Intellectual developmental disorder, autosomal recessive 78

Summary

Intellectual developmental disorder, autosomal recessive 78 (MONDO:0859373) is a disease caused by WDR11 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: WDR11 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal recessive 78
Mondo ID	MONDO:0859373
OMIM	620237
UMLS	C5830269
MedGen	1840905
GARD	0026722
Is cancer (heuristic)	no

Data availability: 13 ClinVar variants · 4 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 recessive non-syndromic intellectual disability › intellectual developmental disorder, autosomal recessive 78

Related subtypes (67): intellectual disability, autosomal recessive 1, intellectual disability, autosomal recessive 2, intellectual disability, autosomal recessive 3, intellectual disability, autosomal recessive 12, intellectual disability, autosomal recessive 5, intellectual disability, autosomal recessive 6, intellectual disability, autosomal recessive 7, intellectual disability, autosomal recessive 9, intellectual disability, autosomal recessive 10, intellectual disability, autosomal recessive 11, intellectual disability, autosomal recessive 4, intellectual disability, autosomal recessive 13, intellectual disability, autosomal recessive 14, Rafiq syndrome, intellectual disability, autosomal recessive 16, intellectual disability, autosomal recessive 18, intellectual disability, autosomal recessive 31, intellectual disability, autosomal recessive 29, intellectual disability, autosomal recessive 27, intellectual disability, autosomal recessive 33, intellectual disability, autosomal recessive 30, intellectual disability, autosomal recessive 19, intellectual disability, autosomal recessive 23, intellectual disability, autosomal recessive 24, intellectual disability, autosomal recessive 25, intellectual disability, autosomal recessive 28, intellectual disability, autosomal recessive 34, intellectual disability, autosomal recessive 42, intellectual disability, autosomal recessive 43, intellectual disability, autosomal recessive 44, intellectual disability, autosomal recessive 45, intellectual disability, autosomal recessive 46, intellectual disability, autosomal recessive 47, Al-Raqad syndrome, intellectual disability, autosomal recessive 50, intellectual disability, autosomal recessive 51, intellectual disability, autosomal recessive 52, intellectual disability, autosomal recessive 54, intellectual disability, autosomal recessive 56, intellectual developmental disorder, autosomal recessive 74, intellectual disability, autosomal recessive 57, intellectual disability, autosomal recessive 58, intellectual disability, autosomal recessive 59, pontocerebellar hypoplasia type 1, intellectual disability, autosomal recessive 64, intellectual disability, autosomal recessive 65, intellectual developmental disorder, autosomal recessive 73, intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, intellectual disability, autosomal recessive 61, intellectual developmental disorder, autosomal recessive 76, intellectual developmental disorder, autosomal recessive 77, intellectual disability, autosomal recessive 66, intellectual developmental disorder, autosomal recessive 67, intellectual developmental disorder, autosomal recessive 68, intellectual developmental disorder, autosomal recessive 69, intellectual developmental disorder, autosomal recessive 70, intellectual developmental disorder, autosomal recessive 71, intellectual developmental disorder, autosomal recessive 72, glycosylphosphatidylinositol biosynthesis defect 16, intellectual disability, autosomal recessive 60, intellectual disability, autosomal recessive 63, adenosine kinase deficiency, intellectual developmental disorder, autosomal recessive 79, intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, intellectual developmental disorder, autosomal recessive 81, intellectual developmental disorder, autosomal recessive 82, intellectual developmental disorder, autosomal recessive 83

