Pervasive developmental disorder

Summary

Pervasive developmental disorder (MONDO:0000594) is a disease (an umbrella term covering 5 Mondo subtypes) with 6 cohort genes and 31 clinical trials. Top therapeutic interventions include guanfacine, aripiprazole, and mecamylamine.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 6
• ClinVar variants: 6
• Clinical trials: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pervasive developmental disorder
Mondo ID	MONDO:0000594
MeSH	D002659
DOID	DOID:0060040
NCIT	C97179
SNOMED CT	35919005
UMLS	C0524528
MedGen	99336
GARD	0027041
Is cancer (heuristic)	no

Also known as: pervasive child development disorders · pervasive development disorders

Data availability: 6 ClinVar variants · 3 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › developmental disorder of mental health › pervasive developmental disorder

Related subtypes (1): specific developmental disorder

Subtypes (5): autism spectrum disorder, Rett syndrome, childhood disintegrative disorder, atypical autism, FOXG1 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

6 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1802167	NM_019042.5(PUS7):c.1097_1098del (p.Leu366fs)	PUS7	Pathogenic	criteria provided, multiple submitters, no conflicts
1326847	NM_003128.3(SPTBN1):c.2275_2285del (p.Trp759fs)	SPTBN1	Pathogenic	criteria provided, single submitter
1703000	NM_001349798.2(FBXW7):c.1439A>G (p.Asp480Gly)	FBXW7	Likely pathogenic	criteria provided, single submitter
871179	NM_001040424.3(PRDM15):c.2420G>A (p.Cys807Tyr)	PRDM15	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1172537	NM_001393504.1(MAST3):c.1615G>A (p.Gly539Ser)	MAST3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3383297	NM_014877.4(HELZ):c.*4461C>T	HELZ	Uncertain significance	criteria provided, single submitter

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
SPTBN1	Orphanet:528084	Non-specific syndromic intellectual disability
FBXW7	Orphanet:528084	Non-specific syndromic intellectual disability
PUS7	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SPTBN1	HGNC:11275	ENSG00000115306	Q01082	Spectrin beta chain, non-erythrocytic 1	clinvar
PRDM15	HGNC:13999	ENSG00000141956	P57071	PR domain zinc finger protein 15	clinvar
FBXW7	HGNC:16712	ENSG00000109670	Q969H0	F-box/WD repeat-containing protein 7	clinvar
HELZ	HGNC:16878	ENSG00000198265	P42694	ATP-dependent RNA helicase with zinc finger domain	clinvar
MAST3	HGNC:19036	ENSG00000099308	O60307	Microtubule-associated serine/threonine-protein kinase 3	clinvar
PUS7	HGNC:26033	ENSG00000091127	Q96PZ0	Pseudouridylate synthase 7 homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPTBN1	Spectrin beta chain, non-erythrocytic 1	Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.
PRDM15	PR domain zinc finger protein 15	Sequence-specific DNA-binding transcriptional regulator.
FBXW7	F-box/WD repeat-containing protein 7	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
HELZ	ATP-dependent RNA helicase with zinc finger domain	ATP-dependent RNA helicase that promotes degradation of mRNAs via its association with the CCR4-NOT deadenylase complex, leading to deadenylation, decapping, and subsequent degradation of target mRNAs.
PUS7	Pseudouridylate synthase 7 homolog	Pseudouridylate synthase that catalyzes pseudouridylation of RNAs.

Protein-family classification

Druggable: 2 · Difficult: 4 · Unknown: 0 · Druggable fraction: 0.33

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	2	5.8×	0.172
Kinase	1	4.6×	0.264
Transcription factor	2	2.8×	0.264
Enzyme (other)	1	2.0×	0.407

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPTBN1	Scaffold/PPI	no		Actinin_actin-bd_CS, PH_dom-spectrin-type, CH_dom
PRDM15	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
FBXW7	Scaffold/PPI	no		WD40_rpt, F-box_dom, WD40/YVTN_repeat-like_dom_sf
HELZ	Transcription factor	no		Znf_CCCH, UvrD-like_ATP-bd, P-loop_NTPase
MAST3	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, PDZ
PUS7	Enzyme (other)	yes	5.4.99.27	PsdUridine_synth_TruD, PsdUridine_synth_TruD_insert, PsdUridine_synth_cat_dom_sf

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
colonic epithelium	2
secondary oocyte	2
endothelial cell	1
skin of hip	1
trigeminal ganglion	1
ileal mucosa	1
primordial germ cell in gonad	1
sural nerve	1
Brodmann (1909) area 23	1
Brodmann (1909) area 10	1
frontal pole	1
middle frontal gyrus	1
buccal mucosa cell	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPTBN1	295	ubiquitous	marker	endothelial cell, trigeminal ganglion, skin of hip
PRDM15	221	ubiquitous	marker	sural nerve, ileal mucosa, primordial germ cell in gonad
FBXW7	290	ubiquitous	marker	Brodmann (1909) area 23, calcaneal tendon, colonic epithelium
HELZ	285	ubiquitous	marker	colonic epithelium, calcaneal tendon, secondary oocyte
MAST3	256	ubiquitous	marker	frontal pole, Brodmann (1909) area 10, middle frontal gyrus
PUS7	254	ubiquitous	marker	buccal mucosa cell, secondary oocyte, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBXW7	7,956
SPTBN1	2,432
PUS7	2,315
HELZ	1,734
PRDM15	1,430
MAST3	968

