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FB2026_01
,
released March 12, 2026
This report describes Coffin-Siris syndrome 12 (CSS12), a syndromic neurodevelopmental disorder caused by mutations in the human gene BICRA. CSS12 shows autosomal dominant inheritance. BICRA encodes a member of the SWI/SNF family of chromatin remodeling complexes; multiple genes within the SWI/SNF family have been implicated in the different subtypes of Coffin-Siris syndrome. The ortholgous gene in Drosophila, Dmel\Bicra, encodes a component of the non-canonical BAP complex (FBgg0001645). RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Bicra. Dmel\Bicra is also related to the human gene BICRAL.
A UAS construct of the human wild-type Hsap\BICRA gene has been introduced into flies and is available.
Work in flies has addressed the intellectual disability phenotype associated with CSS12 (and other subtypes of Coffin-Siris syndrome). RNAi-mediated knockdown of Bicra in the mushroom body (a brain region associated with learning and memory) causes male flies not to reduce courtship attempts after being rejected by a female, a measure of memory formation in flies. Knockdown Bicra in neurons, but not in glia, impairs courtship learning.
[updated Mar. 2022 by FlyBase; FBrf0222196]
Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).
Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).
Coffin-Siris syndrome is a multiple malformation syndrome characterized by mental retardation associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014; pubmed:25169447). [from MIM:135900; 2019.07.19]
Coffin-Siris syndrome is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014; pubmed:25169447). [from MIM:135900; 2019.07.19]
[COFFIN-SIRIS SYNDROME 12; CSS12](https://omim.org/entry/619325)
[BRD4-INTERACTING CHROMATIN REMODELING COMPLEX-ASSOCIATED PROTEIN; BICRA](https://omim.org/entry/605690)
Coffin-Siris syndrome-12 (CSS12) is a neurodevelopmental disorder characterized by global developmental delay with variably impaired intellectual development, speech and language delay, and behavioral abnormalities, such as autism or hyperactivity. Affected individuals may have hypotonia and poor feeding in infancy. There are variable dysmorphic facial features, although most patients do not have the classic hypoplastic fifth digit/nail abnormalities that are often observed in other forms of CSS (Barish et al., 2020; pubmed:33232675). [from MIM:619325; 2022.03.20]
Coffin-Siris syndrome-12 (CSS12) is caused by heterozygous mutation in the BICRA gene. [from MIM:619325; 2022.03.20]
BICRA encodes a component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. [Gene Cards, BICRA; 2022.03.20]
Many to one: 2 human genes to 1 Drosophila gene.
Low-scoring ortholog of human BICRA and BICRAL (1 Drosophila to 2 human).