SALL1

Summary

SALL1 (spalt like transcription factor 1, HGNC:10524) is a protein-coding gene on chromosome 16q12.1, encoding Sal-like protein 1 (Q9NSC2). Transcriptional repressor involved in organogenesis.

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.

Source: NCBI Gene 6299 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Townes-Brocks syndrome 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 77
• Clinical variants (ClinVar): 759 total — 96 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 102
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002968

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10524
Approved symbol	SALL1
Name	spalt like transcription factor 1
Location	16q12.1
Locus type	gene with protein product
Status	Approved
Aliases	Hsal1, ZNF794
Ensembl gene	ENSG00000103449
Ensembl biotype	protein_coding
OMIM	602218
Entrez	6299

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000251020, ENST00000440970, ENST00000562674, ENST00000566102, ENST00000570206, ENST00000685868, ENST00000690502, ENST00000884629, ENST00000911277

RefSeq mRNA: 2 — MANE Select: NM_002968 NM_001127892, NM_002968

CCDS: CCDS10747, CCDS45483

Canonical transcript exons

ENST00000251020 — 3 exons

Exon	Start	End
ENSE00000683837	51151166	51151270
ENSE00003466827	51138688	51142145
ENSE00003896882	51135982	51137552

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 97.53.

FANTOM5 (CAGE): breadth broad, TPM avg 5.7551 / max 286.6308, expressed in 613 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157352	1.8265	460
157353	1.3655	388
157354	0.7560	227
157359	0.6519	302
157356	0.3283	196
157351	0.2657	117
157357	0.1773	104
157358	0.1657	92
157350	0.1161	52
157355	0.1021	51

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.53	gold quality
inferior vagus X ganglion	UBERON:0005363	96.12	gold quality
renal medulla	UBERON:0000362	95.01	gold quality
subthalamic nucleus	UBERON:0001906	92.54	gold quality
superior vestibular nucleus	UBERON:0007227	92.33	gold quality
ganglionic eminence	UBERON:0004023	91.75	gold quality
medial globus pallidus	UBERON:0002477	90.98	gold quality
stromal cell of endometrium	CL:0002255	90.97	gold quality
right lobe of liver	UBERON:0001114	90.56	gold quality
globus pallidus	UBERON:0001875	90.51	gold quality
spinal cord	UBERON:0002240	90.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.12	gold quality
metanephros cortex	UBERON:0010533	89.98	gold quality
endometrium	UBERON:0001295	89.84	gold quality
embryo	UBERON:0000922	89.63	gold quality
medulla oblongata	UBERON:0001896	89.29	gold quality
right lobe of thyroid gland	UBERON:0001119	89.19	gold quality
corpus callosum	UBERON:0002336	88.97	gold quality
ventral tegmental area	UBERON:0002691	88.80	gold quality
adult mammalian kidney	UBERON:0000082	88.22	gold quality
liver	UBERON:0002107	88.01	gold quality
thyroid gland	UBERON:0002046	87.75	gold quality
left lobe of thyroid gland	UBERON:0001120	87.36	gold quality
endocervix	UBERON:0000458	85.72	gold quality
lateral globus pallidus	UBERON:0002476	85.63	gold quality
kidney	UBERON:0002113	85.61	gold quality
dorsal plus ventral thalamus	UBERON:0001897	85.46	gold quality
substantia nigra pars reticulata	UBERON:0001966	85.28	gold quality
midbrain	UBERON:0001891	84.46	gold quality
buccal mucosa cell	CL:0002336	83.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	13.57
E-ANND-3	no	2.64

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
DKK1
FGF2
FOXN1
PER1
POU5F1	Activation
SALL1
VEGFA	Activation

Upstream regulators (CollecTRI, top): ESR1, HOXA13, HOXD13, SALL1, SALL4, SIX1

miRNA regulators (miRDB)

130 targeting SALL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-106A-5P	99.90	73.94	2683

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 31)

