Human Gene Module / Chromosome 18 / SETBP1

SETBP1SET binding protein 1

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 10
Rare Variants / Common Variants
31 / 0
Aliases
SETBP1, SEB
Associated Syndromes
Schinzel-Giedion syndrome
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
18q12.3
Associated Disorders
ID, ASD
Relevance to Autism

A de novo LoF variant (frameshift) was identified in a simplex ASD case from the Simons Simplex Collection (O'Roak et al., 2012). More recently, eight loss-of-function variants, three of which were de novo in origin, were identified in patients from DD/ID cohorts; social difficulties and/or other behavioral difficulties were observed in four of these patients (Coe et al., 2014).

Molecular Function

The protein encoded by this gene has been shown to bind the SET nuclear oncogene, which is involved in DNA replication. Mutations in this gene are associated with Schinzel-Giedion midface retraction syndrome (SGMFS) [MIM:269150], a disorder characterized by severe mental retardation, distinctive facial features, and multiple congenital malformations including skeletal abnormalities, genitourinary and renal malformations, cardiac defects, as well as a higher-than-normal prevalence of tumors, notably neuroepithelial neoplasia.

Reports related to SETBP1 (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. O'Roak BJ , et al. (2012) Yes -
2 Support Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Rauch A , et al. (2012) No ASD
3 Recent recommendation Refining analyses of copy number variation identifies specific genes associated with developmental delay. Coe BP , et al. (2014) No -
4 Support De novo mutations in moderate or severe intellectual disability. Hamdan FF , et al. (2014) No Microcephaly
5 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
6 Support The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
7 Support Large-scale discovery of novel genetic causes of developmental disorders. Deciphering Developmental Disorders Study (2014) No Speech delay
8 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing. Martnez F , et al. (2016) No ID
9 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
10 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families. Trujillano D , et al. (2016) No -
Rare Variants   (31)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
ins(G) - frameshift_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.1774A>T p.Lys592Ter stop_gained De novo - Simplex 23020937 Rauch A , et al. (2012)
del p.Arg143ValfsTer64 frameshift_variant Unknown - Unknown 25217958 Coe BP , et al. (2014)
del p.Leu411GlyfsTer6 frameshift_variant Unknown - Unknown 25217958 Coe BP , et al. (2014)
c.1596G>A p.Trp532Ter stop_gained De novo - Unknown 25217958 Coe BP , et al. (2014)
del p.Ile822TyrfsTer13 frameshift_variant De novo - Unknown 25217958 Coe BP , et al. (2014)
c.3032C>G p.Ser1011Ter stop_gained De novo - Unknown 25217958 Coe BP , et al. (2014)
C>T p.Arg625Ter stop_gained Unknown - Unknown 25217958 Coe BP , et al. (2014)
C>T p.Arg626Ter stop_gained Unknown - Unknown 25217958 Coe BP , et al. (2014)
- p.Gly15ArgfsTer47 frameshift_variant Unknown - Unknown 25217958 Coe BP , et al. (2014)
- - copy_number_loss De novo - - 25217958 Coe BP , et al. (2014)
c.1821delC p.Ser608AlafsTer22 frameshift_variant De novo - Simplex 25356899 Hamdan FF , et al. (2014)
c.2572G>A p.Glu858Lys missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.1877G>A p.Arg626Gln missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2218G>A p.Glu740Lys missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3962G>A p.Arg1321His missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3017A>G p.Tyr1006Cys missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2267C>T p.Pro756Leu missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3029C>T p.Thr1010Ile missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3460C>T p.His1154Tyr missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1198G>A p.Val400Ile missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1877G>A p.Arg626Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3566G>A p.Arg1189Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1553T>C p.Leu518Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3299A>G p.His1100Arg missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3689C>T p.Thr1230Ile missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2717C>G p.Pro906Arg missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.2561C>G p.Ser854Cys missense_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.2612T>C p.Ile871Thr missense_variant De novo - - 27620904 Martnez F , et al. (2016)
c.1202G>A p.Arg401Gln missense_variant Familial Paternal - 27824329 Wang T , et al. (2016)
c.2602G>A p.Asp868Asn missense_variant De novo - Simplex 27848944 Trujillano D , et al. (2016)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

CNVs associated with SETBP1(1 CNVs)
18q12.3 12 Deletion-Duplication 21  /  65
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
LRRC37A11P leucine rich repeat containing 37, member A11, pseudogene Human Protein Binding 342666
NAP1L2 Nucleosome assembly protein 1-like 2 Mouse Protein Binding 17954 P51860
PLEKHF2 pleckstrin homology domain containing, family F (with FYVE domain) member 2 Human Protein Binding 79666 Q9H8W4
SPANXC SPANX family, member C Human Protein Binding 64663 Q8TAD1
SPANXD SPANX family, member D Human Protein Binding 64648 Q9BXN6
XAGE1D Human Protein Binding 9503
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