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Intellectual disability

Gene: SETBP1

Green List (high evidence)
SETBP1 (SET binding protein 1)
EnsemblGeneIds (GRCh38): ENSG00000152217
EnsemblGeneIds (GRCh37): ENSG00000152217
OMIM: 611060, Gene2Phenotype
SETBP1 is in 5 panels

5 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

SETBP1 is associated with two distinct autosomal dominant disorders: Intellectual developmental disorder, known as SETBP1 disorder, and Schinzel-Giedion syndrome.

SETBP1 disorder is characterised by intellectual disability, autism, speech difficulty, motor and developmental delays, seizures, hypotonia, and facial dysmorphisms (PMID: 21037274). The mechanism of disease is haploinsufficiency (PMID: 21037274).
There are at least 7 unrelated individuals reported in literature, diagnosed with SETBP1 disorder and harbouring LOF variants in SETBP1 (nonsense, frameshift, large deletions) - PMIDs: 23020937, 25217958, 29463886, 25356899.

Schinzel-Giedion syndrome is caused by missense variants in SETBP1, particularly variants affecting amino acids 868-871 - a specific ‘hotspot’ region of the SETBP1 gene that codes for a degron. Clinical features of Schinzel-Giedion syndrome include developmental delay, epilepsy, facial dysmorphisms, and genitourinary and skeletal anomalies. The proposed mechanism of Schinzel-Giedion syndrome is gain-of-function (GOF), causing SETBP1 protein to accumulate (PMID: 28346496). There are at least 15 unrelated individuals with Schinzel-Giedion syndrome and heterozygous missense variants in SETBP1 reported in literature (PMIDs: 20436468, 26188272, 32460883, 22473152, 25028416, 25082129, 25663181, 26096993, 32445275, 28346496).

SETBP1 is associated with Intellectual developmental disorder, autosomal dominant 29, OMIM: 616078 and Schinzel-Giedion midface retraction syndrome, OMIM: 269150 (OMIM, accessed 28th Oct 2025).
Created: 28 Oct 2025, 12:06 p.m. | Last Modified: 28 Oct 2025, 12:13 p.m.
Panel Version: 9.151

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual developmental disorder, autosomal dominant 29, OMIM: 616078; Schinzel-Giedion midface retraction syndrome, OMIM: 269150; Schinzel-Giedion syndrome, MONDO:0010010

Publications

Created: 28 Oct 2025, 12:06 p.m.
Last Modified: 28 Oct 2025, 12:13 p.m.
Panel version: 9.151

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
SCHINZEL-GIEDION MIDFACE RETRACTION SYNDROME (SGMFS)

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known . Main mutation mechanism : Activating; Loss of function
Created: 27 Jul 2017, 8:21 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; find_uk10k; gilissen_2014_known; sfari_20150206; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; gonzalez_mantilla_2016; GEL_ID_green_20160217; neuro_20160418_strict; Activating; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 1:20 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

Mode of pathogenicity

Created: 2 Aug 2017, 10:25 p.m.

Panel version: 1.354

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 10:46 a.m.

Panel version: 0.306

emma baple (Genomics England Curator)

Green List (high evidence)

SCHINZEL-GIEDION (gain of function mutations); Intellectual disability (loss of function mutations)
Created: 7 Feb 2016, 4:47 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
SCHINZEL-GIEDION (gain of function mutations); Intellectual disability (loss of function mutations)

Created: 7 Feb 2016, 4:47 p.m.

Panel version: 0.115

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Intellectual developmental disorder, autosomal dominant 29, OMIM: 616078
  • Schinzel-Giedion midface retraction syndrome, OMIM: 269150
  • Schinzel-Giedion syndrome, MONDO:0010010
OMIM
611060
Clinvar variants
Variants in SETBP1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

28 Oct 2025, Gel status: 3

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: SETBP1 were changed from Schinzel-Giedion midface retraction syndrome, 269150; SCHINZEL-GIEDION MIDFACE RETRACTION SYNDROME (SGMFS) to Intellectual developmental disorder, autosomal dominant 29, OMIM: 616078; Schinzel-Giedion midface retraction syndrome, OMIM: 269150; Schinzel-Giedion syndrome, MONDO:0010010

28 Oct 2025, Gel status: 3

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: SETBP1 were set to 20436468

29 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to SETBP1.

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

15 Mar 2017, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for SETBP1 were set to 20436468

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 1

Set Mode of Inheritance, Added New Source

Ellen McDonagh (Genomics England Curator)

SETBP1 was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene SETBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SETBP1 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen