GeneBe

ACER3

protein-coding

alkaline ceramidase 3, the group of Alkaline ceramidases

Gene summary

Enables N-acylsphingosine amidohydrolase activity; calcium ion binding activity; and zinc ion binding activity. Involved in several processes, including myelination; positive regulation of cell population proliferation; and sphingolipid metabolic process. Located in Golgi membrane and endoplasmic reticulum membrane. Biomarker of hepatocellular carcinoma and metabolic dysfunction-associated steatohepatitis. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:
  • PHCA

MANE transcript

NM_018367.7

Inheritance

AR

ClinVar variants

P:7U:64B:21

Top phenotype

Leukodystrophy, progressive, early childhood-onset

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr11:76,860,859-77,026,797

External References & Databases

Ensembl (ENSG00000078124)NCBI Gene (55331)OMIM (617036)HGNC:16066GenCCUniProt (Q9NUN7)AlphaFoldClinVar (ACER3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~165.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

alkaline ceramidase 3 deficiencyLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0044718

Submitter: Labcorp Genetics (formerly Invitae)

alkaline ceramidase 3 deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0044718

Submitter: Ambry Genetics

alkaline ceramidase 3 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044718

Submitter: G2P

leukodystrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0019046

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Leukodystrophy, progressive, early childhood-onsetAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26792856Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACER3 variants in ClinVar

6 Conditions Cataloged
not providedTotal: 78
not specifiedTotal: 23
Alkaline ceramidase 3 deficiencyTotal: 11
ACER3-related disorderTotal: 3
Neuromuscular diseaseTotal: 2
LeukodystrophyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018367.7. 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
18
clinvar
2
clinvar
 21
missense
2
clinvar
1
clinvar
61
clinvar
1
clinvar
 65
nonsense
3
clinvar
1
clinvar
 4
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total526419292

Highest pathogenic variant AF is 0.000018717603

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_018367.7RefSeqNP_060837.311MANE Select
ENST00000532485.6EnsemblENSP00000434480.111MANE Select
NM_001300953.2RefSeqNP_001287882.110Standard
NM_001300954.2RefSeqNP_001287883.18Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Sphingolipid metabolism - Homo sapiens (human)
  • Sphingolipid Metabolism
  • Gaucher Disease
  • Globoid Cell Leukodystrophy
  • Metachromatic Leukodystrophy (MLD)

Biological Process

  • ceramide metabolic process
  • positive regulation of cell population proliferation
  • sphingolipid biosynthetic process
  • sphingosine biosynthetic process
  • phytosphingosine biosynthetic process

Molecular Function

  • phytoceramidase activity

Cellular Component

  • endoplasmic reticulum
  • endoplasmic reticulum membrane
  • integral component of Golgi membrane
  • integral component of endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000532485
Coding exons
11
Length
165931
Individuals with no LoFs
125735
Homozygous LoFs
0
Heterozygous LoFs
10
Defined
125745
p
0.0000398
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.80771360.5660.000006271728
Missense (PolyPhen)2450.5080.47517632
Synonymous0.2004445.70.9620.00000215475
Loss of Function3.52320.00.1509.72e-7242

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000590.000058rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000730.000070rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Hydrolyzes only phytoceramide into phytosphingosine and free fatty acid. Does not have reverse activity.;

Recessive Scores

pRec
0.122

Intolerance Scores

LoFtool
0.497
RVIS EVS
0.06
RVIS percentile EVS
58.26

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.824

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumLowLow
Primary ImmunodeficiencyMediumLowMedium
CancerMediumMediumMedium
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