Autism, susceptibility to, 15

Summary

Autism, susceptibility to, 15 (MONDO:0012801) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 62

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autism, susceptibility to, 15
Mondo ID	MONDO:0012801
OMIM	612100
UMLS	C2677504
MedGen	394302
Is cancer (heuristic)	no

Also known as: autism susceptibility 15 · autism, susceptibility to, 15 · autism, susceptibility to, type 15 · AUTS15

Data availability: 62 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › autism, susceptiblity to › autism, susceptibility to, 15

Related subtypes (25): autism, susceptibility to, X-linked 1, autism, susceptibility to, X-linked 2, autism, susceptibility to, X-linked 3, autism, susceptibility to, X-linked 4, autism, susceptibility to, X-linked 5, epsilon-trimethyllysine hydroxylase deficiency, intellectual developmental disorder with autism and speech delay, autism, susceptibility to, 8, autism, susceptibility to, 3, autism, susceptibility to, 6, autism, susceptibility to, 7, autism, susceptibility to, 11, autism, susceptibility to, 12, autism, susceptibility to, 13, autism, susceptibility to, 9, autism, susceptibility to, 10, autism, susceptibility to, 16, autism, susceptibility to, 17, intellectual developmental disorder with autism and macrocephaly, autism, susceptibility to, 19, autism, susceptibility to, 20, autism, susceptibility to, 14a, autism, susceptibility to, 14b, autism, susceptibility to, 1, autism, susceptibility to, 4

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

62 retrieved; paginated sample, class counts are floors:

33 uncertain significance, 16 conflicting classifications of pathogenicity, 4 likely pathogenic, 3 benign/likely benign, 2 pathogenic/likely pathogenic, 2 pathogenic, 2 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1370808	NM_014141.6(CNTNAP2):c.682G>T (p.Gly228Ter)	CNTNAP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3902654	NC_000007.13:g.(146536997_146740998)_(146997383_147092700)del	CNTNAP2	Pathogenic	criteria provided, single submitter
468428	NM_014141.6(CNTNAP2):c.3480_3481del (p.Gly1161fs)	CNTNAP2	Pathogenic	criteria provided, multiple submitters, no conflicts
536312	NM_014141.6(CNTNAP2):c.2497del (p.Trp833fs)	CNTNAP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3594426	NM_014141.6(CNTNAP2):c.889C>T (p.Gln297Ter)	CNTNAP2	Likely pathogenic	criteria provided, single submitter
3594427	NM_014141.6(CNTNAP2):c.1719G>A (p.Trp573Ter)	CNTNAP2	Likely pathogenic	criteria provided, single submitter
3594428	NM_014141.6(CNTNAP2):c.2383+1G>A	CNTNAP2	Likely pathogenic	criteria provided, single submitter
3594429	NM_014141.6(CNTNAP2):c.2524_2546del (p.Lys842fs)	CNTNAP2	Likely pathogenic	criteria provided, single submitter
5491	NM_014141.6(CNTNAP2):c.2099-26267A>G	CNTNAP2	risk factor	no assertion criteria provided
5492	NM_014141.6(CNTNAP2):c.208+18133A>T	CNTNAP2	risk factor	no assertion criteria provided
136809	NM_014141.6(CNTNAP2):c.755-5C>T	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1494963	NM_014141.6(CNTNAP2):c.3716-2A>G	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
166907	NM_014141.6(CNTNAP2):c.73G>A (p.Ala25Thr)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
166914	NM_014141.6(CNTNAP2):c.3595G>T (p.Ala1199Ser)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196459	NM_014141.6(CNTNAP2):c.341G>A (p.Arg114Gln)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205220	NM_014141.6(CNTNAP2):c.3112G>A (p.Asp1038Asn)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205233	NM_014141.6(CNTNAP2):c.1145G>A (p.Ser382Asn)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205256	NM_014141.6(CNTNAP2):c.2123T>C (p.Val708Ala)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205280	NM_014141.6(CNTNAP2):c.3155G>A (p.Arg1052His)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205319	NM_014141.6(CNTNAP2):c.3758T>C (p.Ile1253Thr)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
421332	NM_014141.6(CNTNAP2):c.682G>A (p.Gly228Arg)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
423625	NM_014141.6(CNTNAP2):c.3271C>G (p.Leu1091Val)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
536331	NM_014141.6(CNTNAP2):c.1634C>T (p.Ala545Val)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5493	NM_014141.6(CNTNAP2):c.2606T>C (p.Ile869Thr)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626089	NM_014141.6(CNTNAP2):c.324T>C (p.Asp108=)	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
95572	NM_014141.6(CNTNAP2):c.3716-6C>G	CNTNAP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1011589	NM_014141.6(CNTNAP2):c.875T>A (p.Leu292Gln)	CNTNAP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1179560	NM_014141.6(CNTNAP2):c.681C>A (p.His227Gln)	CNTNAP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
128808	NM_014141.6(CNTNAP2):c.485T>G (p.Val162Gly)	CNTNAP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1368534	NM_014141.6(CNTNAP2):c.3197A>G (p.Tyr1066Cys)	CNTNAP2	Uncertain significance	criteria provided, multiple submitters, no conflicts

