Hypogonadotropic hypogonadism (GMS)
Gene: PROKR2EnsemblGeneIds (GRCh38): ENSG00000101292
EnsemblGeneIds (GRCh37): ENSG00000101292
OMIM: 607123, Gene2Phenotype
PROKR2 is in 7 panels
3 reviews
Ida Ertmanska (Genomics England Curator)
Comment on mode of inheritance: The majority (up to 90%) of cases reported in literature with Hypogonadotropic hypogonadism and PROKR2 variants are heterozygotes. There are at least 22 patients with HH and biallelic PROKR2 variants - mostly biallelic missense. Hence, the mode of inheritance should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal on this panel.Created: 20 May 2026, 11:26 a.m. | Last Modified: 20 May 2026, 11:26 a.m.
Panel Version: 5.2
PMID: 36843573 Martinez-Mayer and Perez-Millan, 2023
Literature review of 435 cases with PROKR2 variants, 108 with hypogonadotropic hypogonadism (HH) and 236 with Kallmann syndrome (KS). 90% of cases are heterozygous, 7% homozygous and 3% comp het.
Biallelic case examples:
PMID: 18682503 Abreu et al., 2008
PROKR2 p.Y140X change was identified in the homozygous state in an anosmic boy with micropenis, bilateral cryptorchidism, and high-arched palate. His asymptomatic parents were heterozygous.
PMID: 35236788 Sugisawa et al., 2022
Report of a case of a 31-year-old Japanese man with normosmic-CHH, who also had obesity, type 2 diabetes and intellectual disability. Diagnosed with sexual immaturity at 20 yrs old. He was comp het for PROKR2 variants p.Trp178Ser and p.Trp212*.
Literature review in same article found 21 other patients from 17 families with biallelic PROKR2 variants and CHH (86% diagnosed with KS). 17/22 patients had missense variants on both alleles; only 1 had biallelic truncating variants.
PROKR2 is associated with AD,AR Hypogonadotropic hypogonadism 3 with or without anosmia, OMIM:244200 (accessed 20th May 2026).Created: 20 May 2026, 11:17 a.m. | Last Modified: 20 May 2026, 11:24 a.m.
Panel Version: 5.1
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Hypogonadotropic hypogonadism 3 with or without anosmia, OMIM:244200
Publications
Simon Thomas (Wessex Regional Genetics Laboratory)
Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust)
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- Wessex and West Midlands GLH
- NHS GMS
- South West GLH
- Phenotypes
-
- Hypogonadotropic hypogonadism 3 with or without anosmia, OMIM:244200
- Tags
- OMIM
- 607123
- Clinvar variants
- Variants in PROKR2
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Set publications
Ida Ertmanska (Genomics England Curator)Publications for gene: PROKR2 were set to 36694982
Added Tag
Ida Ertmanska (Genomics England Curator)Tag Q2_26_MOI tag was added to gene: PROKR2.
Set Phenotypes
Ida Ertmanska (Genomics England Curator)Phenotypes for gene: PROKR2 were changed from Hypogonadotropic hypogonadism type 3 (OMIM 244200) to Hypogonadotropic hypogonadism 3 with or without anosmia, OMIM:244200
Set publications
Achchuthan Shanmugasundram (Genomics England Curator)Publications for gene: PROKR2 were set to
Entity classified by Genomics England curator
Ivone Leong (Genomics England Curator)Gene: prokr2 has been classified as Green List (High Evidence).
Added New Source
Ivone Leong (Genomics England Curator)Source Wessex and West Midlands GLH was added to PROKR2.
Set Phenotypes
Ivone Leong (Genomics England Curator)Added phenotypes Hypogonadotropic hypogonadism type 3 (OMIM 244200) for gene: PROKR2
Created, Added New Source, Set mode of inheritance
Ivone Leong (Genomics England Curator)gene: PROKR2 was added gene: PROKR2 was added to Hypogonadotropic hypogonadism idiopathic. Sources: South West GLH,NHS GMS Mode of inheritance for gene: PROKR2 was set to BIALLELIC, autosomal or pseudoautosomal