SALL4

spalt like transcription factor 4, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 20:51782331-51802521

Links

ENSG00000101115 ∙ NCBI:57167 ∙ OMIM:607343 ∙ HGNC:15924 ∙ Uniprot:Q9UJQ4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Duane-radial ray syndrome (Strong), mode of inheritance: AD
• Duane-radial ray syndrome (Definitive), mode of inheritance: AD
• Duane retraction syndrome (Supportive), mode of inheritance: AD
• IVIC syndrome (Supportive), mode of inheritance: AD
• Duane-radial ray syndrome (Definitive), mode of inheritance: AD
• Duane-radial ray syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Duane-radial ray/Okohiro syndrome; IVIC syndrome	AD	Audiologic/Otolaryngologic; Cardiovascular; Renal	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with vesicoureteral reflux, and surveillance and management may be helpful to preserve renal function; The conditions can involve congenital cardiac anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic; Renal	843249; 7395922; 12395297; 11826030; 12393809; 12789647; 12843316; 12868480; 15342710; 16086360; 16402211; 16411190; 17256792; 20301547

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SALL4 gene.

• Duane-radial_ray_syndrome (355 variants)
• Oculootoradial_syndrome (159 variants)
• not_provided (132 variants)
• Inborn_genetic_diseases (106 variants)
• SALL4-related_disorder (47 variants)
• not_specified (28 variants)
• SALL4-Related_Spectrum_Disorders (1 variants)
• Severe_combined_immunodeficiency,_autosomal_recessive,_T_cell-negative,_B_cell-negative,_NK_cell-positive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SALL4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020436.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		2	11	101	7	121
missense	1		280	34	4	319
nonsense	11	2	1			14
start loss						0
frameshift	26	9	4			39
splice donor/acceptor (+/-2bp)		2				2
Total	38	15	296	135	11

Highest pathogenic variant AF is 6.84047e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SALL4	protein_coding	protein_coding	ENST00000217086	4	18479

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000285	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	539	614	0.878	0.0000400	6896
Missense in Polyphen		151	219.69	0.68733		2561
Synonymous	-2.39	320	270	1.18	0.0000205	2202
Loss of Function	5.04	0	29.5	0.00	0.00000195	340

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000141	0.000114
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor with a key role in the maintenance and self-renewal of embryonic and hematopoietic stem cells. {ECO:0000269|PubMed:23012367}.
• Disease: DISEASE: Duane-radial ray syndrome (DRRS) [MIM:607323]: Disorder characterized by the association of forearm malformations with Duane retraction syndrome. {ECO:0000269|PubMed:12393809, ECO:0000269|PubMed:12395297, ECO:0000269|PubMed:16402211}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Oculootoradial syndrome (OORS) [MIM:147750]: Autosomal dominant condition characterized by upper limbs anomalies (radial ray defects, carpal bones fusion), extraocular motor disturbances, congenital bilateral non-progressive mixed hearing loss. Other less consistent malformations include heart involvement, mild thrombocytopenia and leukocytosis (before age 50), shoulder girdle hypoplasia, imperforate anus, kidney malrotation or rectovaginal fistula. The IVIC syndrome is an allelic disorder of Duane-radial ray syndrome (DRRS) with a similar phenotype. {ECO:0000269|PubMed:17256792}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Transcriptional regulation of pluripotent stem cells;Vitamin D Receptor Pathway;Wnt-beta-catenin Signaling Pathway in Leukemia;Developmental Biology;Signal Transduction;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Transcriptional regulation of pluripotent stem cells;Intracellular signaling by second messengers;Regulation of nuclear beta catenin signaling and target gene transcription (Consensus)

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.0991
• rvis_EVS: -1.47
• rvis_percentile_EVS: 3.73

Haploinsufficiency Scores

• pHI: 0.622
• hipred: Y
• hipred_score: 0.741
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.811

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sall4
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; 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); 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); reproductive system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary 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; limbs/digits/tail phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;inner cell mass cell proliferation;neural tube closure;ventricular septum development;regulation of transcription, DNA-templated;embryonic limb morphogenesis;somatic stem cell population maintenance;positive regulation of transcription by RNA polymerase II
• Cellular component: heterochromatin;nucleus;nucleoplasm;cytoplasm;protein-containing complex;intracellular membrane-bounded organelle
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein binding;transcription factor binding;metal ion binding