PROK2Prokineticin 2Ligand of PROKR2AD
AR
KS or IHHAnosmia
WDR11WD proteinInteraction with EMX1ADKS or IHHAnosmia
GPR54/KISS1RKisspeptin-1 receptorGPCRARIHHNone
TACR3Neurokinin B receptorGPCRARIHHNone
TAC3Neurokinin BLigand of TACR3ARIHHNone
LEPRleptin receptorSingle transmembrane-domain receptorARIHHObesity
LEPleptinFat-regulating hormoneARIHHObesity
GNRH1GnRHRelease of LH and FSHARIHHNone
GNRHRGnRH receptorGPCRARIHHNone
LHββ-subunit of LHLigand of LH/CG receptorARIHHNone
FSHββ-subunit of FSHLigand of FSH receptorARIHHNone

GPCR: heptahelical transmembrane G-protein-coupled receptor, AD: autosomal dominant.
AR: autosomal recessive.