Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities

Summary

Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (MONDO:0060760) is a disease caused by FBXO11 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: FBXO11 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 167

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder with dysmorphic facies and behavioral abnormalities
Mondo ID	MONDO:0060760
OMIM	618089
DOID	DOID:0061129
UMLS	C4748135
MedGen	1648498
Is cancer (heuristic)	no

Also known as: IDDFBA · INTELLECTUAL developmental disorder with DYSMORPHIC facies and behavioural abnormalities

Data availability: 167 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 › syndromic intellectual disability › autosomal dominant syndromic intellectual disability › intellectual developmental disorder with dysmorphic facies and behavioral abnormalities

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, intellectual disability, autosomal dominant 13, 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 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

167 retrieved; paginated sample, class counts are floors:

55 likely pathogenic, 50 uncertain significance, 31 pathogenic, 11 conflicting classifications of pathogenicity, 8 pathogenic/likely pathogenic, 6 benign/likely benign, 2 benign, 2 not provided, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1329862	NM_001190274.2(FBXO11):c.1797+1G>A	FBXO11	Pathogenic	criteria provided, single submitter
1329863	NM_001190274.2(FBXO11):c.2224C>T (p.Arg742Ter)	FBXO11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1329864	NM_001190274.2(FBXO11):c.2338+1G>A	FBXO11	Pathogenic	criteria provided, single submitter
1329865	NM_001190274.2(FBXO11):c.588-2A>G	FBXO11	Pathogenic	criteria provided, multiple submitters, no conflicts
1329866	NM_001190274.2(FBXO11):c.1696del (p.Ile566fs)	FBXO11	Pathogenic	criteria provided, single submitter
1329869	NM_001190274.2(FBXO11):c.500TCT[1] (p.Phe168del)	FBXO11	Pathogenic	criteria provided, multiple submitters, no conflicts
1329960	NM_001190274.2(FBXO11):c.2592_2593del (p.Ile864fs)	FBXO11	Pathogenic	criteria provided, multiple submitters, no conflicts
1329962	NM_001190274.2(FBXO11):c.2570_2572del (p.Asn857del)	FBXO11	Pathogenic	criteria provided, single submitter
1329963	NM_001190274.2(FBXO11):c.2520_2521del (p.Ser841fs)	FBXO11	Pathogenic	criteria provided, single submitter
1329964	NM_001190274.2(FBXO11):c.552del (p.Lys184fs)	FBXO11	Pathogenic	criteria provided, single submitter
1329965	NM_001190274.2(FBXO11):c.2568_2572del (p.Asn857fs)	FBXO11	Pathogenic	criteria provided, single submitter
1329966	NM_001190274.2(FBXO11):c.1798-1G>A	FBXO11	Pathogenic	criteria provided, single submitter
1329972	NM_001190274.2(FBXO11):c.668del (p.Pro223fs)	FBXO11	Pathogenic	criteria provided, single submitter
1329974	NM_001190274.2(FBXO11):c.1543_1557del (p.Phe515_Lys519del)	FBXO11	Pathogenic	criteria provided, single submitter
1329975	NM_001190274.2(FBXO11):c.2392AAC[1] (p.Asn799del)	FBXO11	Pathogenic	criteria provided, multiple submitters, no conflicts
1329977	NM_001190274.2(FBXO11):c.2748_2749del (p.Pro917fs)	FBXO11	Pathogenic	criteria provided, single submitter
1708215	NM_001190274.2(FBXO11):c.2732_2738del (p.Thr911fs)	FBXO11	Pathogenic	criteria provided, single submitter
3377013	NM_001190274.2(FBXO11):c.1646GAG[1] (p.Gly550del)	FBXO11	Pathogenic	criteria provided, single submitter
3393036	NM_001190274.2(FBXO11):c.2138G>A (p.Trp713Ter)	FBXO11	Pathogenic	criteria provided, single submitter
3393449	NM_001190274.2(FBXO11):c.2147_2150del (p.Thr716fs)	FBXO11	Pathogenic	criteria provided, single submitter
3765654	NM_001190274.2(FBXO11):c.1758dup (p.Asn587Ter)	FBXO11	Pathogenic	criteria provided, single submitter
3897610	NM_001190274.2(FBXO11):c.1399-1G>T	FBXO11	Pathogenic	criteria provided, single submitter
4072064	NM_001190274.2(FBXO11):c.2147_2148del (p.Thr716fs)	FBXO11	Pathogenic	criteria provided, single submitter
4687989	NM_001190274.2(FBXO11):c.1743T>A (p.Cys581Ter)	FBXO11	Pathogenic	criteria provided, single submitter
4818988	NM_001190274.2(FBXO11):c.2015dup (p.Ser672fs)	FBXO11	Pathogenic	criteria provided, single submitter
4845380	NM_001190274.2(FBXO11):c.2454_2458del (p.Lys818fs)	FBXO11	Pathogenic	criteria provided, single submitter
559600	NM_001190274.2(FBXO11):c.1612A>G (p.Ile538Val)	FBXO11	Pathogenic/Likely pathogenic	no assertion criteria provided
559601	NM_001190274.2(FBXO11):c.414A>T (p.Arg138Ser)	FBXO11	Pathogenic/Likely pathogenic	no assertion criteria provided
559603	NM_001190274.2(FBXO11):c.2709dup (p.Glu904Ter)	FBXO11	Pathogenic/Likely pathogenic	no assertion criteria provided
559604	NM_001190274.2(FBXO11):c.2738_2739del (p.Leu912_Tyr913insTer)	FBXO11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · 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
FBXO11	Definitive	Autosomal dominant	intellectual developmental disorder with dysmorphic facies and behavioral abnormalities	4
PRMT9	Limited	Autosomal recessive	intellectual developmental disorder with dysmorphic facies and behavioral abnormalities	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FBXO11	Orphanet:528084	Non-specific syndromic intellectual disability
MSH6	Orphanet:144	Lynch syndrome
MSH6	Orphanet:252202	Constitutional mismatch repair deficiency 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
FBXO11	HGNC:13590	ENSG00000138081	Q86XK2	F-box only protein 11	gencc,clinvar
PRMT9	HGNC:25099	ENSG00000164169	Q6P2P2	Protein arginine N-methyltransferase 9	gencc
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FBXO11	F-box only protein 11	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6, SNAI1 and PRDM1/BLI…
PRMT9	Protein arginine N-methyltransferase 9	Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA).
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).

