Neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies

Summary

Neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies (MONDO:0976130) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies
Mondo ID	MONDO:0976130
OMIM	621067
UMLS	C5975594
MedGen	1875124
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies

Related subtypes (20): intellectual disability, microcephaly, Williams syndrome, Aicardi syndrome, Hao-Fountain syndrome, toluene embryopathy, alternating hemiplegia, atypical Rett syndrome, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, complex neurodevelopmental disorder, Mendelian neurodevelopmental disorder, TCF7L2-related neurodevelopmental disorder, neurodevelopmental disorder with seizures and brain abnormalities, Yoon-Bellen neurodevelopmental syndrome, neurodevelopmental disorder with microcephaly, hypotonia, and absent language, neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss, neurodevelopmental disorder with parkinsonism or other movement abnormalities, neurodevelopmental disorder with seizures and impaired intellectual and language development, Ebstein-Bezieau neurodevelopmental syndrome, Luo-Agrawal neurodevelopmental syndrome

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3602004	M528R	SEL1L	Pathogenic	no assertion criteria provided

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
SEL1L	HGNC:10717	ENSG00000071537	Q9UBV2	Protein sel-1 homolog 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SEL1L	Protein sel-1 homolog 1	Plays a role in the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins.

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)
SEL1L	Other/Unknown	no		FN_type2_dom, Sel1-like, TPR-like_helical_dom_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
body of pancreas	1
colonic epithelium	1
pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SEL1L	290	ubiquitous	marker	body of pancreas, pancreas, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SEL1L	2,064

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SEL1L	Q9UBV2	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. 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×	0.009	SEL1L
Calnexin/calreticulin cycle	1	713.8×	0.009	SEL1L
Pre-NOTCH Processing in Golgi	1	634.4×	0.009	SEL1L
ER Quality Control Compartment (ERQC)	1	543.8×	0.009	SEL1L
ABC transporter disorders	1	439.2×	0.009	SEL1L
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1	423.0×	0.009	SEL1L
Pre-NOTCH Expression and Processing	1	368.4×	0.009	SEL1L
Hh mutants are degraded by ERAD	1	243.0×	0.010	SEL1L
Defective CFTR causes cystic fibrosis	1	219.6×	0.010	SEL1L
Hedgehog ligand biogenesis	1	211.5×	0.010	SEL1L
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	1	193.6×	0.010	SEL1L
Signaling by Hedgehog	1	184.2×	0.010	SEL1L
Signaling by NOTCH	1	175.7×	0.010	SEL1L
Disorders of transmembrane transporters	1	139.3×	0.011	SEL1L
ABC-family protein mediated transport	1	121.5×	0.012	SEL1L
Asparagine N-linked glycosylation	1	60.1×	0.023	SEL1L
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.023	SEL1L
Transport of small molecules	1	25.1×	0.049	SEL1L
Post-translational protein modification	1	19.2×	0.060	SEL1L
Disease	1	13.1×	0.084	SEL1L
Metabolism of proteins	1	12.4×	0.085	SEL1L
Signal Transduction	1	10.2×	0.098	SEL1L

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
retrograde protein transport, ER to cytosol	1	991.3×	0.006	SEL1L
triglyceride metabolic process	1	443.5×	0.007	SEL1L
protein secretion	1	263.3×	0.008	SEL1L
ERAD pathway	1	181.2×	0.008	SEL1L
Notch signaling pathway	1	141.6×	0.008	SEL1L
protein stabilization	1	66.9×	0.015	SEL1L

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SEL1L	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	SEL1L

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)
SEL1L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.