• Mutation in Townes-Brocks syndrome. Product is a transcriptional repressor which interacts with TRF1/PIN2 and localizes to pericentromeric heterochromatin. (PMID:11751684)
• binding of proteins SALL1, UBE2I and SUMO-1 (PMID:12200128)
• sall1 enhances the canonical Wnt signaling by localizing to heterochromatin (PMID:15158448)
• analysis of SALL1 mutations in Townes-Brocks syndrome (PMID:16088922)
• Sall1 is essential for ureteric bud invasion, the initial key step for metanephros development (PMID:16221172)
• there is a different contribution of SALL1 gene function to mouse and human embryonic development (PMID:16429401)
• Data show that SALL1 contains two repression domains, one located at the extreme N-terminus of the protein and the other in the central region. (PMID:16443351)
• SALL1 is a likely target gene for SIX1 during kidney development (PMID:16670092)
• There is an enhancer element in the SALL1 gene. (PMID:17426652)
• SALL1 gene, mutations of which result in the Townes-Brocks phenotype, is expressed in the developing kidney. (PMID:17910067)
• SALL1 and GLI3 may have roles in limb malformation and are affected by nonsense-mediated decay (PMID:18000979)
• analysis of one sporadic case of Townes-Brocks syndrome for SALL1 gene mutations and review of the literature [review] (PMID:18280297)
• truncated SALL1 protein is expressed in cells derived from a TBS patient (PMID:18470945)
• This case increases the demand to examine all children with Townes-Brocks Syndrome (TBS) for ophthalmic abnormalities. (PMID:19005989)
• Familial transmission of Goldenhar syndrome is not due to mutations in SALL1. (PMID:19213029)
• Studies indicate that vertebrate sal orthologues (spalt-like/sall) have important developmental roles during neural development and organogenesis and gentic diseases. (PMID:19247946)
• Data demonstrate that stem cell protein SALL4 represses its target genes, PTEN and SALL1, through the epigenetic repressor Mi-2/NuRD complex. (PMID:19440552)
• Sall1 induces angiogenesis by stimulating VEGF-A promoter activity. (PMID:19942929)
• novel role for Sall1 as a member of the transcriptional network that regulates stem cell pluripotency (PMID:21062744)
• report on a family with features of TBS in whom a novel 149 kb deletion spanning the SALL1 gene was identified by high resolution cytogenetics SNP microarray (PMID:22308078)
• quantity and quality of SALL1 transcript are important for SALL1 function and determine phenotype, and mode of inheritance, of allelic SALL1-related disorders (PMID:23069192)
• Inhibition of SALL1 correlates with reduced levels of CDH1, an important contributor to epithelial-to-mesenchymal transition. (PMID:24292671)
• SALL1 mutations might cause Townes-Brocks Syndrome. (PMID:29395072)
• Data identified SALL1 as a novel tumor suppressor in breast cancer. SALL1 can induce tumor cell senescence as a novel mechanism of tumor suppressor function. This molecular process acts through NuRD recruitment and is controlled by the MAPK and mTOR signaling pathways. (PMID:29625565)
• In human glioblastoma cells and cerebral glioma tissues, SALL1 acted as a tumor suppressor gene by inhibiting Wnt/ss-catenin signaling. (PMID:31040265)
• miR-4286 promotes prostate cancer progression by targeting the expression of SALL1. (PMID:31693770)
• SOX2/SALL4 stemness axis modulates Notch signaling genes to maintain self-renewal capacity of esophageal squamous cell carcinoma. (PMID:33098486)
• Hsa_circ_0043265 Restrains Cell Proliferation, Migration and Invasion of Tongue Squamous Cell Carcinoma via Targeting the miR-1243/SALL1 Axis. (PMID:34257535)
• Townes-Brocks syndrome with craniosynostosis in two siblings. (PMID:36252910)
• Chromosomal Microarray Analysis Identifies a Novel SALL1 Deletion, Supporting the Association of Haploinsufficiency with a Mild Phenotype of Townes-Brocks Syndrome. (PMID:36833185)
• A novel SALL1 C757T mutation in a Chinese family causes a rare disease –Townes-Brocks syndrome. (PMID:38915054)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sall1a	ENSDARG00000074319
danio_rerio	sall1b	ENSDARG00000075891
mus_musculus	Sall1	ENSMUSG00000031665
rattus_norvegicus	Sall1	ENSRNOG00000013907