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)
FBXO11	Transcription factor	no		F-box_dom, Znf_UBR, PbH1
PRMT9	Enzyme (other)	yes	2.1.1.320	TPR-like_helical_dom_sf, TPR_rpt, Arg_MeTrfase
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N

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
ganglionic eminence	2
ventricular zone	2
cortical plate	1
left ovary	1
primordial germ cell in gonad	1
secondary oocyte	1
embryo	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FBXO11	287	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
PRMT9	243	ubiquitous	marker	secondary oocyte, primordial germ cell in gonad, left ovary
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MSH6	4,091
FBXO11	2,000
PRMT9	1,952

Intra-cohort edges

A	B	Sources
FBXO11	MSH6	string_interaction
FBXO11	PRMT9	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MSH6	P52701	8
PRMT9	Q6P2P2	4
FBXO11	Q86XK2	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Defective Mismatch Repair Associated With MSH6	1	2855.0×	0.002	MSH6
Defective Mismatch Repair Associated With MSH2	1	1903.3×	0.002	MSH6
Mismatch Repair	1	1427.5×	0.002	MSH6
Diseases of Mismatch Repair (MMR)	1	1427.5×	0.002	MSH6
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	1	407.9×	0.005	MSH6
Diseases of DNA repair	1	285.5×	0.006	MSH6
DNA Repair	1	49.2×	0.029	MSH6
Neddylation	1	23.7×	0.052	FBXO11
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.059	FBXO11
Disease	1	6.5×	0.147	MSH6

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
meiotic mismatch repair	1	5617.3×	0.004	MSH6
somatic recombination of immunoglobulin gene segments	1	1404.3×	0.008	MSH6
negative regulation of DNA recombination	1	374.5×	0.016	MSH6
somatic hypermutation of immunoglobulin genes	1	351.1×	0.016	MSH6
isotype switching	1	280.9×	0.016	MSH6
mismatch repair	1	216.1×	0.017	MSH6
determination of adult lifespan	1	144.0×	0.018	MSH6
negative regulation of epithelial to mesenchymal transition	1	137.0×	0.018	FBXO11
response to UV	1	122.1×	0.018	MSH6
intrinsic apoptotic signaling pathway	1	119.5×	0.018	MSH6
intrinsic apoptotic signaling pathway in response to DNA damage	1	108.0×	0.018	MSH6
methylation	1	56.7×	0.032	PRMT9
sensory perception of sound	1	33.6×	0.050	FBXO11
regulation of apoptotic process	1	27.8×	0.052	FBXO11
mRNA processing	1	26.2×	0.052	PRMT9
ubiquitin-dependent protein catabolic process	1	24.8×	0.052	FBXO11
chromatin remodeling	1	24.3×	0.052	PRMT9
DNA repair	1	21.3×	0.057	MSH6
proteasome-mediated ubiquitin-dependent protein catabolic process	1	17.4×	0.065	FBXO11
protein ubiquitination	1	13.8×	0.078	FBXO11
spermatogenesis	1	11.7×	0.087	MSH6
regulation of DNA-templated transcription	1	10.5×	0.092	PRMT9

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 3 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MSH6	1	2
FBXO11	0	0
PRMT9	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	MSH6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PRMT9	40	Binding:40
MSH6	10	Binding:10
FBXO11	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRMT9	2.1.1.320	type II protein arginine methyltransferase

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	MSH6

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	MSH6
C	Druggable family + PDB, no drug	1	PRMT9
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FBXO11

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)
FBXO11	2	MSH6
PRMT9	40	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.