Dias-Logan syndrome

Summary

Dias-Logan syndrome (MONDO:0014914) is a disease caused by BCL11A (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: BCL11A (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 77

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Dias-Logan syndrome
Mondo ID	MONDO:0014914
OMIM	617101
UMLS	C4310833
MedGen	934800
Is cancer (heuristic)	no

Also known as: BCL11A-related BAFopathy · BCL11A-related intellectual developmental disorder with persistence of fetal hemoglobin · BCL11A-related intellectual developmental disorder with persistence of foetal haemoglobin · Dias-Logan syndrome · Dias-Logan syndrome; DILOS · DILOS · intellectual developmental disorder with hereditary persistence of foetal Haemoglobin · intellectual developmental disorder with persistence of foetal Haemoglobin · intellectual developmental disorder with persistence of foetal HEMOGLOBIN

Data availability: 77 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › BAFopathy › Dias-Logan syndrome

Related subtypes (14): Coffin-Siris syndrome 1, Baraitser-Winter syndrome 1, intellectual disability-sparse hair-brachydactyly syndrome, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, Coffin-Siris syndrome 5, Coffin-Siris syndrome 8, intellectual developmental disorder with severe speech and ambulation defects, Coffin-Siris syndrome 6, intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities, ACTL6A-related BAFopathy, PBRM1-related BAFopathy, SMARCC1-associated developmental dysgenesis syndrome

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

77 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 21 pathogenic, 18 likely pathogenic, 6 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1334760	NM_022893.4(BCL11A):c.1118dup (p.Val374fs)	BCL11A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342337	NM_022893.4(BCL11A):c.1846_1847delinsA (p.Gly616fs)	BCL11A	Pathogenic	criteria provided, single submitter
1679411	NM_022893.4(BCL11A):c.3G>A (p.Met1Ile)	BCL11A	Pathogenic	criteria provided, single submitter
1687104	NM_022893.4(BCL11A):c.35T>G (p.Leu12Ter)	BCL11A	Pathogenic	criteria provided, single submitter
1698869	NM_022893.4(BCL11A):c.1A>G (p.Met1Val)	BCL11A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1804108	NM_022893.4(BCL11A):c.759_769del (p.Leu254fs)	BCL11A	Pathogenic	criteria provided, single submitter
253300	NM_022893.4(BCL11A):c.139A>C (p.Thr47Pro)	BCL11A	Pathogenic	no assertion criteria provided
253301	NM_022893.4(BCL11A):c.143G>T (p.Cys48Phe)	BCL11A	Pathogenic	criteria provided, single submitter
253302	NM_022893.4(BCL11A):c.198C>A (p.His66Gln)	BCL11A	Pathogenic	no assertion criteria provided
253304	NM_022893.4(BCL11A):c.1775_1776insTGG (p.Gly592dup)	BCL11A	Pathogenic	no assertion criteria provided
2570606	NM_022893.4(BCL11A):c.1486G>T (p.Glu496Ter)	BCL11A	Pathogenic	criteria provided, single submitter
2626885	NM_022893.4(BCL11A):c.875del (p.His292fs)	BCL11A	Pathogenic	criteria provided, single submitter
2664349	NM_022893.4(BCL11A):c.1442del (p.Glu481fs)	BCL11A	Pathogenic	criteria provided, single submitter
2682233	NM_022893.4(BCL11A):c.488-1G>A	BCL11A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3024309	NM_022893.4(BCL11A):c.1417G>T (p.Glu473Ter)	BCL11A	Pathogenic	criteria provided, multiple submitters, no conflicts
3254642	NM_022893.4(BCL11A):c.230T>G (p.Leu77Ter)	BCL11A	Pathogenic	criteria provided, single submitter
3255198	NM_022893.4(BCL11A):c.384A>G (p.Ala128=)	BCL11A	Pathogenic	criteria provided, single submitter
3775480	NM_022893.4(BCL11A):c.1576_1579del (p.Glu526fs)	BCL11A	Pathogenic	criteria provided, single submitter
420316	NM_022893.4(BCL11A):c.793dup (p.Leu265fs)	BCL11A	Pathogenic	criteria provided, multiple submitters, no conflicts
426886	NM_022893.4(BCL11A):c.1078dup (p.Leu360fs)	BCL11A	Pathogenic	criteria provided, multiple submitters, no conflicts
503758	NM_022893.4(BCL11A):c.529C>T (p.Gln177Ter)	BCL11A	Pathogenic	criteria provided, single submitter
521857	NM_022893.4(BCL11A):c.385+2T>C	BCL11A	Pathogenic	criteria provided, multiple submitters, no conflicts
632585	NM_022893.4(BCL11A):c.1601_1631del (p.Val534fs)	BCL11A	Pathogenic/Likely pathogenic	no assertion criteria provided
632586	NM_022893.4(BCL11A):c.295del (p.Val99fs)	BCL11A	Pathogenic/Likely pathogenic	no assertion criteria provided
976351	NM_022893.4(BCL11A):c.1663A>T (p.Met555Leu)	BCL11A	Pathogenic	criteria provided, single submitter
987079	NM_022893.4(BCL11A):c.1078del (p.Leu360fs)	BCL11A	Pathogenic	criteria provided, multiple submitters, no conflicts
987335	NM_022893.4(BCL11A):c.370C>T (p.Gln124Ter)	BCL11A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1251950	NM_022893.4(BCL11A):c.1847del (p.Gly616fs)	BCL11A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1297023	NM_022893.4(BCL11A):c.1519del (p.Glu507fs)	BCL11A	Likely pathogenic	criteria provided, single submitter
1301373	NM_022893.4(BCL11A):c.1135del (p.Cys379fs)	BCL11A	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
BCL11A	Definitive	Autosomal dominant	Dias-Logan syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCL11A	Orphanet:251380	Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
BCL11A	Orphanet:619233	Hereditary persistence of fetal hemoglobin-intellectual disability syndrome
CIC	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

