Intellectual developmental disorder 61

Summary

Intellectual developmental disorder 61 (MONDO:0032485) is a disease caused by MED13 (GenCC Definitive), with 4 cohort genes.

At a glance

• Causal gene: MED13 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 122

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder 61
Mondo ID	MONDO:0032485
OMIM	618009
DOID	DOID:0061034
UMLS	C5231400
MedGen	1684867
GARD	0018514
Is cancer (heuristic)	no

Also known as: MRD61

Data availability: 122 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › autosomal dominant non-syndromic intellectual disability › intellectual developmental disorder 61

Related subtypes (25): intellectual disability, autosomal dominant 22, neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language, intellectual disability, autosomal dominant 33, intellectual disability, autosomal dominant 34, intellectual disability, autosomal dominant 41, intellectual disability, autosomal dominant 43, intellectual disability, autosomal dominant 58, intellectual disability, autosomal dominant 45, intellectual disability, autosomal dominant 46, intellectual disability, autosomal dominant 47, Clark-Baraitser syndrome, intellectual disability, autosomal dominant 50, intellectual disability, autosomal dominant 51, intellectual disability, autosomal dominant 52, intellectual disability, autosomal dominant 53, intellectual disability, autosomal dominant 54, intellectual disability, autosomal dominant 55, with seizures, intellectual disability, autosomal dominant 56, intellectual developmental disorder 59, intellectual developmental disorder 60 with seizures, intellectual developmental disorder 62, intellectual developmental disorder, autosomal dominant 63, with macrocephaly, Coffin-Siris syndrome 6, intellectual disability, autosomal dominant 57, intellectual developmental disorder, autosomal dominant 73

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

122 retrieved; paginated sample, class counts are floors:

76 uncertain significance, 15 likely pathogenic, 14 pathogenic, 9 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 2 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1698767	NM_005121.3(MED13):c.2524C>T (p.Gln842Ter)	MED13	Pathogenic	criteria provided, single submitter
1699136	NM_005121.3(MED13):c.712C>T (p.Gln238Ter)	MED13	Pathogenic	criteria provided, single submitter
1700230	NM_005121.3(MED13):c.4191+1G>A	MED13	Pathogenic	criteria provided, single submitter
1700231	NM_005121.3(MED13):c.5683_5684del (p.Met1895fs)	MED13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1708262	NM_005121.3(MED13):c.2593_2594del (p.Gly865fs)	MED13	Pathogenic	criteria provided, single submitter
1803503	NM_005121.3(MED13):c.2503C>T (p.Pro835Ser)	MED13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2500279	NM_005121.3(MED13):c.4417_4418del (p.Leu1473fs)	MED13	Pathogenic	criteria provided, single submitter
2572179	NM_005121.3(MED13):c.1513C>T (p.Gln505Ter)	MED13	Pathogenic	criteria provided, single submitter
3391180	NM_005121.3(MED13):c.2489T>G (p.Leu830Arg)	MED13	Pathogenic	criteria provided, single submitter
3391500	NM_005121.3(MED13):c.2501A>G (p.Tyr834Cys)	MED13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3602571	NM_005121.3(MED13):c.5405G>A (p.Trp1802Ter)	MED13	Pathogenic	criteria provided, single submitter
3629476	NM_005121.3(MED13):c.1987_1999del (p.Lys663fs)	MED13	Pathogenic	criteria provided, single submitter
4526888	NM_005121.3(MED13):c.1856dup (p.Phe620fs)	MED13	Pathogenic	criteria provided, single submitter
620176	NM_005121.3(MED13):c.1745T>A (p.Leu582Ter)	MED13	Pathogenic	criteria provided, single submitter
810684	NM_005121.3(MED13):c.4487del (p.Thr1496fs)	MED13	Pathogenic	no assertion criteria provided
985201	NM_005121.3(MED13):c.722_726del (p.Pro241fs)	MED13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
810683	NC_000004.12:g.10072573G>A	SLC2A9-AS3	Pathogenic	no assertion criteria provided
810680	NM_017491.5(WDR1):c.392T>G (p.Phe131Cys)	WDR1	Pathogenic	no assertion criteria provided
3775214	NM_005121.3(MED13):c.10_20dup (p.Asn8fs)	LOC130061364	Likely pathogenic	criteria provided, single submitter
1321405	NM_005121.3(MED13):c.1036dup (p.Val346fs)	MED13	Likely pathogenic	criteria provided, single submitter
1803784	NM_005121.3(MED13):c.4802C>A (p.Ser1601Ter)	MED13	Likely pathogenic	criteria provided, single submitter
2441917	NM_005121.3(MED13):c.413_414dup (p.Ile139fs)	MED13	Likely pathogenic	criteria provided, single submitter
2444160	NM_005121.3(MED13):c.3786_3787insAA (p.Pro1263fs)	MED13	Likely pathogenic	criteria provided, single submitter
2575175	NM_005121.3(MED13):c.4225C>T (p.Arg1409Ter)	MED13	Likely pathogenic	criteria provided, single submitter
3242254	NM_005121.3(MED13):c.5541C>A (p.Cys1847Ter)	MED13	Likely pathogenic	no assertion criteria provided
3341076	NM_005121.3(MED13):c.3644G>T (p.Gly1215Val)	MED13	Likely pathogenic	criteria provided, single submitter
3392527	NM_005121.3(MED13):c.5885T>G (p.Val1962Gly)	MED13	Likely pathogenic	criteria provided, single submitter
4082185	NM_005121.3(MED13):c.5393A>G (p.His1798Arg)	MED13	Likely pathogenic	criteria provided, single submitter
4293046	NM_005121.3(MED13):c.1048del (p.Ser350fs)	MED13	Likely pathogenic	criteria provided, single submitter
4528344	NM_005121.3(MED13):c.977C>A (p.Thr326Lys)	MED13	Likely 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
MED13	Definitive	Autosomal dominant	intellectual developmental disorder 61	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MED13	Orphanet:528084	Non-specific syndromic intellectual disability
WDR1	Orphanet:652522	Periodic fever-immunodeficiency-thrombocytopenia syndrome

