Autism, susceptibility to, 17

disease

On this page

Also known as autism susceptibility 17autism, susceptibility to, type 17AUTS17

Summary

Autism, susceptibility to, 17 (MONDO:0013265) is a disease caused by SHANK2 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: SHANK2 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 56

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autism, susceptibility to, 17
Mondo ID	MONDO:0013265
OMIM	613436
UMLS	C3150693
MedGen	462043
Is cancer (heuristic)	no

Also known as: autism susceptibility 17 · autism, susceptibility to, 17 · autism, susceptibility to, type 17 · AUTS17

Data availability: 56 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › autism, susceptiblity to › autism, susceptibility to, 17

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

56 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 12 likely pathogenic, 7 pathogenic, 7 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 2 benign/likely benign, 2 risk factor, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027663	NM_012309.5(SHANK2):c.2439+1G>A	SHANK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1177375	NM_012309.5(SHANK2):c.2593C>T (p.Gln865Ter)	SHANK2	Pathogenic	criteria provided, single submitter
1699379	NM_012309.5(SHANK2):c.601dup (p.Leu201fs)	SHANK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1805933	NM_012309.5(SHANK2):c.4635_4636delinsTAT (p.Val1546fs)	SHANK2	Pathogenic	criteria provided, single submitter
224127	NM_012309.5(SHANK2):c.1896dup (p.Asp633fs)	SHANK2	Pathogenic	criteria provided, multiple submitters, no conflicts
2775433	NM_012309.5(SHANK2):c.4604del (p.Asp1535fs)	SHANK2	Pathogenic	criteria provided, single submitter
3897810	NM_012309.5(SHANK2):c.2374C>T (p.Pro792Ser)	SHANK2	Pathogenic	criteria provided, single submitter
3900647	NM_012309.5(SHANK2):c.4371_4374del (p.Asn1458fs)	SHANK2	Pathogenic	criteria provided, single submitter
992847	NM_012309.5(SHANK2):c.2521C>T (p.Arg841Ter)	SHANK2	Pathogenic	criteria provided, multiple submitters, no conflicts
1174489	NM_012309.5(SHANK2):c.1927G>A (p.Gly643Arg)	SHANK2	Likely pathogenic	no assertion criteria provided
1320184	NM_012309.5(SHANK2):c.2247dup (p.Lys750fs)	SHANK2	Likely pathogenic	criteria provided, single submitter
1803070	NM_012309.5(SHANK2):c.5176_5177del (p.Leu1726fs)	SHANK2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1804793	NM_012309.5(SHANK2):c.1742del (p.Glu581fs)	SHANK2	Likely pathogenic	criteria provided, single submitter
2584776	NM_012309.5(SHANK2):c.2198-1G>A	SHANK2	Likely pathogenic	no assertion criteria provided
2584777	NM_012309.5(SHANK2):c.2310dup (p.Lys771Ter)	SHANK2	Likely pathogenic	no assertion criteria provided
3258113	NM_012309.5(SHANK2):c.3953_3958delinsGC (p.Thr1318fs)	SHANK2	Likely pathogenic	criteria provided, single submitter
3381763	NM_012309.5(SHANK2):c.5156_5157del (p.Lys1719fs)	SHANK2	Likely pathogenic	criteria provided, single submitter
3381861	NM_012309.5(SHANK2):c.2435_2436del (p.Met812fs)	SHANK2	Likely pathogenic	criteria provided, single submitter
4279966	NM_012309.5(SHANK2):c.754G>T (p.Glu252Ter)	SHANK2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4819621	NM_012309.5(SHANK2):c.2197+1G>A	SHANK2	Likely pathogenic	criteria provided, single submitter
4848732	NC_000011.9:g.(70666788_70742605)_(70830079_70858165)dup	SHANK2	Likely pathogenic	criteria provided, single submitter
6516	NG_042866.2:g.496951_616776del	SHANK2	risk factor	no assertion criteria provided
6517	NG_042866.2:g.(460061_462693)_(532018_533659)del	SHANK2	risk factor	no assertion criteria provided
1325553	NM_012309.5(SHANK2):c.790G>A (p.Gly264Ser)	SHANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1676476	NM_012309.5(SHANK2):c.460C>T (p.Gln154Ter)	SHANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
436710	NM_012309.5(SHANK2):c.2338A>C (p.Lys780Gln)	SHANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
620503	NM_012309.5(SHANK2):c.4906C>T (p.Arg1636Ter)	SHANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
739474	NM_012309.5(SHANK2):c.4313T>C (p.Val1438Ala)	SHANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
870793	NM_012309.5(SHANK2):c.227C>T (p.Pro76Leu)	SHANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
978856	NM_012309.5(SHANK2):c.2533C>T (p.Arg845Ter)	SHANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
SHANK2	Strong	Autosomal dominant	autism, susceptibility to, 17	3

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
SHANK2	HGNC:14295	ENSG00000162105	Q9UPX8	SH3 and multiple ankyrin repeat domains protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SHANK2	SH3 and multiple ankyrin repeat domains protein 2	Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors, and the actin-based cytoskeleton.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SHANK2	Scaffold/PPI	no		SH3_domain, PDZ, SAM

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
Brodmann (1909) area 23	1
bronchial epithelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SHANK2	240	broad	marker	Brodmann (1909) area 23, bronchial epithelial cell, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SHANK2	1,920

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SHANK2	Q9UPX8	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Protein-protein interactions at synapses	1	265.6×	0.008	SHANK2
Neurexins and neuroligins	1	196.9×	0.008	SHANK2
Neuronal System	1	44.3×	0.023	SHANK2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
long-term synaptic depression	1	887.0×	0.004	SHANK2
vocalization behavior	1	887.0×	0.004	SHANK2
negative regulation of hippo signaling	1	702.2×	0.004	SHANK2
associative learning	1	481.5×	0.004	SHANK2
adult behavior	1	468.1×	0.004	SHANK2
learning	1	280.9×	0.004	SHANK2
synapse organization	1	280.9×	0.004	SHANK2
long-term synaptic potentiation	1	280.9×	0.004	SHANK2
social behavior	1	271.8×	0.004	SHANK2
synapse assembly	1	230.8×	0.005	SHANK2
positive regulation of cell population proliferation	1	33.6×	0.030	SHANK2

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
SHANK2	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	SHANK2

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)
SHANK2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: SHANK2