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

13 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 4 pathogenic, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1098849	NM_018117.12(WDR11):c.1255C>T (p.Gln419Ter)	WDR11	Pathogenic	criteria provided, multiple submitters, no conflicts
1098850	NM_018117.12(WDR11):c.2931+1G>A	WDR11	Pathogenic	criteria provided, single submitter
1098851	NM_018117.12(WDR11):c.1439del (p.Asn480fs)	WDR11	Pathogenic	criteria provided, single submitter
1098852	NM_018117.12(WDR11):c.3033_3036del	WDR11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4759346	NM_018117.12(WDR11):c.949C>T (p.Arg317Ter)	WDR11	Pathogenic	criteria provided, single submitter
4849292	NM_018117.12(WDR11):c.1748del (p.Leu583fs)	WDR11	Likely pathogenic	criteria provided, single submitter
1306011	NM_018117.12(WDR11):c.3553C>T (p.Arg1185Trp)	WDR11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1979178	NM_018117.12(WDR11):c.403A>G (p.Ile135Val)	WDR11	Uncertain significance	criteria provided, multiple submitters, no conflicts
2369056	NM_018117.12(WDR11):c.394C>G (p.Leu132Val)	WDR11	Uncertain significance	criteria provided, multiple submitters, no conflicts
3590731	NM_018117.12(WDR11):c.3226G>A (p.Ala1076Thr)	WDR11	Uncertain significance	criteria provided, single submitter
3602594	NM_018117.12(WDR11):c.3023G>A (p.Gly1008Asp)	WDR11	Uncertain significance	criteria provided, single submitter
3776277	NM_018117.12(WDR11):c.995-28C>G	WDR11	Uncertain significance	criteria provided, single submitter
3892881	NM_018117.12(WDR11):c.3660A>C (p.Glu1220Asp)	WDR11	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 25 · Orphanet: 4 · 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
PHIP	Definitive	Autosomal dominant	developmental delay, intellectual disability, obesity, and dysmorphic features	15
WDR11	Strong	Autosomal recessive	intellectual developmental disorder, autosomal recessive 78	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR11	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
WDR11	Orphanet:478	Kallmann syndrome
WDR11	Orphanet:95496	Pituitary stalk interruption syndrome
PHIP	Orphanet:589905	PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WDR11	HGNC:13831	ENSG00000120008	Q9BZH6	WD repeat-containing protein 11	gencc,clinvar
PHIP	HGNC:15673	ENSG00000146247	Q8WWQ0	PH-interacting protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WDR11	WD repeat-containing protein 11	Involved in the Hedgehog (Hh) signaling pathway, is essential for normal ciliogenesis.
PHIP	PH-interacting protein	Probable regulator of the insulin and insulin-like growth factor signaling pathways.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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	2	17.3×	0.003

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WDR11	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
PHIP	Scaffold/PPI	no		Bromodomain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
epithelium of nasopharynx	1
nasopharynx	1
bronchial epithelial cell	1
epithelium of bronchus	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WDR11	287	ubiquitous	marker	epithelium of nasopharynx, nasopharynx, calcaneal tendon
PHIP	302	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHIP	3,057
WDR11	1,088

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PHIP	Q8WWQ0	146
WDR11	Q9BZH6	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
RHOBTB2 GTPase cycle	1	237.9×	0.006	PHIP
RHOH GTPase cycle	1	154.3×	0.006	WDR11

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete vesicle tethering to Golgi	1	1685.2×	0.009	WDR11
positive regulation of insulin-like growth factor receptor signaling pathway	1	601.9×	0.009	PHIP
head development	1	601.9×	0.009	WDR11
regulation of protein phosphorylation	1	561.7×	0.009	PHIP
regulation of smoothened signaling pathway	1	312.1×	0.011	WDR11
regulation of cell morphogenesis	1	312.1×	0.011	PHIP
positive regulation of mitotic nuclear division	1	271.8×	0.011	PHIP
negative regulation of extrinsic apoptotic signaling pathway	1	210.7×	0.012	PHIP
insulin receptor signaling pathway	1	110.9×	0.020	PHIP
multicellular organism growth	1	68.5×	0.027	WDR11
cytoskeleton organization	1	66.3×	0.027	PHIP
regulation of cell shape	1	61.5×	0.027	PHIP
heart development	1	39.4×	0.039	WDR11
cilium assembly	1	36.8×	0.039	WDR11
intracellular protein transport	1	32.4×	0.041	WDR11
negative regulation of apoptotic process	1	17.4×	0.069	PHIP
positive regulation of cell population proliferation	1	16.8×	0.069	PHIP
positive regulation of DNA-templated transcription	1	14.0×	0.078	PHIP
positive regulation of transcription by RNA polymerase II	1	7.4×	0.137	PHIP
regulation of transcription by RNA polymerase II	1	5.8×	0.164	PHIP

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
WDR11	0	0
PHIP	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
PHIP	17	Binding:17

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	WDR11, PHIP

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)
WDR11	0	—
PHIP	17	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.