NEU4

protein-coding

neuraminidase 4, the group of Neuraminidases

Gene summary

The protein encoded by this gene belongs to a family of glycohydrolytic enzymes, which remove terminal sialic acid residues from various sialo derivatives, such as glycoproteins, glycolipids, oligosaccharides, and gangliosides. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Nov 2009]

MANE transcript

NM_001167600.3

Inheritance

—

ClinVar variants

U:129B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.96

Max pathogenic AF

—

Genomic locus

chr2:241,809,065-241,817,413

External References & Databases

Ensembl (ENSG00000204099)

Transcript & Mutation Effects

hg38 • Region Span ~8.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NEU4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 132

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001167600.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			129 clinvar	5 clinvar		134
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	129	7	0	136

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001167600.3	RefSeq	NP_001161072.1	3	MANE Select
ENST00000407683.6	Ensembl	ENSP00000385402.1	3	MANE Select
NM_001167599.3	RefSeq	NP_001161071.1	4	Standard
NM_001167601.3	RefSeq	NP_001161073.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Other glycan degradation - Homo sapiens (human)
Sphingolipid metabolism - Homo sapiens (human)
Metabolism of lipids
Post-translational protein modification
Metabolism of proteins

Biological Process

glycoprotein catabolic process
glycosphingolipid metabolic process
ganglioside catabolic process
oligosaccharide catabolic process

Molecular Function

exo-alpha-sialidase activity
protein binding
exo-alpha-(2->3)-sialidase activity
exo-alpha-(2->6)-sialidase activity
exo-alpha-(2->8)-sialidase activity

Cellular Component

cytoplasm
lysosome
membrane
organelle inner membrane
lysosomal lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000325935
Coding exons: 4
Length: 8820
Individuals with no LoFs: 125127
Homozygous LoFs: 0
Heterozygous LoFs: 130
Defined: 125257
p: 0.000519

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.162	348	340	1.02	0.0000247	3093
Missense (PolyPhen)		137	135.48	1.0112		1267
Synonymous	-1.27	175	155	1.13	0.0000121	1124
Loss of Function	0.113	10	10.4	0.962	5.32e-7	103

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00051	0.00043	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.0048	0.0048	notable
East Asian	0	0.0	absent
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00048	0.00045	rare
South Asian	0.00032	0.00029	rare
Other	0.00085	0.00082	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function in lysosomal catabolism of sialylated glycoconjugates. Has sialidase activity towards synthetic substrates, such as 2'-(4-methylumbelliferyl)-alpha-D-N- acetylneuraminic acid (4-MU-NANA or 4MU-NeuAc). Has a broad substrate specificity being active on glycoproteins, oligosaccharides and sialylated glycolipids. {ECO:0000269|PubMed:14962670, ECO:0000269|PubMed:15213228}.;

Recessive Scores

pRec: 0.222

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.986

Gene Damage Prediction

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