SALL1

protein-coding

spalt like transcription factor 1, the group of Zinc fingers C2H2-type

Gene summary

The protein encoded by this gene is a zinc finger transcriptional repressor and may be part of the NuRD histone deacetylase complex (HDAC). Defects in this gene are a cause of Townes-Brocks syndrome (TBS) as well as bronchio-oto-renal syndrome (BOR). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_002968.3

Inheritance

ClinVar variants

P:140U:382B:249

Top phenotype

Townes-Brocks syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr16:51,135,982-51,152,334

External References & Databases

Ensembl (ENSG00000103449)

Transcript & Mutation Effects

hg38 • Region Span ~16.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Townes-Brocks syndrome 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0054581

Submitter: G2P

Townes-Brocks syndrome 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0054581

Submitter: Ambry Genetics

Townes-Brocks syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007142

Submitter: Orphanet

Townes-Brocks syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0054581

Submitter: PanelApp Australia

Townes-Brocks syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0054581

Submitter: Labcorp Genetics (formerly Invitae)

Townes-Brocks syndrome 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0054581

Submitter: ClinGen

The *SALL1* gene is located on chromosome 16 at 16q12.1 and codes for the Spalt-Like 1 protein. *SALL1* includes 3 different DNA-binding zinc finger domains and alanine- and glutamine-rich regions that are frequently seen in transcription factors. The protein is a transcriptional repressor and is suspected to be a component of the NuRD histone deacetylase complex. *SALL1* was first reported in relation to autosomal dominant Townes-Brocks Syndrome (TBS) in 1998 (Kohlhase et al., PMID: 9425907). The most common features of this condition include imperforate anus/anal stenosis, dysplastic ears, hearing loss, limb anomalies, digit anomalies, and renal features. The hearing loss is bilateral and mild-to-profound, and either conductive, sensorineural, or both. Auricular anomalies include overfolded helices and preauricular skin tags (9973281, 16088922, 17221874, 37644569, 38915054, 40348827). 13 variants (nonsense, frameshift) that have been reported in at least 13 probands in 4 publications (PMIDs: 9973281, 16088922, 37644569, 39910415) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be either haploinsufficiency or dominant-negative. This gene-disease relationship is also supported by experimental evidence (mouse models; expression-level evidence). Mouse models indicate that mutant mice have features including reduced body size, decreased kidney weight, other kidney anomalies, limb/digit anomalies, reduced cell proliferation, and exencephaly (PMIDs: 12915476, 26311113). Evidence in mice shows expression in the renal tubular epithelium (PMID: 26311113). In summary, there is definitive evidence supporting the relationship between *SALL1* and autosomal dominant TBS. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date March 20, 2026 (SOP Version 12).

Clinical Genomic Database (CGD)

Townes-Brocks syndrome 1AD

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Renal

Intervention: Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Renal

Rationale: While frequently recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Surveillance for manifestations affecting other organ systems (eg, cardiac, endocrine, and renal) may allow early intervention, potentially reducing morbidity and mortality

Comments: The condition may be recognizable due to the presence of a specific pattern of congenital malformations affecting hearing as well as multiple organ systems

Refs: 5042490; 9072124; 9425907; 10928856; 11484202; 14755477; 16088922; 8000979; 17431915; 20301618

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SALL1 variants in ClinVar

11 Conditions Cataloged

Townes syndromeTotal: 365

not providedTotal: 286

Inborn genetic diseasesTotal: 183

Townes-Brocks syndrome 1Total: 146

not specifiedTotal: 131

SALL1-related disorderTotal: 96

Congenital anomaly of kidney and urinary tractTotal: 5

Townes-Brocks-branchiootorenal-like syndromeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002968.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	164 clinvar	5 clinvar	176
missense		3 clinvar	372 clinvar	74 clinvar	5 clinvar	454
nonsense	32 clinvar	10 clinvar	2 clinvar			44
start loss						0
frameshift	64 clinvar	30 clinvar			1 clinvar	95
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	96	44	382	238	11	771

Highest pathogenic variant AF is 0.000006156709

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002968.3	RefSeq	NP_002959.2	3	MANE Select
ENST00000251020.9	Ensembl	ENSP00000251020.4	3	MANE Select
NM_001127892.2	RefSeq	NP_001121364.1	2	Standard
ENST00000440970.6	Ensembl	ENSP00000407914.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
Olfactory bulb development and olfactory learning
Developmental Biology
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
Transcriptional regulation of pluripotent stem cells

Biological Process

negative regulation of transcription by RNA polymerase II
ureteric bud development
branching involved in ureteric bud morphogenesis
kidney development
ventricular septum development

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity

Cellular Component

heterochromatin
nucleus
nucleoplasm
cytoplasm
chromocenter

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000251020
Coding exons: 3
Length: 15393
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125748
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.722	687	742	0.925	0.0000455	8724
Missense (PolyPhen)		163	241.76	0.67423		2936
Synonymous	-0.504	331	320	1.04	0.0000232	2732
Loss of Function	4.92	2	32.1	0.0623	0.00000178	406

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor involved in organogenesis. {ECO:0000250}.;
Disease: DISEASE: Townes-Brocks syndrome 1 (TBS1) [MIM:107480]: A form of Townes-Brocks syndrome, a rare autosomal dominant disease characterized by the triad of imperforate anus, dysplastic ears, and thumb malformations. Minor features of the condition include hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. {ECO:0000269|PubMed:10533063, ECO:0000269|PubMed:9425907, ECO:0000269|PubMed:9973281}. Note=The disease is caused by mutations affecting the gene represented in this entry. Some individuals with SALL1 mutations manifest a phenotype overlapping with TBS1 and bronchio-oto-renal syndrome. Clinical features include dysplastic ears, hypoplastic kidneys with impaired renal function, gastroesophageal reflux, hypermetropia, hypospadias, and mild developmental delay. Affected individuals lack the characteristic anal or hand malformations of TBS1. {ECO:0000269|PubMed:10928856}.;

Recessive Scores

pRec: 0.278

Intolerance Scores

LoFtool: 0.0480
RVIS EVS: -0.83
RVIS percentile EVS: 11.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.311

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium