SLC33A1

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

Basic information

Region (hg38): 3:155821024-155854456

Previous symbols: [ "ACATN", "SPG42" ]

Links

ENSG00000169359

∙ NCBI:9197 ∙ OMIM:603690 ∙ HGNC:95 ∙ Uniprot:O00400 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hereditary spastic paraplegia 42 (Supportive), mode of inheritance: AD
Huppke-Brendel syndrome (Supportive), mode of inheritance: AR
Huppke-Brendel syndrome (Strong), mode of inheritance: AR
hereditary spastic paraplegia 42 (Limited), mode of inheritance: AD
Huppke-Brendel syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Huppke-Brendel syndrome	AR	Audiologic/Otolaryngologic; Biochemical	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	Audiologic/Otolaryngologic; Biochemical; Neurologic; Ophthalmologic	15902551; 19061983; 20461110; 22243965; 22508683

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC33A1 gene.

Spastic_paraplegia (129 variants)
not_provided (69 variants)
Inborn_genetic_diseases (53 variants)
not_specified (22 variants)
Hereditary_spastic_paraplegia (11 variants)
Huppke-Brendel_syndrome (10 variants)
SLC33A1-related_disorder (9 variants)
Hereditary_spastic_paraplegia_42 (9 variants)
SLC33A1-related_hereditary_spastic_paraplegia (1 variants)
Global_developmental_delay (1 variants)
Hypothyroidism (1 variants)
Failure_to_thrive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC33A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004733.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	56 clinvar	1 clinvar	65
missense	2 clinvar		129 clinvar	8 clinvar	1 clinvar	140
nonsense	2 clinvar		1 clinvar			3
start loss			1			1
frameshift	3 clinvar		2 clinvar			5
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar	1 clinvar			4
Total	9	1	142	64	2

Highest pathogenic variant AF is 0.00000205225

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC33A1	protein_coding	protein_coding	ENST00000392845	6	33406

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000989	0.988	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.98	193	287	0.672	0.0000131	3543
Missense in Polyphen		37	78.652	0.47043		993
Synonymous	-0.350	118	113	1.04	0.00000550	1127
Loss of Function	2.23	10	21.0	0.476	9.56e-7	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000904
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000973	0.0000967
Middle Eastern	0.000218	0.000217
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.;
Pathway: 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;Transport of small molecules (Consensus)

Intolerance Scores

loftool: 0.662
rvis_EVS: 0.2
rvis_percentile_EVS: 67.19

Haploinsufficiency Scores

pHI: 0.672
hipred: Y
hipred_score: 0.566
ghis: 0.541

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.223

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Slc33a1
Phenotype: homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); embryo phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); neoplasm; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: slc33a1
Affected structure: motor neuron
Phenotype tag: abnormal
Phenotype quality: increased branchiness

Gene ontology

Biological process: acetyl-CoA transport;BMP signaling pathway;transmembrane transport;SMAD protein signal transduction;proton transmembrane transport
Cellular component: Golgi membrane;endoplasmic reticulum membrane;integral component of plasma membrane;membrane
Molecular function: acetyl-CoA transmembrane transporter activity;solute:proton symporter activity