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GENATLAS PHENOTYPE
last update : 02-10-2024
Symbol KAL3
Location 20p12.3
Name Kallmann syndrome 3
Other name(s)
  • hypogonadotropic hypogonadism 3 with or without anosmia
    • Corresponding gene PROKR2
    Other symbol(s) HH3
    Main clinical features
  • characterized by hypogonadotropic hypogonadism and anosmia, (variable degrees of olfactory and reproductive dysfunction), or normosmic idiopathic hypogonadotropic hypogonadism maybe associated with renal agenesis or olfactory lobes and ataxia, synkinesia, nystagmus, fibrous dysplasia, sleep disorder, seizures, visual defects, clubfoot, cleft palate
    • Genetic determination autosomal dominant
    Function/system disorder sex-genitalia
    neurology
    endocrinology
    Type disease
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense   abnormal protein/loss of function homozygous loss-of-function mutations either in PROK2 are sufficient to cause disease phenotype (PMID: 18682503)
    Remark(s)
  • loss-of-function mutations in KAL1 and FGFR1 account for approximately 20% of all cases of Kallmann syndrome and mutations in the PROKR2 and PROK2 genes account for an additional 10% (Dode 2006)
  • mutation decreased signalling activities (Monnier 2009)
  • trafficking-defective mutant PROKR2 cycles between endoplasmic reticulum and Golgi to attenuate endoplasmic reticulum stress (PMID: 35173048))
  • certain inactive PROKR2 mutants can cause early puberty by enhancing the functional property of coexisting wild-type proteins (PMID: 28338294))