Table 2:

List of genes associated with spliceosomopathies and ribosomopathies, their disease phenotypes, and known molecular function.

Gene	Syndrome	Human Phenotype	References	Mutation	Function of Gene Product
SF3B4	1. Nager Syndrome 2. Rodriguez Syndrome	Craniofacial – malar and mandibular hypoplasia, down-slanting palpebral fissures, external ear defects and cleft palate. Limb – primarily hypoplastic or absent thumbs.	- Bernier et al., 2012 - Petit et al., 2013 - Champion-Arnaud and Reed, 2004	Frameshift or nonsense resulting in haploinsufficiency.	Member of SF3B complex of U2 snRNP involved in tethering U2 complex to branch site in pre-mRNA.
EFTUD2	Mandibulofacial Dysostosis, Guion-Almeida Type (MFDGA)	Craniofacial – overlaps with Nager syndrome and includes microcephaly. Limb – occasionally involves defects such as proximally placed thumbs and polydactyly of thumbs.	- Lines et al., 2012 - Fabrizio et al., 1997	Frameshift, nonsense, missense, deletions resulting in haploinsufficiency.	Encodes the spliceosomal GTPase U5–116kD, a member of the U5 snRNP.
TXNL4A	Burn-Mckeow Syndrome	Craniofacial – cleft lip and/or palate, short palpebral fissure, coloboma of the lower eyelids, prominent nasal bridge, and choanal atresia. Other – heart defects, large protruding ears.	- Wieczorek et al., 2014 - Reuter et al., 1999	Heterozygous deletion in the promoter region of TXNL4A.	Yeast ortholog of TXNL4A (Dib1) encodes essential component of the U4/U6-U5 tri-snRNP complex
EIF4A3	Richieri-Costa-Pereira Syndrome	Craniofacial – midline cleft mandible, cleft palate, glossoptosis, and micrognathia. Limb – limb reductions and clubbed feet.	- Favaro et al., 2014 - Andreou and Klostermeier 2013	Expansion of 18–20 nucleotide motifs in the 5’ UTR of EIF4A3.	Member of the exon junction complex (EJC). Anchors the EJC to the RNA.
SNRNPB	Cerebro-costo-mandibular Syndrome (CCMS)	Craniofacial – cleft palate, glossoptosis, and micrognathia. Rib defects – posterior gaps and missing ribs.	- Tooley et al., 2016 - Lynch et al., 2014 - Bacrot et al., 2014 - Will and Lührmann, 2011	SNRPB codes for three splice variants, one containing an alternative exon that contains a premature stop and functions to auto-regulate protein levels. In CCMS, mutation in the splicing silencer region of the alternative exon increase its inclusion and result in lower levels of SmB and SmB’.	SNRNPB-encoded SmB and SmB’ are splicing isoforms of one of the seven Sm proteins found in each snRNP.
CHD7 FAM172A	CHARGE Syndrome	Coloboma of the eye, Heart defects, Atresia of choanae, Retardation of growth and development, Genital abnormalities, and Ear anomalies. Craniofacial – temporal bone anomalies and cleft lip and/or cleft palate.	- Zentner et al., 2010 - Vissers et al., 2004 - Bajpai et al., 2010 - Schulz et al., 2014	Nonsense, missense, and single-copy 8q12 deletions of CHD7.	CHD7 is a chromatin remodeling factor that regulates the expression of key genes in the NCC GRN.
TCOF1, POLR1C, POLR1D, DDX2	Treacher Collins Syndrome (TCS)	Craniofacial – down-slanting palpebral fissures, micrognathia, facial bone hypoplasia, and cleft palate. Other – external ear defects, inner ear, and lower eyelid anomalies.	- Fazen et al., 1967 - Phelps et al., 1981 - Edwards et al., 1997 - Dauwerse et al., 2011 - Valdez et al., 2004 - Gonzales et al., 2005	Mutations in the TCOF1 gene include splice site, missense, and nonsense mutations as well as insertions and deletions.	TCOF1, along with other factors, plays an important role in rDNA transcription and rRNA processing.
Ribosomal protein genes including: RPS19, RPS26, RPS27, RPL5, RPL11, GATA1	Diamond-Blackfan anemia (DBA)	Craniofacial – resemble defects observed in TCS. Limb – thumb abnormalities. Other – anemia caused by decrease of erythroid precursors.	- Delaporta et al., 2014 - Kim et al., 2012 - Gazda et al., 2008 - Willing et al., 1999 - Fylgare et al., 2007 - Choesmel et al., 2007 - Doherty et al., 2010 - Sankaran et al., 2012	Mutations in RPS19 include nonsense, missense, frameshift, and splice site mutations as well as deletions.	RPS19 is required for 18S rRNA synthesis and 40S ribosomal subunit maturation.