Pitt-Hopkins-like syndrome

Summary

Pitt-Hopkins-like syndrome (MONDO:0016377) 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	Pitt-Hopkins-like syndrome
Mondo ID	MONDO:0016377
Orphanet	221150
UMLS	C4751168
MedGen	1648432
GARD	0011967
Is cancer (heuristic)	no

Also known as: PTHSL

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › Pitt-Hopkins or Pitt-Hopkins-like syndrome › Pitt-Hopkins-like syndrome

Related subtypes (1): Pitt-Hopkins syndrome

Subtypes (2): cortical dysplasia-focal epilepsy syndrome, Pitt-Hopkins-like syndrome 2

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
1805512	NM_014141.6(CNTNAP2):c.2569del (p.Ser857fs)	CNTNAP2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNTNAP2	Orphanet:163681	CNTNAP2-related developmental and epileptic encephalopathy

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
CNTNAP2	HGNC:13830	ENSG00000174469	Q9UHC6	Contactin-associated protein-like 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CNTNAP2	Contactin-associated protein-like 2	Required for gap junction formation.

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)
CNTNAP2	Other/Unknown	no		FA58C, EGF, Laminin_G

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
C1 segment of cervical spinal cord	1
corpus callosum	1
superior frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CNTNAP2	127	broad	marker	corpus callosum, superior frontal gyrus, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CNTNAP2	2,097

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNTNAP2	Q9UHC6	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
limbic system development	1	8426.0×	0.001	CNTNAP2
superior temporal gyrus development	1	8426.0×	0.001	CNTNAP2
clustering of voltage-gated potassium channels	1	4213.0×	0.001	CNTNAP2
protein localization to juxtaparanode region of axon	1	4213.0×	0.001	CNTNAP2
neuron recognition	1	3370.4×	0.001	CNTNAP2
positive regulation of gap junction assembly	1	2407.4×	0.001	CNTNAP2
vocal learning	1	2106.5×	0.001	CNTNAP2
thalamus development	1	1404.3×	0.002	CNTNAP2
striatum development	1	1123.5×	0.002	CNTNAP2
prepulse inhibition	1	1123.5×	0.002	CNTNAP2
vocalization behavior	1	887.0×	0.002	CNTNAP2
transmission of nerve impulse	1	648.1×	0.003	CNTNAP2
adult behavior	1	468.1×	0.003	CNTNAP2
learning	1	280.9×	0.005	CNTNAP2
neuron projection morphogenesis	1	276.3×	0.005	CNTNAP2
social behavior	1	271.8×	0.005	CNTNAP2
cerebral cortex development	1	205.5×	0.006	CNTNAP2
neuron projection development	1	122.1×	0.010	CNTNAP2
cell population proliferation	1	102.8×	0.011	CNTNAP2
brain development	1	79.5×	0.013	CNTNAP2
cell adhesion	1	37.5×	0.027	CNTNAP2

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
CNTNAP2	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	CNTNAP2

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)
CNTNAP2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.