SLC33A1

Chr 3ARAD

solute carrier family 33 member 1

Also known as: ACATN, AT-1, AT1, CCHLND, HPBDS, SPG42

This protein is an acetyl-CoA transporter that imports acetyl-CoA into the endoplasmic reticulum for protein acetylation and is necessary for O-acetylation of gangliosides. Mutations cause Huppke-Brendel syndrome (autosomal recessive) and spastic paraplegia 42 (autosomal dominant), affecting the nervous system with spasticity as a key feature. The gene shows low constraint to loss-of-function variation (pLI 0.0001, LOEUF 0.807).

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.812 OMIM phenotypes
Clinical SummarySLC33A1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.23
OE 0.48 (0.290.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.98Z-score
OE missense 0.67 (0.600.76)
193 obs / 287.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.290.81)
00.351.4
Missense OE0.67 (0.600.76)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 10 / 21.0Missense obs/exp: 193 / 287.3Syn Z: -0.35
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC33A1-related congenital cataracts and hearing loss with low serum copper and ceruloplasminLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.73top 25%
GOF
0.6638th %ile
LOF
0.2776th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNCoinjection of S113R mutant human SLC33A1 reduced the rescue effect of wildtype human SLC33A1, suggesting that the S113R mutation has a dominant-negative effect.PMID:25402622
LOFCross-species alignment of the amino acid sequences for SLC33A1 also shows that the serine at position 113 is highly conserved among vertebrates (Figure 3E). Thus, the S113R mutation probably renders SLC33A1 nonfunctional and leads to a functional haploinsufficiency in the heterozogtes.PMID:19061983

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC33A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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