Paralogs (14): HIVEP2 (ENSG00000010818), HIVEP1 (ENSG00000095951), SALL4 (ENSG00000101115), ZNF516 (ENSG00000101493), BCL11A (ENSG00000119866), ZNF831 (ENSG00000124203), RREB1 (ENSG00000124782), HIVEP3 (ENSG00000127124), BCL11B (ENSG00000127152), ZNF219 (ENSG00000165804), SALL2 (ENSG00000165821), ZNF217 (ENSG00000171940), ZNF536 (ENSG00000198597), SALL3 (ENSG00000256463)

Protein

Protein identifiers

Sal-like protein 1 — Q9NSC2 (reviewed: Q9NSC2)

Alternative names: Spalt-like transcription factor 1, Zinc finger protein 794, Zinc finger protein SALL1, Zinc finger protein Spalt-1

All UniProt accessions (4): A0A8I5KRF8, Q9NSC2, H3BQ32, H3BSM9

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor involved in organogenesis. Plays an essential role in ureteric bud invasion during kidney development.

Subunit / interactions. May associate with NuRD histone deacetylase complex (HDAC). Interacts with components of HDAC complex including HDAC1, HDAC2, RBBP4, RBPP7, MTA1 and MTA2. Interacts with CCNQ. Interacts with NSD2 (via PHD-type zinc fingers 1, 2 and 3).

Subcellular location. Nucleus.

Tissue specificity. Highest levels in kidney. Lower levels in adult brain (enriched in corpus callosum, lower expression in substantia nigra) and liver.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. The pathogenic mechanism includes abnormal interactions of mutant SALL1 protein with proteins that control cilium formation and function, resulting in ciliary defects. 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.

Similarity. Belongs to the sal C2H2-type zinc-finger protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NSC2-1	1	yes
Q9NSC2-2	2

RefSeq proteins (2): NP_001121364, NP_002959* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051565	Sal_C2H2-zinc-finger	Family

Pfam: PF00096, PF12874

UniProt features (55 total): compositionally biased region 11, zinc finger region 10, cross-link 10, region of interest 9, modified residue 5, sequence variant 5, sequence conflict 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSC2-F1	49.54	0.01

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (15): 590, 593, 595, 941, 943, 439, 673, 690, 701, 947, 982, 1086, 1219, 1299, 1319

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2892247	POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
R-HSA-9830674	Formation of the ureteric bud
R-HSA-1266738	Developmental Biology
R-HSA-452723	Transcriptional regulation of pluripotent stem cells
R-HSA-9830369	Kidney development

MSigDB gene sets: 575 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, MYAATNNNNNNNGGC_UNKNOWN, E2F_Q4_01, GOBP_OLFACTORY_BULB_INTERNEURON_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, WWTAAGGC_UNKNOWN, GOBP_METANEPHROS_DEVELOPMENT, PAX4_01, GOBP_MESENCHYMAL_TO_EPITHELIAL_TRANSITION, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, LFA1_Q6

GO Biological Process (27): negative regulation of transcription by RNA polymerase II (GO:0000122), ureteric bud development (GO:0001657), branching involved in ureteric bud morphogenesis (GO:0001658), kidney development (GO:0001822), ventricular septum development (GO:0003281), mesenchymal to epithelial transition involved in metanephros morphogenesis (GO:0003337), regulation of transcription by RNA polymerase II (GO:0006357), heart development (GO:0007507), gonad development (GO:0008406), olfactory nerve development (GO:0021553), olfactory bulb interneuron differentiation (GO:0021889), pituitary gland development (GO:0021983), positive regulation of Wnt signaling pathway (GO:0030177), adrenal gland development (GO:0030325), inductive cell-cell signaling (GO:0031129), embryonic digit morphogenesis (GO:0042733), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic digestive tract development (GO:0048566), limb development (GO:0060173), olfactory bulb mitral cell layer development (GO:0061034), kidney epithelium development (GO:0072073), ureteric bud invasion (GO:0072092), regulation of signal transduction (GO:0009966), olfactory bulb development (GO:0021772), tube development (GO:0035295)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), beta-catenin binding (GO:0008013), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), chromocenter (GO:0010369)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Developmental Biology	2
Transcriptional regulation of pluripotent stem cells	1
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
animal organ development	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
endocrine system development	2
gland development	2
DNA-templated transcription	2
chromatin	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
mesonephric tubule development	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
renal system development	1
cardiac ventricle development	1
cardiac septum development	1
metanephros morphogenesis	1
epithelial cell differentiation involved in kidney development	1
mesenchymal to epithelial transition	1
metanephric renal vesicle morphogenesis	1
circulatory system development	1
development of primary sexual characteristics	1
reproductive structure development	1
cranial nerve development	1
olfactory bulb development	1
forebrain neuron differentiation	1
diencephalon development	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
developmental induction	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
digestive tract development	1
embryonic organ development	1
cis-regulatory region sequence-specific DNA binding	1

