Intellectual disability, autosomal dominant 33

Summary

Intellectual disability, autosomal dominant 33 (MONDO:0014580) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 33

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 33
Mondo ID	MONDO:0014580
OMIM	616311
DOID	DOID:0070063
UMLS	C4225375
MedGen	899389
GARD	0016082
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 33 · autosomal dominant non-syndromic intellectual disability caused by mutation in DPP6 · DPP6 autosomal dominant non-syndromic intellectual disability · intellectual disability, autosomal dominant 33 · intellectual disability, autosomal dominant type 33 · mental retardation, autosomal dominant 33 · mental retardation, autosomal dominant type 33 · MRD33

Data availability: 33 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 › intellectual disability › non-syndromic intellectual disability › autosomal dominant non-syndromic intellectual disability › intellectual disability, autosomal dominant 33

Related subtypes (25): intellectual disability, autosomal dominant 22, neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language, intellectual disability, autosomal dominant 34, intellectual disability, autosomal dominant 41, intellectual disability, autosomal dominant 43, intellectual disability, autosomal dominant 58, intellectual disability, autosomal dominant 45, intellectual disability, autosomal dominant 46, intellectual disability, autosomal dominant 47, Clark-Baraitser syndrome, intellectual disability, autosomal dominant 50, intellectual disability, autosomal dominant 51, intellectual disability, autosomal dominant 52, intellectual disability, autosomal dominant 53, intellectual disability, autosomal dominant 54, intellectual disability, autosomal dominant 55, with seizures, intellectual disability, autosomal dominant 56, intellectual developmental disorder 61, intellectual developmental disorder 59, intellectual developmental disorder 60 with seizures, intellectual developmental disorder 62, intellectual developmental disorder, autosomal dominant 63, with macrocephaly, Coffin-Siris syndrome 6, intellectual disability, autosomal dominant 57, intellectual developmental disorder, autosomal dominant 73

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

33 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 3 conflicting classifications of pathogenicity, 2 benign, 2 pathogenic, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
189389	NM_130797.4(DPP6):c.1153A>C (p.Met385Leu)	DPP6	Pathogenic	no assertion criteria provided
189390	NC_000007.13:g.153649777_153985995del	DPP6	Pathogenic	no assertion criteria provided
4820094	NM_130797.4(DPP6):c.615C>A (p.Tyr205Ter)	DPP6	Likely pathogenic	criteria provided, single submitter
1049455	NM_130797.4(DPP6):c.58G>A (p.Ala20Thr)	DPP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
802383	NM_130797.4(DPP6):c.627+21101A>G	DPP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
810229	NM_130797.4(DPP6):c.167GCG[8] (p.Gly62dup)	DPP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028479	NM_001039350.3(DPP6):c.19A>G (p.Ile7Val)	DPP6	Uncertain significance	criteria provided, single submitter
1032378	NM_130797.4(DPP6):c.88G>A (p.Gly30Ser)	DPP6	Uncertain significance	criteria provided, single submitter
1049266	NM_130797.4(DPP6):c.1621G>A (p.Ala541Thr)	DPP6	Uncertain significance	criteria provided, single submitter
1213816	NM_001364497.2(DPP6):c.39T>A (p.Cys13Ter)	DPP6	Uncertain significance	criteria provided, single submitter
1342568	NM_130797.4(DPP6):c.1391C>T (p.Thr464Met)	DPP6	Uncertain significance	criteria provided, single submitter
1701761	NM_130797.4(DPP6):c.1888G>A (p.Gly630Ser)	DPP6	Uncertain significance	criteria provided, single submitter
1992326	NM_130797.4(DPP6):c.1033C>T (p.Pro345Ser)	DPP6	Uncertain significance	criteria provided, single submitter
2441027	NM_130797.4(DPP6):c.668A>G (p.Lys223Arg)	DPP6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441028	NM_130797.4(DPP6):c.975C>G (p.Ile325Met)	DPP6	Uncertain significance	criteria provided, single submitter
2441029	NM_130797.4(DPP6):c.457+3G>A	DPP6	Uncertain significance	criteria provided, single submitter
2627608	NM_130797.4(DPP6):c.3G>A (p.Met1Ile)	DPP6	Uncertain significance	criteria provided, single submitter
3255400	NM_130797.4(DPP6):c.2183dup (p.Asn728fs)	DPP6	Uncertain significance	no assertion criteria provided
3594439	NM_130797.4(DPP6):c.685C>A (p.Pro229Thr)	DPP6	Uncertain significance	criteria provided, multiple submitters, no conflicts
3594440	NM_130797.4(DPP6):c.965G>A (p.Arg322His)	DPP6	Uncertain significance	criteria provided, single submitter
3594441	NM_130797.4(DPP6):c.1578G>C (p.Gln526His)	DPP6	Uncertain significance	criteria provided, single submitter
4078527	NM_130797.4(DPP6):c.298C>T (p.Leu100=)	DPP6	Uncertain significance	criteria provided, single submitter
4078528	NM_130797.4(DPP6):c.2593del (p.Asp865fs)	DPP6	Uncertain significance	criteria provided, single submitter
4277520	NM_130797.4(DPP6):c.2464G>A (p.Glu822Lys)	DPP6	Uncertain significance	criteria provided, single submitter
523018	NM_130797.4(DPP6):c.1388T>C (p.Ile463Thr)	DPP6	Uncertain significance	criteria provided, single submitter
802384	NM_130797.4(DPP6):c.2304G>C (p.Glu768Asp)	DPP6	Uncertain significance	criteria provided, single submitter
802385	NM_130797.4(DPP6):c.2304+2T>C	DPP6	Uncertain significance	criteria provided, single submitter
930297	NM_130797.4(DPP6):c.109G>T (p.Gly37Cys)	DPP6	Uncertain significance	criteria provided, single submitter
982749	NM_130797.4(DPP6):c.914G>A (p.Trp305Ter)	DPP6	Uncertain significance	criteria provided, single submitter
992764	NM_130797.4(DPP6):c.1565A>G (p.Asn522Ser)	DPP6	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
DPP6	Limited	Autosomal dominant	intellectual disability, autosomal dominant 33	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DPP6	Orphanet:228140	Idiopathic ventricular fibrillation
DPP6	Orphanet:2514	Autosomal dominant primary microcephaly

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
DPP6	HGNC:3010	ENSG00000130226	P42658	A-type potassium channel modulatory protein DPP6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DPP6	A-type potassium channel modulatory protein DPP6	Promotes cell surface expression of the potassium channel KCND2.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DPP6	Protease	yes		Peptidase_S9_cat, Peptidase_S9B_N, AB_hydrolase_fold

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
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DPP6	221	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DPP6	2,224

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DPP6	P42658	8

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
regulation of potassium ion transmembrane transport	1	624.1×	0.005	DPP6
protein localization to plasma membrane	1	108.7×	0.014	DPP6
proteolysis	1	34.2×	0.029	DPP6

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
DPP6	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	1	DPP6
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
DPP6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.