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FBXW7	Q969H0	7
SPTBN1	Q01082	3
MAST3	O60307	2
PUS7	Q96PZ0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HELZ	P42694	59.24
PRDM15	P57071	56.66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 42. Enrichment computed across 6 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling	1	761.3×	0.040	FBXW7
FLT3 signaling in disease	1	380.7×	0.040	SPTBN1
Signaling by FLT3 fusion proteins	1	190.3×	0.040	SPTBN1
Nephrin family interactions	1	158.6×	0.040	SPTBN1
Interaction between L1 and Ankyrins	1	122.8×	0.040	SPTBN1
Sensory processing of sound	1	102.9×	0.040	SPTBN1
Association of TriC/CCT with target proteins during biosynthesis	1	97.6×	0.040	FBXW7
tRNA modification in the nucleus and cytosol	1	97.6×	0.040	PUS7
RHOV GTPase cycle	1	95.2×	0.040	SPTBN1
RHOU GTPase cycle	1	92.8×	0.040	SPTBN1
NCAM signaling for neurite out-growth	1	90.6×	0.040	SPTBN1
NOTCH1 Intracellular Domain Regulates Transcription	1	79.3×	0.040	FBXW7
Negative regulation of NOTCH4 signaling	1	79.3×	0.040	FBXW7
Sensory processing of sound by outer hair cells of the cochlea	1	68.0×	0.040	SPTBN1
Constitutive Signaling by NOTCH1 PEST Domain Mutants	1	65.6×	0.040	FBXW7
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	1	65.6×	0.040	FBXW7
Sensory processing of sound by inner hair cells of the cochlea	1	54.4×	0.045	SPTBN1
Cell-Cell communication	1	45.9×	0.048	SPTBN1
ER to Golgi Anterograde Transport	1	44.3×	0.048	SPTBN1
MAPK1/MAPK3 signaling	1	43.8×	0.048	SPTBN1
L1CAM interactions	1	40.1×	0.050	SPTBN1
COPI-mediated anterograde transport	1	36.6×	0.051	SPTBN1
MAPK family signaling cascades	1	34.3×	0.051	SPTBN1
Transport to the Golgi and subsequent modification	1	34.3×	0.051	SPTBN1
Sensory Perception	1	31.7×	0.052	SPTBN1
RAF/MAP kinase cascade	1	20.4×	0.074	SPTBN1
Asparagine N-linked glycosylation	1	20.0×	0.074	SPTBN1
RHO GTPase cycle	1	20.0×	0.074	SPTBN1
Diseases of signal transduction by growth factor receptors and second messengers	1	18.9×	0.075	SPTBN1
Neddylation	1	15.8×	0.087	FBXW7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of mesoderm development	1	2808.7×	0.008	PUS7
negative regulation of SREBP signaling pathway	1	2808.7×	0.008	FBXW7
negative regulation of translation	2	65.3×	0.008	HELZ, PUS7
central nervous system formation	1	1404.3×	0.009	SPTBN1
regulation of SMAD protein signal transduction	1	1404.3×	0.009	SPTBN1
pseudouridine synthesis	1	936.2×	0.009	PUS7
negative regulation of hepatocyte proliferation	1	936.2×	0.009	FBXW7
negative regulation of triglyceride biosynthetic process	1	702.2×	0.009	FBXW7
membrane assembly	1	702.2×	0.009	SPTBN1
positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	1	702.2×	0.009	FBXW7
ubiquitin recycling	1	561.7×	0.009	FBXW7
negative regulation of osteoclast development	1	561.7×	0.009	FBXW7
tRNA pseudouridine synthesis	1	468.1×	0.010	PUS7
regulation of lipid storage	1	401.2×	0.011	FBXW7
mRNA pseudouridine synthesis	1	280.9×	0.013	PUS7
actin filament capping	1	255.3×	0.013	SPTBN1
regulation of hematopoietic stem cell differentiation	1	255.3×	0.013	PUS7
regulation of cell cycle G1/S phase transition	1	255.3×	0.013	FBXW7
regulation of stem cell division	1	234.1×	0.014	PRDM15
regulatory ncRNA-mediated post-transcriptional gene silencing	1	200.6×	0.014	HELZ
regulation of mitophagy	1	200.6×	0.014	FBXW7
vasculature development	1	187.2×	0.014	FBXW7
positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1	187.2×	0.014	HELZ
positive regulation of proteasomal protein catabolic process	1	165.2×	0.016	FBXW7
plasma membrane organization	1	147.8×	0.017	SPTBN1
sister chromatid cohesion	1	127.7×	0.019	FBXW7
regulation of protein localization to plasma membrane	1	108.0×	0.021	SPTBN1
positive regulation of ubiquitin-dependent protein catabolic process	1	93.6×	0.024	FBXW7
Golgi to plasma membrane protein transport	1	87.8×	0.024	SPTBN1
positive regulation of epidermal growth factor receptor signaling pathway	1	82.6×	0.024	FBXW7

