SLC35G6

Chr 17

solute carrier family 35 member G6

Also known as: AMAC1L3, TMEM21B

SLC35G6 encodes a predicted membrane transporter protein. The gene is highly constrained against loss-of-function variants (pLI = 0.0005), suggesting that mutations would likely cause severe developmental disorders, though specific associated phenotypes have not yet been clearly defined in humans. Inheritance pattern for potential SLC35G6-related disorders is expected to be autosomal recessive based on the high constraint against heterozygous loss-of-function.

ResearchSummary from RefSeq
MultiplemechanismLOEUF 1.35
Clinical SummarySLC35G6
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 61 VUS of 94 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.35LOEUF
pLI 0.001
Z-score 0.86
OE 0.68 (0.371.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.04Z-score
OE missense 0.99 (0.881.12)
186 obs / 187.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.371.35)
00.351.4
Missense OE0.99 (0.881.12)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 6 / 8.8Missense obs/exp: 186 / 187.7Syn Z: 0.75
DN
0.6938th %ile
GOF
0.80top 10%
LOF
0.2092th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

94 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic3
VUS61
Likely Benign6
24
Pathogenic
3
Likely Pathogenic
61
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
3
0
3
VUS
0
54
7
0
61
Likely Benign
0
6
0
0
6
Benign
0
0
0
0
0
Total06034094

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC35G6 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found