SLC35D1

Chr 1AR

solute carrier family 35 member D1

Also known as: SHNKND, UGTREL7

This protein functions as an antiporter that transports UDP-sugars (including UDP-GlcNAc, UDP-GalNAc, and UDP-GlcA) across the endoplasmic reticulum membrane, providing sugar donors essential for glycoprotein synthesis and chondroitin sulfate biosynthesis. Mutations cause Schneckenbecken dysplasia, a severe skeletal dysplasia affecting cartilage and bone development, with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (low pLI), consistent with the recessive inheritance pattern observed clinically.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Schneckenbecken dysplasiaMIM #269250
AR
0
Active trials
1
Pubs (1 yr)
40
P/LP submissions
5%
P/LP missense
0.78
LOEUF
LOF
Mechanism· G2P
Clinical SummarySLC35D1
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Gene-Disease Validity (ClinGen)
schneckenbecken dysplasia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 106 VUS of 313 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.78LOEUF
pLI 0.000
Z-score 2.28
OE 0.45 (0.270.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.03Z-score
OE missense 0.99 (0.881.12)
186 obs / 187.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.270.78)
00.351.4
Missense OE0.99 (0.881.12)
00.61.4
Synonymous OE1.25
01.21.6
LoF obs/exp: 9 / 20.0Missense obs/exp: 186 / 187.0Syn Z: -1.75
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC35D1-related Schneckenbecken dysplasiaLOFAR

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

DN
0.83top 10%
GOF
0.83top 10%
LOF
0.1993th %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

313 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic8
VUS106
Likely Benign93
Benign49
Conflicting6
31
Pathogenic
8
Likely Pathogenic
106
VUS
93
Likely Benign
49
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
25
0
31
Likely Pathogenic
3
1
4
0
8
VUS
1
95
10
0
106
Likely Benign
0
4
57
32
93
Benign
0
1
47
1
49
Conflicting
6
Total910214333293

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC35D1 · 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 →
Clinical Literature
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