GeneBe

SLC33A1

protein-coding

solute carrier family 33 member 1, the group of Solute carrier family 33

Gene summary

The protein encoded by this gene is required for the formation of O-acetylated (Ac) gangliosides. The encoded protein is predicted to contain 6 to 10 transmembrane domains, and a leucine zipper motif in transmembrane domain III. Defects in this gene have been reported to cause spastic paraplegia autosomal dominant type 42 (SPG42) in one Chinese family, but not in similar patients of European descent. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

Previous symbols:
  • ACATN
  • SPG42

MANE transcript

NM_004733.4

Inheritance

AD, AR

ClinVar variants

P:10U:165B:81

Top phenotype

Huppke-Brendel syndrome

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr3:155,821,024-155,854,456

External References & Databases

Ensembl (ENSG00000169359)NCBI Gene (9197)OMIM (603690)HGNC:95GenCCUniProt (O00400)AlphaFoldClinVar (SLC33A1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~33.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary spastic paraplegia 42LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012928

Submitter: PanelApp Australia

Huppke-Brendel syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013772

Submitter: G2P

Huppke-Brendel syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013772

Submitter: Orphanet

Huppke-Brendel syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013772

Submitter: Labcorp Genetics (formerly Invitae)

hereditary spastic paraplegia 42SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012928

Submitter: Orphanet

hereditary spastic paraplegia 42LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012928

Submitter: Illumina

Huppke-Brendel syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013772

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Huppke-Brendel syndromeAR

Manifestation: Audiologic/Otolaryngologic; Biochemical; Neurologic; Ophthalmologic

Intervention: Audiologic/Otolaryngologic; Biochemical

Rationale: Medical treatment (with copper supplementation) has been reported as biochemically and clinically beneficial in some individuals; Awareness of the potential of hearing loss may allow early identification and interventions to support speech and language development

Refs: 15902551; 19061983; 20461110; 22243965; 22508683Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC33A1 variants in ClinVar

12 Conditions Cataloged
Spastic paraplegiaTotal: 137
not providedTotal: 94
Inborn genetic diseasesTotal: 60
not specifiedTotal: 37
Hereditary spastic paraplegiaTotal: 11
SLC33A1-related disorderTotal: 11
Huppke-Brendel syndromeTotal: 10
Hereditary spastic paraplegia 42Total: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004733.4. 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
7
clinvar
70
clinvar
1
clinvar
 78
missense
2
clinvar
151
clinvar
9
clinvar
1
clinvar
 163
nonsense
2
clinvar
1
clinvar
 3
start loss
2
clinvar
 2
frameshift
3
clinvar
2
clinvar
 5
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
2
clinvar
 5
Total91165792256

Highest pathogenic variant AF is 0.0000020522532

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004733.4RefSeqNP_004724.16MANE Select
ENST00000643144.2EnsemblENSP00000496241.16MANE Select
NM_001190992.2RefSeqNP_001177921.16Standard
NM_001363883.1RefSeqNP_001350812.14Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
slc33a1Danio rerio

Structure: motor neuron

Quality: increased branchiness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Glycosphingolipid biosynthesis - ganglio series - Homo sapiens (human)
  • Ganglio Sphingolipid Metabolism
  • 3-oxo-10R-octadecatrienoate beta-oxidation
  • Transport of vitamins, nucleosides, and related molecules
  • SLC-mediated transmembrane transport

Biological Process

  • acetyl-CoA transport
  • BMP signaling pathway
  • transmembrane transport
  • SMAD protein signal transduction
  • proton transmembrane transport

Molecular Function

  • acetyl-CoA transmembrane transporter activity
  • solute:proton symporter activity

Cellular Component

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

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000392845
Coding exons
6
Length
33406
Individuals with no LoFs
125730
Homozygous LoFs
0
Heterozygous LoFs
18
Defined
125748
p
0.0000716
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.981932870.6720.00001313543
Missense (PolyPhen)3778.6520.47043993
Synonymous-0.3501181131.040.000005501127
Loss of Function2.231021.00.4769.56e-7271

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.000220.00022rare
Finnish00.0absent
European (Non-Finnish)0.0000970.000097rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Probable acetyl-CoA transporter necessary for O- acetylation of gangliosides (PubMed:9096318). Negatively regulates BMP signaling (PubMed:25402622). {ECO:0000269|PubMed:25402622, ECO:0000269|PubMed:9096318}.;
Disease
DISEASE: Congenital cataracts, hearing loss, and neurodegeneration (CCHLND) [MIM:614482]: An autosomal recessive disorder characterized by congenital cataracts, severe psychomotor retardation, and hearing loss associated with decreased serum ceruloplasmin and copper. Brain MRI shows cerebral and cerebellar atrophy and hypomyelination. {ECO:0000269|PubMed:22243965}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool
0.662
RVIS EVS
0.2
RVIS percentile EVS
67.19

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.223

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.