chromosome 5Q14.3 deletion syndrome, distal

Summary

chromosome 5Q14.3 deletion syndrome, distal (MONDO:0013031) 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	chromosome 5Q14.3 deletion syndrome, distal
Mondo ID	MONDO:0013031
MeSH	C567876
OMIM	612881
UMLS	C2752071
MedGen	442882
GARD	0015589
Is cancer (heuristic)	no

Also known as: chromosome 5Q14.3 deletion syndrome, distal

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › periventricular nodular heterotopia › chromosome 5Q14.3 deletion syndrome, distal

Related subtypes (7): heterotopia, periventricular, X-linked dominant, periventricular heterotopia with microcephaly, autosomal recessive, heterotopia, periventricular, associated with chromosome 5P anomalies, periventricular nodular heterotopia 6, periventricular nodular heterotopia 7, periventricular nodular heterotopia 9, periventricular nodular heterotopia 8

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:

2 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4685561	GRCh38/hg38 5q14.3-21.2(chr5:90079852-103658165)x1	LOC123497944	Pathogenic	criteria provided, single submitter
3572902	NM_005909.5(MAP1B):c.2079_2082del (p.Lys694fs)	MAP1B	Pathogenic	criteria provided, single submitter
225191	NM_001144967.3(NEDD4L):c.2677G>A (p.Glu893Lys)	NEDD4L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAP1B	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MAP1B	Orphanet:98892	Periventricular nodular heterotopia
NEDD4L	Orphanet:98892	Periventricular nodular heterotopia

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
MAP1B	HGNC:6836	ENSG00000131711	P46821	Microtubule-associated protein 1B	clinvar
NEDD4L	HGNC:7728	ENSG00000049759	Q96PU5	E3 ubiquitin-protein ligase NEDD4-like	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAP1B	Microtubule-associated protein 1B	Facilitates tyrosination of alpha-tubulin in neuronal microtubules.
NEDD4L	E3 ubiquitin-protein ligase NEDD4-like	E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repai…

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAP1B	Other/Unknown	no		MAP1B_neuraxin, MAP1, MAP1B/S_N
NEDD4L	Scaffold/PPI	no	2.3.2.26	C2_dom, HECT_dom, WW_dom

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
lateral nuclear group of thalamus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1
ganglionic eminence	1
olfactory segment of nasal mucosa	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAP1B	299	ubiquitous	marker	lateral nuclear group of thalamus, substantia nigra pars compacta, substantia nigra pars reticulata
NEDD4L	281	ubiquitous	marker	ventricular zone, ganglionic eminence, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAP1B	3,724
NEDD4L	3,458

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NEDD4L	Q96PU5	20

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAP1B	P46821	46.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. 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
Budding and maturation of HIV virion	1	203.9×	0.020	NEDD4L
Downregulation of TGF-beta receptor signaling	1	203.9×	0.020	NEDD4L
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	184.2×	0.020	NEDD4L
Downregulation of SMAD2/3:SMAD4 transcriptional activity	1	184.2×	0.020	NEDD4L
TGF-beta receptor signaling activates SMADs	1	163.1×	0.020	NEDD4L
Viral Infection Pathways	2	30.8×	0.020	MAP1B, NEDD4L
Infectious disease	2	24.8×	0.020	MAP1B, NEDD4L
Disease	2	13.1×	0.020	MAP1B, NEDD4L
Signaling by TGF-beta Receptor Complex	1	100.2×	0.025	NEDD4L
Respiratory Syncytial Virus Infection Pathway	1	98.5×	0.025	MAP1B
Late Phase of HIV Life Cycle	1	84.0×	0.025	NEDD4L
HIV Life Cycle	1	80.4×	0.025	NEDD4L
RSV-host interactions	1	78.2×	0.025	MAP1B
Stimuli-sensing channels	1	68.0×	0.027	NEDD4L
HIV Infection	1	59.5×	0.028	NEDD4L
Signaling by TGFB family members	1	57.7×	0.028	NEDD4L
Ion channel transport	1	48.0×	0.032	NEDD4L
Class I MHC mediated antigen processing & presentation	1	35.0×	0.041	NEDD4L
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.073	NEDD4L
Adaptive Immune System	1	14.9×	0.086	NEDD4L
Transport of small molecules	1	12.6×	0.096	NEDD4L
RNA Polymerase II Transcription	1	11.3×	0.103	NEDD4L
Gene expression (Transcription)	1	8.9×	0.123	NEDD4L
Generic Transcription Pathway	1	7.5×	0.139	NEDD4L
Immune System	1	6.5×	0.154	NEDD4L
Signal Transduction	1	5.1×	0.187	NEDD4L

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
developmental maturation	1	8426.0×	0.002	MAP1B
induction of synaptic plasticity by chemical substance	1	8426.0×	0.002	MAP1B
neuron projection development	2	122.1×	0.002	MAP1B, NEDD4L
establishment of monopolar cell polarity	1	4213.0×	0.003	MAP1B
negative regulation of sodium ion import across plasma membrane	1	4213.0×	0.003	NEDD4L
negative regulation of intracellular transport	1	2808.7×	0.003	MAP1B
regulation of microtubule depolymerization	1	2106.5×	0.003	MAP1B
positive regulation of caveolin-mediated endocytosis	1	2106.5×	0.003	NEDD4L
response to insecticide	1	1404.3×	0.004	MAP1B
negative regulation of sodium ion transmembrane transport	1	1404.3×	0.004	NEDD4L
negative regulation of potassium ion export across plasma membrane	1	1203.7×	0.004	NEDD4L
peripheral nervous system axon regeneration	1	1053.2×	0.004	MAP1B
odontoblast differentiation	1	1053.2×	0.004	MAP1B
regulation of membrane depolarization	1	936.2×	0.004	NEDD4L
response to carbohydrate	1	842.6×	0.004	MAP1B
mitochondrion transport along microtubule	1	702.2×	0.004	MAP1B
negative regulation of potassium ion transmembrane transport	1	702.2×	0.004	NEDD4L
regulation of membrane repolarization	1	648.1×	0.004	NEDD4L
negative regulation of protein localization to cell surface	1	648.1×	0.004	NEDD4L
receptor catabolic process	1	561.7×	0.005	NEDD4L
response to vitamin A	1	526.6×	0.005	MAP1B
regulation of sodium ion transmembrane transport	1	526.6×	0.005	NEDD4L
ventricular cardiac muscle cell action potential	1	495.6×	0.005	NEDD4L
cellular response to peptide hormone stimulus	1	421.3×	0.005	MAP1B
regulation of dendrite morphogenesis	1	366.4×	0.006	NEDD4L
positive regulation of dendrite extension	1	366.4×	0.006	NEDD4L
positive regulation of microtubule polymerization	1	337.0×	0.006	MAP1B
regulation of synapse organization	1	324.1×	0.006	NEDD4L
neuromuscular junction development	1	263.3×	0.007	NEDD4L
microtubule bundle formation	1	255.3×	0.007	MAP1B

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
MAP1B	0	0
NEDD4L	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
MAP1B	10	Binding:6, Functional:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NEDD4L	2.3.2.26, 2.3.2.B8	HECT-type E3 ubiquitin transferase,

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	MAP1B, NEDD4L

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)
MAP1B	10	—
NEDD4L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.