SIAE

protein-coding

sialic acid acetylesterase

Gene summary

This gene encodes an enzyme which removes 9-O-acetylation modifications from sialic acids. Mutations in this gene are associated with susceptibility to autoimmune disease 6. Multiple transcript variants encoding different isoforms, found either in the cytosol or in the lysosome, have been found for this gene.[provided by RefSeq, Feb 2011]

Previous symbols:

YSG2

MANE transcript

NM_170601.5

Inheritance

—

ClinVar variants

U:324B:121

Top phenotype

SIAE-related disorder

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr11:124,633,113-124,695,707

External References & Databases

Ensembl (ENSG00000110013)

Transcript & Mutation Effects

hg38 • Region Span ~62.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autoimmune disease, susceptibility to, 6LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013303

Submitter: Labcorp Genetics (formerly Invitae)

autoimmune disease, susceptibility to, 6LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013303

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SIAE variants in ClinVar

5 Conditions Cataloged

not providedTotal: 504

not specifiedTotal: 60

SIAE-related disorderTotal: 14

Autoimmune disease, susceptibility to, 6Total: 6

Juvenile idiopathic arthritisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_170601.5. 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			3 clinvar	94 clinvar	6 clinvar	103
missense			261 clinvar	13 clinvar	8 clinvar	282
nonsense			14 clinvar			14
start loss			4 clinvar			4
frameshift			30 clinvar			30
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	0	324	107	14	445

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_170601.5	RefSeq	NP_733746.1	10	MANE Select
ENST00000263593.8	Ensembl	ENSP00000263593.3	10	MANE Select
NM_001199922.2	RefSeq	NP_001186851.1	9	Standard
ENST00000545756.5	Ensembl	ENSP00000437877.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of immune system process
carbohydrate metabolic process

Molecular Function

sialate O-acetylesterase activity

Cellular Component

extracellular space
lysosome
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263593
Coding exons: 10
Length: 62595
Individuals with no LoFs: 125640
Homozygous LoFs: 1
Heterozygous LoFs: 107
Defined: 125748
p: 0.000430

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.125	281	287	0.979	0.0000163	3411
Missense (PolyPhen)		68	91.487	0.74328		1052
Synonymous	-0.780	119	109	1.10	0.00000633	1028
Loss of Function	0.939	20	25.1	0.798	0.00000123	280

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00068	0.00068	rare
Latino/Admixed American	0.00087	0.00084	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0015	0.0015	notable
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the removal of O-acetyl ester groups from position 9 of the parent sialic acid, N-acetylneuraminic acid.;

Recessive Scores

pRec: 0.195

Intolerance Scores

LoFtool: 0.208
RVIS EVS: 0.38
RVIS percentile EVS: 75.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.176

Gene Damage Prediction

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