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MED13	HGNC:22474	ENSG00000108510	Q9UHV7	Mediator of RNA polymerase II transcription subunit 13	gencc,clinvar
WDR1	HGNC:12754	ENSG00000071127	O75083	WD repeat-containing protein 1	clinvar
DZIP1	HGNC:20908	ENSG00000134874	Q86YF9	Cilium assembly protein DZIP1	clinvar
SLC2A9-AS3	HGNC:59109	ENSG00000250413		SLC2A9 antisense RNA 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
WDR1	WD repeat-containing protein 1	Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins.
DZIP1	Cilium assembly protein DZIP1	Molecular adapter that recruits protein complexes required for cilium assembly and function to the cilium basal body.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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
Scaffold/PPI	1	4.3×	0.605
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MED13	Other/Unknown	no		Med13_C, MID_MedPIWI, Mediator_complx_sub13
WDR1	Scaffold/PPI	no		WD40_rpt, N2O_reductase_N, WD40/YVTN_repeat-like_dom_sf
DZIP1	Transcription factor	no		Znf_C2H2_type, DZIP1_N, DZIP_RILPL
SLC2A9-AS3	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	1
germinal epithelium of ovary	1
visceral pleura	1
aorta	1
popliteal artery	1
tibial artery	1
left testis	1
male germ cell	1
sperm	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MED13	295	ubiquitous	marker	endothelial cell, visceral pleura, germinal epithelium of ovary
WDR1	295	ubiquitous	marker	popliteal artery, tibial artery, aorta
DZIP1	261	ubiquitous	marker	sperm, male germ cell, left testis
SLC2A9-AS3	118	tissue_specific	marker	colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WDR1	2,071
MED13	1,956
DZIP1	1,380
SLC2A9-AS3	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MED13	Q9UHV7	5
WDR1	O75083	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DZIP1	Q86YF9	65.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	71.8×	0.056	MED13
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	65.6×	0.056	MED13
Respiratory Syncytial Virus Infection Pathway	1	65.6×	0.056	MED13
Hedgehog ‘on’ state	1	52.9×	0.056	DZIP1
RSV-host interactions	1	52.1×	0.056	MED13
Adipogenesis	1	52.1×	0.056	MED13
Epigenetic regulation by WDR5-containing histone modifying complexes	1	51.4×	0.056	MED13
Regulation of lipid metabolism by PPARalpha	1	47.0×	0.056	MED13
Transcriptional regulation of white adipocyte differentiation	1	43.3×	0.056	MED13
PPARA activates gene expression	1	31.5×	0.066	MED13
Platelet degranulation	1	29.3×	0.066	WDR1
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	27.6×	0.066	MED13
Epigenetic regulation of gene expression	1	23.8×	0.070	MED13
Metabolism of lipids	1	10.5×	0.138	MED13
Viral Infection Pathways	1	10.3×	0.138	MED13
Infectious disease	1	8.3×	0.160	MED13
RNA Polymerase II Transcription	1	7.5×	0.165	MED13
Gene expression (Transcription)	1	6.0×	0.194	MED13
Generic Transcription Pathway	1	5.0×	0.213	MED13
Developmental Biology	1	4.8×	0.213	MED13
Disease	1	4.4×	0.222	MED13
Metabolism	1	3.9×	0.237	MED13

