Intellectual disability, autosomal dominant 3

Summary

Intellectual disability, autosomal dominant 3 (MONDO:0012946) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 3
Mondo ID	MONDO:0012946
MeSH	C567241
OMIM	612580
DOID	DOID:0070033
UMLS	C2675488
MedGen	436447
GARD	0016454
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 3 · autosomal dominant non-syndromic intellectual disability caused by mutation in CDH15 · CDH15 autosomal dominant non-syndromic intellectual disability · intellectual disability, autosomal dominant 3 · intellectual disability, autosomal dominant type 3 · mental retardation, autosomal dominant 3 · mental retardation, autosomal dominant type 3 · MRD3

Data availability: 34 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › intellectual disability, autosomal dominant › intellectual disability, autosomal dominant 3

Related subtypes (28): intellectual disability, autosomal dominant 1, intellectual disability, autosomal dominant 4, intellectual disability, autosomal dominant 5, intellectual disability, autosomal dominant 6, intellectual disability, autosomal dominant 2, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, intellectual disability, autosomal dominant 9, intellectual disability, autosomal dominant 10, intellectual disability, autosomal dominant 11, intellectual disability, autosomal dominant 24, intellectual disability, autosomal dominant 38, intellectual disability, autosomal dominant 39, intellectual disability, autosomal dominant 40, intellectual disability, autosomal dominant 42, autosomal dominant non-syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 65, intellectual developmental disorder, autosomal dominant 69, intellectual developmental disorder, autosomal dominant 66, intellectual developmental disorder, autosomal dominant 64, intellectual developmental disorder, autosomal dominant 67, intellectual developmental disorder, autosomal dominant 68, autosomal dominant syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 70, intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, intellectual developmental disorder, autosomal dominant 72, intellectual developmental disorder, autosomal dominant 74, intellectual developmental disorder, autosomal dominant 75, intellectual developmental disorder, autosomal dominant 76

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

34 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 5 likely benign, 3 benign, 2 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
434633	NM_004933.3(CDH15):c.2369C>T (p.Ala790Val)	CDH15	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
803282	NM_004933.3(CDH15):c.568C>T (p.Arg190Trp)	CDH15	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028309	NM_004933.3(CDH15):c.1039C>T (p.Pro347Ser)	CDH15	Uncertain significance	criteria provided, multiple submitters, no conflicts
1028310	NM_004933.3(CDH15):c.1540G>A (p.Gly514Arg)	CDH15	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034129	NM_004933.3(CDH15):c.1376-17G>A	CDH15	Uncertain significance	criteria provided, single submitter
1034130	NM_004933.3(CDH15):c.1615+5G>A	CDH15	Uncertain significance	criteria provided, single submitter
1034131	NM_004933.3(CDH15):c.1742G>A (p.Arg581His)	CDH15	Uncertain significance	criteria provided, single submitter
1034132	NM_004933.3(CDH15):c.472A>G (p.Thr158Ala)	CDH15	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034133	NM_004933.3(CDH15):c.658C>T (p.Arg220Cys)	CDH15	Uncertain significance	criteria provided, single submitter
1098632	NM_004933.3(CDH15):c.607A>T (p.Ser203Cys)	CDH15	Uncertain significance	criteria provided, single submitter
1213779	NM_004933.3(CDH15):c.2218G>C (p.Glu740Gln)	CDH15	Uncertain significance	criteria provided, single submitter
1341857	NM_004933.3(CDH15):c.2071G>T (p.Ala691Ser)	CDH15	Uncertain significance	criteria provided, single submitter
1683624	NM_004933.3(CDH15):c.479G>T (p.Arg160Leu)	CDH15	Uncertain significance	criteria provided, single submitter
1686550	NM_004933.3(CDH15):c.100del (p.Trp34fs)	CDH15	Uncertain significance	criteria provided, multiple submitters, no conflicts
17643	NM_004933.3(CDH15):c.274C>T (p.Arg92Trp)	CDH15	Uncertain significance	criteria provided, multiple submitters, no conflicts
2647030	NM_004933.3(CDH15):c.1040C>T (p.Pro347Leu)	CDH15	Uncertain significance	criteria provided, multiple submitters, no conflicts
3242152	NM_004933.3(CDH15):c.274C>G (p.Arg92Gly)	CDH15	Uncertain significance	criteria provided, single submitter
3377614	NM_004933.3(CDH15):c.2081G>C (p.Gly694Ala)	CDH15	Uncertain significance	criteria provided, single submitter
3391399	NM_004933.3(CDH15):c.2095del (p.Gln699fs)	CDH15	Uncertain significance	criteria provided, single submitter
3391400	NM_004933.3(CDH15):c.2122C>T (p.Pro708Ser)	CDH15	Uncertain significance	criteria provided, single submitter
3581409	NM_004933.3(CDH15):c.1741C>A (p.Arg581Ser)	CDH15	Uncertain significance	criteria provided, single submitter
3581410	NM_004933.3(CDH15):c.2268G>C (p.Gln756His)	CDH15	Uncertain significance	criteria provided, single submitter
3779032	NM_004933.3(CDH15):c.2215_2217del (p.Tyr739del)	CDH15	Uncertain significance	criteria provided, multiple submitters, no conflicts
816675	NM_004933.3(CDH15):c.1031A>T (p.Asn344Ile)	CDH15	Uncertain significance	criteria provided, single submitter
872527	NM_004933.3(CDH15):c.127G>T (p.Val43Leu)	CDH15	Uncertain significance	criteria provided, multiple submitters, no conflicts
128641	NM_004933.3(CDH15):c.1023G>A (p.Ser341=)	CDH15	Benign	criteria provided, multiple submitters, no conflicts
128646	NM_004933.3(CDH15):c.1750A>C (p.Lys584Gln)	CDH15	Benign	criteria provided, multiple submitters, no conflicts
128647	NM_004933.3(CDH15):c.1971A>G (p.Gln657=)	CDH15	Benign	criteria provided, multiple submitters, no conflicts
128652	NM_004933.3(CDH15):c.387A>G (p.Gly129=)	CDH15	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
17642	NM_004933.3(CDH15):c.178C>T (p.Arg60Cys)	CDH15	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
CDH15	Supportive	Autosomal dominant	autosomal dominant non-syndromic intellectual disability	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDH15	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

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
CDH15	HGNC:1754	ENSG00000129910	P55291	Cadherin-15	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDH15	Cadherin-15	Cadherins are calcium-dependent cell adhesion proteins.

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)
CDH15	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDH15	139	broad	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDH15	1,775

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDH15	P55291	78.70

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Myogenesis	1	380.7×	0.008	CDH15
Adherens junctions interactions	1	248.3×	0.008	CDH15
Cell-cell junction organization	1	248.3×	0.008	CDH15
Cell junction organization	1	187.2×	0.008	CDH15
Cell-Cell communication	1	137.6×	0.009	CDH15
Developmental Biology	1	14.5×	0.069	CDH15

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
adherens junction organization	1	510.7×	0.005	CDH15
calcium-dependent cell-cell adhesion	1	481.5×	0.005	CDH15
cell-cell junction assembly	1	443.5×	0.005	CDH15
cell-cell adhesion mediated by cadherin	1	411.0×	0.005	CDH15
cell morphogenesis	1	157.5×	0.009	CDH15
homophilic cell-cell adhesion	1	140.4×	0.009	CDH15
cell migration	1	61.5×	0.019	CDH15
cell adhesion	1	37.5×	0.027	CDH15

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
CDH15	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	CDH15

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)
CDH15	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.