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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CNTNAP2	HGNC:13830	ENSG00000174469	Q9UHC6	Contactin-associated protein-like 2	clinvar
KCTD3	HGNC:21305	ENSG00000136636	Q9Y597	BTB/POZ domain-containing protein KCTD3	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.
KCTD3	BTB/POZ domain-containing protein KCTD3	Accessory subunit of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) up-regulating its cell-surface expression and current density without affecting its voltage dependence and kinetics.

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)
CNTNAP2	Other/Unknown	no		FA58C, EGF, Laminin_G
KCTD3	Scaffold/PPI	no		BTB/POZ_dom, WD40_rpt, T1-type_BTB

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
C1 segment of cervical spinal cord	1
corpus callosum	1
superior frontal gyrus	1
jejunal mucosa	1
right adrenal gland	1
right adrenal gland cortex	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
KCTD3	284	ubiquitous	marker	jejunal mucosa, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CNTNAP2	2,097
KCTD3	1,222

Intra-cohort edges

A	B	Sources
CNTNAP2	KCTD3	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNTNAP2	Q9UHC6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCTD3	Q9Y597	70.88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 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
CDC42 GTPase cycle	1	72.3×	0.037	KCTD3
RHO GTPase cycle	1	60.1×	0.037	KCTD3
Signaling by Rho GTPases	1	34.2×	0.037	KCTD3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.037	KCTD3
Signal Transduction	1	10.2×	0.098	KCTD3

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
limbic system development	1	4213.0×	0.003	CNTNAP2
superior temporal gyrus development	1	4213.0×	0.003	CNTNAP2
clustering of voltage-gated potassium channels	1	2106.5×	0.003	CNTNAP2
protein localization to juxtaparanode region of axon	1	2106.5×	0.003	CNTNAP2
neuron recognition	1	1685.2×	0.003	CNTNAP2
positive regulation of gap junction assembly	1	1203.7×	0.003	CNTNAP2
vocal learning	1	1053.2×	0.003	CNTNAP2
thalamus development	1	702.2×	0.004	CNTNAP2
striatum development	1	561.7×	0.004	CNTNAP2
prepulse inhibition	1	561.7×	0.004	CNTNAP2
vocalization behavior	1	443.5×	0.005	CNTNAP2
transmission of nerve impulse	1	324.1×	0.006	CNTNAP2
adult behavior	1	234.1×	0.007	CNTNAP2
learning	1	140.4×	0.010	CNTNAP2
neuron projection morphogenesis	1	138.1×	0.010	CNTNAP2
social behavior	1	135.9×	0.010	CNTNAP2
cerebral cortex development	1	102.8×	0.013	CNTNAP2
neuron projection development	1	61.1×	0.019	CNTNAP2
protein homooligomerization	1	61.1×	0.019	KCTD3
cell population proliferation	1	51.4×	0.021	CNTNAP2
brain development	1	39.8×	0.026	CNTNAP2
cell adhesion	1	18.7×	0.053	CNTNAP2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
KCTD3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	CNTNAP2, KCTD3

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)
CNTNAP2	0	—
KCTD3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.