Townes-Brocks syndrome 1

Summary

Townes-Brocks syndrome 1 (MONDO:0054581) is a disease caused by SALL1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: SALL1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 146

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Townes-Brocks syndrome 1
Mondo ID	MONDO:0054581
OMIM	107480
UMLS	C4551481
MedGen	1635275
GARD	0025951
Is cancer (heuristic)	no

Also known as: TBS1 · townes-brocks branchiootorenal-like syndrome · Townes-Brocks syndrome 1

Data availability: 146 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Townes-Brocks syndrome › Townes-Brocks syndrome 1

Related subtypes (1): Townes-Brocks syndrome 2

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

146 retrieved; paginated sample, class counts are floors:

43 uncertain significance, 43 pathogenic, 15 benign/likely benign, 14 likely benign, 10 likely pathogenic, 10 conflicting classifications of pathogenicity, 6 pathogenic/likely pathogenic, 5 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1679304	NM_002968.3(SALL1):c.601C>T (p.Gln201Ter)	SALL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1679359	NM_002968.3(SALL1):c.1363_1369delinsTGAAACA (p.Ala455_Val457delinsTer)	SALL1	Pathogenic	criteria provided, single submitter
1693559	NM_002968.3(SALL1):c.709C>T (p.Gln237Ter)	SALL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705680	NM_002968.3(SALL1):c.1228G>T (p.Gly410Ter)	SALL1	Pathogenic	criteria provided, single submitter
219151	NM_002968.3(SALL1):c.3160C>T (p.Arg1054Ter)	SALL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681784	NM_002968.3(SALL1):c.2283_2284del (p.Leu762fs)	SALL1	Pathogenic	criteria provided, single submitter
2687773	NM_002968.3(SALL1):c.1148del (p.Leu383fs)	SALL1	Pathogenic	criteria provided, multiple submitters, no conflicts
3062088	NM_002968.3(SALL1):c.953del (p.Pro318fs)	SALL1	Pathogenic	criteria provided, single submitter
3254898	NM_002968.3(SALL1):c.1606A>T (p.Lys536Ter)	SALL1	Pathogenic	criteria provided, single submitter
3764693	NM_002968.3(SALL1):c.952_953del (p.Pro318fs)	SALL1	Pathogenic	criteria provided, single submitter
3765519	NM_002968.3(SALL1):c.1444del (p.Cys482fs)	SALL1	Pathogenic	criteria provided, single submitter
3765520	NM_002968.3(SALL1):c.1146_1152dup (p.Ser385fs)	SALL1	Pathogenic	criteria provided, single submitter
3765521	NM_002968.3(SALL1):c.3397C>T (p.Gln1133Ter)	SALL1	Pathogenic	criteria provided, single submitter
3765522	NM_002968.3(SALL1):c.1069del (p.Ala357fs)	SALL1	Pathogenic	criteria provided, single submitter
3765523	NM_002968.3(SALL1):c.645_658del (p.Arg215fs)	SALL1	Pathogenic	criteria provided, single submitter
3765524	NM_002968.3(SALL1):c.824T>G (p.Leu275Ter)	SALL1	Pathogenic	criteria provided, single submitter
3765525	NM_002968.3(SALL1):c.1147_1148insA (p.Leu383fs)	SALL1	Pathogenic	criteria provided, single submitter
3765526	NM_002968.3(SALL1):c.477_480dup (p.Gly161fs)	SALL1	Pathogenic	criteria provided, single submitter
3765527	NM_002968.3(SALL1):c.1411del (p.His471fs)	SALL1	Pathogenic	criteria provided, single submitter
3765528	NM_002968.3(SALL1):c.2390del (p.Pro797fs)	SALL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3765529	NM_002968.3(SALL1):c.3034del (p.Cys1012fs)	SALL1	Pathogenic	criteria provided, single submitter
3765530	NM_002968.3(SALL1):c.1340_1341delinsAA (p.Phe447Ter)	SALL1	Pathogenic	criteria provided, single submitter
3765531	NM_002968.3(SALL1):c.278del (p.Asn93fs)	SALL1	Pathogenic	criteria provided, single submitter
3765532	NM_002968.3(SALL1):c.2999del (p.Asn1000fs)	SALL1	Pathogenic	criteria provided, single submitter
3765533	NM_002968.3(SALL1):c.2285del (p.Leu762fs)	SALL1	Pathogenic	criteria provided, single submitter
3765534	NM_002968.3(SALL1):c.902dup (p.Ser302fs)	SALL1	Pathogenic	criteria provided, single submitter
3899974	NM_002968.3(SALL1):c.1384_1385del (p.Ser462fs)	SALL1	Pathogenic	no assertion criteria provided
3902249	NM_002968.3(SALL1):c.829_830delinsTA (p.Thr277Ter)	SALL1	Pathogenic	criteria provided, single submitter
4075811	NM_002968.3(SALL1):c.675dup (p.Val226fs)	SALL1	Pathogenic	no assertion criteria provided
418466	NM_002968.3(SALL1):c.3414_3415del (p.Cys1139fs)	SALL1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SALL1	Definitive	Autosomal dominant	Townes-Brocks syndrome 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SALL1	Orphanet:857	Townes-Brocks 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
SALL1	HGNC:10524	ENSG00000103449	Q9NSC2	Sal-like protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SALL1	Sal-like protein 1	Transcriptional repressor involved in organogenesis.

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)
SALL1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sal_C2H2-zinc-finger

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
inferior vagus X ganglion	1
renal medulla	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SALL1	195	broad	marker	ventricular zone, inferior vagus X ganglion, renal medulla

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SALL1	2,189

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SALL1	Q9NSC2	49.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation	1	878.5×	0.003	SALL1
Kidney development	1	815.7×	0.003	SALL1
Transcriptional regulation of pluripotent stem cells	1	543.8×	0.003	SALL1
Formation of the ureteric bud	1	496.5×	0.003	SALL1
Developmental Biology	1	14.5×	0.069	SALL1

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
inductive cell-cell signaling	1	16852.0×	7e-04	SALL1
olfactory bulb mitral cell layer development	1	8426.0×	7e-04	SALL1
kidney epithelium development	1	8426.0×	7e-04	SALL1
ureteric bud invasion	1	8426.0×	7e-04	SALL1
olfactory nerve development	1	5617.3×	9e-04	SALL1
olfactory bulb interneuron differentiation	1	3370.4×	0.001	SALL1
mesenchymal to epithelial transition involved in metanephros morphogenesis	1	2106.5×	0.002	SALL1
gonad development	1	1123.5×	0.003	SALL1
embryonic digestive tract development	1	991.3×	0.003	SALL1
adrenal gland development	1	674.1×	0.003	SALL1
pituitary gland development	1	648.1×	0.003	SALL1
ventricular septum development	1	495.6×	0.004	SALL1
ureteric bud development	1	455.5×	0.004	SALL1
limb development	1	411.0×	0.004	SALL1
positive regulation of Wnt signaling pathway	1	383.0×	0.004	SALL1
branching involved in ureteric bud morphogenesis	1	366.4×	0.004	SALL1
embryonic digit morphogenesis	1	300.9×	0.005	SALL1
kidney development	1	140.4×	0.009	SALL1
heart development	1	78.8×	0.016	SALL1
negative regulation of DNA-templated transcription	1	31.6×	0.038	SALL1
positive regulation of DNA-templated transcription	1	27.9×	0.041	SALL1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.062	SALL1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.070	SALL1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	SALL1

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
SALL1	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	SALL1

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)
SALL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.