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
establishment of planar polarity of follicular epithelium	1	5617.3×	0.004	WDR1
regulation of actin filament depolymerization	1	2808.7×	0.004	WDR1
protein-containing complex localization to centriolar satellite	1	2808.7×	0.004	DZIP1
actin filament fragmentation	1	1404.3×	0.005	WDR1
ciliary basal body organization	1	1123.5×	0.005	DZIP1
regulation of oligodendrocyte differentiation	1	936.2×	0.005	WDR1
positive regulation of protein localization to cilium	1	936.2×	0.005	DZIP1
maintenance of epithelial cell apical/basal polarity	1	802.5×	0.005	WDR1
apical junction assembly	1	702.2×	0.005	WDR1
positive regulation of actin filament depolymerization	1	624.1×	0.005	WDR1
cortical cytoskeleton organization	1	561.7×	0.005	WDR1
locomotion	1	510.7×	0.005	WDR1
neutrophil mediated immunity	1	468.1×	0.005	WDR1
neutrophil migration	1	468.1×	0.005	WDR1
actin filament depolymerization	1	432.1×	0.006	WDR1
regulation of ventricular cardiac muscle cell membrane repolarization	1	280.9×	0.008	WDR1
positive regulation of cilium assembly	1	255.3×	0.008	DZIP1
platelet formation	1	234.1×	0.008	WDR1
sperm flagellum assembly	1	224.7×	0.008	DZIP1
triglyceride homeostasis	1	160.5×	0.011	MED13
germ cell development	1	151.8×	0.011	DZIP1
establishment of protein localization	1	144.0×	0.011	DZIP1
protein localization to cilium	1	133.8×	0.012	DZIP1
sarcomere organization	1	127.7×	0.012	WDR1
positive regulation of transcription initiation by RNA polymerase II	1	90.6×	0.016	MED13
smoothened signaling pathway	1	60.4×	0.023	DZIP1
establishment of localization in cell	1	53.5×	0.025	DZIP1
cholesterol homeostasis	1	52.0×	0.025	MED13
regulation of cell shape	1	41.0×	0.030	WDR1
sensory perception of sound	1	33.6×	0.035	WDR1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MED13	0	0
WDR1	0	0
DZIP1	0	0
SLC2A9-AS3	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
WDR1	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

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	4	MED13, WDR1, DZIP1, SLC2A9-AS3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MED13	0	—
WDR1	1	—
DZIP1	0	—
SLC2A9-AS3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.