Intellectual disability, autosomal dominant 13

Summary

Intellectual disability, autosomal dominant 13 (MONDO:0013805) is a disease caused by DYNC1H1 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: DYNC1H1 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 239

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 13
Mondo ID	MONDO:0013805
OMIM	614563
DOID	DOID:0061144, DOID:0070043
UMLS	C3281202
MedGen	482832
GARD	0016462
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 13 · autosomal dominant non-syndromic intellectual disability caused by mutation in DYNC1H1 · DYNC1H1 autosomal dominant non-syndromic intellectual disability · intellectual disability, autosomal dominant 13 · intellectual disability, autosomal dominant 13, with neuronal migration defects · intellectual disability, autosomal dominant type 13 · mental retardation, autosomal dominant 13 · mental retardation, autosomal dominant type 13 · mental retardation, autosomal dominant, 13, with neuronal migration defects · MRD13

Data availability: 239 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › autosomal dominant syndromic intellectual disability › intellectual disability, autosomal dominant 13

Related subtypes (33): Myhre syndrome, KBG syndrome, Rubinstein-Taybi syndrome due to CREBBP mutations, Mowat-Wilson syndrome, Schinzel-Giedion syndrome, intellectual disability-sparse hair-brachydactyly syndrome, Pierpont syndrome, Bohring-Opitz syndrome, hereditary cryohydrocytosis with reduced stomatin, intellectual disability-severe speech delay-mild dysmorphism syndrome, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency, DYRK1A-related intellectual disability syndrome, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, CTCF-related neurodevelopmental disorder, Bosch-Boonstra-Schaaf optic atrophy syndrome, autism spectrum disorder due to AUTS2 deficiency, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, intellectual developmental disorder with dysmorphic facies and ptosis, intellectual disability, autosomal dominant 48, SETD2-related microcephaly-severe intellectual disability-multiple congenital anomalies syndrome, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, SIN3A-related intellectual disability syndrome, Ververi-Brady syndrome 1, intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities, SATB2 associated disorder

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

239 retrieved; paginated sample, class counts are floors:

