RPS28

protein-coding

ribosomal protein S28, the group of S ribosomal proteins

Gene summary

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S28E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001031.5

Inheritance

ClinVar variants

P:1U:6B:14

Top phenotype

Diamond-Blackfan anemia 15 with mandibulofacial dysostosis

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:8,321,158-8,323,340

External References & Databases

Ensembl (ENSG00000233927)

Transcript & Mutation Effects

hg38 • Region Span ~2.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Diamond-Blackfan anemia 15 with mandibulofacial dysostosisLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011639

Submitter: Labcorp Genetics (formerly Invitae)

Diamond-Blackfan anemia 15 with mandibulofacial dysostosisMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0011639

Submitter: PanelApp Australia

Diamond-Blackfan anemiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015253

Submitter: Orphanet

Diamond-Blackfan anemia 15 with mandibulofacial dysostosisMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0011639

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Diamond-Blackfan anemia 15 with mandibulofacial dysostosisAD

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Hematologic; Musculoskeletal; Oncologic

Intervention: Audiologic/Otolaryngologic; Hematologic; Oncologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management

Refs: 11424144; 24942156

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RPS28 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 30

RPS28-related disorderTotal: 1

Diamond-Blackfan anemiaTotal: 1

Diamond-Blackfan anemia 15 with mandibulofacial dysostosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001031.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				14 clinvar		14
missense			6 clinvar			6
nonsense						0
start loss		1 clinvar				1
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	6	14	0	21

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001031.5	RefSeq	NP_001022.1	3	MANE Select
ENST00000600659.3	Ensembl	ENSP00000472469.1	3	MANE Select
ENST00000930315.1	Ensembl	ENSP00000600374.1	2	Standard
ENST00000930316.1	Ensembl	ENSP00000600375.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rps28	Danio rerio	Structure: whole organism Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

rps28

Danio rerio

Structure: whole organism

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ribosome - Homo sapiens (human)
Cytoplasmic Ribosomal Proteins
SRP-dependent cotranslational protein targeting to membrane
Formation of the ternary complex, and subsequently, the 43S complex
Translation initiation complex formation

Biological Process

ribosomal small subunit assembly
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
cytoplasmic translation
rRNA processing
translation

Molecular Function

RNA binding
structural constituent of ribosome
protein binding

Cellular Component

nucleoplasm
cytosol
small ribosomal subunit
cytosolic small ribosomal subunit
polysomal ribosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000600659
Coding exons: 3
Length: 2183
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	12	38.4	0.313	0.00000176	425
Missense (PolyPhen)		0	6.442	0		108
Synonymous	-0.912	20	15.4	1.30	6.88e-7	140
Loss of Function	1.79	0	3.75	0.00	1.63e-7	43

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Diamond-Blackfan anemia 15, with mandibulofacial dysostosis (DBA15) [MIM:606164]: A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. {ECO:0000269|PubMed:24942156}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

RVIS EVS: 0.17
RVIS percentile EVS: 65.04

Essentials

Essential (CRISPR): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.833

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low