NPL

N-acetylneuraminate pyruvate lyase

Basic information

Region (hg38): 1:182789293-182830384

Previous symbols: [ "C1orf13" ]

Links

ENSG00000135838 ∙ NCBI:80896 ∙ OMIM:611412 ∙ HGNC:16781 ∙ Uniprot:Q9BXD5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPL 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				2	2	4
missense			18	1		19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			1			1
Total	0	0	19	3	2

Variants in NPL

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

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

Position	Type	Phenotype	Significance	ClinVar
1-182794384-A-G		not specified	Uncertain significance (Jan 24, 2025)
1-182794406-T-C		not specified	Uncertain significance (Jul 30, 2023)
1-182803757-T-C		not specified	Uncertain significance (Nov 21, 2024)
1-182803762-A-G		NPL-related disorder	Likely benign (Jul 14, 2020)
1-182803766-T-G		not specified	Uncertain significance (Oct 22, 2021)
1-182803769-T-C		not specified	Uncertain significance (Oct 01, 2024)
1-182806167-C-T			Likely benign (Jun 01, 2024)
1-182812178-G-A			Likely benign (Jun 01, 2023)
1-182814832-C-T		not specified	Uncertain significance (Mar 11, 2024)
1-182814848-A-G			Benign (May 08, 2018)
1-182816749-G-A		not specified	Uncertain significance (Jul 14, 2023)
1-182818544-G-A		not specified	Uncertain significance (Dec 16, 2022)
1-182818557-G-T		not specified	Uncertain significance (Dec 03, 2024)
1-182818576-A-G		not specified	Uncertain significance (Jan 22, 2024)
1-182818578-G-T		not specified	Uncertain significance (Nov 03, 2022)
1-182818634-A-G			Uncertain significance (Jun 01, 2022)
1-182818662-G-A			Benign (Aug 09, 2018)
1-182818681-G-A		not specified	Uncertain significance (Jan 20, 2025)
1-182822125-T-C		not specified	Uncertain significance (Sep 26, 2024)
1-182822129-T-G		not specified	Uncertain significance (May 31, 2022)
1-182822159-C-T		not specified	Uncertain significance (May 09, 2023)
1-182822206-G-A			Benign (Jul 23, 2018)
1-182828754-T-A		not specified	Uncertain significance (Dec 08, 2023)
1-182828777-A-G		not specified	Uncertain significance (Mar 06, 2023)
1-182828811-C-T		not specified	Uncertain significance (Apr 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NPL	protein_coding	protein_coding	ENST00000367553	11	41092

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.57e-7	0.639	125600	0	148	125748	0.000589

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.185	161	168	0.960	0.00000879	2090
Missense in Polyphen		60	65.044	0.92245		749
Synonymous	-0.221	64	61.8	1.04	0.00000331	613
Loss of Function	1.12	13	18.2	0.715	7.80e-7	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000680	0.000680
Ashkenazi Jewish	0.000694	0.000695
East Asian	0.000163	0.000163
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000818	0.000818
Middle Eastern	0.000163	0.000163
South Asian	0.000588	0.000588
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetylmannosamine via a Schiff base intermediate. It prevents sialic acids from being recycled and returning to the cell surface. Involved in the N- glycolylneuraminic acid (Neu5Gc) degradation pathway. Although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded (By similarity). {ECO:0000250}.
• Pathway: Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Sialuria or French Type Sialuria;Sialuria or French Type Sialuria;Amino Sugar Metabolism;G(M2)-Gangliosidosis: Variant B, Tay-sachs disease;Tay-Sachs Disease;Salla Disease/Infantile Sialic Acid Storage Disease;Post-translational protein modification;Metabolism of proteins;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 (Consensus)

Recessive Scores

• pRec: 0.584

Intolerance Scores

• loftool: 0.330
• rvis_EVS: -0.2
• rvis_percentile_EVS: 38.82

Haploinsufficiency Scores

• pHI: 0.348
• hipred: N
• hipred_score: 0.253
• ghis: 0.526

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.964

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Npl
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: carbohydrate metabolic process;N-acetylneuraminate catabolic process
• Cellular component: cytosol
• Molecular function: protein binding;N-acetylneuraminate lyase activity;identical protein binding