SLC6A17

Chr 1

solute carrier family 6 member 17

Also known as: MRT48, NTT4

NCBI Gene: 388662 ENSG00000197106 UniProt: Q9H1V8

The protein is a synaptic vesicle transporter that uptakes neutral amino acids including proline, glycine, leucine and alanine in a sodium-coupled, proton gradient-driven mechanism, contributing to neurotransmitter precursor availability. Mutations cause autosomal recessive intellectual developmental disorder. The gene shows high constraint against loss-of-function variants (LOEUF 0.42), with strongest expression in cortical and hippocampal brain regions during development.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.42

Clinical Summary— SLC6A17

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Gene-Disease Validity (ClinGen)

progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.50) — some intolerance to loss-of-function variants.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 95 VUS of 143 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

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.21 (0.12–0.42)

0≤0.351.4

Missense OE?0.69 (0.62–0.75)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 6 / 28.0Missense obs/exp: 313 / 456.4Syn Z: 1.05

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongSLC6A17-related intellectual developmental disorderOTHERAR

This gene — mechanism propensity

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

0.6357th %ile

GOF

0.81top 10%

LOF

0.3164th %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

143 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS95

Likely Benign27

Benign8

Conflicting4

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	0	2	0	0	2
Likely Pathogenic	0	0	0	0	0
VUS	2	92	1	0	95
Likely Benign	0	5	0	22	27
Benign	0	2	1	5	8
Conflicting	—				4
Total	2	101	2	27	136

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap SLC6A17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →