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. Author manuscript; available in PMC: 2024 Mar 1.
Published in final edited form as: Lancet Diabetes Endocrinol. 2023 Jan 5;11(3):203–216. doi: 10.1016/S2213-8587(22)00339-4

Table:

Genes associated with congenital hypogonadotropic hypogonadism or self-limited delayed puberty

Inheritance Contributes to oligogenity Kallmann syndrome CHH Reversal Self-limited delayed puberty Other phenotypic or syndromic features Phenotype MIM ID
AMH AD ·· Yes Yes ·· Yes ·· ··
AMHR2 AD ·· Yes Yes ·· Yes ·· ··
ANOS1 (KAL1) XLR Yes Yes Yes Yes Yes Bimanual synkinesis, aplasia or hypoplasia of olfactory bulbs, unilateral renal aplasia 308700
AXL AD ·· Yes Yes ·· Yes ·· ··
BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, TRIM32, BBS12 AR, DR Yes ·· Yes ·· ·· Bardet-Biedl syndrome 209900
CCDC141 AD, AR ·· Yes Yes ·· Yes ·· ··
CHD7 AD Yes Yes Yes Yes Yes CHARGE syndrome 612370
CPE AR ·· ·· Yes ·· ·· BDV syndrome 114855
DCAF17 AR ·· ·· Yes ·· ·· Woodhouse-Sakati syndrome, alopecia, diabetes mellitus, mental retardation, deafness 241080
DCC/NTN1 AD Yes Yes Yes ·· Yes Synkinesis, mid brain malformation, deafness ··
DMXL2 AD, AR ·· ·· Yes ·· ·· PEPNS (polyendocrine polyneuropathy) 616113
DUSP6 AD ·· Yes Yes ·· ·· Dental agenesis, syndactyly, color blindness 615269
EAP1 (IRF2BPL) AD ·· ·· ·· ·· Yes ·· 611720
FEZF1 AR ·· Yes Yes ·· Yes ·· 616030
FGF17 AD Yes Yes Yes ·· ·· ·· 615270
FGF8 AD Yes Yes Yes ·· ·· Combined pituitary hormone deficiency 612702
FGFR1 AD Yes Yes Yes Yes Yes SOD, Hartsfield syndrome, split hand/foot malformation, combined pituitary hormone deficiency, bimanual synkinesis 147950
FLRT3 AD Yes Yes Yes ·· ·· ·· 615271
FSHB AR ·· ·· Yes ·· ·· ·· 229070
FTO AD ·· ·· ·· ·· Yes ·· 612938
GNRH1 AR ·· ·· Yes ·· ·· ·· 614841
GNRHR AR Yes ·· Yes Yes Yes ·· 146110
HDAC8 XLR ·· ·· ·· ·· Cornelia de Lange syndrome 300882
HESX1 AD, AR ·· Yes Yes ·· ·· Combined pituitary hormone deficiency, SOD 182230
HFE AD, AR ·· ·· ·· ·· ·· Hereditary hemochromatosis 235200
HS6ST1 AD Yes Yes Yes Yes Yes ·· 614880
IGSF1 XLR ·· ·· Yes ·· Yes Central hypothyroidism, macroorchidism 300888
IGSF10 AD ·· ·· ·· ·· Yes ·· 617351
IL17RD (SEF) AD, AR or digenic dominant Yes Yes Yes ·· Yes ·· 615267
KISS1 AR ·· ·· Yes ·· ·· ·· 614842
KISS1R AR Yes ·· Yes ·· ·· ·· 614837
KLB AD, complex Yes Yes Yes Yes Yes Obesity, insulin resistance ··
LEP AR ·· ·· Yes ·· ·· Obesity, recurrent respiratory infections 614962
LEPR AR Yes ·· Yes ·· Obesity, recurrent respiratory infections 614963
LGR4 AD ·· ·· ·· Yes ·· 619613
LHB AR ·· ·· Yes ·· ·· ·· 228300
LHX AR ·· ·· Yes ·· ·· Combined pituitary hormone deficiency, sensorineural deafness (variable) 221750
