NEU1

neuraminidase 1, the group of Neuraminidases

Basic information

Region (hg38): 6:31857658-31862905

Previous symbols: [ "NEU" ]

Links

ENSG00000204386 ∙ NCBI:4758 ∙ OMIM:608272 ∙ HGNC:7758 ∙ Uniprot:Q99519 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sialidosis type 2 (Definitive), mode of inheritance: AR
• sialidosis type 2 (Strong), mode of inheritance: AR
• sialidosis type 2 (Strong), mode of inheritance: AR
• sialidosis type 1 (Supportive), mode of inheritance: AR
• juvenile sialidosis type 2 (Supportive), mode of inheritance: AR
• congenital sialidosis type 2 (Supportive), mode of inheritance: AR
• sialidosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuraminidase deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic ; Ophthalmologic	610425; 610423; 107795; 6777097; 6839532; 3742847; 8985184; 9054950; 11063730; 11829139; 14695530; 15908988; 19568825

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NEU1 gene.

• not provided (158 variants)
• Sialidosis type 2 (49 variants)
• Inborn genetic diseases (14 variants)
• Sialidosis (13 variants)
• not specified (4 variants)
• Sialidosis type 1 (2 variants)
• - (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NEU1 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	39		40
missense	11	10	55	3	1	80
nonsense	6	2				8
start loss	1					1
frameshift	5	2				7
inframe indel						0
splice donor/acceptor (+/-2bp)	2	1				3
splice region		1	1			2
non coding			10	15	4	29
Total	25	15	66	57	5

Highest pathogenic variant AF is 0.0000197

Variants in NEU1

This is a list of pathogenic ClinVar variants found in the NEU1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-31859075-T-C		Sialidosis type 2	Uncertain significance (Jan 13, 2018)
6-31859123-C-A		Sialidosis type 2	Uncertain significance (Jan 12, 2018)
6-31859138-C-T		Sialidosis type 2	Benign (Jan 12, 2018)
6-31859195-G-A		Sialidosis type 2	Uncertain significance (Jan 12, 2018)
6-31859265-T-C		Sialidosis type 2	Uncertain significance (Jan 12, 2018)
6-31859274-A-C		Sialidosis type 2	Likely benign (Jan 13, 2018)
6-31859425-C-T		Sialidosis type 2	Uncertain significance (Jan 12, 2018)
6-31859450-G-A		Sialidosis type 2	Uncertain significance (Jan 13, 2018)
6-31859509-A-T		Sialidosis type 2	Benign (Dec 31, 2018)
6-31859539-C-T		Sialidosis type 2	Uncertain significance (Jan 12, 2018)
6-31859650-C-T		Sialidosis type 2	Uncertain significance (Apr 27, 2017)
6-31859720-C-G		Sialidosis type 2	Uncertain significance (Aug 19, 2022)
6-31859728-C-T		NEU1-related disorder	Benign/Likely benign (Jan 31, 2024)
6-31859733-AGACA-TTTGGC			Likely pathogenic (Nov 06, 2015)
6-31859740-G-A			Likely benign (Sep 20, 2021)
6-31859750-A-T		Sialidosis type 2	Uncertain significance (Jan 12, 2018)
6-31859751-C-T			Uncertain significance (Aug 06, 2022)
6-31859752-G-A			Likely benign (Dec 29, 2023)
6-31859758-GC-G		Sialidosis type 2	Pathogenic (Aug 15, 2018)
6-31859767-G-A			Likely benign (May 30, 2023)
6-31859776-C-G			Likely benign (Nov 20, 2023)
6-31859777-C-T		Inborn genetic diseases • NEU1-related disorder	Conflicting classifications of pathogenicity (Jan 11, 2024)
6-31859778-G-A		Sialidosis type 2	Uncertain significance (Oct 08, 2021)
6-31859791-C-T			Likely benign (Dec 26, 2023)
6-31859793-G-C		NEU1-related disorder	Uncertain significance (Dec 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NEU1	protein_coding	protein_coding	ENST00000375631	6	5248

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000734	0.982	125713	0	23	125736	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.42	187	250	0.747	0.0000160	2677
Missense in Polyphen		71	103.67	0.68485		1122
Synonymous	1.52	87	107	0.813	0.00000690	886
Loss of Function	2.11	10	20.2	0.494	0.00000135	178

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.0000906	0.0000879
Middle Eastern	0.000164	0.000163
South Asian	0.000132	0.000131
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moities from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage. {ECO:0000269|PubMed:25153125, ECO:0000269|PubMed:8985184}.
• Disease: DISEASE: Sialidosis (SIALIDOSIS) [MIM:256550]: Lysosomal storage disease occurring as two types with various manifestations. Type 1 sialidosis (cherry red spot-myoclonus syndrome or normosomatic type) is late-onset and it is characterized by the formation of cherry red macular spots in childhood, progressive debilitating myoclonus, insiduous visual loss and rarely ataxia. The diagnosis can be confirmed by the screening of the urine for sialyloligosaccharides. Type 2 sialidosis (also known as dysmorphic type) occurs as several variants of increasing severity with earlier age of onset. It is characterized by the presence of abnormal somatic features including coarse facies and dysostosis multiplex, vertebral deformities, mental retardation, cherry-red spot/myoclonus, sialuria, cytoplasmic vacuolation of peripheral lymphocytes, bone marrow cells and conjunctival epithelial cells. {ECO:0000269|PubMed:10767332, ECO:0000269|PubMed:10944856, ECO:0000269|PubMed:11063730, ECO:0000269|PubMed:11279074, ECO:0000269|PubMed:11829139, ECO:0000269|PubMed:14695530, ECO:0000269|PubMed:25153125, ECO:0000269|PubMed:8985184, ECO:0000269|PubMed:9054950}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Other glycan degradation - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Neutrophil degranulation;Metabolism of lipids;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Metabolism;Glycosphingolipid metabolism;Sialic acid metabolism;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Intolerance Scores

• loftool: 0.303
• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.11

Haploinsufficiency Scores

• pHI: 0.172
• hipred: N
• hipred_score: 0.272
• ghis: 0.489

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Neu1
• 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); vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: glycosphingolipid metabolic process;ganglioside catabolic process;oligosaccharide catabolic process;neutrophil degranulation
• Cellular component: extracellular region;cytoplasm;lysosome;lysosomal membrane;plasma membrane;membrane;cell junction;specific granule lumen;lysosomal lumen;intracellular membrane-bounded organelle;extracellular exosome
• Molecular function: exo-alpha-sialidase activity;protein binding;alpha-sialidase activity;exo-alpha-(2->3)-sialidase activity;exo-alpha-(2->6)-sialidase activity;exo-alpha-(2->8)-sialidase activity