Intellectual developmental disorder with autism and speech delay

disease

On this page

Also known as autism, susceptibility to, 5autism-related speech delayAUTS5phrase speech delay, autism-related

Summary

Intellectual developmental disorder with autism and speech delay (MONDO:0011627) is a disease caused by TBR1 (GenCC Strong), with 1 cohort gene and 2 clinical trials.

At a glance

Causal gene: TBR1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 73
Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder with autism and speech delay
Mondo ID	MONDO:0011627
OMIM	606053
UMLS	C1853755
MedGen	340048
Is cancer (heuristic)	no

Also known as: autism, susceptibility to, 5 · autism-related speech delay · AUTS5 · intellectual developmental disorder with autism and speech delay · phrase speech delay, autism-related

Data availability: 73 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › autism, susceptiblity to › intellectual developmental disorder with autism and speech delay

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

73 retrieved; paginated sample, class counts are floors:

32 uncertain significance, 17 pathogenic, 12 likely pathogenic, 6 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
224144	NM_006593.4(TBR1):c.1588_1594dup (p.Thr532fs)	LOC129935026	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1064798	NM_006593.4(TBR1):c.1174C>T (p.Arg392Trp)	TBR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1164049	NM_006593.4(TBR1):c.1132A>T (p.Thr378Ser)	TBR1	Pathogenic	no assertion criteria provided
1308658	NM_006593.4(TBR1):c.969+1G>C	TBR1	Pathogenic	criteria provided, single submitter
1343070	NM_006593.4(TBR1):c.196_199del (p.Asp66fs)	TBR1	Pathogenic	criteria provided, multiple submitters, no conflicts
1804068	NM_006593.4(TBR1):c.1250C>A (p.Ser417Ter)	TBR1	Pathogenic	criteria provided, single submitter
1895456	NM_006593.4(TBR1):c.1126G>C (p.Asp376His)	TBR1	Pathogenic	criteria provided, single submitter
2573063	NM_006593.4(TBR1):c.412_413dup (p.Ile139fs)	TBR1	Pathogenic	criteria provided, single submitter
3065986	NM_006593.4(TBR1):c.1190+2T>G	TBR1	Pathogenic	no assertion criteria provided
3242447	NM_006593.4(TBR1):c.163dup (p.Ile55fs)	TBR1	Pathogenic	criteria provided, single submitter
3254867	NM_006593.4(TBR1):c.1220dup (p.Thr408fs)	TBR1	Pathogenic	criteria provided, single submitter
3777734	NM_006593.4(TBR1):c.507C>A (p.Tyr169Ter)	TBR1	Pathogenic	criteria provided, single submitter
523674	NM_006593.4(TBR1):c.713_719del (p.Ser238fs)	TBR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523678	NM_006593.4(TBR1):c.896G>A (p.Trp299Ter)	TBR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
599048	NM_006593.4(TBR1):c.405del (p.Ala136fs)	TBR1	Pathogenic	no assertion criteria provided
599049	NM_006593.4(TBR1):c.1049dup (p.Thr350_Ser351insTer)	TBR1	Pathogenic	no assertion criteria provided
599050	NM_006593.4(TBR1):c.682A>G (p.Lys228Glu)	TBR1	Pathogenic	no assertion criteria provided
599051	NM_006593.4(TBR1):c.1120A>C (p.Asn374His)	TBR1	Pathogenic	no assertion criteria provided
599052	NM_006593.4(TBR1):c.813G>T (p.Trp271Cys)	TBR1	Pathogenic	no assertion criteria provided
599053	NM_006593.4(TBR1):c.1165A>G (p.Lys389Glu)	TBR1	Pathogenic	no assertion criteria provided
807510	NM_006593.4(TBR1):c.1731dup (p.Ala578fs)	TBR1	Pathogenic	criteria provided, single submitter
801771	NM_006593.4(TBR1):c.1547del (p.Tyr516fs)	LOC129935026	Likely pathogenic	criteria provided, single submitter
1299335	NM_006593.4:c.(1128+1_1129-1)_(1190+1_1191-1)del	TBR1	Likely pathogenic	criteria provided, single submitter
1342892	NM_006593.4(TBR1):c.1162G>C (p.Ala388Pro)	TBR1	Likely pathogenic	criteria provided, single submitter
1710258	NM_006593.4(TBR1):c.1206T>A (p.Cys402Ter)	TBR1	Likely pathogenic	no assertion criteria provided
2428648	NM_006593.4(TBR1):c.1168G>C (p.Gly390Arg)	TBR1	Likely pathogenic	criteria provided, single submitter
2434094	NM_006593.4(TBR1):c.1349_1355dup (p.Pro453fs)	TBR1	Likely pathogenic	criteria provided, single submitter
2683943	NM_006593.4(TBR1):c.691A>G (p.Arg231Gly)	TBR1	Likely pathogenic	criteria provided, single submitter
3381749	NM_006593.4(TBR1):c.1271del (p.Arg424fs)	TBR1	Likely pathogenic	criteria provided, single submitter
3381934	NM_006593.4(TBR1):c.1013A>C (p.His338Pro)	TBR1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
TBR1	Definitive	Autosomal dominant	autism	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBR1	Orphanet:1617	Developmental delay-language impairment-dopa responsive dystonia-parkinsonism syndrome due to 2q24 microdeletion
TBR1	Orphanet:528084	Non-specific syndromic intellectual disability

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
TBR1	HGNC:11590	ENSG00000136535	Q16650	T-box brain protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBR1	T-box brain protein 1	Transcriptional repressor involved in multiple aspects of cortical development, including neuronal migration, laminar and areal identity, and axonal projection.

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)
TBR1	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS

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
Brodmann (1909) area 10	1
cortical plate	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBR1	58	tissue_specific	marker	cortical plate, ganglionic eminence, Brodmann (1909) area 10

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBR1	2,438

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBR1	Q16650	56.17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
specification of animal organ identity	1	16852.0×	9e-04	TBR1
conditioned taste aversion	1	5617.3×	0.001	TBR1
amygdala development	1	2808.7×	0.001	TBR1
commitment of neuronal cell to specific neuron type in forebrain	1	2808.7×	0.001	TBR1
regulation of axon guidance	1	2407.4×	0.001	TBR1
hindbrain development	1	1123.5×	0.002	TBR1
cell fate specification	1	526.6×	0.004	TBR1
regulation of neuron projection development	1	432.1×	0.004	TBR1
cerebral cortex development	1	205.5×	0.008	TBR1
gene expression	1	79.9×	0.017	TBR1
brain development	1	79.5×	0.017	TBR1
chromatin remodeling	1	73.0×	0.017	TBR1
negative regulation of DNA-templated transcription	1	31.6×	0.037	TBR1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.072	TBR1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	TBR1

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
TBR1	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	TBR1

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)
TBR1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05663970	Not specified	ACTIVE_NOT_RECRUITING	Virtual Group Social ABCs - Multi-site Randomized Controlled Trial
NCT04100863	Not specified	WITHDRAWN	A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Autism

Cohort genes: TBR1