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Infertility and Recurrent Pregnancy Loss v1.96 INSL3 Zornitza Stark Marked gene: INSL3 as ready
Infertility and Recurrent Pregnancy Loss v1.96 INSL3 Zornitza Stark Gene: insl3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.96 Zornitza Stark Copied gene INSL3 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.96 INSL3 Zornitza Stark gene: INSL3 was added
gene: INSL3 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: INSL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: INSL3 were set to 12601553; 12970298; 11095425; 41369823; 37208861; 33095795
Phenotypes for gene: INSL3 were set to Cryptorchidism, MIM# 219050; Infertility disorder MONDO:0005047, INSL3-related
Infertility and Recurrent Pregnancy Loss v0.12 RXFP2 Jasmine Chew changed review comment from: i) PMID: 39222519 (2024)- a compound heterozygous variant (intragenic deletion of exon 1-5 and missense variant p.Glu77Lys) in a family with two male members affected by impaired fertility due to spermatogenic maturation arrest and a history of bilateral cryptorchidism. The Glu77Lys mutant showed no cAMP activity and hence failed to signal in response to INSL3, confirming a loss-of-function mechanism.

ii) PMID: 37208861 (2023)- Homozygous LOF (p.Phe469Serfs*8) and missense (p.Asn339Asp) variants in two unrelated infertile man with impaired spermatogenesis. The missense variant primarily impacts cell surface expression of the protein which directly correlates with reduced INSL3 activation (following protein expression studies).

iii) PMID: 38430325 - a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in a case with cryptorchidism and NOA, which was confirmed to cause aberrant splicing of exons 15 and 16, leading to an abnormal transcript initiation and a frameshift using minigene assay.

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature; to: i) PMID: 39222519- a compound heterozygous variant (intragenic deletion of exon 1-5 and missense variant p.Glu77Lys) in a family with two male members affected by impaired fertility due to spermatogenic maturation arrest and a history of bilateral cryptorchidism. The Glu77Lys mutant showed no cAMP activity and hence failed to signal in response to INSL3, confirming a loss-of-function mechanism.

ii) PMID: 37208861- Homozygous LOF (p.Phe469Serfs*8) and missense (p.Asn339Asp) variants in two unrelated infertile man with impaired spermatogenesis. The missense variant primarily impacts cell surface expression of the protein which directly correlates with reduced INSL3 activation (following protein expression studies).

iii) PMID: 38430325 - a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in a case with cryptorchidism and NOA, which was confirmed to cause aberrant splicing of exons 15 and 16, leading to an abnormal transcript initiation and a frameshift using minigene assay.

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 RXFP2 Jasmine Chew gene: RXFP2 was added
gene: RXFP2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: RXFP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RXFP2 were set to 39222519; 37208861; 38430325
Review for gene: RXFP2 was set to GREEN
Added comment: i) PMID: 39222519 (2024)- a compound heterozygous variant (intragenic deletion of exon 1-5 and missense variant p.Glu77Lys) in a family with two male members affected by impaired fertility due to spermatogenic maturation arrest and a history of bilateral cryptorchidism. The Glu77Lys mutant showed no cAMP activity and hence failed to signal in response to INSL3, confirming a loss-of-function mechanism.

ii) PMID: 37208861 (2023)- Homozygous LOF (p.Phe469Serfs*8) and missense (p.Asn339Asp) variants in two unrelated infertile man with impaired spermatogenesis. The missense variant primarily impacts cell surface expression of the protein which directly correlates with reduced INSL3 activation (following protein expression studies).

iii) PMID: 38430325 - a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in a case with cryptorchidism and NOA, which was confirmed to cause aberrant splicing of exons 15 and 16, leading to an abnormal transcript initiation and a frameshift using minigene assay.

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature