NSMF

NMDA receptor synaptonuclear signaling and neuronal migration factor, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 9:137447570-137459334

Previous symbols: [ "NELF" ]

Links

ENSG00000165802 ∙ NCBI:26012 ∙ OMIM:608137 ∙ HGNC:29843 ∙ Uniprot:Q6X4W1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypogonadotropic hypogonadism (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism 9 with or without anosmia (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 9 with or without anosmia	AD	Endocrine	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease	Endocrine; Neurologic	15362570; 17235395; 21300340; 21700882; 22035731
Syngergistic effects (eg, with FGFR1) have been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NSMF gene.

• Pituitary stalk interruption syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NSMF gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	27	1	29
missense			50	3	1	54
nonsense	1		1			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				4	3	7
non coding			1	30	20	51
Total	1	1	53	60	22

Variants in NSMF

This is a list of pathogenic ClinVar variants found in the NSMF region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-137449138-G-A			Benign (May 14, 2019)
9-137449402-C-A		not specified	Uncertain significance (Feb 13, 2023)
9-137449402-C-T		not specified	Uncertain significance (Jul 14, 2021)
9-137449406-G-A			Likely benign (Nov 04, 2021)
9-137449435-G-A		not specified	Uncertain significance (Jan 24, 2024)
9-137449463-G-A			Likely benign (Dec 21, 2018)
9-137449472-C-T			Likely benign (Jan 15, 2023)
9-137449498-G-A			Likely benign (May 20, 2023)
9-137449500-A-G			Likely benign (Jan 22, 2024)
9-137449558-C-T			Benign (Jun 19, 2018)
9-137449627-G-A		not specified	Benign/Likely benign (Jan 18, 2024)
9-137449656-T-C		Hypogonadotropic hypogonadism 9 with or without anosmia	risk factor (Jul 12, 2011)
9-137449659-T-C		Hypogonadotropic hypogonadism 9 with or without anosmia	Uncertain significance (Aug 01, 2018)
9-137449664-T-C		not specified	Uncertain significance (Nov 17, 2022)
9-137449752-C-T			Benign (Jun 19, 2018)
9-137449876-G-A			Benign (Jun 26, 2018)
9-137449920-T-C			Likely benign (Nov 08, 2022)
9-137449928-C-T			Uncertain significance (Apr 03, 2017)
9-137449938-G-T			Uncertain significance (Jun 30, 2017)
9-137449941-C-T		not specified	Benign/Likely benign (Mar 05, 2021)
9-137449949-T-C		not specified	Uncertain significance (Jan 06, 2023)
9-137449974-G-A			Likely benign (Dec 18, 2023)
9-137449992-T-C			Likely benign (Oct 07, 2023)
9-137449995-G-A		NSMF-related disorder	Benign/Likely benign (Mar 22, 2023)
9-137450012-G-A		NSMF-related disorder	Benign (Jan 18, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NSMF	protein_coding	protein_coding	ENST00000371475	16	11765

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.265	0.735	125706	0	6	125712	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.88	233	329	0.708	0.0000228	3458
Missense in Polyphen		80	132.13	0.60547		1414
Synonymous	-1.82	157	131	1.20	0.00000933	1025
Loss of Function	3.86	7	29.7	0.236	0.00000160	324

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000549	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000440
Middle Eastern	0.0000549	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Couples NMDA-sensitive glutamate receptor signaling to the nucleus and triggers long-lasting changes in the cytoarchitecture of dendrites and spine synapse processes. Part of the cAMP response element-binding protein (CREB) shut-off signaling pathway. Stimulates outgrowth of olfactory axons and migration of gonadotropin-releasing hormone (GnRH) and luteinizing-hormone-releasing hormone (LHRH) neuronal cells. {ECO:0000269|PubMed:20025934}.
• Disease: DISEASE: Hypogonadotropic hypogonadism 9 with or without anosmia (HH9) [MIM:614838]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic- pituitary axis. In some cases, it is associated with non- reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:15362570, ECO:0000269|PubMed:21700882, ECO:0000269|PubMed:23643382}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in NSMF as well as in other HH-associated genes including FGFR1 (PubMed:23643382). {ECO:0000269|PubMed:23643382}.

Recessive Scores

• pRec: 0.238

Intolerance Scores

• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

• pHI: 0.153
• hipred: Y
• hipred_score: 0.639
• ghis: 0.682

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nsmf
• Phenotype: endocrine/exocrine gland phenotype; hematopoietic system phenotype; reproductive system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: positive regulation of protein dephosphorylation;regulation of neuron apoptotic process;regulation of neuronal synaptic plasticity;regulation of dendrite morphogenesis;cellular response to amino acid stimulus;cellular response to electrical stimulus;cellular response to gonadotropin stimulus;positive regulation of neuron migration
• Cellular component: nucleus;nuclear envelope;nucleoplasm;nuclear euchromatin;cytoplasm;postsynaptic density;membrane;nuclear matrix;cell junction;dendrite;cortical cytoskeleton;nuclear membrane;neuron projection;perikaryon;synapse;postsynaptic membrane;apical dendrite
• Molecular function: calcium-dependent protein binding