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Aripiprazole	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 3 of 6 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
SPTBN1	1	2
PRDM15	0	0
FBXW7	0	0
HELZ	0	0
MAST3	0	0
PUS7	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SPTBN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MAST3	38	Binding:38
SPTBN1	7	Binding:7
HELZ	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PUS7	5.4.99.27	tRNA pseudouridine13 synthase

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	SPTBN1

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	1	SPTBN1
C	Druggable family + PDB, no drug	2	MAST3, PUS7
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	PRDM15, FBXW7, HELZ

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PRDM15	0	—
FBXW7	0	—
HELZ	1	—
MAST3	38	—
PUS7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 31.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	17
PHASE2	4
PHASE4	3
PHASE3	3
PHASE1	2
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00205699	PHASE4	COMPLETED	Metabolic Effects of Antipsychotics in Children
NCT01238575	PHASE4	COMPLETED	Guanfacine for the Treatment of Hyperactivity in Pervasive Developmental Disorder
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT00399698	PHASE3	COMPLETED	Study to Determine Whether There Are Any Cognitive or Motor Effects From Taking the Medicine Risperidone.
NCT00870727	PHASE3	COMPLETED	Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders
NCT01243905	PHASE2/PHASE3	UNKNOWN	Group Psychoeducational Program for Mothers of Children With High Functional Pervasive Developmental Disorders
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT05664841	PHASE2	RECRUITING	The Impact of a Virtual Magic Trick Training Program
NCT00198055	PHASE2	COMPLETED	A Study of Aripiprazole in Children and Adolescents With Aspergers and Pervasive Developmental Disorder.
NCT00308074	PHASE2	COMPLETED	An Open-Label Trial of Aripiprazole in Autism Spectrum Disorders
NCT00318162	PHASE1/PHASE2	UNKNOWN	Trial of Low-Dose Naltrexone for Children With Pervasive Developmental Disorder (PDD)
NCT01602016	PHASE2	TERMINATED	A Folinic Acid Intervention for Autism Spectrum Disorders
NCT00325572	PHASE1	TERMINATED	Evaluation and Treatment of Copper/Zinc Imbalance in Children With Autism
NCT00773812	PHASE1	COMPLETED	Placebo-Controlled Pilot Trial of Mecamylamine for Treatment of Autism Spectrum Disorders
NCT01160783	Not specified	ACTIVE_NOT_RECRUITING	Genetic Contributions to Autism Spectrum Disorders
NCT04654260	Not specified	ACTIVE_NOT_RECRUITING	Behavior Therapy for Irritability in Autism
NCT00004458	Not specified	TERMINATED	Longitudinal and Biological Study of Childhood Disintegrative Disorder
NCT00025779	Not specified	COMPLETED	Methylphenidate in Children and Adolescents With Pervasive Developmental Disorders
NCT00464477	Not specified	COMPLETED	Advanced Grandparental Age as a Risk Factor for Autism
NCT00531830	Not specified	UNKNOWN	Assessment of Factors Which Predict Improvement in Children With PDD After a Year of Integrative Therapy
NCT00579267	Not specified	COMPLETED	Reliability and Validity of the MINI International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)
NCT00902798	Not specified	COMPLETED	Cognitive Enhancement Therapy for Adult Autism Spectrum Disorder
NCT01553240	Not specified	TERMINATED	Neurocircuitry of Autism- fMRI and Transcranial Magnetic Stimulation Studies
NCT01631851	Not specified	COMPLETED	Cognitive-Behavioral Therapy for Irritability in Adolescents With High Functioning Autism Spectrum Disorder
NCT01808066	Not specified	COMPLETED	GroundsKeeper: A Qualitative Study of Applied Game-based Interactives in Special Education Programs
NCT01921244	Not specified	COMPLETED	Shared Decision Making to Improve Care and Outcomes for Children With Autism
NCT03170453	Not specified	COMPLETED	Confirmatory Efficacy Trial of Cognitive Enhancement Therapy for Adult Autism Spectrum Disorder
NCT03177590	Not specified	COMPLETED	Recording Facial and Vocal Emotional Productions in Children With Autism as Part of the JEMImE Project
NCT03560453	Not specified	COMPLETED	Facilitating Employment for Youth With Autism
NCT03602378	Not specified	UNKNOWN	QoL and Stress in Parents of Children With Developmental Disabilities and Chronic Disease
NCT04788537	Not specified	COMPLETED	Services to Enhance Social Functioning in Adults With Autism Spectrum Disorders

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GUANFACINE	4	6
ARIPIPRAZOLE	4	4
MECAMYLAMINE	4	3
HUMAN IMMUNOGLOBULIN G	4	1
OLANZAPINE	4	1
OXYTOCIN	4	1
RISPERIDONE	4	1
ZINC ION	3	1
CHEMBL4303358	0	1
CHEMBL1201279	0	1
CHEMBL46909	0	1
FOLINIC ACID	0	1