91 uncertain significance, 59 conflicting classifications of pathogenicity, 35 likely pathogenic, 13 benign/likely benign, 11 pathogenic/likely pathogenic, 10 benign, 10 likely benign, 10 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1075692	NM_001376.5(DYNC1H1):c.1739A>C (p.Glu580Ala)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1298386	NM_001376.5(DYNC1H1):c.10016G>A (p.Arg3339His)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1359385	NM_001376.5(DYNC1H1):c.11015C>T (p.Ser3672Leu)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
139652	NM_001376.5(DYNC1H1):c.1792C>T (p.Arg598Cys)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1700199	NM_001376.5(DYNC1H1):c.8234C>A (p.Thr2745Lys)	DYNC1H1	Pathogenic	criteria provided, single submitter
208709	NM_001376.5(DYNC1H1):c.4700G>A (p.Arg1567Gln)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208734	NM_001376.5(DYNC1H1):c.9754AAG[2] (p.Lys3254del)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
209107	NM_001376.5(DYNC1H1):c.926G>A (p.Arg309His)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
209108	NM_001376.5(DYNC1H1):c.1706G>C (p.Arg569Pro)	DYNC1H1	Pathogenic/Likely pathogenic	no assertion criteria provided
224130	NM_001376.5(DYNC1H1):c.10573C>T (p.Arg3525Cys)	DYNC1H1	Pathogenic	criteria provided, multiple submitters, no conflicts
2579938	NM_001376.5(DYNC1H1):c.4867C>T (p.Arg1623Trp)	DYNC1H1	Pathogenic	criteria provided, multiple submitters, no conflicts
3358996	NM_001376.5(DYNC1H1):c.10975dup (p.Arg3659fs)	DYNC1H1	Pathogenic	criteria provided, single submitter
372934	NM_001376.5(DYNC1H1):c.2327C>T (p.Pro776Leu)	DYNC1H1	Pathogenic	criteria provided, multiple submitters, no conflicts
374190	NM_001376.5(DYNC1H1):c.6994C>T (p.Arg2332Cys)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
424046	NM_001376.5(DYNC1H1):c.4868G>A (p.Arg1623Gln)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449962	NM_001376.5(DYNC1H1):c.3278T>C (p.Phe1093Ser)	DYNC1H1	Pathogenic	criteria provided, multiple submitters, no conflicts
472535	NM_001376.5(DYNC1H1):c.4532C>T (p.Pro1511Leu)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
55854	NM_001376.5(DYNC1H1):c.10151G>A (p.Arg3384Gln)	DYNC1H1	Pathogenic	criteria provided, multiple submitters, no conflicts
55855	NM_001376.5(DYNC1H1):c.10031G>A (p.Arg3344Gln)	DYNC1H1	Pathogenic	criteria provided, multiple submitters, no conflicts
800542	NM_001376.5(DYNC1H1):c.874C>T (p.Arg292Trp)	DYNC1H1	Pathogenic	criteria provided, multiple submitters, no conflicts
975382	NM_001376.5(DYNC1H1):c.3781T>G (p.Trp1261Gly)	DYNC1H1	Pathogenic	no assertion criteria provided
1033420	NM_001376.5(DYNC1H1):c.7474C>T (p.Arg2492Ter)	DYNC1H1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065624	NM_001376.5(DYNC1H1):c.9751G>A (p.Glu3251Lys)	DYNC1H1	Likely pathogenic	criteria provided, single submitter
1251929	NM_001376.5(DYNC1H1):c.2868+2_2868+5delinsCCACAAA	DYNC1H1	Likely pathogenic	criteria provided, single submitter
1320087	NM_001376.5(DYNC1H1):c.12214G>T (p.Gly4072Cys)	DYNC1H1	Likely pathogenic	criteria provided, single submitter
1320210	NM_001376.5(DYNC1H1):c.7145_7148dup (p.Ser2384fs)	DYNC1H1	Likely pathogenic	criteria provided, single submitter
1334533	NM_001376.5(DYNC1H1):c.9547dup (p.Tyr3183fs)	DYNC1H1	Likely pathogenic	criteria provided, single submitter
1697224	NM_001376.5(DYNC1H1):c.9055G>A (p.Gly3019Ser)	DYNC1H1	Likely pathogenic	criteria provided, single submitter
1708257	NM_001376.5(DYNC1H1):c.6872T>G (p.Val2291Gly)	DYNC1H1	Likely pathogenic	criteria provided, single submitter
210861	NM_001376.5(DYNC1H1):c.11183G>C (p.Arg3728Pro)	DYNC1H1	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 5 · 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
DYNC1H1	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 13	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DYNC1H1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
DYNC1H1	Orphanet:209341	DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy
DYNC1H1	Orphanet:284232	Autosomal dominant Charcot-Marie-Tooth disease type 2O
MED13	Orphanet:528084	Non-specific syndromic intellectual disability
HIVEP2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

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
DYNC1H1	HGNC:2961	ENSG00000197102	Q14204	Cytoplasmic dynein 1 heavy chain 1	gencc,clinvar
MED13	HGNC:22474	ENSG00000108510	Q9UHV7	Mediator of RNA polymerase II transcription subunit 13	clinvar
HIVEP2	HGNC:4921	ENSG00000010818	P31629	Transcription factor HIVEP2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DYNC1H1	Cytoplasmic dynein 1 heavy chain 1	Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules.
MED13	Mediator of RNA polymerase II transcription subunit 13	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
HIVEP2	Transcription factor HIVEP2	This protein specifically binds to the DNA sequence 5’-GGGACTTTCC-3’ which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DYNC1H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
MED13	Other/Unknown	no		Med13_C, MID_MedPIWI, Mediator_complx_sub13
HIVEP2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf,

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
cortical plate	1
ganglionic eminence	1
ventricular zone	1
endothelial cell	1
germinal epithelium of ovary	1
visceral pleura	1
lateral nuclear group of thalamus	1
tendon of biceps brachii	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DYNC1H1	290	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
MED13	295	ubiquitous	marker	endothelial cell, visceral pleura, germinal epithelium of ovary
HIVEP2	296	ubiquitous	marker	tendon of biceps brachii, vena cava, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DYNC1H1	4,215
MED13	1,956
HIVEP2	1,489

