SLC6A17

Chr 1AR

solute carrier family 6 member 17

Also known as: MRT48, NTT4

NCBI Gene: 388662ENSG00000197106UniProt: Q9H1V8

The protein encoded by this gene is a member of the SLC6 family of transporters, which are responsible for the presynaptic uptake of most neurotransmitters. The encoded vesicular transporter is selective for proline, glycine, leucine and alanine. In mouse, the strongest expression of this gene was in cortical and hippocampal tissues where expression increased during embryonic brain development and peaked postnatally. Defects in this gene cause a form of autosomal recessive intellectual disability. [provided by RefSeq, Jul 2017]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 48MIM #616269
AR
159
ClinVar variants
18
Pathogenic / LP
0.50
pLI score
0
Active trials
Clinical Summary— SLC6A17
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.50) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 94 VUS of 159 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.42LOEUF
pLI 0.504
Z-score 3.86
OE 0.21 (0.12–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.39Z-score
OE missense 0.69 (0.62–0.75)
313 obs / 456.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.21 (0.12–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.62–0.75)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 6 / 28.0Missense obs/exp: 313 / 456.4Syn Z: 1.05

ClinVar Variant Classifications

159 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic2
VUS94
Likely Benign27
Benign8
Conflicting4
16
Pathogenic
2
Likely Pathogenic
94
VUS
27
Likely Benign
8
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
14
0
16
Likely Pathogenic
0
0
2
0
2
VUS
0
89
5
0
94
Likely Benign
0
5
0
22
27
Benign
0
2
1
5
8
Conflicting
—4
Total0982227151

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC6A17 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SLC6A17-related intellectual developmental disorder

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal recessive 48

MIM #616269

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools