MRPL28

Summary

MRPL28 (mitochondrial ribosomal protein L28, HGNC:14484) is a protein-coding gene on chromosome 16p13.3, encoding Large ribosomal subunit protein bL28m (Q13084). It is a selective cancer dependency (DepMap: 51.5% of cell lines).

Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein, a part of which was originally isolated by its ability to recognize tyrosinase in an HLA-A24-restricted fashion.

Source: NCBI Gene 10573 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 68 total
• Cancer dependency (DepMap): dependent in 51.5% of screened cell lines
• MANE Select transcript: NM_006428

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14484
Approved symbol	MRPL28
Name	mitochondrial ribosomal protein L28
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	p15, bL28m
Ensembl gene	ENSG00000086504
Ensembl biotype	protein_coding
OMIM	604853
Entrez	10573

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 22 protein_coding, 4 retained_intron

ENST00000199706, ENST00000389675, ENST00000441883, ENST00000447696, ENST00000450882, ENST00000461550, ENST00000469744, ENST00000481453, ENST00000483764, ENST00000648346, ENST00000875015, ENST00000875016, ENST00000875017, ENST00000875018, ENST00000875019, ENST00000875020, ENST00000933144, ENST00000933145, ENST00000933146, ENST00000933147, ENST00000933148, ENST00000933149, ENST00000933150, ENST00000933151, ENST00000933152, ENST00000933153

RefSeq mRNA: 1 — MANE Select: NM_006428 NM_006428

CCDS: CCDS32349

Canonical transcript exons

ENST00000199706 — 6 exons

Exon	Start	End
ENSE00001506621	368501	368635
ENSE00001506622	369068	369220
ENSE00001529988	370499	370538
ENSE00003622338	369931	370225
ENSE00003646235	368328	368414
ENSE00003831738	366969	367782

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.4721 / max 142.2393, expressed in 1819 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155726	27.6957	1819
155724	2.8918	1443
155725	0.8846	627

Top tissues by expression

297 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.51	gold quality
left testis	UBERON:0004533	96.29	gold quality
right testis	UBERON:0004534	96.27	gold quality
right frontal lobe	UBERON:0002810	96.04	gold quality
putamen	UBERON:0001874	95.95	gold quality
nucleus accumbens	UBERON:0001882	95.90	gold quality
prefrontal cortex	UBERON:0000451	95.84	gold quality
caudate nucleus	UBERON:0001873	95.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.72	gold quality
cingulate cortex	UBERON:0003027	95.42	gold quality
heart left ventricle	UBERON:0002084	95.37	gold quality
anterior cingulate cortex	UBERON:0009835	95.30	gold quality
amygdala	UBERON:0001876	95.16	gold quality
cardiac ventricle	UBERON:0002082	95.08	gold quality
right adrenal gland	UBERON:0001233	95.04	gold quality
right atrium auricular region	UBERON:0006631	95.04	gold quality
right adrenal gland cortex	UBERON:0035827	94.91	gold quality
left adrenal gland	UBERON:0001234	94.73	gold quality
mucosa of transverse colon	UBERON:0004991	94.73	gold quality
granulocyte	CL:0000094	94.66	gold quality
gastrocnemius	UBERON:0001388	94.61	gold quality
left adrenal gland cortex	UBERON:0035825	94.55	gold quality
cardiac atrium	UBERON:0002081	94.49	gold quality
testis	UBERON:0000473	94.45	gold quality
heart	UBERON:0000948	94.21	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.18	gold quality
metanephros cortex	UBERON:0010533	94.16	gold quality
muscle of leg	UBERON:0001383	94.09	gold quality
adrenal cortex	UBERON:0001235	94.05	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.99	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.89
E-GEOD-106540	no	447.99
E-MTAB-6678	no	3.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting MRPL28, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-1247-3P	83.69	63.18	99
HSA-MIR-5587-3P	82.90	60.79	138

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 51.5% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrpl28	ENSDARG00000057805
mus_musculus	Mrpl28	ENSMUSG00000024181
rattus_norvegicus	Mrpl28	ENSRNOG00000042720
drosophila_melanogaster	mRpL28	FBGN0031660
caenorhabditis_elegans		WBGENE00020796

Protein

Protein identifiers

Large ribosomal subunit protein bL28m — Q13084 (reviewed: Q13084)

Alternative names: 39S ribosomal protein L28, mitochondrial, Melanoma antigen p15, Melanoma-associated antigen recognized by T-lymphocytes

All UniProt accessions (4): Q13084, A2IDC6, A2IDC7, Q4TT37

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Component of the mitochondrial large ribosomal subunit (mt-LSU). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins. Interacts with OXA1L.

Subcellular location. Mitochondrion.

Tissue specificity. Found in a variety of normal tissues including spleen, testes, thymus, liver, kidney, brain, adrenal, lung and retinal tissue.

Miscellaneous. Potentially represents an important therapeutic reagent for HLA-A24 patients. This antigen is recognized by tumor-infiltrating lymphocyte (TIL) 1290 in the context of HLA-A24.

Similarity. Belongs to the bacterial ribosomal protein bL28 family.

RefSeq proteins (1): NP_006419* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026569	Ribosomal_bL28	Family
IPR034704	Ribosomal_bL28/bL31-like_sf	Homologous_superfamily
IPR037147	Ribosomal_bL28_sf	Homologous_superfamily

Pfam: PF00830

UniProt features (34 total): helix 16, strand 7, turn 3, sequence variant 3, sequence conflict 3, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

86 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7OF0	ELECTRON MICROSCOPY	2.2
7QI4	ELECTRON MICROSCOPY	2.21
8RRI	ELECTRON MICROSCOPY	2.4
8QU5	ELECTRON MICROSCOPY	2.42
9OLF	ELECTRON MICROSCOPY	2.46
7OF7	ELECTRON MICROSCOPY	2.5
7PO4	ELECTRON MICROSCOPY	2.56
6ZM6	ELECTRON MICROSCOPY	2.59
7O9M	ELECTRON MICROSCOPY	2.6
7OF6	ELECTRON MICROSCOPY	2.6
9CN3	ELECTRON MICROSCOPY	2.62
7QI5	ELECTRON MICROSCOPY	2.63
7OF2	ELECTRON MICROSCOPY	2.7
7OF3	ELECTRON MICROSCOPY	2.7
7OF4	ELECTRON MICROSCOPY	2.7
8QU1	ELECTRON MICROSCOPY	2.74
9PR4	ELECTRON MICROSCOPY	2.77
9PRA	ELECTRON MICROSCOPY	2.83
8ANY	ELECTRON MICROSCOPY	2.85
6ZM5	ELECTRON MICROSCOPY	2.89
7QH7	ELECTRON MICROSCOPY	2.89
7ODR	ELECTRON MICROSCOPY	2.9
7OF5	ELECTRON MICROSCOPY	2.9
8K2A	ELECTRON MICROSCOPY	2.9
8OIT	ELECTRON MICROSCOPY	2.9
9PGL	ELECTRON MICROSCOPY	2.9
9PGF	ELECTRON MICROSCOPY	2.93
6VMI	ELECTRON MICROSCOPY	2.96
6VLZ	ELECTRON MICROSCOPY	2.97
7QI6	ELECTRON MICROSCOPY	2.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13084-F1	92.58	0.89

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-5368286	Mitochondrial translation initiation
R-HSA-5389840	Mitochondrial translation elongation
R-HSA-5419276	Mitochondrial translation termination
R-HSA-9937383	Mitochondrial ribosome-associated quality control
R-HSA-392499	Metabolism of proteins
R-HSA-5368287	Mitochondrial translation
R-HSA-72766	Translation

MSigDB gene sets: 131 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, MORF_MTA1, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, XU_GH1_AUTOCRINE_TARGETS_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MITOCHONDRIAL_TRANSLATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, HNF1_Q6, GOBP_TRANSLATION, MORF_RAF1, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, HP1SITEFACTOR_Q6, GOCC_MITOCHONDRIAL_ENVELOPE

GO Biological Process (2): translation (GO:0006412), mitochondrial translation (GO:0032543)

GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (7): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial ribosome (GO:0005761), mitochondrial large ribosomal subunit (GO:0005762), cytosol (GO:0005829), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitochondrial translation	4
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
mitochondrion	1
translation	1
mitochondrial gene expression	1
nucleic acid binding	1
structural molecule activity	1
ribosome	1
binding	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
organellar ribosome	1
mitochondrial matrix	1
organellar large ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
cellular anatomical structure	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL28	MRPS26	Q9BYN8	536
MRPL28	TYR	P14679	513
MRPL28	CSF2	P04141	490
MRPL28	ACP6	Q9NPH0	437
MRPL28	IL2	P01585	384
MRPL28	EME2	A4GXA9	381
MRPL28	MRPL38	Q96DV4	372
MRPL28	WDR27	A2RRH5	349
MRPL28	POLR2D	O15514	344
MRPL28	EMC3	Q9P0I2	340
MRPL28	ABHD2	P08910	325
MRPL28	ARRDC4	Q8NCT1	318
MRPL28	HCCS	P53701	317
MRPL28	MPG	P29372	315
MRPL28	MRPL12	P52815	311

IntAct

212 interactions, top by confidence:

A	B	Type	Score
MRPL28	TRAF4	psi-mi:“MI:0915”(physical association)	0.670
TRAF4	MRPL28	psi-mi:“MI:0915”(physical association)	0.670
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
TRAF3IP2	MRPL28	psi-mi:“MI:0915”(physical association)	0.560
CDR2	MRPL28	psi-mi:“MI:0915”(physical association)	0.560
MRPL28	TEF	psi-mi:“MI:0915”(physical association)	0.560
HMBOX1	MRPL28	psi-mi:“MI:0915”(physical association)	0.560
MRPL28	FAM9B	psi-mi:“MI:0915”(physical association)	0.560
BANP	MRPL28	psi-mi:“MI:0915”(physical association)	0.560
MRPL28	IKZF3	psi-mi:“MI:0915”(physical association)	0.560
MRPL28	CDR2	psi-mi:“MI:0915”(physical association)	0.560
MRPL28	HMBOX1	psi-mi:“MI:0915”(physical association)	0.560
FAM9B	MRPL28	psi-mi:“MI:0915”(physical association)	0.560
MRPL28	BANP	psi-mi:“MI:0915”(physical association)	0.560
TEF	MRPL28	psi-mi:“MI:0915”(physical association)	0.560
TSHZ3	MRPL28	psi-mi:“MI:0915”(physical association)	0.560
MRPL28	LARP1B	psi-mi:“MI:0915”(physical association)	0.560
MRPL28	LENG1	psi-mi:“MI:0915”(physical association)	0.560
MRPL28	SCNM1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (386): MRPL28 (Two-hybrid), MRPL28 (Two-hybrid), MRPL28 (Two-hybrid), TRAF3IP2 (Two-hybrid), IKZF3 (Two-hybrid), BANP (Two-hybrid), HMBOX1 (Two-hybrid), FAM9B (Two-hybrid), MRPL28 (Affinity Capture-MS), MRPL45 (Affinity Capture-MS), MRPL46 (Affinity Capture-MS), MRPL9 (Affinity Capture-MS), MRPL32 (Affinity Capture-MS), MRPL40 (Affinity Capture-MS), MRPL3 (Affinity Capture-MS)

ESM2 similar proteins: A0AJY7, B1VKG7, O60783, P56556, P82915, P82920, P82933, Q02366, Q0MQA3, Q0MQA4, Q0MQA5, Q0VFH6, Q13084, Q19V89, Q1JQ99, Q29IK4, Q2HJJ1, Q2TA12, Q2TBR2, Q3T040, Q3T0J3, Q498T4, Q58DQ5, Q58DV5, Q5I0K8, Q5T653, Q5U4Z8, Q5ZMU0, Q6B860, Q6DDY9, Q6P1L8, Q71YD4, Q7M0E7, Q7SF85, Q7ZUH5, Q80X85, Q8MFA1, Q8Y620, Q92AC7, Q9BYC9

