Scoliosis, isolated, susceptibility to, 6

Summary

Scoliosis, isolated, susceptibility to, 6 (MONDO:0980986) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	scoliosis, isolated, susceptibility to, 6
Mondo ID	MONDO:0980986
OMIM	621428
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › scoliosis, isolated, susceptibility to › scoliosis, isolated, susceptibility to, 6

Related subtypes (5): scoliosis, isolated, susceptibility to, 1, scoliosis, isolated, susceptibility to, 2, scoliosis, isolated, susceptibility to, 3, scoliosis, isolated, susceptibility to, 4, scoliosis, isolated, susceptibility to, 5

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 likely benign, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
4531187	NM_001024845.3(SLC6A9):c.1765C>T (p.Arg589Trp)	SLC6A9	risk factor	no assertion criteria provided
1151370	NM_001024845.3(SLC6A9):c.398A>T (p.Tyr133Phe)	SLC6A9	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC6A9	Orphanet:289860	Infantile glycine encephalopathy
SLC6A9	Orphanet:289863	Atypical glycine encephalopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC6A9	HGNC:11056	ENSG00000196517	P48067	Sodium- and chloride-dependent glycine transporter 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC6A9	Sodium- and chloride-dependent glycine transporter 1	Sodium- and chloride-dependent glycine transporter.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC6A9	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_glycine_GLY1, SNS_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
C1 segment of cervical spinal cord	1
skin of leg	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC6A9	180	ubiquitous	marker	C1 segment of cervical spinal cord, spinal cord, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC6A9	1,061

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC6A9	P48067	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SLC-mediated transport of neurotransmitters	1	407.9×	0.010	SLC6A9
R-HSA-425366	1	181.3×	0.011	SLC6A9
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC6A9
Transport of small molecules	1	25.1×	0.040	SLC6A9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of synaptic transmission, glycinergic	1	16852.0×	3e-04	SLC6A9
glycine secretion, neurotransmission	1	16852.0×	3e-04	SLC6A9
positive regulation of heme biosynthetic process	1	5617.3×	5e-04	SLC6A9
positive regulation of hemoglobin biosynthetic process	1	2808.7×	7e-04	SLC6A9
glycine import across plasma membrane	1	2407.4×	7e-04	SLC6A9
neurotransmitter uptake	1	1404.3×	9e-04	SLC6A9
glycine transport	1	1404.3×	9e-04	SLC6A9
sodium ion transmembrane transport	1	203.0×	0.006	SLC6A9
transport across blood-brain barrier	1	179.3×	0.006	SLC6A9

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SLC6A9	GLYCINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC6A9	6	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GLYCINE	4	SLC6A9
BITOPERTIN	3	SLC6A9
ICLEPERTIN	3	SLC6A9
SARCOSINE	2	SLC6A9
ORG-25935	2	SLC6A9
PF-03463275	2	SLC6A9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SLC6A9	88	Binding:83, Functional:5

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

6 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
GLYCINE	4	SLC6A9
BITOPERTIN	3	SLC6A9
ICLEPERTIN	3	SLC6A9
SARCOSINE	2	SLC6A9
ORG-25935	2	SLC6A9
PF-03463275	2	SLC6A9

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC6A9
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.