Neurodevelopmental disorder with severe motor impairment and absent language

Summary

Neurodevelopmental disorder with severe motor impairment and absent language (MONDO:0060622) is a disease caused by DHX30 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DHX30 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 55

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neurodevelopmental disorder with severe motor impairment and absent language
Mondo ID	MONDO:0060622
OMIM	617804
Orphanet	647788
UMLS	C4540496
MedGen	1622162
GARD	0013608
Is cancer (heuristic)	no

Also known as: DHX30-related complex neurodevelopmental disorder · NEDMIAL · neurodevelopmental delay-intellectual disability-ataxia-feeding difficulty syndrome · neurodevelopmental disorder with severe motor impairment and absent language

Data availability: 55 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › complex neurodevelopmental disorder › neurodevelopmental disorder with severe motor impairment and absent language

Related subtypes (14): pervasive developmental disorder, Prader-Willi syndrome, intellectual disability, autosomal dominant 29, neurodevelopmental disorder with language impairment and behavioral abnormalities, X-linked complex neurodevelopmental disorder, neonatal encephalopathy with non-epileptic myoclonus, complex neurodevelopmental disorder with or without congenital anomalies, complex neurodevelopmental disorder with motor features, AFG2B-related complex neurodevelopmental disorder with motor features and hearing loss, developmental and epileptic encephalopathy, syndromic complex neurodevelopmental disorder, DEAF1-associated neurodevelopmental disorder, NACC1-related neurodevelopmental disorder with epilepsy, cataracts and episodic irritability, GRIN-related complex neurodevelopmental disorder

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

55 retrieved; paginated sample, class counts are floors:

36 uncertain significance, 7 conflicting classifications of pathogenicity, 7 pathogenic, 2 likely pathogenic, 2 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1330305	NM_138615.3(DHX30):c.2345G>A (p.Arg782Gln)	DHX30	Pathogenic	criteria provided, single submitter
2443976	NM_138615.3(DHX30):c.2389C>T (p.Arg797Ter)	DHX30	Pathogenic	no assertion criteria provided
375373	NM_138615.3(DHX30):c.2344C>T (p.Arg782Trp)	DHX30	Pathogenic	criteria provided, multiple submitters, no conflicts
375374	NM_138615.3(DHX30):c.1478G>A (p.Arg493His)	DHX30	Pathogenic	no assertion criteria provided
402130	NM_138615.3(DHX30):c.1685A>G (p.His562Arg)	DHX30	Pathogenic	criteria provided, single submitter
426111	NM_138615.3(DHX30):c.2353C>T (p.Arg785Cys)	DHX30	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
453269	NM_138615.3(DHX30):c.2342G>A (p.Gly781Asp)	DHX30	Pathogenic	no assertion criteria provided
453272	NM_138615.3(DHX30):c.2354G>A (p.Arg785His)	DHX30	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
801964	NM_138615.3(DHX30):c.1390A>G (p.Thr464Ala)	DHX30	Pathogenic	criteria provided, single submitter
2444127	NM_138615.3(DHX30):c.2345G>C (p.Arg782Pro)	DHX30	Likely pathogenic	criteria provided, single submitter
3376258	NM_138615.3(DHX30):c.3545C>G (p.Pro1182Arg)	DHX30	Likely pathogenic	criteria provided, single submitter
1066052	NM_138615.3(DHX30):c.245C>T (p.Pro82Leu)	DHX30	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1341878	NM_138615.3(DHX30):c.2575+2dup	DHX30	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1679773	NM_138615.3(DHX30):c.618C>A (p.Asp206Glu)	DHX30	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1686619	NM_138615.3(DHX30):c.2387C>G (p.Pro796Arg)	DHX30	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2440778	NM_138615.3(DHX30):c.509C>G (p.Pro170Arg)	DHX30	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3501571	NM_138615.3(DHX30):c.2215A>G (p.Thr739Ala)	DHX30	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523233	NM_138615.3(DHX30):c.2723G>A (p.Arg908Gln)	DHX30	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029135	NM_138615.3(DHX30):c.2006-6T>C	DHX30	Uncertain significance	criteria provided, single submitter
1213813	NM_138615.3(DHX30):c.2845G>T (p.Val949Leu)	DHX30	Uncertain significance	criteria provided, single submitter
1285408	NM_138615.3(DHX30):c.3523C>G (p.Leu1175Val)	DHX30	Uncertain significance	criteria provided, single submitter
1305752	NM_138615.3(DHX30):c.2099T>G (p.Leu700Arg)	DHX30	Uncertain significance	criteria provided, multiple submitters, no conflicts
1341913	NM_138615.3(DHX30):c.1237C>T (p.Leu413Phe)	DHX30	Uncertain significance	criteria provided, single submitter
1342348	NM_138615.3(DHX30):c.2134G>A (p.Asp712Asn)	DHX30	Uncertain significance	criteria provided, multiple submitters, no conflicts
1683742	NM_138615.3(DHX30):c.1028G>A (p.Arg343His)	DHX30	Uncertain significance	criteria provided, single submitter
1878599	NM_138615.3(DHX30):c.3379C>T (p.Arg1127Trp)	DHX30	Uncertain significance	criteria provided, single submitter
1878607	NM_138615.3(DHX30):c.3407G>A (p.Arg1136Gln)	DHX30	Uncertain significance	criteria provided, single submitter
2431925	NM_138615.3(DHX30):c.2493+19G>T	DHX30	Uncertain significance	criteria provided, single submitter
2440767	NM_138615.3(DHX30):c.3287C>T (p.Pro1096Leu)	DHX30	Uncertain significance	criteria provided, single submitter
2440768	NM_138615.3(DHX30):c.3403G>A (p.Val1135Met)	DHX30	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
DHX30	Strong	Autosomal dominant	neurodevelopmental disorder with severe motor impairment and absent language	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DHX30	Orphanet:647788	Neurodevelopmental delay-intellectual disability-ataxia-feeding difficulty syndrome

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
DHX30	HGNC:16716	ENSG00000132153	Q7L2E3	ATP-dependent RNA helicase DHX30	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DHX30	ATP-dependent RNA helicase DHX30	RNA-dependent helicase.

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)
DHX30	Other/Unknown	no		Helicase_C-like, DNA/RNA_helicase_DEAH_CS, Helicase-assoc_dom

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
left testis	1
right hemisphere of cerebellum	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DHX30	245	ubiquitous	marker	left testis, right testis, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DHX30	4,364

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DHX30	Q7L2E3	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
mitochondrial large ribosomal subunit assembly	1	991.3×	0.002	DHX30
central nervous system development	1	115.4×	0.009	DHX30

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
DHX30	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
DHX30	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	DHX30

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)
DHX30	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.