Protein interactions and networks

STRING

2020 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SALL1	NANOG	Q9H9S0	908
SALL1	NSD2	O96028	870
SALL1	SIX2	Q9NPC8	859
SALL1	EYA1	Q99502	832
SALL1	CCNQ	Q8N1B3	816
SALL1	SIX1	Q15475	807
SALL1	TERF1	P54274	777
SALL1	TMEM119	Q4V9L6	753
SALL1	P2RY12	Q9H244	690
SALL1	PAX2	Q02962	684
SALL1	SETD2	Q9BYW2	680
SALL1	SOX2	P48431	651
SALL1	NKX3-2	P78367	650
SALL1	TBX5	Q99593	630
SALL1	NKX2-5	P52952	622

IntAct

43 interactions, top by confidence:

A	B	Type	Score
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
PPP1R13B	SALL1	psi-mi:“MI:0915”(physical association)	0.560
TIMM50	ZNF724	psi-mi:“MI:0914”(association)	0.530
DSN1	EXOC5	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
SALL1	TIMM50	psi-mi:“MI:0914”(association)	0.530
USP7	SALL1	psi-mi:“MI:0407”(direct interaction)	0.440
DCLK3	SALL1	psi-mi:“MI:0915”(physical association)	0.370
FOXA2	FOXN2	psi-mi:“MI:0914”(association)	0.350
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXC1	NFIX	psi-mi:“MI:0914”(association)	0.350
FOXC2	ZNF536	psi-mi:“MI:0914”(association)	0.350
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXG1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
TEAD2	DDX39A	psi-mi:“MI:0914”(association)	0.350
GRHL1	POLRMT	psi-mi:“MI:0914”(association)	0.350
HDAC1		psi-mi:“MI:0914”(association)	0.350
HDAC2		psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
RFPL4B	KRBA1	psi-mi:“MI:0914”(association)	0.350
TEX19	ZNF316	psi-mi:“MI:0914”(association)	0.350
SALL1	MTA2	psi-mi:“MI:0914”(association)	0.350
VRTN	CCT6B	psi-mi:“MI:0914”(association)	0.350
HPS1	ZBTB10	psi-mi:“MI:0914”(association)	0.350
SOX7	NFIB	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (126): SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), SALL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A5E4M3Q4, A0A5S9MMK5, G5EBU4, G5EC77, G5ECU7, G5EFF4, G5EGF4, G5EGN3, O17862, O44757, O60315, O88368, P08044, P08155, P15619, P25932, P25992, P34447, P34536, P39770, P40650, P41885, P41934, P55879, P97836, Q05192, Q08874, Q0KIC3, Q10938, Q21446, Q22024, Q23045, Q24459, Q27355, Q28G71, Q28XY0, Q66JF1, Q6XDT4, Q8I7Z8, Q8MT36

Diamond homologs: A1L2U9, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, O35615, O62836, O77459, P08048, P10925, P15822, P17010, P17012, P20662, P31505, P31629, P60319, P78871, P80944, Q00900, Q01611, Q02031, Q03172, Q0IH98, Q0VCJ6, Q292R5, Q29419, Q3UHF7, Q52V16, Q5JPB2, Q5T1R4, Q6B4Z5, Q7JM44, Q811F1, Q86UZ6, Q8BID6, Q8CII0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SALL4	“down-regulates quantity by repression”	SALL1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of TP53 Activity through Acetylation	5	60.1×	4e-06
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	5	50.1×	5e-06
Deactivation of the beta-catenin transactivating complex	5	30.7×	2e-05
RNA Polymerase I Transcription Initiation	5	29.5×	3e-05
Regulation of PTEN gene transcription	5	23.5×	7e-05
NuRD complex assembly	6	22.3×	2e-05
Interaction of NuRD complexes with transcription factors	6	20.0×	2e-05
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	5	20.0×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	6	82.1×	7e-09
negative regulation of neuron differentiation	5	24.3×	1e-04
anatomical structure morphogenesis	5	12.4×	2e-03
chromatin remodeling	7	9.1×	5e-04
chromatin organization	5	8.8×	5e-03
brain development	6	8.5×	2e-03
transcription by RNA polymerase II	6	7.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

759 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	96
Likely pathogenic	21
Uncertain significance	369
Likely benign	147
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013100	NM_002968.3(SALL1):c.824T>A (p.Leu275Ter)	Pathogenic
1069244	NM_002968.3(SALL1):c.1423_1424del (p.Arg475fs)	Pathogenic
1069953	NM_002968.3(SALL1):c.1028dup (p.Leu344fs)	Pathogenic
1070663	NM_002968.3(SALL1):c.881_893dup (p.Leu299fs)	Pathogenic
1071229	NM_002968.3(SALL1):c.1027dup (p.Ile343fs)	Pathogenic
1075840	NM_002968.3(SALL1):c.870dup (p.Gln291fs)	Pathogenic
1179917	NM_002968.3(SALL1):c.388_391delinsTTTGCTAACAAAGCGGCAGCGGCACTT (p.Pro130fs)	Pathogenic
1204271	NM_002968.3(SALL1):c.565_566dup (p.Val190fs)	Pathogenic
1353868	NM_002968.3(SALL1):c.691del (p.Glu231fs)	Pathogenic
1679359	NM_002968.3(SALL1):c.1363_1369delinsTGAAACA (p.Ala455_Val457delinsTer)	Pathogenic
1704095	NM_002968.3(SALL1):c.1112C>G (p.Ser371Ter)	Pathogenic
1705680	NM_002968.3(SALL1):c.1228G>T (p.Gly410Ter)	Pathogenic
2005719	NM_002968.3(SALL1):c.1417G>T (p.Gly473Ter)	Pathogenic
2031602	NM_002968.3(SALL1):c.878_887del (p.Leu293fs)	Pathogenic
2103715	NM_002968.3(SALL1):c.469_512dup (p.Ile172fs)	Pathogenic
2137807	NM_002968.3(SALL1):c.874C>T (p.Gln292Ter)	Pathogenic
2424574	NC_000016.9:g.(?51185057)(51185152_?)del	Pathogenic
2498664	NM_002968.3(SALL1):c.718C>T (p.Gln240Ter)	Pathogenic
2575075	NM_002968.3(SALL1):c.1240G>T (p.Glu414Ter)	Pathogenic
2646526	NM_002968.3(SALL1):c.633_634del (p.Gln212fs)	Pathogenic
2681784	NM_002968.3(SALL1):c.2283_2284del (p.Leu762fs)	Pathogenic
2687773	NM_002968.3(SALL1):c.1148del (p.Leu383fs)	Pathogenic
2694137	NM_002968.3(SALL1):c.1183C>T (p.Gln395Ter)	Pathogenic
2703340	NM_002968.3(SALL1):c.1309G>T (p.Glu437Ter)	Pathogenic
2745434	NM_002968.3(SALL1):c.76+5G>A	Pathogenic
279887	NM_002968.3(SALL1):c.870_871dup (p.Gln291fs)	Pathogenic
280886	NM_002968.3(SALL1):c.3099_3105dup (p.Arg1036fs)	Pathogenic
2828754	NM_002968.3(SALL1):c.3128_3129del (p.Asn1043fs)	Pathogenic
2837510	NM_002968.3(SALL1):c.2325_2331dup (p.Ala778fs)	Pathogenic
291272	NM_002968.3(SALL1):c.727C>T (p.Gln243Ter)	Pathogenic

SpliceAI

397 predictions. Top by Δscore:

Variant	Effect	Δscore
16:51137551:ACC:A	acceptor_loss	1.0000
16:51143316:T:TA	donor_gain	1.0000
16:51143339:T:TA	donor_gain	1.0000
16:51143340:C:A	donor_gain	1.0000
16:51137548:TGTAC:T	acceptor_gain	0.9900
16:51137558:A:AC	acceptor_gain	0.9900
16:51137560:A:AC	acceptor_gain	0.9900
16:51137560:A:C	acceptor_gain	0.9900
16:51137574:C:CT	acceptor_gain	0.9900
16:51143305:C:CA	donor_gain	0.9900
16:51151164:A:AC	donor_gain	0.9900
16:51151165:C:CC	donor_gain	0.9900
16:51151165:CCAT:C	donor_gain	0.9900
16:51137553:C:CC	acceptor_gain	0.9800
16:51137558:A:C	acceptor_gain	0.9800
16:51137570:C:CT	acceptor_gain	0.9800
16:51137571:A:T	acceptor_gain	0.9800
16:51137582:C:CT	acceptor_gain	0.9800
16:51143302:A:AC	donor_gain	0.9800
16:51143303:C:CC	donor_gain	0.9800
16:51151158:GCACT:G	donor_loss	0.9800
16:51151159:CACTC:C	donor_loss	0.9800
16:51151160:ACTCA:A	donor_loss	0.9800
16:51151161:CT:C	donor_loss	0.9800
16:51151162:T:TC	donor_loss	0.9800
16:51151163:C:CC	donor_loss	0.9800
16:51151165:C:CT	donor_loss	0.9800
16:51137549:GTAC:G	acceptor_gain	0.9700
16:51137550:TAC:T	acceptor_gain	0.9700
16:51137551:AC:A	acceptor_gain	0.9700

AlphaMissense

8761 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:51137535:G:C	H1184Q	1.000
16:51137535:G:T	H1184Q	1.000
16:51137537:G:C	H1184D	1.000
16:51137547:G:C	H1180Q	1.000
16:51137547:G:T	H1180Q	1.000
16:51137548:T:C	H1180R	1.000
16:51137549:G:C	H1180D	1.000
16:51137549:G:T	H1180N	1.000
16:51138692:A:G	L1177P	1.000
16:51138694:A:C	N1176K	1.000
16:51138694:A:T	N1176K	1.000
16:51138696:T:C	N1176D	1.000
16:51138698:C:A	G1175V	1.000
16:51138698:C:T	G1175D	1.000
16:51138699:C:A	G1175C	1.000
16:51138699:C:G	G1175R	1.000
16:51138704:G:A	T1173I	1.000
16:51138709:G:C	F1171L	1.000
16:51138709:G:T	F1171L	1.000
16:51138710:A:C	F1171C	1.000
16:51138710:A:G	F1171S	1.000
16:51138711:A:G	F1171L	1.000
16:51138711:A:T	F1171I	1.000
16:51138715:T:A	R1169S	1.000
16:51138715:T:G	R1169S	1.000
16:51138721:A:C	C1167W	1.000
16:51138722:C:A	C1167F	1.000
16:51138722:C:T	C1167Y	1.000
16:51138723:A:G	C1167R	1.000
16:51138730:G:C	C1164W	1.000

dbSNP variants (sampled 300 via entrez): RS1000044366 (16:51144580 C>T), RS1000105275 (16:51150830 G>GCTCC), RS1000272546 (16:51154311 AG>A,AGG), RS1000315627 (16:51144853 G>GA), RS1000379475 (16:51146169 C>T), RS1000515375 (16:51153385 TC>T), RS1001350338 (16:51144165 C>A,T), RS1001755555 (16:51149707 T>C), RS1002062792 (16:51141633 T>A,C,G), RS1002387491 (16:51142447 T>C), RS1002756668 (16:51148234 A>C), RS1003018810 (16:51151751 C>CA,CG), RS1003650623 (16:51152925 G>C), RS1003748856 (16:51146285 T>C), RS1004160621 (16:51145415 C>T)

Disease associations

OMIM: gene MIM:602218 | disease phenotypes: MIM:107480, MIM:610805, MIM:276950

GenCC curated gene-disease

Disease	Classification	Inheritance
Townes-Brocks syndrome 1	Definitive	Autosomal dominant
Townes-Brocks syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Townes-Brocks syndrome 1	Definitive	AD

Mondo (6): Townes-Brocks syndrome (MONDO:0007142), Townes-Brocks syndrome 1 (MONDO:0054581), hearing loss disorder (MONDO:0005365), congenital anomaly of kidney and urinary tract (MONDO:0019719), VACTERL with hydrocephalus (MONDO:0010172), microcephaly (MONDO:0001149)

Orphanet (3): Townes-Brocks syndrome (Orphanet:857), Renal or urinary tract malformation (Orphanet:93545), VACTERL with hydrocephalus (Orphanet:3412)

HPO phenotypes

102 total (30 of 102 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000048	Bifid scrotum
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000086	Ectopic kidney
HP:0000089	Renal hypoplasia
HP:0000110	Renal dysplasia
HP:0000130	Abnormality of the uterus
HP:0000136	Bifid uterus
HP:0000142	Abnormal vagina morphology
HP:0000143	Rectovaginal fistula
HP:0000154	Wide mouth
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000324	Facial asymmetry
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000384	Preauricular skin tag
HP:0000394	Lop ear
HP:0000396	Overfolded helix
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000453	Choanal atresia
HP:0000486	Strabismus
HP:0000504	Abnormality of vision
HP:0000518	Cataract
HP:0000567	Chorioretinal coloboma

GWAS associations

77 associations (top):

Study	Trait	p-value
GCST000699_1	Optic disc parameters	5.000000e-09
GCST000965_13	C-reactive protein levels	9.000000e-13
GCST001991_4	Weight loss (gastric bypass surgery)	4.000000e-06
GCST002252_3	Blood pressure measurement (high sodium and potassium intervention)	7.000000e-13
GCST002252_8	Blood pressure measurement (high sodium and potassium intervention)	2.000000e-06
GCST002626_13	Vertical cup-disc ratio	4.000000e-13
GCST002762_17	Optic cup area	2.000000e-08
GCST002762_2	Optic cup area	2.000000e-08
GCST002765_10	Optic disc area	2.000000e-11
GCST002765_5	Optic disc area	9.000000e-11
GCST003069_5	Left superior temporal gyrus thickness (schizophrenia interaction)	6.000000e-06
GCST004076_23	Optic disc area	2.000000e-13
GCST004076_9	Optic disc area	4.000000e-13
GCST004137_27	Optic cup area	9.000000e-09
GCST004137_42	Optic cup area	5.000000e-09
GCST005748_8	Digit length ratio (right hand)	2.000000e-11
GCST005749_19	Digit length ratio (left hand)	6.000000e-16
GCST005749_20	Digit length ratio (left hand)	5.000000e-15
GCST005750_9	Digit length ratio	7.000000e-17
GCST005766_1	Diabetes mellitus	2.000000e-06
GCST005984_72	Glomerular filtration rate	4.000000e-09
GCST005985_15	Creatinine levels	9.000000e-10
GCST006462_40	Uterine fibroids	1.000000e-09
GCST006979_663	Heel bone mineral density	2.000000e-30
GCST006979_664	Heel bone mineral density	5.000000e-11
GCST006979_665	Heel bone mineral density	2.000000e-14
GCST007324_110	Adventurousness	1.000000e-08
GCST007344_102	Estimated glomerular filtration rate	2.000000e-07
GCST007344_3	Estimated glomerular filtration rate	2.000000e-14
GCST007614_51	C-reactive protein levels	2.000000e-22

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0005245	body weight loss
EFO:0005401	response to high sodium diet
EFO:0005403	response to dietary potassium supplementation
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0004841	digit length ratio
EFO:0009270	heel bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0007785	femoral neck bone mineral density
EFO:0010078	dentures
EFO:0006939	cup-to-disc ratio measurement
EFO:0007710	cognitive decline measurement
EFO:0004509	hemoglobin measurement
EFO:0004918	age at diagnosis
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004840	cortical thickness
EFO:0005665	white matter hyperintensity measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C566906	Cakut (supp.)
C536974	Townes-Brocks syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol A	affects methylation, affects cotreatment, decreases methylation, increases methylation	3
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	decreases expression	2
Acetaminophen	decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tamoxifen	decreases expression, affects expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
bisphenol S	decreases methylation	1
Venlafaxine Hydrochloride	increases expression	1
Decitabine	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Cyclophosphamide	affects response to substance	1
Diethylhexyl Phthalate	decreases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A6A6	SEES3-1V human SALL1, clone1	Embryonic stem cell	Male
CVCL_A6A7	SEES3-1V human SALL1, clone2	Embryonic stem cell	Male
CVCL_A6A8	SEES3-1V human SALL1, clone3	Embryonic stem cell	Male
CVCL_XV79	HEK293 eGFP-SALL1	Transformed cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	EARLY_PHASE1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss