SLC33A1

Chr 3ARAD

solute carrier family 33 member 1

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

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]

GeneReviewsOMIMResearchGenerating clinical summary…
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.
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ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 160 VUS of 297 total submissions
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GeneReview available — SLC33A1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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 OE?0.48 (0.290.81)
00.351.4
Missense OE?0.67 (0.600.76)
00.61.4
Synonymous OE?1.04
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

This gene — mechanism propensity

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.1
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.2

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

297 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS160
Likely Benign88
Benign16
Conflicting7
10
Pathogenic
1
Likely Pathogenic
160
VUS
88
Likely Benign
16
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
2
1
0
10
Likely Pathogenic
1
0
0
0
1
VUS
5
144
4
7
160
Likely Benign
1
11
19
57
88
Benign
0
1
14
1
16
Conflicting
7
Total141583865282

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

16 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap SLC33A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

SLC33A1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →