Intellectual developmental disorder, autosomal dominant 68

Summary

Intellectual developmental disorder, autosomal dominant 68 (MONDO:0030969) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 39

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal dominant 68
Mondo ID	MONDO:0030969
OMIM	619934
DOID	DOID:0061041
UMLS	C5677008
MedGen	1802176
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, autosomal dominant 68 · mental retardation, autosomal dominant 68 · MRD68

Data availability: 39 ClinVar variants · 1 GenCC gene-disease record.

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 developmental disorder, autosomal dominant 68

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

39 retrieved; paginated sample, class counts are floors:

20 uncertain significance, 7 pathogenic, 5 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 likely benign, 1 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2499574	NM_014727.3(KMT2B):c.2937del (p.Ser980fs)	KMT2B	Pathogenic	criteria provided, single submitter
2506464	NM_014727.3(KMT2B):c.4999delinsTC (p.Ala1667fs)	KMT2B	Pathogenic	criteria provided, single submitter
2692577	NM_014727.3(KMT2B):c.5111dup (p.Arg1705fs)	KMT2B	Pathogenic	criteria provided, single submitter
3381835	NM_014727.3(KMT2B):c.4090del (p.Val1364fs)	KMT2B	Pathogenic	criteria provided, single submitter
450816	NM_014727.3(KMT2B):c.12_24dup (p.Ser9fs)	KMT2B	Pathogenic	criteria provided, multiple submitters, no conflicts
4531717	NM_014727.3(KMT2B):c.1545dup (p.Lys516fs)	KMT2B	Pathogenic	criteria provided, single submitter
817423	NM_014727.3(KMT2B):c.15_24dup (p.Ser9fs)	KMT2B	Pathogenic	criteria provided, multiple submitters, no conflicts
3381999	NM_014727.3(KMT2B):c.4202G>A (p.Trp1401Ter)	KMT2B	Likely pathogenic	criteria provided, single submitter
3382636	NM_014727.3(KMT2B):c.286_287del (p.Gly96fs)	KMT2B	Likely pathogenic	criteria provided, single submitter
3775217	NM_014727.3(KMT2B):c.6495G>A (p.Trp2165Ter)	KMT2B	Likely pathogenic	criteria provided, single submitter
4291701	NM_014727.3(KMT2B):c.5975dup (p.Asp1992fs)	KMT2B	Likely pathogenic	criteria provided, single submitter
4293924	NM_014727.3(KMT2B):c.1154del (p.Ala385fs)	KMT2B	Likely pathogenic	criteria provided, single submitter
2193260	NM_014727.3(KMT2B):c.3769C>T (p.Arg1257Cys)	KMT2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2484655	NM_014727.3(KMT2B):c.977G>A (p.Gly326Asp)	KMT2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
710483	NM_014727.3(KMT2B):c.398C>T (p.Ala133Val)	KMT2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2482954	NM_014727.3(KMT2B):c.2455C>T (p.Pro819Ser)	KMT2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2572971	NM_014727.3(KMT2B):c.5821G>A (p.Val1941Met)	KMT2B	Uncertain significance	criteria provided, single submitter
2574120	NM_014727.3(KMT2B):c.3743G>A (p.Arg1248His)	KMT2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2582490	NM_014727.3(KMT2B):c.5786C>T (p.Ala1929Val)	KMT2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2664431	NM_014727.3(KMT2B):c.7658+1G>T	KMT2B	Uncertain significance	criteria provided, single submitter
2672098	NM_014727.3(KMT2B):c.7187C>T (p.Pro2396Leu)	KMT2B	Uncertain significance	criteria provided, single submitter
3236568	NM_014727.3(KMT2B):c.6992T>C (p.Val2331Ala)	KMT2B	Uncertain significance	criteria provided, single submitter
3237502	NM_014727.3(KMT2B):c.3458C>G (p.Ser1153Cys)	KMT2B	Uncertain significance	criteria provided, single submitter
3238778	NM_014727.3(KMT2B):c.848G>T (p.Gly283Val)	KMT2B	Uncertain significance	criteria provided, single submitter
3376182	NM_014727.3(KMT2B):c.3053A>C (p.Lys1018Thr)	KMT2B	Uncertain significance	criteria provided, single submitter
3377653	NM_014727.3(KMT2B):c.4792C>G (p.Leu1598Val)	KMT2B	Uncertain significance	criteria provided, single submitter
3572540	NM_014727.3(KMT2B):c.6370C>T (p.Pro2124Ser)	KMT2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3583641	NM_014727.3(KMT2B):c.5452G>A (p.Glu1818Lys)	KMT2B	Uncertain significance	criteria provided, single submitter
3602747	NM_014727.3(KMT2B):c.7232G>T (p.Gly2411Val)	KMT2B	Uncertain significance	criteria provided, single submitter
3776063	NM_014727.3(KMT2B):c.5150G>A (p.Arg1717Gln)	KMT2B	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
KMT2B	Limited	Unknown	intellectual developmental disorder, autosomal dominant 68	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KMT2B	Orphanet:528084	Non-specific syndromic intellectual disability
KMT2B	Orphanet:589618	Dystonia 28

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
KMT2B	HGNC:15840	ENSG00000272333	Q9UMN6	Histone-lysine N-methyltransferase 2B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KMT2B	Histone-lysine N-methyltransferase 2B	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4) via a non-processive mechanism.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KMT2B	Transcription factor	no		SET_dom, Znf_PHD, Znf_CXXC

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
left testis	1
lower esophagus mucosa	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KMT2B	269	ubiquitous	marker	right testis, left testis, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KMT2B	2,639

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KMT2B	Q9UMN6	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Formation of WDR5-containing histone-modifying complexes	1	265.6×	0.015	KMT2B
Deactivation of the beta-catenin transactivating complex	1	233.1×	0.015	KMT2B
PKMTs methylate histone lysines	1	160.8×	0.015	KMT2B
Epigenetic regulation by WDR5-containing histone modifying complexes	1	154.3×	0.015	KMT2B
Transcriptional regulation by RUNX1	1	146.4×	0.015	KMT2B
Formation of the beta-catenin:TCF transactivating complex	1	120.2×	0.015	KMT2B
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.015	KMT2B
Chromatin organization	1	81.6×	0.018	KMT2B
Chromatin modifying enzymes	1	72.3×	0.018	KMT2B
Epigenetic regulation of gene expression	1	71.4×	0.018	KMT2B
RNA Polymerase II Transcription	1	22.5×	0.052	KMT2B
Gene expression (Transcription)	1	17.8×	0.061	KMT2B
Generic Transcription Pathway	1	15.1×	0.066	KMT2B

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
methylation	1	170.2×	0.012	KMT2B
positive regulation of DNA-templated transcription	1	27.9×	0.036	KMT2B

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KMT2B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KMT2B	15	Binding:15

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	KMT2B

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)
KMT2B	15	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.