Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities

Summary

Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities (MONDO:0060763) is a disease caused by BCL11B (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: BCL11B (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 60
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities
Mondo ID	MONDO:0060763
OMIM	618092
Orphanet	662829
UMLS	C4748152
MedGen	1648327
GARD	0027142
Is cancer (heuristic)	no

Also known as: BCL11B-related BAFopathy · BCL11B-related disorder · IDDSFTA · intellectual developmental disorder with dysmorphic facies, speech delay, and t-cell abnormalities

Data availability: 60 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 speech delay, dysmorphic facies, and t-cell 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 dysmorphic facies and behavioral 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

60 retrieved; paginated sample, class counts are floors:

20 pathogenic, 14 uncertain significance, 13 likely pathogenic, 8 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 1 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177342	NM_138576.4(BCL11B):c.211del (p.Leu71fs)	BCL11B	Pathogenic	criteria provided, single submitter
1184138	NM_138576.4(BCL11B):c.2346_2361del (p.Gly783fs)	BCL11B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1292046	NM_138576.4(BCL11B):c.427+1G>A	BCL11B	Pathogenic	no assertion criteria provided
1292051	NM_138576.4(BCL11B):c.2448_2461dup (p.Glu821fs)	BCL11B	Pathogenic	criteria provided, multiple submitters, no conflicts
1342021	NM_138576.4(BCL11B):c.1662_1668del (p.Ser555fs)	BCL11B	Pathogenic	criteria provided, single submitter
1698957	NM_138576.4(BCL11B):c.1272_1278del (p.Lys425fs)	BCL11B	Pathogenic	criteria provided, single submitter
1801832	NM_138576.4(BCL11B):c.2605del (p.Leu869fs)	BCL11B	Pathogenic	criteria provided, single submitter
1804880	NM_138576.4(BCL11B):c.2443del (p.Arg815fs)	BCL11B	Pathogenic	criteria provided, single submitter
2442366	NM_138576.4(BCL11B):c.1216_1219dup (p.Pro407fs)	BCL11B	Pathogenic	criteria provided, single submitter
2663815	NM_138576.4(BCL11B):c.1852C>T (p.Gln618Ter)	BCL11B	Pathogenic	criteria provided, single submitter
3897620	NM_138576.4(BCL11B):c.2224_2227dup (p.His743fs)	BCL11B	Pathogenic	criteria provided, single submitter
4531491	NM_138576.4(BCL11B):c.658_706del (p.Ser220fs)	BCL11B	Pathogenic	criteria provided, single submitter
560174	NM_138576.4(BCL11B):c.2421C>G (p.Asn807Lys)	BCL11B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
560175	NM_138576.4(BCL11B):c.2449_2456dup (p.Gly820fs)	BCL11B	Pathogenic	no assertion criteria provided
560176	NM_138576.4(BCL11B):c.2671del (p.Ala891fs)	BCL11B	Pathogenic	no assertion criteria provided
560177	NM_138576.4(BCL11B):c.242del (p.Cys81fs)	BCL11B	Pathogenic	no assertion criteria provided
560178	NM_138576.4(BCL11B):c.1495G>T (p.Glu499Ter)	BCL11B	Pathogenic	no assertion criteria provided
807549	NM_138576.4(BCL11B):c.2048del (p.Ser683fs)	BCL11B	Pathogenic	criteria provided, single submitter
807550	NM_138576.4(BCL11B):c.1500dup (p.Gly501fs)	BCL11B	Pathogenic	criteria provided, single submitter
870217	NM_138576.4(BCL11B):c.1944_1965del (p.Gly649fs)	BCL11B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
976002	NM_138576.4(BCL11B):c.1770_1771del (p.Lys591fs)	BCL11B	Pathogenic	criteria provided, single submitter
988777	NM_138576.4(BCL11B):c.682C>T (p.Gln228Ter)	BCL11B	Pathogenic	criteria provided, single submitter
995958	NM_138576.4(BCL11B):c.2435_2436insAA (p.Val813fs)	BCL11B	Pathogenic	criteria provided, single submitter
1177351	NM_138576.4(BCL11B):c.1582del (p.His528fs)	BCL11B	Likely pathogenic	criteria provided, single submitter
1177353	NM_138576.4(BCL11B):c.2448_2461del (p.Ser817fs)	BCL11B	Likely pathogenic	criteria provided, single submitter
1703240	NM_138576.4(BCL11B):c.1535_1536del (p.Ala512fs)	BCL11B	Likely pathogenic	criteria provided, single submitter
1804030	NM_138576.4(BCL11B):c.2513A>G (p.Lys838Arg)	BCL11B	Likely pathogenic	criteria provided, single submitter
1806467	NM_138576.4(BCL11B):c.1206del (p.Phe403fs)	BCL11B	Likely pathogenic	criteria provided, single submitter
3370483	NM_138576.4(BCL11B):c.2474dup (p.Cys826fs)	BCL11B	Likely pathogenic	criteria provided, single submitter
3382096	NM_138576.4(BCL11B):c.1707del (p.Gly570fs)	BCL11B	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 1 · 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
BCL11B	Definitive	Autosomal dominant	intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCL11B	Orphanet:662829	Intellectual disability-speech delay-dysmorphic features-T cell abnormalities syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BCL11B	HGNC:13222	ENSG00000127152	Q9C0K0	B-cell lymphoma/leukemia 11B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCL11B	B-cell lymphoma/leukemia 11B	Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BCL11B	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Dev/Hematopoietic_TF

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
thymus	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCL11B	211	broad	marker	thymus, upper leg skin, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCL11B	2,523

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BCL11B	Q9C0K0	51.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 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
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.002	BCL11B
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.002	BCL11B

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
olfactory bulb axon guidance	1	16852.0×	7e-04	BCL11B
positive T cell selection	1	8426.0×	7e-04	BCL11B
lymphoid lineage cell migration into thymus	1	8426.0×	7e-04	BCL11B
striatal medium spiny neuron differentiation	1	4213.0×	7e-04	BCL11B
post-embryonic camera-type eye development	1	4213.0×	7e-04	BCL11B
T cell receptor V(D)J recombination	1	4213.0×	7e-04	BCL11B
hematopoietic stem cell migration	1	4213.0×	7e-04	BCL11B
commitment of neuronal cell to specific neuron type in forebrain	1	2808.7×	1e-03	BCL11B
alpha-beta T cell differentiation	1	1872.4×	0.001	BCL11B
negative regulation of thymocyte apoptotic process	1	1685.2×	0.001	BCL11B
keratinocyte development	1	1532.0×	0.001	BCL11B
regulation of keratinocyte proliferation	1	1532.0×	0.001	BCL11B
thymocyte apoptotic process	1	1404.3×	0.001	BCL11B
epithelial cell morphogenesis	1	936.2×	0.002	BCL11B
regulation of neuron differentiation	1	732.7×	0.002	BCL11B
regulation of lipid metabolic process	1	432.1×	0.003	BCL11B
T cell differentiation in thymus	1	411.0×	0.003	BCL11B
thymus development	1	337.0×	0.004	BCL11B
odontogenesis of dentin-containing tooth	1	300.9×	0.004	BCL11B
transcription by RNA polymerase II	1	70.5×	0.016	BCL11B
negative regulation of cell population proliferation	1	42.1×	0.025	BCL11B
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	BCL11B

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BCL11B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	BCL11B

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BCL11B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04541927	Not specified	COMPLETED	Better Delineation of BCL11B Related Phenotype and Epigenetic Signature.