Neuromuscular disorder, congenital, with dysmorphic facies

Summary

Neuromuscular disorder, congenital, with dysmorphic facies (MONDO:0958332) is a disease caused by FILIP1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FILIP1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuromuscular disorder, congenital, with dysmorphic facies
Mondo ID	MONDO:0958332
OMIM	620775
UMLS	C5935643
MedGen	1857169
GARD	0027012
Is cancer (heuristic)	no

Data availability: 7 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neuromuscular disease › hereditary neuromuscular disease › neuromuscular disorder, congenital, with dysmorphic facies

Related subtypes (21): Meniere disease, myotonia congenita, autosomal dominant, Andersen-Tawil syndrome, myotonia congenita, autosomal recessive, myofibrillar myopathy 1, early-onset myopathy with fatal cardiomyopathy, periodic paralysis with later-onset distal motor neuropathy, malignant hyperthermia of anesthesia, congenital myasthenic syndrome, hereditary spastic paraplegia, muscular dystrophy, hereditary peripheral neuropathy, hereditary motor neuron disease, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, CNGB3-related retinopathy, SCN4A-related channelopathy, Morimoto-Ryu-Malicdan neuromuscular syndrome, KY-related neuromyopathy, benign paroxysmal positional vertigo, vertigo, benign recurrent, 1

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

7 retrieved; paginated sample, class counts are floors:

6 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3066458	NM_015687.5(FILIP1):c.463G>T (p.Glu155Ter)	FILIP1	Pathogenic	no assertion criteria provided
3066459	NM_015687.5(FILIP1):c.2665C>T (p.Arg889Ter)	FILIP1	Pathogenic	no assertion criteria provided
3066460	NC_000006.12:g.75288632_75374566del	FILIP1	Pathogenic	no assertion criteria provided
3066461	NM_015687.5(FILIP1):c.169C>T (p.Arg57Ter)	FILIP1	Pathogenic	no assertion criteria provided
3066462	NM_015687.5(FILIP1):c.3398C>T (p.Pro1133Leu)	FILIP1	Pathogenic	no assertion criteria provided
4293894	NM_015687.5(FILIP1):c.1039G>T (p.Glu347Ter)	FILIP1	Pathogenic	criteria provided, single submitter
3391155	NM_015687.5(FILIP1):c.694C>T (p.Arg232Ter)	FILIP1	Likely pathogenic	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
FILIP1	Strong	Autosomal recessive	neuromuscular disorder, congenital, with dysmorphic facies	2

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
FILIP1	HGNC:21015	ENSG00000118407	Q7Z7B0	Filamin-A-interacting protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FILIP1	Filamin-A-interacting protein 1	By acting through a filamin-A/F-actin axis, it controls the start of neocortical cell migration from the ventricular zone.

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)
FILIP1	Other/Unknown	no		Cortactin-binding_p2_N, Cortactin-Actin_Reg

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
cardiac muscle of right atrium	1
left ventricle myocardium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FILIP1	226	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FILIP1	1,151

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FILIP1	Q7Z7B0	68.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
RHOD GTPase cycle	1	203.9×	0.005	FILIP1

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
protein localization to actin cytoskeleton	1	2808.7×	0.001	FILIP1
modification of postsynaptic structure	1	1872.4×	0.001	FILIP1
corpus callosum development	1	842.6×	0.002	FILIP1
cerebral cortex development	1	205.5×	0.006	FILIP1
neuron migration	1	133.8×	0.007	FILIP1

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
FILIP1	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	FILIP1

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)
FILIP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.