GeneBe

ACER2

protein-coding

alkaline ceramidase 2, the group of Alkaline ceramidases

Gene summary

The sphingolipid metabolite sphingosine-1-phosphate promotes cell proliferation and survival, whereas its precursor, sphingosine, has the opposite effect. The ceramidase ACER2 hydrolyzes very long chain ceramides to generate sphingosine (Xu et al., 2006 [PubMed 16940153]).[supplied by OMIM, Jul 2010]

Previous symbols:
  • ASAH3L

MANE transcript

NM_001010887.3

Inheritance

—

ClinVar variants

U:47B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr9:19,409,009-19,452,505

External References & Databases

Ensembl (ENSG00000177076)NCBI Gene (340485)OMIM (613492)HGNC:23675GenCCUniProt (Q5QJU3)AlphaFoldClinVar (ACER2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~43.5 kb
Loading mutation effect viewer...

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 ACER2 variants in ClinVar

1 Conditions Cataloged
not specifiedTotal: 47

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001010887.3. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
 1
missense
44
clinvar
3
clinvar
 47
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total00473050
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001010887.3RefSeqNP_001010887.26MANE Select
ENST00000340967.3EnsemblENSP00000342609.26MANE Select
ENST00001118051.1EnsemblENSP00000787856.11Standard
XM_011517858.2RefSeqXP_011516160.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Sphingolipid signaling pathway - Homo sapiens (human)
  • Sphingolipid metabolism - Homo sapiens (human)
  • Metabolism of lipids
  • Metabolism
  • Glycosphingolipid metabolism

Biological Process

  • negative regulation of cell-matrix adhesion
  • ceramide metabolic process
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • positive regulation of cell population proliferation
  • positive regulation of cell death

Molecular Function

  • N-acylsphingosine amidohydrolase activity
  • dihydroceramidase activity
  • ceramidase activity

Cellular Component

  • Golgi membrane
  • Golgi apparatus
  • integral component of Golgi membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000340967
Coding exons
6
Length
43094
Individuals with no LoFs
125723
Homozygous LoFs
0
Heterozygous LoFs
25
Defined
125748
p
0.0000994
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.3741661531.080.000008001783
Missense (PolyPhen)6562.5221.0396699
Synonymous-0.5666761.41.090.00000344524
Loss of Function2.41515.10.3307.33e-7155

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000260.00025rare
Latino/Admixed American0.000220.00020rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.000110.00011rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid. Unsaturated long-chain ceramides are the best substrates, saturated long-chain ceramides and unsaturated very long-chain ceramides are good substrates, whereas saturated very long-chain ceramides and short-chain ceramides were poor substrates. The substrate preference is D-erythro-C(18:1)-, C(20:1)-, C(20:4)-ceramide > D-erythro-C(16:0)-, C(18:0), C(20:0)- ceramide > D-erythro-C(24:1)-ceramide > D-erythro-C(12:0)- ceramide, D-erythro-C(14:0)-ceramides > D-erythro-C(24:0)-ceramide > D-erythro-C(6:0)-ceramide. Inhibits the maturation of protein glycosylation in the Golgi complex, including that of integrin beta-1 (ITGB1) and of LAMP1, by increasing the levels of sphingosine. Inhibits cell adhesion by reducing the level of ITGB1 in the cell surface. May have a role in cell proliferation and apoptosis that seems to depend on the balance between sphingosine and sphingosine-1-phosphate. {ECO:0000269|PubMed:16940153, ECO:0000269|PubMed:18945876, ECO:0000269|PubMed:20089856}.;

Recessive Scores

pRec
0.0858

Intolerance Scores

LoFtool
0.724
RVIS EVS
0.17
RVIS percentile EVS
65.76

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.900

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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