SLC6A9

Chr 1ADAR

solute carrier family 6 member 9

Also known as: GCENSG, GLYT1, IS6

NCBI Gene: 6536 ENSG00000196517 UniProt: P48067 OMIM: 601019

The protein is a sodium- and chloride-dependent glycine transporter that regulates glycine concentrations at inhibitory glycinergic synapses. Mutations cause glycine encephalopathy with normal serum glycine and increase susceptibility to isolated scoliosis. The gene shows both autosomal dominant and autosomal recessive inheritance patterns.

GeneReviews OMIM ResearchSummary from OMIM, UniProt

The amino acid glycine acts as an inhibitory neurotransmitter in the central nervous system. The protein encoded by this gene is one of two transporters that stop glycine signaling by removing it from the synaptic cleft. [provided by RefSeq, Jun 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.632 OMIM phenotypes

Clinical Summary— SLC6A9

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Gene-Disease Validity (ClinGen)

atypical glycine encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 150 VUS of 381 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SLC6A9

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.000

Z-score 3.24

OE 0.40 (0.27–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.98Z-score

OE missense 0.74 (0.67–0.81)

331 obs / 449.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.27–0.63)

0≤0.351.4

Missense OE?0.74 (0.67–0.81)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 14 / 34.6Missense obs/exp: 331 / 449.4Syn Z: 0.12

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongSLC6A9-related glycine encephalopathy with arthrogryposisLOFAR

This gene — mechanism propensity

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

0.78top 25%

GOF

0.82top 10%

LOF

0.2287th %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

381 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic8

VUS150

Likely Benign164

Benign39

Conflicting5

Pathogenic

Likely Pathogenic

150

VUS

164

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	1	0	0	6
Likely Pathogenic	5	3	0	0	8
VUS	5	138	5	2	150
Likely Benign	1	13	51	99	164
Benign	0	1	31	7	39
Conflicting	—				5
Total	16	156	87	108	372

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap SLC6A9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →