NPL

protein-coding

N-acetylneuraminate pyruvate lyase

Gene summary

This gene encodes a member of the N-acetylneuraminate lyase sub-family of (beta/alpha)(8)-barrel enzymes. N-acetylneuraminate lyases regulate cellular concentrations of N-acetyl-neuraminic acid (sialic acid) by mediating the reversible conversion of sialic acid into N-acetylmannosamine and pyruvate. A pseudogene of this gene is located on the short arm of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

Previous symbols:

C1orf13

MANE transcript

NM_030769.3

Inheritance

—

ClinVar variants

U:41B:5

Top phenotype

NPL-related disorder

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr1:182,789,293-182,830,384

External References & Databases

Ensembl (ENSG00000135838)

Transcript & Mutation Effects

hg38 • Region Span ~41.1 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 NPL variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 7

NPL-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030769.3. 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				1 clinvar	2 clinvar	3
missense			34 clinvar	2 clinvar		36
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	41	3	2	46

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 124 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030769.3	RefSeq	NP_110396.1	11	MANE Select
ENST00000367553.6	Ensembl	ENSP00000356524.1	11	MANE Select
NM_001200050.2	RefSeq	NP_001186979.1	9	Standard
NM_001200051.2	RefSeq	NP_001186980.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

carbohydrate metabolic process
N-acetylneuraminate catabolic process

Molecular Function

protein binding
N-acetylneuraminate lyase activity
identical protein binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367553
Coding exons: 11
Length: 41092
Individuals with no LoFs: 125600
Homozygous LoFs: 0
Heterozygous LoFs: 148
Defined: 125748
p: 0.000589

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.185	161	168	0.960	0.00000879	2090
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00043	0.00043	rare
Ashkenazi Jewish	0.00069	0.00069	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00082	0.00082	rare
South Asian	0.00059	0.00059	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.584

Intolerance Scores

LoFtool: 0.330
RVIS EVS: -0.2
RVIS percentile EVS: 38.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.964

Gene Damage Prediction

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