SALL1

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

Basic information

Region (hg38): 16:51135982-51152334

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 (309 variants)
not_provided (238 variants)
Inborn_genetic_diseases (147 variants)
Townes-Brocks_syndrome_1 (140 variants)
SALL1-related_disorder (69 variants)
not_specified (54 variants)
Congenital_anomaly_of_kidney_and_urinary_tract (5 variants)
Townes-Brocks-branchiootorenal-like_syndrome (2 variants)
VACTERL_with_hydrocephalus (1 variants)
Hearing_impairment (1 variants)
Microcephaly (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. These statistics are base on transcript: NM_000002968.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	112 clinvar	13 clinvar	132
missense	1 clinvar	3 clinvar	305 clinvar	64 clinvar	7 clinvar	380
nonsense	28 clinvar	8 clinvar				36
start loss						0
frameshift	58 clinvar	17 clinvar				75
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	87	29	312	176	20

Highest pathogenic variant AF is 0.00000615671

Loading clinvar variants...

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