Intellectual disability, autosomal dominant 39

Summary

Intellectual disability, autosomal dominant 39 (MONDO:0014678) is a disease caused by MYT1L (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: MYT1L (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 118

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 39
Mondo ID	MONDO:0014678
OMIM	616521
DOID	DOID:0070069
UMLS	C4225296
MedGen	909304
GARD	0027861
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 39 · autosomal dominant non-syndromic intellectual disability caused by mutation in MYT1L · intellectual developmental disorder, autosomal dominant 39 · intellectual disability, autosomal dominant 39 · intellectual disability, autosomal dominant type 39 · mental retardation, autosomal dominant 39 · mental retardation, autosomal dominant type 39 · MRD39 · MYT1L autosomal dominant non-syndromic intellectual disability

Data availability: 118 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

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 39

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 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

118 retrieved; paginated sample, class counts are floors:

41 uncertain significance, 27 pathogenic, 26 likely pathogenic, 7 pathogenic/likely pathogenic, 6 conflicting classifications of pathogenicity, 4 benign, 4 not provided, 2 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1330210	GRCh37/hg19 2p25.3(chr2:10501-2386917)x1	ACP1	Pathogenic	criteria provided, single submitter
2671972	GRCh37/hg19 2p25.3(chr2:12770-2832894)x1	ACP1	Pathogenic	no assertion criteria provided
1064796	NM_001303052.2(MYT1L):c.1807del (p.Arg603fs)	MYT1L	Pathogenic	criteria provided, multiple submitters, no conflicts
1700213	NM_001303052.2(MYT1L):c.591C>G (p.Tyr197Ter)	MYT1L	Pathogenic	criteria provided, single submitter
1802188	NM_001303052.2(MYT1L):c.2821C>T (p.Gln941Ter)	MYT1L	Pathogenic	criteria provided, single submitter
208428	NM_001303052.2(MYT1L):c.2642+1G>A	MYT1L	Pathogenic	criteria provided, multiple submitters, no conflicts
208429	NM_001303052.2(MYT1L):c.1923T>G (p.Tyr641Ter)	MYT1L	Pathogenic	no assertion criteria provided
235469	NM_001303052.2(MYT1L):c.1706G>A (p.Arg569Gln)	MYT1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2429945	NM_001303052.2(MYT1L):c.2677C>T (p.Arg893Ter)	MYT1L	Pathogenic	criteria provided, single submitter
2572327	NM_001303052.2(MYT1L):c.1996C>T (p.Gln666Ter)	MYT1L	Pathogenic	criteria provided, single submitter
2575086	NM_001303052.2(MYT1L):c.1532G>A (p.Cys511Tyr)	MYT1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2637811	NM_001303052.2(MYT1L):c.165T>A (p.Cys55Ter)	MYT1L	Pathogenic	criteria provided, single submitter
280701	NM_001303052.2(MYT1L):c.1705C>T (p.Arg569Ter)	MYT1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280803	NM_001303052.2(MYT1L):c.2123dup (p.Ser709fs)	MYT1L	Pathogenic	criteria provided, single submitter
3024337	NM_001303052.2(MYT1L):c.982G>T (p.Glu328Ter)	MYT1L	Pathogenic	criteria provided, single submitter
3255172	NM_001303052.2(MYT1L):c.377del (p.Glu126fs)	MYT1L	Pathogenic	criteria provided, single submitter
3382527	NM_001303052.2(MYT1L):c.4G>T (p.Glu2Ter)	MYT1L	Pathogenic	criteria provided, single submitter
3383976	NM_001303052.2(MYT1L):c.1543_1561dup (p.Tyr521fs)	MYT1L	Pathogenic	criteria provided, single submitter
3778755	NM_001303052.2(MYT1L):c.1586G>A (p.Gly529Glu)	MYT1L	Pathogenic	criteria provided, single submitter
4056327	NM_001303052.2(MYT1L):c.3086C>G (p.Ser1029Ter)	MYT1L	Pathogenic	criteria provided, single submitter
4056440	NM_001303052.2(MYT1L):c.2775-2A>T	MYT1L	Pathogenic	criteria provided, single submitter
4531803	NM_001303052.2(MYT1L):c.2845dup (p.Gln949fs)	MYT1L	Pathogenic	criteria provided, single submitter
4684982	NM_001303052.2(MYT1L):c.2515_2518dup (p.Thr840fs)	MYT1L	Pathogenic	criteria provided, single submitter
4818979	NM_001303052.2(MYT1L):c.2395C>T (p.Gln799Ter)	MYT1L	Pathogenic	criteria provided, single submitter
488449	NM_001303052.2(MYT1L):c.760dup (p.Asp254fs)	MYT1L	Pathogenic	no assertion criteria provided
592088	NM_001303052.2(MYT1L):c.1585G>A (p.Gly529Arg)	MYT1L	Pathogenic	criteria provided, multiple submitters, no conflicts
617454	NM_001303052.2(MYT1L):c.2221_2230del (p.Thr741fs)	MYT1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
633566	NM_001303052.2(MYT1L):c.535C>T (p.Arg179Ter)	MYT1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973241	NM_001303052.2(MYT1L):c.1682T>A (p.Val561Asp)	MYT1L	Pathogenic	criteria provided, single submitter
973249	NM_001303052.2(MYT1L):c.1968T>A (p.Tyr656Ter)	MYT1L	Pathogenic	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
MYT1L	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 39	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYT1L	Orphanet:647799	MYT1L-related developmental delay-intellectual disability-obesity syndrome
MYT1L	Orphanet:699850	2p25.3 microduplication syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYT1L	HGNC:7623	ENSG00000186487	Q9UL68	Myelin transcription factor 1-like protein	gencc,clinvar
ACP1	HGNC:122	ENSG00000143727	P24666	Low molecular weight phosphotyrosine protein phosphatase	clinvar
NDUFAB1	HGNC:7694	ENSG00000004779	O14561	Acyl carrier protein, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYT1L	Myelin transcription factor 1-like protein	Transcription factor that plays a key role in neuronal differentiation by specifically repressing expression of non-neuronal genes during neuron differentiation.
ACP1	Low molecular weight phosphotyrosine protein phosphatase	Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates with differences in substrate specificity between isoform 1 and isoform 2.
NDUFAB1	Acyl carrier protein, mitochondrial	Carrier of the growing fatty acid chain in fatty acid biosynthesis.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Enzyme (other)	1	4.0×	0.482
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYT1L	Transcription factor	no		Znf_C2H2C, Myelin_TF, Znf_C2H2C_sf
ACP1	Enzyme (other)	yes	3.1.3.48	Tyr_Pase_low_mol_wt_mml, Tyr_phospatase_low_mol_wt, Ptyr_pPase
NDUFAB1	Other/Unknown	no		ACP, Ppantetheine_attach_site, PP-bd_ACP

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
cortical plate	1
endothelial cell	1
adrenal tissue	1
male germ cell	1
sperm	1
heart right ventricle	1
left ventricle myocardium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYT1L	192	tissue_specific	marker	endothelial cell, cortical plate, Brodmann (1909) area 23
ACP1	299	ubiquitous	marker	sperm, adrenal tissue, male germ cell
NDUFAB1	298	ubiquitous	marker	heart right ventricle, left ventricle myocardium, myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDUFAB1	5,533
ACP1	2,752
MYT1L	2,037

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDUFAB1	O14561	42
ACP1	P24666	17

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYT1L	Q9UL68	55.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 3 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
Protein lipoylation	1	1038.2×	0.011	NDUFAB1
Mitochondrial Fatty Acid Beta-Oxidation	1	380.7×	0.014	NDUFAB1
Complex I biogenesis	1	165.5×	0.018	NDUFAB1
Fatty acid metabolism	1	131.3×	0.018	NDUFAB1
Mitochondrial ribosome-associated quality control	1	122.8×	0.018	NDUFAB1
Respiratory electron transport	1	95.2×	0.018	NDUFAB1
Aerobic respiration and respiratory electron transport	1	88.5×	0.018	NDUFAB1
Metabolism of lipids	1	31.6×	0.044	NDUFAB1
Post-translational protein modification	1	19.2×	0.064	NDUFAB1
Metabolism of proteins	1	12.4×	0.086	NDUFAB1
Metabolism	1	11.6×	0.086	NDUFAB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein lipoylation	1	802.5×	0.013	NDUFAB1
[2Fe-2S] cluster assembly	1	468.1×	0.013	NDUFAB1
mitochondrial large ribosomal subunit assembly	1	330.4×	0.013	NDUFAB1
neuron fate commitment	1	267.5×	0.013	MYT1L
neuron fate specification	1	234.1×	0.013	MYT1L
iron-sulfur cluster assembly	1	200.6×	0.013	NDUFAB1
mitochondrial electron transport, NADH to ubiquinone	1	119.5×	0.017	NDUFAB1
fatty acid biosynthetic process	1	117.0×	0.017	NDUFAB1
proton motive force-driven mitochondrial ATP synthesis	1	87.8×	0.018	NDUFAB1
neuron development	1	85.1×	0.018	MYT1L
aerobic respiration	1	82.6×	0.018	NDUFAB1
neuron differentiation	1	33.4×	0.039	MYT1L
chemical synaptic transmission	1	25.8×	0.047	ACP1
nervous system development	1	15.3×	0.073	MYT1L
negative regulation of transcription by RNA polymerase II	1	5.9×	0.171	MYT1L
regulation of transcription by RNA polymerase II	1	3.9×	0.236	MYT1L

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACP1	2	3
MYT1L	0	0
NDUFAB1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRIDOXAL PHOSPHATE ANHYDROUS	3	ACP1
URSOLIC ACID	2	ACP1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ACP1	84	Binding:80, Functional:4
NDUFAB1	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ACP1	3.1.3.48	protein-tyrosine-phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 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)
PYRIDOXAL PHOSPHATE ANHYDROUS	3	ACP1
URSOLIC ACID	2	ACP1

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	ACP1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	MYT1L, NDUFAB1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYT1L	0	—
NDUFAB1	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.