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
BCL11A	HGNC:13221	ENSG00000119866	Q9H165	BCL11 transcription factor A	gencc,clinvar
CIC	HGNC:14214	ENSG00000079432	Q96RK0	Protein capicua homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCL11A	BCL11 transcription factor A	Transcription factor.
CIC	Protein capicua homolog	Transcriptional repressor which plays a role in development of the central nervous system (CNS).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BCL11A	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Dev/Hematopoietic_TF
CIC	Other/Unknown	no		HMG_box_dom, Cic_dom, HMG_box_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
cortical plate	1
ganglionic eminence	1
primary visual cortex	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCL11A	247	ubiquitous	marker	cortical plate, ganglionic eminence, primary visual cortex
CIC	274	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCL11A	2,389
CIC	1,720

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCL11A	Q9H165	17
CIC	Q96RK0	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 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
ALK mutants bind TKIs	1	951.7×	0.005	BCL11A
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.005	BCL11A
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.005	BCL11A
Signaling by ALK in cancer	1	271.9×	0.006	BCL11A
Signaling by ALK fusions and activated point mutants	1	150.3×	0.009	BCL11A
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.021	BCL11A
Disease	1	13.1×	0.076	BCL11A

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
negative regulation of neuron remodeling	1	8426.0×	0.001	BCL11A
negative regulation of branching morphogenesis of a nerve	1	8426.0×	0.001	BCL11A
negative regulation of protein homooligomerization	1	2808.7×	0.003	BCL11A
negative regulation of dendrite extension	1	2106.5×	0.003	BCL11A
negative regulation of dendrite development	1	1053.2×	0.004	BCL11A
positive regulation of collateral sprouting	1	936.2×	0.004	BCL11A
cellular response to L-glutamate	1	842.6×	0.004	BCL11A
negative regulation of collateral sprouting	1	766.0×	0.004	BCL11A
regulation of dendrite development	1	495.6×	0.005	BCL11A
negative regulation of axon extension	1	366.4×	0.007	BCL11A
negative regulation of transcription by RNA polymerase II	2	17.7×	0.007	BCL11A, CIC
lung alveolus development	1	175.5×	0.011	CIC
protein sumoylation	1	162.0×	0.011	BCL11A
learning	1	140.4×	0.011	CIC
social behavior	1	135.9×	0.011	CIC
regulation of transcription by RNA polymerase II	2	11.7×	0.011	BCL11A, CIC
negative regulation of neuron projection development	1	118.7×	0.012	BCL11A
memory	1	91.6×	0.015	CIC
positive regulation of neuron projection development	1	68.5×	0.018	BCL11A
brain development	1	39.8×	0.030	CIC
transcription by RNA polymerase II	1	35.3×	0.032	CIC
positive regulation of gene expression	1	19.4×	0.056	BCL11A
negative regulation of DNA-templated transcription	1	15.8×	0.065	CIC
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	BCL11A

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
BCL11A	0	0
CIC	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	BCL11A, CIC

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)
BCL11A	0	—
CIC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.