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYNC1H1	Q14204	97
MED13	Q9UHV7	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HIVEP2	P31629	36.43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Aggrephagy	1	124.1×	0.036	DYNC1H1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	107.7×	0.036	MED13
COPI-independent Golgi-to-ER retrograde traffic	1	103.8×	0.036	DYNC1H1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	98.5×	0.036	MED13
Respiratory Syncytial Virus Infection Pathway	1	98.5×	0.036	MED13
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	96.8×	0.036	DYNC1H1
Loss of Nlp from mitotic centrosomes	1	79.3×	0.036	DYNC1H1
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.036	DYNC1H1
RSV-host interactions	1	78.2×	0.036	MED13
Adipogenesis	1	78.2×	0.036	MED13
Epigenetic regulation by WDR5-containing histone modifying complexes	1	77.2×	0.036	MED13
AURKA Activation by TPX2	1	76.1×	0.036	DYNC1H1
Regulation of lipid metabolism by PPARalpha	1	70.5×	0.036	MED13
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.036	DYNC1H1
Transcriptional regulation of white adipocyte differentiation	1	64.9×	0.036	MED13
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.036	DYNC1H1
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	58.3×	0.036	DYNC1H1
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.036	DYNC1H1
Anchoring of the basal body to the plasma membrane	1	56.5×	0.036	DYNC1H1
COPI-mediated anterograde transport	1	54.9×	0.036	DYNC1H1
PPARA activates gene expression	1	47.2×	0.038	MED13
EML4 and NUDC in mitotic spindle formation	1	46.4×	0.038	DYNC1H1
MHC class II antigen presentation	1	44.6×	0.038	DYNC1H1
Resolution of Sister Chromatid Cohesion	1	43.3×	0.038	DYNC1H1
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	41.4×	0.038	MED13
HCMV Early Events	1	40.5×	0.038	DYNC1H1
RHO GTPases Activate Formins	1	38.8×	0.038	DYNC1H1
Epigenetic regulation of gene expression	1	35.7×	0.040	MED13
Mitotic Prometaphase	1	34.6×	0.040	DYNC1H1
Separation of Sister Chromatids	1	30.4×	0.044	DYNC1H1

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
regulation of metaphase plate congression	1	1123.5×	0.008	DYNC1H1
establishment of spindle localization	1	936.2×	0.008	DYNC1H1
positive regulation of spindle assembly	1	702.2×	0.008	DYNC1H1
positive regulation of intracellular transport	1	561.7×	0.008	DYNC1H1
retrograde axonal transport	1	510.7×	0.008	DYNC1H1
P-body assembly	1	351.1×	0.009	DYNC1H1
regulation of mitotic spindle organization	1	280.9×	0.010	DYNC1H1
nuclear migration	1	244.2×	0.010	DYNC1H1
stress granule assembly	1	200.6×	0.011	DYNC1H1
triglyceride homeostasis	1	160.5×	0.012	MED13
cytoplasmic microtubule organization	1	114.6×	0.016	DYNC1H1
mitotic spindle organization	1	90.6×	0.017	DYNC1H1
positive regulation of transcription initiation by RNA polymerase II	1	90.6×	0.017	MED13
positive regulation of cold-induced thermogenesis	1	54.5×	0.025	DYNC1H1
cholesterol homeostasis	1	52.0×	0.025	MED13
cell division	1	15.4×	0.079	DYNC1H1
positive regulation of DNA-templated transcription	1	9.3×	0.122	MED13
negative regulation of transcription by RNA polymerase II	1	5.9×	0.178	MED13
positive regulation of transcription by RNA polymerase II	1	5.0×	0.198	MED13
regulation of transcription by RNA polymerase II	1	3.9×	0.236	HIVEP2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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
DYNC1H1	1	2
MED13	0	0
HIVEP2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	DYNC1H1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
DYNC1H1	7	Binding:7
HIVEP2	1	Binding:1

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

1 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)
MOLIBRESIB	2	DYNC1H1

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	DYNC1H1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	MED13, HIVEP2

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)
MED13	0	—
HIVEP2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.