Intellectual disability, autosomal dominant 4

Summary

Intellectual disability, autosomal dominant 4 (MONDO:0012947) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 4
Mondo ID	MONDO:0012947
MeSH	C567240
OMIM	612581
DOID	DOID:0070034
UMLS	C2675487
MedGen	393397
GARD	0016455
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 4 · intellectual disability, autosomal dominant 4 · intellectual disability, autosomal dominant type 4 · KIRREL3 autosomal dominant non-syndromic intellectual disability · mental retardation, autosomal dominant 4 · mental retardation, autosomal dominant type 4 · MRD4

Data availability: 6 ClinVar variants · 2 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 4

Related subtypes (28): intellectual disability, autosomal dominant 1, intellectual disability, autosomal dominant 3, 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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 likely benign, 1 likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
375632	NM_032531.4(KIRREL3):c.2019G>A (p.Met673Ile)	KIRREL3	Likely pathogenic	criteria provided, single submitter
1032294	NM_032531.4(KIRREL3):c.742C>T (p.His248Tyr)	KIRREL3	Uncertain significance	criteria provided, single submitter
2886	NM_032531.4(KIRREL3):c.118C>T (p.Arg40Trp)	KIRREL3	Uncertain significance	no assertion criteria provided
2888	NM_032531.4(KIRREL3):c.2191G>T (p.Val731Phe)	KIRREL3	Uncertain significance	criteria provided, single submitter
2887	NM_032531.4(KIRREL3):c.1007G>A (p.Arg336Gln)	KIRREL3	Likely benign	criteria provided, single submitter
585148	NM_032531.4(KIRREL3):c.1238C>T (p.Thr413Ile)	KIRREL3	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
KIRREL3	Supportive	Autosomal dominant	autosomal dominant non-syndromic intellectual disability	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIRREL3	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
KIRREL3	HGNC:23204	ENSG00000149571	Q8IZU9	Kin of IRRE-like protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIRREL3	Kin of IRRE-like protein 3	Synaptic adhesion molecule required for the formation of target-specific synapses.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIRREL3	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom

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
middle temporal gyrus	1
nucleus accumbens	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIRREL3	179	broad	marker	middle temporal gyrus, nucleus accumbens, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIRREL3	1,290

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIRREL3	Q8IZU9	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Nephrin family interactions	1	475.8×	0.004	KIRREL3
Cell-Cell communication	1	137.6×	0.007	KIRREL3

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
inter-male aggressive behavior	1	8426.0×	6e-04	KIRREL3
principal sensory nucleus of trigeminal nerve development	1	5617.3×	6e-04	KIRREL3
glomerulus morphogenesis	1	5617.3×	6e-04	KIRREL3
neuron projection morphogenesis	1	276.3×	0.006	KIRREL3
hemopoiesis	1	267.5×	0.006	KIRREL3
synapse assembly	1	230.8×	0.006	KIRREL3
hippocampus development	1	230.8×	0.006	KIRREL3
homophilic cell-cell adhesion	1	140.4×	0.008	KIRREL3
neuron migration	1	133.8×	0.008	KIRREL3
cell-cell adhesion	1	101.5×	0.010	KIRREL3

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
KIRREL3	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	KIRREL3
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)
KIRREL3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.