SALL1
spalt like transcription factor 1, the group of Zinc fingers C2H2-type
Basic information
Region (hg38): 16:51135981-51152334
Previous symbols: [ "TBS" ]
Links
Phenotypes
GenCC
Source:
- 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
Clinical Genomic Database
Source:
| 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
- Townes syndrome (189 variants)
- not provided (175 variants)
- Townes-Brocks syndrome 1 (109 variants)
- not specified (49 variants)
- Inborn genetic diseases (30 variants)
- Congenital anomaly of kidney and urinary tract (4 variants)
- Townes-Brocks-branchiootorenal-like syndrome (2 variants)
- VACTERL with hydrocephalus (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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 64 | 14 | 82 | ||
| missense | 2 | 129 | 39 | 9 | 179 | |
| nonsense | 20 | 3 | 1 | 1 | 25 | |
| start loss | 0 | |||||
| frameshift | 21 | 7 | 4 | 9 | 5 | 46 |
| inframe indel | 8 | 8 | ||||
| splice variant | 2 | 2 | ||||
| non coding | 2 | 6 | 6 | 14 | ||
| Total | 51 | 12 | 138 | 120 | 35 |
Highest pathogenic variant AF is 0.0000131
Variants in SALL1
This is a list of pathogenic ClinVar variants found in the SALL1 region.
| 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 interpretations of pathogenicity (Nov 01, 2022) | ||
| 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) | |||
| 16-51137123-C-T | Townes syndrome • Inborn genetic diseases | Conflicting interpretations of pathogenicity (Nov 07, 2022) | ||
| 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 • Townes-Brocks syndrome 1 • not specified | Benign/Likely benign (Jul 01, 2023) | ||
| 16-51137149-C-T | Townes syndrome • Inborn genetic diseases | Conflicting interpretations of pathogenicity (Jul 12, 2022) | ||
| 16-51137150-G-A | Townes syndrome | Uncertain significance (Jun 04, 2022) | ||
| 16-51137172-G-A | not specified • Townes syndrome | Benign (Jul 06, 2022) | ||
| 16-51137197-A-C | Townes syndrome • Inborn genetic diseases | Uncertain significance (Nov 08, 2022) | ||
| 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 (Oct 21, 2022) | ||
| 16-51137219-G-A | Inborn genetic diseases | Uncertain significance (Mar 17, 2023) | ||
| 16-51137240-C-T | Townes-Brocks syndrome 1 | Uncertain significance (Mar 31, 2020) | ||
| 16-51137244-G-C | Townes syndrome | Uncertain significance (Jul 26, 2022) | ||
| 16-51137251-G-A | Townes-Brocks syndrome 1 • Inborn genetic diseases • Townes syndrome | Uncertain significance (Mar 04, 2022) | ||
| 16-51137255-G-C | Inborn genetic diseases | Uncertain significance (Feb 15, 2023) | ||
| 16-51137264-C-T | not specified • Townes-Brocks syndrome 1 • Townes syndrome | Benign (Nov 01, 2022) |
GnomAD
Source:
| 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:
- 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