Table 1.

Functions of human ribosomopathy genes.

Disease	Gene	Function in ribosome assembly	Clinical phenotype	References
Autosomal recessive
Shwachman-Diamond syndrome	SBDS (yeast SDO1)	Cofactor for EFL1 in eIF6 release	Neutropenia, exocrine pancreatic insufficiency, metaphyseal chondrodysplasia, predisposition to MDS/AML	(Finch et al., 2011, Menne et al., 2007, Wong et al., 2011)
	DNAJC21 (yeast JJJ1)	J-protein, HSP70 co-chaperone, Arx1 release		(Meyer et al., 2010)
Bowen-Conradi syndrome	EMG1 (yeast Nep1)	SPOUT family pseudouridine methyltransferase; required for maturation of 18S rRNA and 40S ribosomal subunit production independent of methyltransferase activity	Growth retardation, psychomotor delay microcephaly, micrognathia, joint contractures, rockerbottom feet	(Meyer et al., 2011, Schilling et al., 2012)
North American Indian Childhood Cirrhosis	CIRHIN (yeast UTP14)	t-Utp subcomplex of the U3-containing 90S particle; rDNA transcription and 18S pre-rRNA processing	Cirrhosis	(Prieto and McStay, 2007)
Cartilage Hair Hypoplasia	RMRP	RNA component of RNase MRP; endonucleolytic cleavage that separates the 18S rRNA from the 5.8S–28S portion of the rRNA precursor	Short limb dwarfism, metaphyseal dysplasia, hypoplastic anaemia, defective B and T cell-mediated immunity, variable intestinal aganglionosis	(Goldfarb and Cech, 2017)
Dyskeratosis congenita, Høyeraal-Hreidarsson syndrome	PARN	18S-E pre-rRNA processing	Bone marrow failure, hypomyelination, mucocutaneous defects, pulmonary fibrosis, developmental delay, cerebellar hypoplasia, eosophageal, urethral stenosis	(Ishikawa et al., 2017, Montellese et al., 2017)
Alopecia, neurological and endocrinopathy syndrome	RBM28 (yeast NOP4)	Nucleolar protein, component of 66S pre-ribosomes, 27S pre-rRNA processing	Hair loss, microcephaly, mental retardation, progressive motor retardation, adrenal insufficiency	(Nousbeck et al., 2008, Sun and Woolford, 1994)
Autosomal Dominant
Diamond-Blackfan anaemia	RPS7, RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS27, RPS28, RPS29	40S subunit proteins	Macrocytic anaemia, craniofacial and thumb abnormalities, short stature, cancer predisposition	(Cmejla et al., 2007, Doherty et al., 2010, Farrar et al., 2008, Gazda et al., 2006, Gazda et al., 2012, Gazda et al., 2008, Gripp et al., 2014, Landowski et al., 2013, Mirabello et al., 2014, Wang et al., 2015)
	RPL5, RPL11, RPL15, RPL19, RPL26, RPL27, RPL31, RPL35A	60S subunit proteins
	GATA1 TSR2	Transcription factor eS26 escortin		(Sankaran et al., 2012) (Gripp et al., 2014)
Treacher-Collins syndrome	TCOF1 POLR1C POLR1D	rDNA transcription, NBS1 recruitment during DNA damage response	Craniofacial defects, mental retardation	(Ciccia et al., 2014, Larsen et al., 2014)
Congenital asplenia	RPSA	40S subunit protein	Absence of spleen	(Bolze et al., 2013)
Aplasia cutis congenita	BMS1	Component of the 90S particle, GTPase	Skin agenesis on scalp vertex	(Marneros, 2013)
Familial colorectal cancer type X	RPS20	40S subunit protein	Hereditary nonpolyposis colorectal carcinoma with no mismatch repair defects	(Nieminen et al., 2014)
RPS23-related ribosomopathy	RPS23	40S subunit protein	Microcephaly, hearing loss, intellectual disability, autism	(Paolini et al., 2017)
Leukoencephalopathy, intracranial calcifications and cysts (LCC)	SNORD118	box C/D snoRNA U8	Progressive cerebral degeneration	(Jenkinson et al., 2016)
X-linked recessive
Dyskeratosis congenita, Høyeraal-Hreidarsson syndrome	DKC1	H/ACA ribonucleoprotein complex subunit 4; rRNA pseudouridine synthase, telomere maintenance	Abnormal skin pigmentation, nail dystrophy, oral leukoplakia, bone marrow failure, cancer predisposition, short stature, microcephaly, immunodeficiency	(Heiss et al., 1998, Lafontaine et al., 1998)
Autism	RPL10	60S subunit protein	Microcephaly, growth retardation, seizures	(Brooks et al., 2014)
Microcephaly	RPL10		Autism	(Klauck et al., 2006)
Sporadic
Relapsed CLL	RPS15, RPSA, RPS20	40S subunit proteins, binds MDM2	Adverse prognosis CLL after first line therapy	(Ljungstrom et al., 2015)
Paediatric T-ALL	RPL5, RPL10, RPL22	60S subunit protein	T-ALL	(De Keersmaecker et al., 2013)
5q- syndrome	RPS14	40S subunit protein	MDS and macrocytic anaemia	(Ebert et al., 2008)