Diamond homologs: A0L5U1, A1B4S6, A1UR12, A3PHM3, A4WX84, A5CC87, A5G211, A5VSY2, A6UCK6, A6WXD5, A7HTU2, A7IHE7, A8IMG3, A8LHY2, A9HS05, A9M9A0, B0CJB7, B2IEP2, B2S8R7, B3CV48, B3PPE3, B3QAG7, B4RFQ5, B5ZRX6, B6IW31, B8EQN3, B9JBS8, B9JTL3, C0RFQ6, C3MHW1, O60091, P36525, P66140, P66141, Q0AMB1, Q0BWH4, Q11DS9, Q13084, Q1GIW2, Q1GPG7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPL28	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 166 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial translation	27	33.2×	8e-33
Mitochondrial ribosome-associated quality control	30	32.9×	5e-36
Mitochondrial translation initiation	28	31.7×	2e-33
Mitochondrial translation elongation	28	31.7×	2e-33
Mitochondrial translation termination	28	27.4×	1e-31
Transport of Mature Transcript to Cytoplasm	5	17.0×	2e-04
Translation	29	16.1×	1e-25
Peptide chain elongation	11	12.5×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	29	33.8×	4e-34
translation	28	19.3×	1e-25
cytoplasmic translation	11	13.7×	1e-07
regulation of signal transduction by p53 class mediator	5	12.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

68 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

906 predictions. Top by Δscore:

Variant	Effect	Δscore
16:367782:CCT:C	acceptor_loss	1.0000
16:367783:C:CC	acceptor_gain	1.0000
16:367783:CTG:C	acceptor_loss	1.0000
16:368325:CACC:C	donor_loss	1.0000
16:368326:A:AC	donor_gain	1.0000
16:368326:A:C	donor_loss	1.0000
16:368327:C:CC	donor_gain	1.0000
16:368327:CCTT:C	donor_gain	1.0000
16:368410:AATTC:A	acceptor_gain	1.0000
16:368411:ATTC:A	acceptor_gain	1.0000
16:368412:TTC:T	acceptor_gain	1.0000
16:368413:TC:T	acceptor_gain	1.0000
16:368414:CC:C	acceptor_gain	1.0000
16:368415:C:CC	acceptor_gain	1.0000
16:368415:CT:C	acceptor_loss	1.0000
16:368420:C:CT	acceptor_gain	1.0000
16:368421:A:T	acceptor_gain	1.0000
16:368424:C:CT	acceptor_gain	1.0000
16:368425:A:T	acceptor_gain	1.0000
16:368496:CTCAC:C	donor_loss	1.0000
16:368497:TCAC:T	donor_loss	1.0000
16:368499:A:AC	donor_gain	1.0000
16:368499:A:AT	donor_loss	1.0000
16:368499:AC:A	donor_gain	1.0000
16:368500:C:CC	donor_gain	1.0000
16:368500:C:CT	donor_loss	1.0000
16:368500:CC:C	donor_gain	1.0000
16:369063:CTTG:C	donor_loss	1.0000
16:369064:TTGC:T	donor_loss	1.0000
16:369065:TG:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000412168 (16:369460 T>A), RS1001531675 (16:368877 G>A,T), RS1001585924 (16:369302 C>A,G,T), RS1001887965 (16:366471 C>T), RS1002183000 (16:370728 G>C), RS1002526305 (16:368216 A>G), RS1002558680 (16:368074 T>C), RS1003341911 (16:371490 G>A), RS1003388015 (16:371253 C>G,T), RS1003442993 (16:367599 G>A), RS1003497797 (16:371731 A>G), RS1005478347 (16:366956 C>CCAA), RS1005589259 (16:366535 C>T), RS1005653603 (16:370409 C>T), RS1006035397 (16:370571 G>A,C)

Disease associations

OMIM: gene MIM:604853 | disease phenotypes: MIM:157900

GenCC curated gene-disease

Mondo (1): Mobius syndrome (MONDO:0008006)

Orphanet (1): Moebius syndrome (Orphanet:570)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005951_12	Body mass index	5.000000e-11
GCST006288_170	Heel bone mineral density	5.000000e-11
GCST006288_338	Heel bone mineral density	2.000000e-17
GCST006288_444	Heel bone mineral density	1.000000e-25
GCST010002_107	Refractive error	6.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009270	heel bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020331	Mobius Syndrome	C07.465.299.825; C10.292.319.825; C10.292.562.700.375.750; C11.590.436.400.750; C16.131.077.578; C16.614.595

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	increases expression, decreases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
nobiletin	decreases reaction, increases expression	1
sodium arsenate	increases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
nickel sulfate	increases expression	1
K 7174	decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Dinitrochlorobenzene	affects binding	1
Manganese	decreases expression, increases abundance	1
Methapyrilene	decreases methylation	1
Phenobarbital	affects expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies