SETBP1

SET binding protein 1

Basic information

Region (hg38): 18:44680172-45068510

Links

ENSG00000152217 ∙ NCBI:26040 ∙ OMIM:611060 ∙ HGNC:15573 ∙ Uniprot:Q9Y6X0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Schinzel-Giedion syndrome (Definitive), mode of inheritance: AD
• Schinzel-Giedion syndrome (Strong), mode of inheritance: AD
• Schinzel-Giedion syndrome (Supportive), mode of inheritance: AD
• intellectual disability-expressive aphasia-facial dysmorphism syndrome (Supportive), mode of inheritance: AD
• Schinzel-Giedion syndrome (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 29 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• Schinzel-Giedion syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schinzel-Giedion midface retraction syndrome	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Renal	665725; 7506484; 7864048; 8849020; 9738870; 18398855; 20436468; 21371013; 22333924; 23400866; 25217958
The condition can involve neoplasms (neuroepithelial neoplasia)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SETBP1 gene.

• not provided (1094 variants)
• Schinzel-Giedion syndrome (64 variants)
• Intellectual disability, autosomal dominant 29 (57 variants)
• Inborn genetic diseases (54 variants)
• not specified (41 variants)
• SETBP1-related condition (19 variants)
• Intellectual disability, autosomal dominant 29;Schinzel-Giedion syndrome (8 variants)
• Intellectual disability (7 variants)
• Schinzel-Giedion syndrome;Intellectual disability, autosomal dominant 29 (5 variants)
• See cases (5 variants)
• Developmental disorder (2 variants)
• Hereditary spastic paraplegia 8 (1 variants)
• Fetal akinesia deformation sequence 1;Arthrogryposis multiplex congenita (1 variants)
• Neurodevelopmental disorder (1 variants)
• Generalized joint hypermobility;Joint laxity;Delayed speech and language development;Macrocephaly;Seizure (1 variants)
• Abnormality of the nervous system (1 variants)
• SETBP1-Related Disorder (1 variants)
• 8 conditions (1 variants)
• Chronic myelogenous leukemia, BCR-ABL1 positive (1 variants)
• SETBP1-related disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SETBP1 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			6	263	31	300
missense	5	7	438	165	58	673
nonsense	18	4	1	1		24
start loss						0
frameshift	28	8	6		1	43
inframe indel			7	5		12
splice donor/acceptor (+/-2bp)		4	1			5
splice region			2	8	2	12
non coding			9	36	11	56
Total	51	23	468	470	101

Highest pathogenic variant AF is 0.00000658

Variants in SETBP1

This is a list of pathogenic ClinVar variants found in the SETBP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-44680945-T-TG		Schinzel-Giedion syndrome	Conflicting classifications of pathogenicity (Apr 01, 2023)
18-44680946-G-T			Benign (Jul 01, 2023)
18-44700980-G-A			Benign (Dec 17, 2018)
18-44701044-TA-T			Likely benign (Aug 14, 2018)
18-44701183-C-G			Likely benign (Aug 01, 2023)
18-44701356-A-G			Uncertain significance (Nov 08, 2022)
18-44701371-A-G			Benign (Aug 31, 2022)
18-44701372-G-C			Uncertain significance (Nov 27, 2023)
18-44701377-C-G			Uncertain significance (Apr 17, 2023)
18-44701377-C-T			Likely benign (Nov 08, 2023)
18-44701378-G-A			Likely benign (Nov 11, 2023)
18-44701385-A-AG		Intellectual disability, autosomal dominant 29	Pathogenic (Sep 27, 2022)
18-44701390-G-A			Uncertain significance (Jun 30, 2023)
18-44701390-G-T			Uncertain significance (Dec 05, 2022)
18-44701391-C-T			Benign (Jan 11, 2024)
18-44701392-G-A		Schinzel-Giedion syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 07, 2024)
18-44701395-T-C			Uncertain significance (Feb 22, 2023)
18-44701401-T-G			Uncertain significance (Sep 10, 2021)
18-44701405-T-C			Uncertain significance (Feb 02, 2022)
18-44701408-C-T			Conflicting classifications of pathogenicity (Nov 27, 2023)
18-44701409-G-A			Likely benign (Feb 03, 2023)
18-44701413-T-C			Benign (Sep 22, 2023)
18-44701417-C-T			Uncertain significance (Dec 15, 2023)
18-44701424-G-A			Likely benign (Jun 05, 2018)
18-44701425-C-T		Inborn genetic diseases	Uncertain significance (Feb 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SETBP1	protein_coding	protein_coding	ENST00000282030	5	388338

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	8.70e-7	125674	0	7	125681	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	776	867	0.895	0.0000528	10480
Missense in Polyphen		324	439.79	0.73671		5491
Synonymous	-1.06	381	356	1.07	0.0000242	3183
Loss of Function	5.95	1	43.3	0.0231	0.00000262	588

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000445	0.000431
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Note=SETBP1 somatic mutations are frequently found in myeloid malignancies. They cause gain of function associated with myeloid leukemic transformation (PubMed:23832012). Myeloid malignancies are separated into three main categories: myeloproliferative neoplasms (MPN) characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, myelodysplastic syndromes (MDS) and MDS/MPN. The MDS/MPN category shows overlapping characteristics of both MDS and MPN and includes chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia (ACML) and unclassified MDS/MPN (PubMed:23628959). {ECO:0000269|PubMed:23628959, ECO:0000269|PubMed:23832012}.; DISEASE: Myelodysplastic syndrome (MDS) [MIM:614286]: A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). {ECO:0000269|PubMed:23648668, ECO:0000269|PubMed:23889083}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Mental retardation, autosomal dominant 29 (MRD29) [MIM:616078]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD29 patients manifest severe intellectual disability, behavioral difficulties, speech and motor delays, and dysmorphic facial features. {ECO:0000269|PubMed:25217958}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. {ECO:0000269|PubMed:23648668, ECO:0000269|PubMed:23889083}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Leukemia, chronic myeloid, atypical (ACML) [MIM:608232]: A myeloproliferative disorder that shares clinical and laboratory features with chronic myeloid leukemia but lacks the pathognomonic Philadelphia chromosome and the corresponding BCR/ABL1 fusion transcript. Features include myeloid predominance in the bone marrow, myeloid proliferation and low leukocyte alkaline phosphatase value, splenomegaly, hepatomegaly, elevated white blood cell count. Enlarged spleen may also be associated with a hypermetabolic state, fever, weight loss, and chronic fatigue. The enlarged liver may contribute to the patient's weight loss. {ECO:0000269|PubMed:23222956}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages. {ECO:0000269|PubMed:23832011}. Note=The gene represented in this entry is involved in disease pathogenesis.
• Pathway: Histone Modifications (Consensus)

Recessive Scores

• pRec: 0.300

Intolerance Scores

• loftool: 0.0297
• rvis_EVS: -1.12
• rvis_percentile_EVS: 6.61

Haploinsufficiency Scores

• pHI: 0.755
• hipred: Y
• hipred_score: 0.774
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.959

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Setbp1
• Phenotype: homeostasis/metabolism 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)

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II
• Cellular component: nucleus;cytosol;nuclear body
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein binding