Leukodystrophy, childhood-onset, remitting

Summary

Leukodystrophy, childhood-onset, remitting (MONDO:0859246) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	leukodystrophy, childhood-onset, remitting
Mondo ID	MONDO:0859246
OMIM	619864
UMLS	C5676979
MedGen	1804145
GARD	0026680
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › leukodystrophy › leukodystrophy, childhood-onset, remitting

Related subtypes (64): Alexander disease, cerebrotendinous xanthomatosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, dermatoleukodystrophy, Krabbe disease, Sjogren-Larsson syndrome, Canavan disease, Pelizaeus-Merzbacher spectrum disorder, hereditary spastic paraplegia 2, megalencephalic leukoencephalopathy with subcortical cysts, ribose-5-P isomerase deficiency, hypomyelinating leukodystrophy 5, leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome, hypomyelinating leukodystrophy 6, cystic leukoencephalopathy without megalencephaly, sterol carrier protein 2 deficiency, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome, hypomyelination with brain stem and spinal cord involvement and leg spasticity, leukoencephalopathy with mild cerebellar ataxia and white matter edema, progressive encephalopathy with leukodystrophy due to DECR deficiency, hypomyelinating leukodystrophy 9, multiple mitochondrial dysfunctions syndrome 4, hypomyelinating leukodystrophy 10, hypomyelinating leukodystrophy 12, hypomyelinating leukodystrophy 13, leukoencephalopathy with bilateral anterior temporal lobe cysts, progressive cavitating leukoencephalopathy, Pelizaeus-Merzbacher-like disease, CADDS, adrenoleukodystrophy, non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy, Aicardi-Goutieres syndrome, metachromatic leukodystrophy, peroxisome biogenesis disorder, unknown leukodystrophy, ravine syndrome, leukodystrophy, hypomyelinating, 22, leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy, neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, leukodystrophy, hypomyelinating, 18, leukodystrophy, hypomyelinating, 19, transient infantile, spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, leukodystrophy, hypomyelinating, 14, leukodystrophy, hypomyelinating, 20, early-onset calcifying leukoencephalopathy-skeletal dysplasia, c11orf73-related autosomal recessive hypomyelinating leukodystrophy, alkaline ceramidase 3 deficiency, leukodystrophy, hypomyelinating, 15, leukodystrophy, hypomyelinating, 16, leukodystrophy, hypomyelinating, 17, POLR-related leukodystrophy, leukoencephalopathy, diffuse hereditary, with spheroids 1, leukoencephalopathy with vanishing white matter, leukodystrophy, hypomyelinating, 24, leukodystrophy, hypomyelinating, 25, leukodystrophy, hypomyelinating, 26, with chondrodysplasia, adult-onset progressive leukoencephalopathy-early-onset deafness, leukoencephalopathy, porphyria-related, episodic memory defect leukoencephalopathy, leukodystrophy, hypomyelinating, 28, leukodystrophy, demyelinating, adult-onset, leukodystrophy, adult-onset, autosomal dominant, without amyloid angiopathy, leukoencephalopathy without lacunae, adult-onset, AARS1-related leukoencephalopathy

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

3 retrieved; paginated sample, class counts are floors:

3 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1809604	NM_003837.4(FBP2):c.343G>A (p.Val115Met)	FBP2	Uncertain significance	criteria provided, single submitter
3391367	NM_003837.4(FBP2):c.104T>C (p.Leu35Pro)	FBP2	Uncertain significance	criteria provided, single submitter
4532252	NM_003837.4(FBP2):c.364G>A (p.Asp122Asn)	FBP2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
FBP2	Moderate	Autosomal dominant	leukodystrophy, childhood-onset, remitting
KHSRP	Moderate	Autosomal dominant	leukodystrophy, childhood-onset, remitting

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FBP2	HGNC:3607	ENSG00000130957	O00757	Fructose-1,6-bisphosphatase isozyme 2	gencc,clinvar
KHSRP	HGNC:6316	ENSG00000088247	Q92945	Far upstream element-binding protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FBP2	Fructose-1,6-bisphosphatase isozyme 2	Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations and probably participates in glycogen synthesis from carbohydrate precursors, such as lactate.
KHSRP	Far upstream element-binding protein 2	Binds to the dendritic targeting element and may play a role in mRNA trafficking.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Phosphatase	1	42.0×	0.047
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FBP2	Phosphatase	yes	3.1.3.11	FBPase_class-1, Fructose_bisphosphatase_AS, FBPtase
KHSRP	Other/Unknown	no		KH_dom, KH_dom_type_1, FUBP_C

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
hindlimb stylopod muscle	1
vastus lateralis	1
body of uterus	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FBP2	149	tissue_specific	marker	hindlimb stylopod muscle, biceps brachii, vastus lateralis
KHSRP	294	ubiquitous	marker	ventricular zone, ganglionic eminence, body of uterus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KHSRP	3,024
FBP2	2,011

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FBP2	O00757	14
KHSRP	Q92945	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
KSRP (KHSRP) binds and destabilizes mRNA	1	317.2×	0.005	KHSRP
Gluconeogenesis	1	219.6×	0.005	FBP2
ATF4 activates genes in response to endoplasmic reticulum stress	1	203.9×	0.005	KHSRP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fructose 1,6-bisphosphate metabolic process	1	1053.2×	0.005	FBP2
fructose metabolic process	1	842.6×	0.005	FBP2
negative regulation of low-density lipoprotein particle clearance	1	766.0×	0.005	KHSRP
miRNA metabolic process	1	702.2×	0.005	KHSRP
positive regulation of mRNA catabolic process	1	601.9×	0.005	KHSRP
fructose 6-phosphate metabolic process	1	561.7×	0.005	FBP2
negative regulation of nitric oxide biosynthetic process	1	495.6×	0.005	KHSRP
3’-UTR-mediated mRNA destabilization	1	383.0×	0.005	KHSRP
RNA splicing, via transesterification reactions	1	312.1×	0.006	KHSRP
cellular response to cytokine stimulus	1	271.8×	0.006	KHSRP
regulation of mRNA stability	1	210.7×	0.007	KHSRP
gluconeogenesis	1	162.0×	0.008	FBP2
mRNA transport	1	131.7×	0.009	KHSRP
RNA splicing	1	44.1×	0.026	KHSRP
mRNA processing	1	39.4×	0.027	KHSRP
regulation of transcription by RNA polymerase II	1	5.8×	0.164	KHSRP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FBP2	0	0
KHSRP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KHSRP	25	Binding:25

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FBP2	3.1.3.11	fructose-bisphosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	FBP2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	KHSRP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FBP2	0	—
KHSRP	25	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.