SLC6A9

Chr 1ADAR

solute carrier family 6 member 9

Also known as: GCENSG, GLYT1, IS6

NCBI Gene: 6536ENSG00000196517UniProt: P48067

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]

Primary Disease Associations & Inheritance

{Scoliosis, isolated, susceptibility to, 6}MIM #621428
AD
Glycine encephalopathy with normal serum glycineMIM #617301
AR
388
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC6A9
🧬
Gene-Disease Validity (ClinGen)
atypical glycine encephalopathy · 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.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 157 VUS of 388 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.63LOEUF
pLI 0.000
Z-score 3.24
OE 0.40 (0.27–0.63)
Tolerant

Typical tolerance to LoF variation

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.
1.98Z-score
OE missense 0.74 (0.67–0.81)
331 obs / 449.4 exp
Tolerant

Mild missense constraint

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.0.40 (0.27–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.67–0.81)
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.0.99
0≤1.21.6
LoF obs/exp: 14 / 34.6Missense obs/exp: 331 / 449.4Syn Z: 0.12

ClinVar Variant Classifications

388 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic8
VUS157
Likely Benign164
Benign39
Conflicting5
15
Pathogenic
8
Likely Pathogenic
157
VUS
164
Likely Benign
39
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
10
0
15
Likely Pathogenic
4
1
3
0
8
VUS
5
138
12
2
157
Likely Benign
1
13
51
99
164
Benign
0
1
31
7
39
Conflicting
—5
Total13155107108388

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC6A9 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SLC6A9-related glycine encephalopathy with arthrogryposis

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Scoliosis, isolated, susceptibility to, 6}

MIM #621428

Molecular basis of disorder known

Autosomal dominant

Glycine encephalopathy with normal serum glycine

MIM #617301

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SLC6A9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Impaired glycine neurotransmission causes adolescent idiopathic scoliosis.
Wang X et al.·J Clin Invest
2024
GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
Docherty AR et al.·Am J Psychiatry
2023Meta-analysis
A lethal and rare cause of arthrogryposis: Glyt1 encephalopathy.
Daşar T et al.·Eur J Med Genet
2022
Transcriptional regulation of solute carrier family 6 member 9 gene.
Kirii M et al.·Mol Biol Rep
2025
LncRNA-SLC6A9-5:2: A potent sensitizer in 131I-resistant papillary thyroid carcinoma with PARP-1 induction.
Xiang C et al.·Oncotarget
2017
GlyT1 encephalopathy: Characterization of presumably disease causing GlyT1 mutations.
Hauf K et al.·Neurochem Int
2020
Senescence Induced by UVB in Keratinocytes Impairs Amino Acids Balance.
Bauwens E et al.·J Invest Dermatol
2023
GLYT1 encephalopathy: Further delineation of disease phenotype and discussion of pathophysiological mechanisms.
Mademont-Soler I et al.·Am J Med Genet A
2021Functional
Mutation in SLC6A9 encoding a glycine transporter causes a novel form of non-ketotic hyperglycinemia in humans.
Alfadhel M et al.·Hum Genet
2016Case report
In silico evidence of bitopertin's broad interactions within the SLC6 transporter family.
de Carvalho GA et al.·J Pharm Pharmacol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Unveiling the Roles of PRDX6 and SLC6A9 in Intracerebral Hemorrhage-Associated White Matter Lesions.
Du W et al.·FASEB J
2026
Progesterone regulates endometrial expression of SLC6A9 to potentially increase glycine transport to the developing pig conceptus†.
Ross A et al.·Biol Reprod
2025
ALG5 downregulation inhibits osteogenesis and promotes adipogenesis by regulating the N-glycosylation of SLC6A9 in osteoporosis.
Li Q et al.·Cell Mol Life Sci
2025🔓 Open Access
Oocyte-Specific Deletion of Slc6a9 Encoding the GLYT1 Glycine Transporter Eliminates Glycine Transport in Mouse Preimplantation Embryos and Their Ability to Counter Hypertonic Stress.
Tscherner AK et al.·Cells
2023🔓 Open AccessFunctional
Association Study of the SLC1A2 (rs4354668), SLC6A9 (rs2486001), and SLC6A5 (rs2000959) Polymorphisms in Major Depressive Disorder.
Rodek P et al.·J Clin Med
2022🔓 Open Access
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