Table 1 |.

Ribosomal proteins with specialized translation functions and human and mouse phenotypes

RP	Human phenotype	Mouse phenotype	Effects of RP downregulation on translation	Specialized translation functions
RPS6/eS6	Unknown	• Embryonic lethal203 • Keratinocyte-specific heterozygosity: hyperpigmentation of ears, tail and footpads204 • Bone marrow-specific heterozygosity: decreased haematopoietic stem cell number, decreased erythropoiesis, macrocytic anaemia and haematopoietic defects205 • Thymus-specific heterozygosity: decrease in numbers of peripheral T cells206	Ribosome biogenesis defects in haploinsufficient embryos203 and in activated heterozygous T cells206	NR
RPS7/eS7	Diamond–Blackfan anaemia207	Missense mutations: microphthalmia and uveal coloboma, fused and disorganized vertebrae, cortical thinning, eye, brain and skeletal abnormalities, and white belly spot208	Ribosome biogenesis defects in heterozygous mice208 and in patient cells207	NR
RPS10/eS10	Diamond–Blackfan anaemia209	Unknown	Ribosome biogenesis defect in patient cells209	NR
RPS14/uS11	5q-Myelodysplastic syndrome210	Macrocytic anaemia211	Decreased protein synthesis upon knockdown in TF-1 cells and ribosome biogenesis defects in 5q-myelodysplastic syndrome patient cells210	NR
RPS15a/uS8	Diamond–Blackfan anaemia212	Unknown	Ribosome biogenesis defect in K562 cells heterozygous for the mutation observed in patients with Diamond–Blackfan anaemia212	NR
RPS17/eS17	Missense mutations in start codon: Diamond–Blackfan anaemia213,214	Unknown	Unknown	NR
RPS19/eS19	Diamond–Blackfan anaemia215	Missense mutation: hyperpigmentation of ears, tail and footpads; white belly spot; mild reduction in red blood cell counts; and erythroid defects204	Decreased protein synthesis (knockdown in K562 cells or mouse erythroblasts)84,90	Promotes cellular IRES activity in mouse erythroblasts84
RPS20/uS10	Unknown	Missense mutation: hyperpigmentation of ears, tail and footpads204	Unknown	NR
RPS23/uS12	Missense mutations: microcephaly , hearing loss, autism spectrum disorders, craniofacial abnormalities, atypical palm creases and finger pads and short fingers190	Unknown	No global protein synthesis changes in patient cells190	Promotes translation fidelity188
RPS24/eS24	Diamond–Blackfan anaemia216	Unknown	Unknown	NR
RPS25/eS25	Unknown	Unknown	–	• Promotes viral and cellular IRES activity69,70 • Promotes translation of several hundred mRNAs in mES cells18
RPS26/eS26	Diamond–Blackfan anaemia209,217	Unknown	Ribosome biogenesis defects in patient cells209	Promotes translation from start codons in Kozak sequence contexts in yeast218
RPS27/eS27	Diamond–Blackfan anaemia and abnormal skin pigmentation219	Unknown	Ribosome biogenesis defects (knockdown in K562 cells)219	NR
RPS28/eS28	Missense mutation in start codon: Diamond–Blackfan anaemia220	Unknown	Unknown	NR
RPS29/uS14	Diamond–Blackfan anaemia221	Unknown	Ribosome biogenesis defect in patient mononuclear cells221	NR
RPS30/eS30	Unknown Heterozygous deletion of entire FAU/MNSFβ gene: decreased female fertility222	Unknown	NR	RPS30/eS30
RPSA/uS2	Isolated congenital asplenia74	• No phenotype observed for heterozygote • Homozygote embryonic lethal74	No ribosome biogenesis defects in patient cells74	NR
RACK1	Unknown	White belly spot and hypopigmented paws and tail87	• Decreased protein synthesis in livers from heterozygous mice87 • No change in protein synthesis upon knockdown in primary normal human dermal fibroblasts192 or S2 cells85	• CrPV and HCV IRES translation85 • Translation of poxvirus genes192
RPLP1	Unknown	Brain atrophy , male infertility and kinked tail223	No global protein synthesis changes in mouse embryonic fibroblasts lacking RPLP1 (Ref.223)	NR
RPL5/uL18	Diamond–Blackfan anaemia, heart abnormalities, craniofacial defects (including cleft lip and palate), thumb malformations (including triphalangeal thumbs) and tumour predisposition207	Unknown	Decreased protein synthesis (knockdown in HeLa cells)207	NR
RPL10/uL16	Missense mutations: autism spectrum disorders, intellectual disability , microcephaly and seizures in males75,224	Unknown	Decreased protein synthesis upon knockdown in zebrafish224 and upon introduction of the mutant human RPL10/uL16 alleles into yeast75	NR
RPL10a/uL1	Unknown	Unknown	–	Promotes translation of several hundred genes, including several with known RPL10a/uL1-dependent IRES elements, in mES cells; promotes HCV and CrPV IRES activity18
RPL11/uL5	Diamond–Blackfan anaemia, thumb malformations (including triphalangeal thumbs) and tumour predisposition207	• Embryonic lethal • Heterozygosity induced in adult mice: anaemia and tumour predisposition225	Decreased protein synthesis (knockdown in HeLa cells207) and ribosome biogenesis defects in RPL11-deficient mouse embryonic fibroblasts and spleens225	Promotes cellular IRES activity in mouse erythroblasts84
RPL13a/uL13	Unknown	Macrophage-specific knockout: increased inflammation upon endotoxin stimulation226	Increased expression of GAIT complex targets but no effect on global protein synthesis in macrophages lacking RPL13a/uL13 or upon knockdown in U937 cells226,227	Inhibition of translation of target mRNAs as part of GAIT complex58
RPL15/eL15	Diamond–Blackfan anaemia228	Unknown	Decreased protein synthesis (knockdown in HeLa cells)228	NR
RPL21/eL21	Missense mutation: hereditary hypotrichosis simplex76	Unknown	Unknown	NR
RPL22/eL22	T cell acute lymphoblastic leukaemia229	Knockout: αβ T cell ablation78	No change in global protein synthesis in heterozygous mice229; mild decrease in protein synthesis in knockout mice78	Represses smad1 translation in zebrafish29
RPL22L/eL22L	Unknown	Knockout: embryonic lethal79	No change in global protein synthesis observed upon morpholino knockdown in zebrafish embryos29	NR
RPL24/eL24	Unknown	Abnormal retinal cell differentiation, incomplete or absent optic nerve, white belly spot, kinked tail and polydactyly77	Decreased protein synthesis in primary mouse embryonic fibroblasts from haploinsufficient mice77	NR
RPL26/uL24	Diamond–Blackfan anaemia, cleft palate, missing or narrowed external auditory meatus, left kidney agenesis, bicuspid aortic valve, missing or fused radius and ulna, and oligodactyly230	Unknown	Decreased protein synthesis (knockdown in HeLa cells)230	NR
RPL27/eL27	Diamond–Blackfan anaemia and atrial septal defect219	Unknown	Ribosome biogenesis defects (knockdown in K562 cells)219	NR
RPL27A/uL15	Unknown	Cerebellar ataxia; hyperpigmentation of ears, tail, footpads and genital areas; and pancytopenia231	Unknown	NR
RPL29/eL29	Unknown	Homozygous deletion: small size and increased bone fragility232,233	Decreased protein synthesis in primary mouse embryonic fibroblasts from null mice233	NR
RPL31/eL31	Diamond–Blackfan anaemia, triphalangeal thumb and thenar hypoplasia and fused radius and ulna234	Unknown	Ribosome biogenesis defects in Diamond–Blackfan anaemia patient primary cells and upon knockdown in K562 cells234	NR
RPL35A/eL33	Diamond–Blackfan anaemia, ventricular septal defect, hypertelorism and low-set ears235	Unknown	Decreased protein synthesis (knockdown in UT-7/Epo and HEK293 cell lines)235	NR
RPL38/eL38	Unknown	Midline facial cleft, microphthalmia and incomplete optic fissure closure, exencephaly , kinked tail and homeotic axial skeleton transformations13	Decreased translation of several Hox genes but no effects on global translation in neural tubes and somites of haploinsufficient mice13	Promotes translation of several Hox genes via IRES elements in their 5′ UTRs13,83
RPL40/eL40	Unknown	Homozygous deletion of entire UBA52 gene: embryonic lethal194	Decreased protein synthesis (knockdown in DLD-1 cells)194	Promotes translation of VSV genes and several stress response transcripts in yeast88

Published human diseases and mouse models resulting from mutations in core ribosomal proteins (RPs) are listed with their phenotypes. All phenotypes are the result of haploinsufficient RP expression unless noted otherwise. Where known, the resulting impact on translation is also listed, as are any additional specialized translation functions, which may come from studies in a variety of model systems. CrPV, cricket paralysis virus; GAIT, γ-interferon inhibitor of translation; HCV, hepatitis C virus; IRES, internal ribosome entry site; mES, mouse embryonic stem; NR, not reported; UTR, untranslated region; VSV, vesicular stomatitis virus.