Intellectual developmental disorder, autosomal dominant 76

Summary

Intellectual developmental disorder, autosomal dominant 76 (MONDO:0979575) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal dominant 76
Mondo ID	MONDO:0979575
OMIM	621285
UMLS	C6012756
MedGen	1876508
Is cancer (heuristic)	no

Data availability: 16 ClinVar variants.

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 76

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 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

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

16 retrieved; paginated sample, class counts are floors:

8 pathogenic, 6 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3253625	NM_001039469.3(MARK2):c.812del (p.Phe271fs)	MARK2	Pathogenic	no assertion criteria provided
3253639	NM_001039469.3(MARK2):c.2168_2169del (p.Cys723fs)	MARK2	Pathogenic	no assertion criteria provided
3253640	NM_001039469.3(MARK2):c.2239C>T (p.Gln747Ter)	MARK2	Pathogenic	no assertion criteria provided
3253643	NM_001039469.3(MARK2):c.239C>T (p.Ala80Val)	MARK2	Pathogenic/Likely pathogenic	no assertion criteria provided
3253646	NM_001039469.3(MARK2):c.337+1G>T	MARK2	Pathogenic	criteria provided, single submitter
4071509	c.1514+2G-T	MARK2	Pathogenic	no assertion criteria provided
4071510	MARK2, EX2-19DEL	MARK2	Pathogenic	no assertion criteria provided
4819133	NM_001039469.3(MARK2):c.1737_1738dup (p.Gly580fs)	MARK2	Pathogenic	criteria provided, single submitter
4845390	NM_001039469.3(MARK2):c.800dup (p.Tyr267Ter)	MARK2	Pathogenic	criteria provided, single submitter
3253647	NM_001039469.3(MARK2):c.403G>A (p.Gly135Arg)	MARK2	Likely pathogenic	criteria provided, single submitter
3900984	NM_001039469.3(MARK2):c.645_646insA (p.Ala216fs)	MARK2	Uncertain significance	criteria provided, single submitter
4795137	NM_001039469.3(MARK2):c.1230C>G (p.Asp410Glu)	MARK2	Uncertain significance	criteria provided, single submitter
4819716	NM_001039469.3(MARK2):c.652C>T (p.Pro218Ser)	MARK2	Uncertain significance	criteria provided, single submitter
4819885	NM_001039469.3(MARK2):c.769-222C>T	MARK2	Uncertain significance	criteria provided, single submitter
4845343	NM_001039469.3(MARK2):c.740C>T (p.Ser247Phe)	MARK2	Uncertain significance	criteria provided, single submitter
982301	NM_001039469.3(MARK2):c.904C>T (p.Arg302Ter)	MARK2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
MARK2	HGNC:3332	ENSG00000072518	Q7KZI7	Serine/threonine-protein kinase MARK2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MARK2	Serine/threonine-protein kinase MARK2	Serine/threonine-protein kinase.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MARK2	Kinase	yes		Prot_kinase_dom, KA1_dom, Ser/Thr_kinase_AS

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
esophagus mucosa	1
granulocyte	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MARK2	188	ubiquitous	marker	lower esophagus mucosa, granulocyte, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MARK2	2,461

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MARK2	Q7KZI7	5

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 neurofibrillary tangle assembly	1	5617.3×	0.002	MARK2
establishment or maintenance of cell polarity regulating cell shape	1	4213.0×	0.002	MARK2
mitochondrion localization	1	1685.2×	0.003	MARK2
regulation of axonogenesis	1	887.0×	0.004	MARK2
autophagy of mitochondrion	1	732.7×	0.004	MARK2
regulation of cytoskeleton organization	1	648.1×	0.004	MARK2
establishment or maintenance of epithelial cell apical/basal polarity	1	581.1×	0.004	MARK2
regulation of microtubule cytoskeleton organization	1	543.6×	0.004	MARK2
axon development	1	455.5×	0.004	MARK2
establishment of cell polarity	1	383.0×	0.004	MARK2
protein autophosphorylation	1	145.3×	0.010	MARK2
positive regulation of neuron projection development	1	137.0×	0.010	MARK2
neuron migration	1	133.8×	0.010	MARK2
microtubule cytoskeleton organization	1	121.2×	0.010	MARK2
Wnt signaling pathway	1	99.7×	0.011	MARK2
protein phosphorylation	1	68.0×	0.016	MARK2
intracellular signal transduction	1	38.1×	0.026	MARK2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MARK2	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MARK2	45	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	MARK2
FEDRATINIB	4	MARK2
RUXOLITINIB	4	MARK2
BARICITINIB	4	MARK2
TOFACITINIB	4	MARK2
BRIGATINIB	4	MARK2
NINTEDANIB	4	MARK2
SUNITINIB	4	MARK2
MIDOSTAURIN	4	MARK2
CRENOLANIB	3	MARK2
LINIFANIB	3	MARK2
DEFACTINIB	3	MARK2
RIPASUDIL	3	MARK2
DOVITINIB	3	MARK2
LESTAURTINIB	3	MARK2
RUBOXISTAURIN	3	MARK2
DORAMAPIMOD	2	MARK2
SILMITASERTIB	2	MARK2
SU-014813	2	MARK2
CENISERTIB	2	MARK2
ILORASERTIB	2	MARK2
OSI-632	2	MARK2
DECERNOTINIB	2	MARK2
NARAZACICLIB	2	MARK2
UPROSERTIB	2	MARK2
BMS-690514	2	MARK2
DANUSERTIB	2	MARK2
CERDULATINIB	2	MARK2
R-406	2	MARK2
AT-9283	2	MARK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MARK2	356	Binding:355, Functional:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MARK2	356

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

30 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)
MOMELOTINIB	4	MARK2
FEDRATINIB	4	MARK2
RUXOLITINIB	4	MARK2
BARICITINIB	4	MARK2
TOFACITINIB	4	MARK2
BRIGATINIB	4	MARK2
NINTEDANIB	4	MARK2
SUNITINIB	4	MARK2
MIDOSTAURIN	4	MARK2
CRENOLANIB	3	MARK2
LINIFANIB	3	MARK2
DEFACTINIB	3	MARK2
RIPASUDIL	3	MARK2
DOVITINIB	3	MARK2
LESTAURTINIB	3	MARK2
RUBOXISTAURIN	3	MARK2
DORAMAPIMOD	2	MARK2
SILMITASERTIB	2	MARK2
SU-014813	2	MARK2
CENISERTIB	2	MARK2
ILORASERTIB	2	MARK2
OSI-632	2	MARK2
DECERNOTINIB	2	MARK2
NARAZACICLIB	2	MARK2
UPROSERTIB	2	MARK2
BMS-690514	2	MARK2
DANUSERTIB	2	MARK2
CERDULATINIB	2	MARK2
R-406	2	MARK2
AT-9283	2	MARK2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MARK2
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	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.