NDN, SNRPN AD, deletion of the paternal copy ·· ·· Yes ·· ·· Prader-Willi syndrome 176270
NDNF AD ·· Yes Yes ·· Yes ·· 616506
NR0B1 (DAX1) XLR ·· ·· Yes ·· ·· Congenital adrenal hypoplasia 300200
NRP1 AD Yes Yes Yes ·· ·· ·· ··
NRP2 AD Yes Yes Yes ·· ·· ·· ··
NSMF (NELF) AD Yes Yes Yes Yes ·· ·· 614838
OTUD4, RNF216 AR ·· ·· Yes ·· ·· Gordon Holmes syndrome 212840
PCSK1 AR ·· ·· Yes ·· ·· Obesity, small-intestinal dysfunction, complex endocrinopathies 600955
PHF6 XLR ·· ·· Yes ·· ·· Börjeson-Forssman-Lehmann syndrome 301900
PLXNA1 AD Yes Yes Yes ·· Yes ··
PLXNA3 Complex Yes Yes Yes ·· ·· ·· ··
PNPLA6 AR ·· ·· Yes ·· ·· Boucher-Neuhauser, Gordon Holmes, Oliver McFarlane, Lawrence Moon syndromes 215470
POLR3A AR ·· ·· Yes ·· ·· Leukodystrophy, oligodontia, ataxia 607694
POLR3B AR ·· ·· Yes ·· ·· Leukodystrophy, oligodontia, ataxia 614381
PROK2 AD Yes Yes Yes ·· ·· ·· 610628
PROKR2 AD Yes Yes Yes Yes Yes Combined pituitary hormone deficiency, synkinesis 244200
PROP1 AR ·· ·· Yes ·· ·· Combined pituitary hormone deficiency 262600
RAB18 AR ·· ·· Yes ·· ·· Warburg micro syndrome 614222
RAB3GAP1 AR ·· ·· Yes ·· ·· Warburg micro syndrome 600118
RAB3GAP2 AR ·· ·· Yes ·· ·· Martsolf syndrome 212720
REV3L/PLXND1 AD ·· Yes ·· Yes ·· Moebius syndrome ··
RMB28 AR ·· ·· ·· ·· ·· Alopecia, neurological defects, and endocrinopathy syndrome 612079
SEMA3A AD Yes Yes ·· ·· Yes ·· 614897
SEMA3F complex Yes Yes Yes ·· ·· ·· ··
SEMA3E AD ·· Yes Yes ·· ·· CHARGE syndrome 608166
SEMA7A * DR Yes Yes Yes ·· ·· Pending full validation ··
SMCHD1 AD ·· ·· Yes ·· ·· Bosma arhinia microphthalmia syndrome 603457
SOX10 AD ·· Yes Yes ·· ·· Waardenburg syndrome type 2E 611584
SOX2 AD ·· ·· Yes ·· ·· Optic nerve hypoplasia, CNS abnormalities 206900
SOX3 XLR Yes ·· Yes ·· ·· Intellectual disability, craniofacial abnormalities, multiple pituitary hormone deficiency ··
SPRY4 AD Yes Yes Yes ·· ·· Hearing loss 615266
SRA1 AD ·· ·· Yes ·· ·· ·· ··
STUB1 AR ·· ·· ·· ·· ·· Spinocerebellar ataxia 615768
TAC3 AR Yes Yes Yes Yes Yes ·· 614839
TACR3 AR Yes ·· Yes Yes Yes ·· 614840
TBC1D20 AR ·· ·· Yes ·· ·· Warburg micro syndrome 615663
TCF12 AD ·· Yes Yes ·· ·· Craniosynostosis 3 615314
TUBB3 AD ·· Yes Yes ·· ·· Congenital fibrosis of the extraocular muscles 600638
WDR11 AD Yes Yes Yes Yes ·· Combined pituitary hormone deficiency 614858

AD=autosomal dominant. AR=autosomal recessive. CHARGE=coloboma of the eye, heart defects, atresia choanae, retardation of growth, genital abnormalities, and ear abnormalities. CHH=congenital hypogonadotropic hypogonadism. DR=digenic recessive. XLR=X-linked recessive. MIM=Mendelian Inheritance in Man.

*

Pending full validation.