Hypogonadotropic hypogonadism (GMS)

Gene: NSMF

Red List (low evidence)

NSMF (NMDA receptor synaptonuclear signaling and neuronal migration factor)
EnsemblGeneIds (GRCh38): ENSG00000165802
EnsemblGeneIds (GRCh37): ENSG00000165802
OMIM: 608137, Gene2Phenotype
NSMF is in 3 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

Comment on mode of inheritance: Updated from biallelic to monoallelic as only heterozygous variants in this gene have been reported in association with IHH, even though this is only partially explains the phenotype due to possible oligogenic variants in other genes such as FGFR1 and HS6ST1.
Created: 30 Nov 2023, 12:04 p.m. | Last Modified: 30 Nov 2023, 12:04 p.m.
Panel Version: 3.14

Ivone Leong (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Demoted from Amber to Red as per my previous comment.
Created: 24 Mar 2021, 4:01 p.m. | Last Modified: 24 Mar 2021, 4:01 p.m.
Panel Version: 1.24
This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. PMID:27803842 describes a murine Nsmf knockout model that shows that Nsmf does not have a role in the migration of GnRH-positive neurons during early development.

Given the available evidence, this gene should be demoted to Red status.
Created: 24 Mar 2021, 4:01 p.m. | Last Modified: 24 Mar 2021, 4:01 p.m.
Panel Version: 1.22

Publications

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Rare variants reported in individuals with IHH; however, variants in other IHH genes also present, and at least one of the variants has a very high population frequency in gnomad (intronic 8-bp deletion ending 14 bp before exon 10 (1159-14_-22del), present in 258 individuals).
Created: 18 Jul 2020, 10:23 a.m. | Last Modified: 18 Jul 2020, 10:23 a.m.
Panel Version: 1.8

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838

Publications

Simon Thomas (Wessex Regional Genetics Laboratory)

Red List (low evidence)

Complicated by oligogenic inheritance
Created: 22 Mar 2019, 5:03 p.m.

Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust)

Green List (high evidence)

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Wessex and West Midlands GLH
  • NHS GMS
  • South West GLH
Phenotypes
  • Hypogonadotropic hypogonadism 9 with or without anosmia, OMIM:614838
OMIM
608137
Clinvar variants
Variants in NSMF
Penetrance
None
Publications
Panels with this gene

History Filter Activity

30 Nov 2023, Gel status: 1

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: NSMF was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

24 Mar 2021, Gel status: 1

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: nsmf has been classified as Red List (Low Evidence).

24 Mar 2021, Gel status: 2

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: NSMF were set to 15362570; 17235395; 21700882

24 Mar 2021, Gel status: 2

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: NSMF were changed from Hypogonadotropic hypogonadism type 9 (OMIM 614838) to Hypogonadotropic hypogonadism 9 with or without anosmia, OMIM:614838

24 Mar 2021, Gel status: 2

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: NSMF were set to

22 Mar 2019, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: nsmf has been classified as Amber List (Moderate Evidence).

22 Mar 2019, Gel status: 1

Added New Source

Ivone Leong (Genomics England Curator)

Source Wessex and West Midlands GLH was added to NSMF.

15 Mar 2019, Gel status: 1

Set Phenotypes

Ivone Leong (Genomics England Curator)

Added phenotypes Hypogonadotropic hypogonadism type 9 (OMIM 614838) for gene: NSMF

15 Mar 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Ivone Leong (Genomics England Curator)

gene: NSMF was added gene: NSMF was added to Hypogonadotropic hypogonadism idiopathic. Sources: South West GLH,NHS GMS Mode of inheritance for gene: NSMF was set to BIALLELIC, autosomal or pseudoautosomal