Peripheral motor neuropathy, childhood-onset, biotin-responsive

Summary

Peripheral motor neuropathy, childhood-onset, biotin-responsive (MONDO:0859255) is a disease caused by SLC5A6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC5A6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peripheral motor neuropathy, childhood-onset, biotin-responsive
Mondo ID	MONDO:0859255
OMIM	619903
UMLS	C5676997
MedGen	1809728
GARD	0026682
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › motor peripheral neuropathy › peripheral motor neuropathy, childhood-onset, biotin-responsive

Related subtypes (8): motor nerve neuritis, glossopharyngeal motor neuropathy, Charcot-Marie-Tooth disease type 5, neuropathy, hereditary motor and sensory, type 6A, hereditary motor and sensory neuropathy, Okinawa type, Charcot-Marie-Tooth disease type 4G, Charcot-Marie-Tooth disease axonal type 2C, neuropathy, hereditary motor and sensory, type 6B

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

5 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 1 uncertain significance, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1341352	NM_021095.4(SLC5A6):c.1285A>G (p.Ser429Gly)	SLC5A6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
975023	NM_021095.4(SLC5A6):c.280C>T (p.Arg94Ter)	SLC5A6	Pathogenic	criteria provided, multiple submitters, no conflicts
1341577	NM_021095.4(SLC5A6):c.1865_1866del (p.Gln622fs)	SLC5A6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4845873	NM_021095.4(SLC5A6):c.957C>G (p.Tyr319Ter)	SLC5A6	Likely pathogenic	criteria provided, single submitter
1315902	NM_021095.4(SLC5A6):c.485A>G (p.Tyr162Cys)	SLC5A6	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SLC5A6	Strong	Autosomal recessive	neurodegeneration, infantile-onset, biotin-responsive	6

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
SLC5A6	HGNC:11041	ENSG00000138074	Q9Y289	Sodium-dependent multivitamin transporter	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC5A6	Sodium-dependent multivitamin transporter	Sodium-dependent multivitamin transporter that mediates the electrogenic transport of pantothenate, biotin, lipoate and iodide.

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)
SLC5A6	Other/Unknown	no		Na/solute_symporter, Na/solute_symporter_CS, Na/Glc_symporter_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
left testis	1
right lobe of liver	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC5A6	222	ubiquitous	marker	right lobe of liver, right testis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC5A6	1,281

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC5A6	Q9Y289	79.99

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Biotin transport and metabolism	1	1038.2×	0.005	SLC5A6
Vitamin B5 (pantothenate) metabolism	1	761.3×	0.005	SLC5A6
Transport of vitamins, nucleosides, and related molecules	1	271.9×	0.010	SLC5A6
Metabolism of water-soluble vitamins and cofactors	1	181.3×	0.011	SLC5A6
Metabolism of vitamins and cofactors	1	116.5×	0.014	SLC5A6
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC5A6
Transport of small molecules	1	25.1×	0.045	SLC5A6
Metabolism	1	11.6×	0.086	SLC5A6

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
pantothenate transmembrane transport	1	16852.0×	3e-04	SLC5A6
iodide transmembrane transport	1	8426.0×	3e-04	SLC5A6
biotin import across plasma membrane	1	8426.0×	3e-04	SLC5A6
biotin transport	1	5617.3×	3e-04	SLC5A6
biotin metabolic process	1	4213.0×	3e-04	SLC5A6
sodium ion transport	1	271.8×	0.004	SLC5A6
transport across blood-brain barrier	1	179.3×	0.006	SLC5A6

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC5A6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC5A6	1	Binding:1

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	SLC5A6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC5A6	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.