SLC6A5

Chr 11ADAR

solute carrier family 6 member 5

Also known as: GLYT-2, GLYT2, HKPX3, NET1

This gene encodes a sodium- and chloride-dependent glycine transporter that terminates glycinergic neurotransmission by reuptaking glycine into presynaptic terminals. Mutations cause hyperekplexia 3, a neurological disorder characterized by exaggerated startle responses and neonatal apnea. The condition follows both autosomal dominant and autosomal recessive inheritance patterns.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.971 OMIM phenotype
Clinical SummarySLC6A5
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Gene-Disease Validity (ClinGen)
hyperekplexia 3 · 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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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — SLC6A5
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.72
OE 0.71 (0.520.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.09Z-score
OE missense 1.01 (0.941.10)
442 obs / 436.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.71 (0.520.97)
00.351.4
Missense OE1.01 (0.941.10)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 28 / 39.7Missense obs/exp: 442 / 436.5Syn Z: -1.99
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC6A5-related hyperekplexiaLOFAR

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

DN
0.75top 25%
GOF
0.82top 10%
LOF
0.2970th %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.

Literature Evidence

DNIn vitro functional expression studies showed that S510R formed intracellular aggregates, abolished glycine uptake, and caused a dominant-negative effect.PMID:16751771

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC6A5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