Encephalomalacia

Summary

Encephalomalacia (MONDO:0006741) is a disease with 1 cohort gene and 2 clinical trials. Top therapeutic interventions include hydrocortisone.

At a glance

• Cohort genes: 1
• ClinVar variants: 2
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	encephalomalacia
Mondo ID	MONDO:0006741
EFO	EFO:1000915
MeSH	D004678
DOID	DOID:2034
ICD-11	689481271
NCIT	C98920
SNOMED CT	58762006
UMLS	C0014068
MedGen	4936
MedDRA	10051818
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › encephalomalacia

Related subtypes (70): leukoencephalopathy, megalencephalic, encephalopathy, acute, infection-induced, diabetic encephalopathy, complex cortical dysplasia with other brain malformations, hydrocephalus, brain compression, cerebral sarcoidosis, hepatic encephalopathy, visual pathway disorder, central nervous system origin vertigo, cerebellar disorder, cerebritis, olfactory nerve disorder, thalamic disorder, pituitary gland disorder, disorder of optic chiasm, basal ganglia disorder, epilepsy, mental disorder, central nervous system cyst, migraine disorder, multiple sclerosis, prion disease, carbon monoxide-induced delayed encephalopathy, cerebral malaria, akinetic mutism, bulbar polio, Reye syndrome, brain edema, intracranial hypertension, intracranial hypotension, Wernicke encephalopathy, encephalopathy, recurrent, of childhood, XK aprosencephaly, progressive bulbar palsy, cerebrovascular disorder, glycine encephalopathy, autosomal recessive frontotemporal pachygyria, occipital pachygyria and polymicrogyria, insomnia, narcolepsy-cataplexy syndrome, megalencephaly, meningoencephalocele, cerebral cortical dysplasia, encephaloclastic disorder, bilirubin encephalopathy, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, narcolepsy without cataplexy, hypothalamic hamartomas with gelastic seizures, encephalitis, cerebral lipidosis with dementia, brain neoplasm, colpocephaly, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cerebral degeneration, acute bilirubin encephalopathy, chronic bilirubin encephalopathy, atelencephaly, aprosencephaly, brain injury, traumatic encephalopathy, cluster headache syndrome, cerebral cortex disorder, midbrain disorder, encephalopathy due to mitochondrial and peroxisomal fission defect, brain malformations with or without urinary tract defects, encephalopathy, acute transient

Subtypes (1): periventricular leukomalacia

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:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2570663	NM_172230.3(SYVN1):c.38C>T (p.Ala13Val)	SYVN1	Uncertain significance	criteria provided, single submitter
2570664	NM_172230.3(SYVN1):c.68A>G (p.Tyr23Cys)	SYVN1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
SYVN1	HGNC:20738	ENSG00000162298	Q86TM6	E3 ubiquitin-protein ligase synoviolin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SYVN1	E3 ubiquitin-protein ligase synoviolin	E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SYVN1	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, HRD1_E3_ubiq-ligases

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
body of pancreas	1
ileal mucosa	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SYVN1	255	ubiquitous	marker	ileal mucosa, body of pancreas, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SYVN1	2,205

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SYVN1	Q86TM6	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
Hh mutants abrogate ligand secretion	1	1427.5×	0.008	SYVN1
Calnexin/calreticulin cycle	1	713.8×	0.008	SYVN1
ER Quality Control Compartment (ERQC)	1	543.8×	0.008	SYVN1
IRE1alpha activates chaperones	1	519.1×	0.008	SYVN1
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1	423.0×	0.008	SYVN1
Unfolded Protein Response (UPR)	1	356.9×	0.008	SYVN1
Hh mutants are degraded by ERAD	1	243.0×	0.009	SYVN1
XBP1(S) activates chaperone genes	1	215.5×	0.009	SYVN1
Hedgehog ligand biogenesis	1	211.5×	0.009	SYVN1
Signaling by Hedgehog	1	184.2×	0.010	SYVN1
Asparagine N-linked glycosylation	1	60.1×	0.026	SYVN1
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.026	SYVN1
Cellular responses to stress	1	36.8×	0.038	SYVN1
Cellular responses to stimuli	1	31.5×	0.041	SYVN1
Post-translational protein modification	1	19.2×	0.063	SYVN1
Disease	1	13.1×	0.086	SYVN1
Metabolism of proteins	1	12.4×	0.086	SYVN1
Signal Transduction	1	10.2×	0.098	SYVN1

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
immature B cell differentiation	1	2407.4×	0.003	SYVN1
endoplasmic reticulum mannose trimming	1	1203.7×	0.003	SYVN1
retrograde protein transport, ER to cytosol	1	991.3×	0.003	SYVN1
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	1	842.6×	0.003	SYVN1
ERAD pathway	1	181.2×	0.010	SYVN1
protein K48-linked ubiquitination	1	168.5×	0.010	SYVN1
ubiquitin-dependent protein catabolic process	1	74.2×	0.019	SYVN1
protein stabilization	1	66.9×	0.019	SYVN1
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.021	SYVN1
protein ubiquitination	1	41.4×	0.024	SYVN1

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
SYVN1	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
SYVN1	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	SYVN1

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)
SYVN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00167544	PHASE2	COMPLETED	Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants
NCT06027411	Not specified	UNKNOWN	Assess the Clinical Effectiveness in AI Prioritising CT Heads

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
HYDROCORTISONE	4	1