Intellectual developmental disorder, autosomal dominant 70

Summary

Intellectual developmental disorder, autosomal dominant 70 (MONDO:0859333) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal dominant 70
Mondo ID	MONDO:0859333
OMIM	620157
DOID	DOID:0061043
UMLS	C5774271
MedGen	1824044
Is cancer (heuristic)	no

Data availability: 20 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 70

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, intellectual developmental disorder, autosomal dominant 68, autosomal dominant syndromic intellectual disability, 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

20 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 7 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1338780	NM_014159.7(SETD2):c.5219G>A (p.Arg1740Gln)	SETD2	Pathogenic	criteria provided, single submitter
3024480	NC_000010.11:g.(?59792917)(68231677_?)del	LOC126860947	Likely pathogenic	criteria provided, single submitter
1337950	NM_014159.7(SETD2):c.3168G>A (p.Ser1056=)	SETD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135240	NM_014159.7(SETD2):c.4262T>C (p.Leu1421Pro)	SETD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1800819	NM_014159.7(SETD2):c.79G>C (p.Glu27Gln)	SETD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3892409	NM_014159.7(SETD2):c.2210T>C (p.Met737Thr)	SETD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
475534	NM_014159.7(SETD2):c.664C>A (p.Leu222Ile)	SETD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
833850	NM_014159.7(SETD2):c.3026T>C (p.Met1009Thr)	SETD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
965125	NM_014159.7(SETD2):c.1523G>T (p.Gly508Val)	SETD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1057214	NM_014159.7(SETD2):c.1202G>A (p.Arg401Gln)	SETD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1334579	NM_014159.7(SETD2):c.435G>C (p.Lys145Asn)	SETD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2047164	NM_014159.7(SETD2):c.796C>T (p.His266Tyr)	SETD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2500086	NM_014159.7(SETD2):c.2589T>A (p.Ser863=)	SETD2	Uncertain significance	criteria provided, single submitter
3024481	NM_014159.7(SETD2):c.4612T>A (p.Tyr1538Asn)	SETD2	Uncertain significance	criteria provided, single submitter
3341384	NM_014159.7(SETD2):c.3169G>A (p.Asp1057Asn)	SETD2	Uncertain significance	criteria provided, single submitter
3367205	NM_014159.7(SETD2):c.4840-1G>A	SETD2	Uncertain significance	criteria provided, single submitter
3370399	NM_014159.7(SETD2):c.4427T>C (p.Ile1476Thr)	SETD2	Uncertain significance	criteria provided, single submitter
3892410	NM_014159.7(SETD2):c.5369G>A (p.Arg1790Gln)	SETD2	Uncertain significance	criteria provided, single submitter
4813561	NM_014159.7(SETD2):c.7256C>G (p.Pro2419Arg)	SETD2	Uncertain significance	criteria provided, single submitter
758127	NM_014159.7(SETD2):c.3621T>C (p.Ser1207=)	SETD2	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
SETD2	Strong	Autosomal dominant	SETD2-related microcephaly-severe intellectual disability-multiple congenital anomalies syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SETD2	Orphanet:597738	Luscan-Lumish syndrome
SETD2	Orphanet:597743	SETD2-related microcephaly-severe intellectual disability-multiple congenital anomalies syndrome

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
SETD2	HGNC:18420	ENSG00000181555	Q9BYW2	Histone-lysine N-methyltransferase SETD2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SETD2	Histone-lysine N-methyltransferase SETD2	Histone methyltransferase that specifically trimethylates ‘Lys-36’ of histone H3 (H3K36me3) using dimethylated ‘Lys-36’ (H3K36me2) as substrate.

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)
SETD2	Scaffold/PPI	no	2.1.1.359	WW_dom, SET_dom, Post-SET_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
colonic epithelium	1
endothelial cell	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SETD2	291	ubiquitous	marker	tendon of biceps brachii, endothelial cell, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SETD2	4,668

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SETD2	Q9BYW2	43

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
PKMTs methylate histone lysines	1	160.8×	0.014	SETD2
Chromatin organization	1	81.6×	0.014	SETD2
Chromatin modifying enzymes	1	72.3×	0.014	SETD2

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 protein localization to chromatin	1	5617.3×	0.002	SETD2
microtubule cytoskeleton organization involved in mitosis	1	4213.0×	0.002	SETD2
peptidyl-lysine trimethylation	1	2808.7×	0.002	SETD2
nucleosome organization	1	2808.7×	0.002	SETD2
regulation of mRNA export from nucleus	1	2106.5×	0.002	SETD2
response to type I interferon	1	1872.4×	0.002	SETD2
response to metal ion	1	1532.0×	0.002	SETD2
response to alkaloid	1	1532.0×	0.002	SETD2
regulation of double-strand break repair via homologous recombination	1	991.3×	0.002	SETD2
positive regulation of ossification	1	936.2×	0.002	SETD2
mismatch repair	1	648.1×	0.003	SETD2
positive regulation of interferon-alpha production	1	648.1×	0.003	SETD2
endodermal cell differentiation	1	495.6×	0.003	SETD2
transcription elongation by RNA polymerase II	1	443.5×	0.003	SETD2
regulation of cytokinesis	1	421.3×	0.003	SETD2
stem cell differentiation	1	300.9×	0.004	SETD2
positive regulation of autophagy	1	208.1×	0.006	SETD2
regulation of gene expression	1	83.4×	0.013	SETD2
defense response to virus	1	69.3×	0.015	SETD2
regulation of DNA-templated transcription	1	31.6×	0.032	SETD2

Therapeutics

Drug target analysis

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

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
SETD2	3	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SINEFUNGIN	2	SETD2
MOLIBRESIB	2	SETD2
EZM-0414	1	SETD2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SETD2	64	Binding:64

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SETD2	2.1.1.359	[histone H3]-lysine36 N-trimethyltransferase

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

3 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.

Compound	Max phase	Cohort target (bioactivity)
SINEFUNGIN	2	SETD2
MOLIBRESIB	2	SETD2
EZM-0414	1	SETD2

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	1	SETD2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.