SALL1

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

Basic information

Region (hg38): 16:51135981-51152334

Previous symbols: [ "TBS" ]

Links

ENSG00000103449 ∙ NCBI:6299 ∙ OMIM:602218 ∙ HGNC:10524 ∙ Uniprot:Q9NSC2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Townes-Brocks syndrome 1 (Strong), mode of inheritance: AD
• Townes-Brocks syndrome 1 (Definitive), mode of inheritance: AD
• Townes-Brocks syndrome (Supportive), mode of inheritance: AD
• Townes-Brocks syndrome 1 (Definitive), mode of inheritance: AD
• Townes-Brocks syndrome 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Townes-Brocks syndrome 1	AD	Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Renal	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	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Renal	5042490; 9072124; 9425907; 10928856; 11484202; 14755477; 16088922; 8000979; 17431915; 20301618
The condition may be recognizable due to the presence of a specific pattern of congenital malformations affecting hearing as well as multiple organ systems

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SALL1 gene.

• Townes syndrome (215 variants)
• not provided (194 variants)
• Townes-Brocks syndrome 1 (104 variants)
• Inborn genetic diseases (54 variants)
• not specified (49 variants)
• SALL1-related condition (11 variants)
• Congenital anomaly of kidney and urinary tract (3 variants)
• VACTERL with hydrocephalus (1 variants)
• Microcephaly (1 variants)
• Townes-Brocks-branchiootorenal-like syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SALL1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	67	12	83
missense		1	167	28	9	205
nonsense	19	4	1			24
start loss						0
frameshift	27	6				33
inframe indel			7	6	1	14
splice donor/acceptor (+/-2bp)						0
splice region	1			2		3
non coding			3	9	8	20
Total	46	11	182	110	30

Highest pathogenic variant AF is 0.0000131

Variants in SALL1

This is a list of pathogenic ClinVar variants found in the SALL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-51135999-C-CA		Townes-Brocks syndrome 1	Likely benign (Jun 14, 2016)
16-51136078-A-AC		Townes-Brocks syndrome 1	Uncertain significance (Jun 14, 2016)
16-51136183-CAAG-C		Townes-Brocks syndrome 1	Conflicting classifications of pathogenicity (Apr 01, 2023)
16-51136405-CTT-C		Townes-Brocks syndrome 1	Uncertain significance (Jun 14, 2016)
16-51136523-CA-C		Townes-Brocks syndrome 1	Benign (Jun 14, 2016)
16-51136548-TA-T		Townes-Brocks syndrome 1	Uncertain significance (Jun 14, 2016)
16-51137019-AGGGGC-A		Townes-Brocks syndrome 1	Likely benign (Mar 31, 2019)
16-51137019-A-AGGGGC			Benign (Mar 03, 2015)
16-51137103-C-T		SALL1-related disorder	Likely benign (Aug 13, 2019)
16-51137121-G-A		Townes syndrome	Likely benign (Dec 21, 2022)
16-51137123-C-T		Townes syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 07, 2022)
16-51137124-G-A		Townes syndrome	Likely benign (Apr 07, 2023)
16-51137124-G-C			Benign (Oct 14, 2020)
16-51137130-C-T		Townes syndrome	Likely benign (Jul 14, 2021)
16-51137140-T-C		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
16-51137145-G-A		Townes syndrome • not specified • Townes-Brocks syndrome 1 • SALL1-related disorder	Benign/Likely benign (Jan 15, 2024)
16-51137149-C-T		Townes syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 01, 2023)
16-51137150-G-A		Townes syndrome	Uncertain significance (Jun 04, 2022)
16-51137159-G-A		Townes syndrome	Uncertain significance (May 01, 2023)
16-51137172-G-A		not specified • Townes syndrome	Benign (Dec 02, 2023)
16-51137197-A-C		Townes syndrome • Inborn genetic diseases • SALL1-related disorder	Uncertain significance (Sep 20, 2023)
16-51137201-C-T		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
16-51137212-G-T		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
16-51137215-T-C		not specified • Townes-Brocks syndrome 1 • Townes syndrome	Benign/Likely benign (Jan 22, 2024)
16-51137219-G-A		Inborn genetic diseases	Uncertain significance (Mar 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SALL1	protein_coding	protein_coding	ENST00000251020	3	15393

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000295	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.722	687	742	0.925	0.0000455	8724
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000448	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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 (Consensus)

Recessive Scores

• pRec: 0.278

Intolerance Scores

• loftool: 0.0480
• rvis_EVS: -0.83
• rvis_percentile_EVS: 11.53

Haploinsufficiency Scores

• pHI: 0.933
• hipred: Y
• hipred_score: 0.852
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.311

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sall1
• Phenotype: cellular phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; skeleton phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;ureteric bud development;branching involved in ureteric bud morphogenesis;kidney development;ventricular septum development;mesenchymal to epithelial transition involved in metanephros morphogenesis;regulation of transcription, DNA-templated;heart development;gonad development;histone deacetylation;olfactory nerve development;olfactory bulb interneuron differentiation;pituitary gland development;positive regulation of Wnt signaling pathway;adrenal gland development;inductive cell-cell signaling;somatic stem cell population maintenance;outer ear morphogenesis;embryonic digit morphogenesis;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;embryonic digestive tract development;limb development;olfactory bulb mitral cell layer development;kidney epithelium development;ureteric bud invasion
• Cellular component: heterochromatin;nucleus;nucleoplasm;cytoplasm;chromocenter
• 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;histone deacetylase activity;protein binding;beta-catenin binding;metal ion binding