SLC35B2

Chr 6

solute carrier family 35 member B2

Also known as: HLD26, PAPST1, SLL, UGTrel4

NCBI Gene: 347734 ENSG00000157593 UniProt: Q8TB61

The SLC35B2 protein transports PAPS (3'-phosphoadenylyl sulfate) from the cytosol into the Golgi lumen, where it serves as the universal sulfate donor for sulfation of glycoproteins, proteoglycans, and glycolipids. Biallelic mutations cause autosomal recessive leukodystrophy, hypomyelinating, 26, with chondrodysplasia, affecting both the central nervous system and skeletal development. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.628).

ResearchSummary from RefSeq, OMIM, UniProt

Sulfotransferases (e.g., SULT4A1; MIM 608359) use an activated form of sulfate, 3-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS), as a common sulfate donor for sulfation of glycoproteins, proteoglycans, and glycolipids in the endoplasmic reticulum and Golgi apparatus. SLC35B2 is located in the microsomal membrane and transports PAPS from the cytosol, where it is synthesized, into the Golgi lumen (Kamiyama et al., 2003 [PubMed 12716889]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.63

Clinical Summary— SLC35B2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 86 VUS of 102 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.071

Z-score 2.66

OE 0.30 (0.15–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.26Z-score

OE missense 1.05 (0.94–1.16)

263 obs / 251.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.30 (0.15–0.63)

0≤0.351.4

Missense OE?1.05 (0.94–1.16)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 5 / 16.7Missense obs/exp: 263 / 251.4Syn Z: -2.37

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedSLC35B2-related chondrodysplasia with hypomyelinating leukodystrophyOTHERAR

This gene — mechanism propensity

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

0.7035th %ile

GOF

0.5856th %ile

LOF

0.3261th %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.

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

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS86

Likely Benign5

Benign2

Conflicting1

Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	1	0	0	3
Likely Pathogenic	0	0	0	0	0
VUS	3	83	0	0	86
Likely Benign	0	2	0	3	5
Benign	0	1	0	1	2
Conflicting	—				1
Total	5	87	0	4	97

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap SLC35B2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →