MRPS21

Summary

MRPS21 (mitochondrial ribosomal protein S21, HGNC:14046) is a protein-coding gene on chromosome 1q21.2, encoding Small ribosomal subunit protein bS21m (P82921). It is a common-essential gene (DepMap: required in 97.4% of cancer 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 28S subunit protein that belongs to the ribosomal protein S21P family. Pseudogenes corresponding to this gene are found on chromosomes 1p, 1q, 9p, 10p, 10q, 16q, and 17q. Available sequence data analyses identified splice variants that differ in the 5’ UTR; both transcripts encode the same protein.

Source: NCBI Gene 54460 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 25 total
• GTEx eGene: eQTL in 46 tissues, sQTL in 28 (q < 0.05)
• Cancer dependency (DepMap): dependent in 97.4% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 1.61 (unconstrained)
• MANE Select transcript: NM_031901
• Interaction hub: 1,777 STRING partners (top 10% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14046
Approved symbol	MRPS21
Name	mitochondrial ribosomal protein S21
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Aliases	bS21m
Ensembl gene	ENSG00000266472
Ensembl biotype	protein_coding
OMIM	611984
Entrez	54460

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 5 nonsense_mediated_decay

MANE Select: ENST00000614145

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000614145, ENST00000581066, ENST00000877736, ENST00000877737, ENST00000877738, ENST00000877739, ENST00000935111, ENST00000935112, ENST00000935113, ENST00000935114, ENST00000935115, ENST00000935116, ENST00000935117, ENST00000935118, ENST00001097046, ENST00001097047, ENST00001097048, ENST00001097049, ENST00001097050, ENST00001097051, ENST00001097052, ENST00001097053, ENST00001097054, ENST00001097055, ENST00001097056, ENST00001097057, ENST00001145401

RefSeq mRNA: 2 — MANE Select: NM_031901 NM_018997, NM_031901

CCDS: CCDS950

Canonical transcript exons

ENST00000614145 — 3 exons

Exon	Start	End
ENSE00002710928	150308048	150308979
ENSE00003716402	150293861	150293898
ENSE00003734455	150294335	150294449

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 84.5425 / max 1019.3506, expressed in 1824 samples.

Highest expression (Bgee): cardiac muscle of right atrium, ventricle myocardium, lateral nuclear group of thalamus, pons, sperm.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MRPS21 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 46 tissues and its splicing (sQTL) in 28 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 74 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	9.2e-62	-0.43	1:150293918:T:A
Esophagus Muscularis	eqtl	2.9e-34	+0.30	1:150501861:G:A
Pituitary	eqtl	7.8e-34	-0.55	1:150293918:T:A
Nerve Tibial	eqtl	9.2e-33	-0.27	1:150293918:T:A
Muscle Skeletal	eqtl	6.2e-32	-0.28	1:150291686:C:T
Heart Atrial Appendage	eqtl	3.1e-30	+0.37	1:150479023:G:C
Testis	eqtl	6.1e-30	+0.44	1:150323220:G:A
Lung	eqtl	4.5e-25	-0.29	1:150293918:T:A
Skin Sun Exposed Lower leg	eqtl	2.3e-20	-0.23	1:150293918:T:A
Heart Left Ventricle	eqtl	2.8e-20	+0.29	1:150494449:C:T
Testis	sqtl	2.6e-19	+0.94	1:150308908:C:T
Esophagus Gastroesophageal Junction	eqtl	2.2e-18	+0.28	1:150494261:A:G
Colon Sigmoid	eqtl	4.4e-18	+0.32	1:150396861:G:A
Skin Not Sun Exposed Suprapubic	eqtl	6.0e-18	-0.24	1:150293918:T:A
Adipose Visceral Omentum	eqtl	2.3e-17	+0.24	1:150479356:G:A
Artery Aorta	eqtl	4.1e-16	-0.23	1:150291686:C:T
Whole Blood	eqtl	7.3e-16	-0.15	1:150293918:T:A
Cells Cultured fibroblasts	eqtl	7.4e-16	+0.32	1:150325557:C:T
Breast Mammary Tissue	eqtl	1.9e-15	+0.21	1:150393993:C:A
Pituitary	sqtl	1.1e-14	+0.54	1:150526339:A:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
5089	84.0442	1824
5090	0.4983	254

Top tissues by expression

showing 100 of 256 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	98.66	gold quality
left ventricle myocardium	UBERON:0006566	98.60	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.43	gold quality
pons	UBERON:0000988	98.37	gold quality
sperm	CL:0000019	98.30	gold quality
myocardium	UBERON:0002349	98.21	gold quality
pancreatic ductal cell	CL:0002079	98.14	gold quality
epithelial cell of pancreas	CL:0000083	98.06	gold quality
kidney epithelium	UBERON:0004819	98.06	gold quality
upper arm skin	UBERON:0004263	97.98	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.53	gold quality
renal medulla	UBERON:0000362	97.51	gold quality
lateral globus pallidus	UBERON:0002476	97.40	gold quality
adult organism	UBERON:0007023	97.38	gold quality
cerebellar vermis	UBERON:0004720	97.37	gold quality
superior vestibular nucleus	UBERON:0007227	97.36	gold quality
vena cava	UBERON:0004087	97.35	gold quality
seminal vesicle	UBERON:0000998	97.32	gold quality
substantia nigra pars compacta	UBERON:0001965	97.32	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.21	gold quality
hypothalamus	UBERON:0001898	97.15	gold quality
ventral tegmental area	UBERON:0002691	97.10	gold quality
middle temporal gyrus	UBERON:0002771	97.09	gold quality
pharyngeal mucosa	UBERON:0000355	97.03	gold quality
trachea	UBERON:0003126	97.03	gold quality
layer of synovial tissue	UBERON:0007616	97.03	gold quality
superior surface of tongue	UBERON:0007371	96.98	gold quality
anterior cingulate cortex	UBERON:0009835	96.98	gold quality
body of tongue	UBERON:0011876	96.96	gold quality
tongue	UBERON:0001723	96.95	gold quality
pigmented layer of retina	UBERON:0001782	96.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.91	gold quality
pericardium	UBERON:0002407	96.88	gold quality
medulla oblongata	UBERON:0001896	96.86	gold quality
pylorus	UBERON:0001166	96.85	gold quality
nucleus accumbens	UBERON:0001882	96.85	gold quality
bronchus	UBERON:0002185	96.80	gold quality
bronchial epithelial cell	CL:0002328	96.78	gold quality
oral cavity	UBERON:0000167	96.76	gold quality
putamen	UBERON:0001874	96.75	gold quality
amygdala	UBERON:0001876	96.72	gold quality
adrenal cortex	UBERON:0001235	96.71	gold quality
caudate nucleus	UBERON:0001873	96.67	gold quality
midbrain	UBERON:0001891	96.65	gold quality
left adrenal gland cortex	UBERON:0035825	96.64	gold quality
substantia nigra	UBERON:0002038	96.62	gold quality
tendon of biceps brachii	UBERON:0008188	96.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.59	gold quality
heart right ventricle	UBERON:0002080	96.54	gold quality
adenohypophysis	UBERON:0002196	96.54	gold quality
urethra	UBERON:0000057	96.53	gold quality
left adrenal gland	UBERON:0001234	96.52	gold quality
trigeminal ganglion	UBERON:0001675	96.51	gold quality
gingiva	UBERON:0001828	96.51	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.51	gold quality
thymus	UBERON:0002370	96.50	gold quality
pituitary gland	UBERON:0000007	96.49	gold quality
prefrontal cortex	UBERON:0000451	96.49	gold quality
saphenous vein	UBERON:0007318	96.49	gold quality
forebrain	UBERON:0001890	96.46	gold quality
gingival epithelium	UBERON:0001949	96.46	gold quality
right adrenal gland	UBERON:0001233	96.45	gold quality
neocortex	UBERON:0001950	96.45	gold quality
primary visual cortex	UBERON:0002436	96.45	gold quality
occipital lobe	UBERON:0002021	96.44	gold quality
right adrenal gland cortex	UBERON:0035827	96.44	gold quality
cardiac atrium	UBERON:0002081	96.43	gold quality
cerebral cortex	UBERON:0000956	96.42	gold quality
dorsal root ganglion	UBERON:0000044	96.40	gold quality
decidua	UBERON:0002450	96.40	gold quality
frontal cortex	UBERON:0001870	96.37	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.37	gold quality
cortical plate	UBERON:0005343	96.36	gold quality
synovial joint	UBERON:0002217	96.35	gold quality
penis	UBERON:0000989	96.28	gold quality
right frontal lobe	UBERON:0002810	96.28	gold quality
right atrium auricular region	UBERON:0006631	96.27	gold quality
caput epididymis	UBERON:0004358	96.25	gold quality
temporal lobe	UBERON:0001871	96.21	gold quality
metanephros	UBERON:0000081	96.19	gold quality
brain	UBERON:0000955	96.19	gold quality
mammalian vulva	UBERON:0000997	96.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.08	gold quality
inferior vagus X ganglion	UBERON:0005363	96.07	gold quality
trabecular bone tissue	UBERON:0002483	96.02	gold quality
heart	UBERON:0000948	96.01	gold quality
nasal cavity epithelium	UBERON:0005384	95.98	silver quality
cardiac ventricle	UBERON:0002082	95.96	gold quality
heart left ventricle	UBERON:0002084	95.94	gold quality
corpus epididymis	UBERON:0004359	95.94	gold quality
cortex of kidney	UBERON:0001225	95.89	gold quality
epithelium of mammary gland	UBERON:0003244	95.89	gold quality
mammary duct	UBERON:0001765	95.87	gold quality
superior frontal gyrus	UBERON:0002661	95.87	gold quality
Ammon’s horn	UBERON:0001954	95.86	gold quality
ganglionic eminence	UBERON:0004023	95.86	gold quality
islet of Langerhans	UBERON:0000006	95.82	gold quality
adrenal gland	UBERON:0002369	95.82	gold quality
nipple	UBERON:0002030	95.78	gold quality
apex of heart	UBERON:0002098	95.78	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-8559	no	1029.92
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Caudate putamen	tissue	231.4
Frontal cortex	tissue	195.9
Postcentral gyrus	tissue	71.7
Ovary	tissue	70.6
Pituitary gland	tissue	69.7
Choroid plexus	tissue	69.7
Tongue	tissue	62.1
Parathyroid gland	tissue	61.5
Adrenal gland	tissue	58.7
Nucleus accumbens	tissue	58.5
Locus coeruleus	tissue	57.6
Heart muscle	tissue	56.5
Epididymis	tissue	50.7
Hippocampus	tissue	50.7
Skeletal muscle	tissue	49.7
Breast	tissue	48.4
Kidney	tissue	46.9
Vagina	tissue	46.7
Thymus	tissue	45.6
Liver	tissue	44.9
Tonsil	tissue	43.7
Fallopian tube	tissue	41.8
Urinary bladder	tissue	41.5
Thyroid gland	tissue	41.1
Lymph node	tissue	39.9
Adipose tissue	tissue	39.6
Retina	tissue	39.2
Seminal vesicle	tissue	36.9
Stomach 1	tissue	36.8
Bone marrow	tissue	36.7
Spleen	tissue	36.6
Endometrium 1	tissue	36.4
Smooth muscle	tissue	36.2
Duodenum	tissue	36.0
Salivary gland	tissue	35.9
Appendix	tissue	33.7
Pancreas	tissue	33.6
Cervix	tissue	33.5
Prostate	tissue	32.3
Skin 1	tissue	32.2
Small intestine	tissue	32.2
Placenta	tissue	30.6
Lung	tissue	30.1
Testis	tissue	30.0
Putamen	tissue	28.4
Rectum	tissue	27.2
Basal ganglia	tissue	27.2
Esophagus	tissue	27.0
Pons	tissue	26.8
Colon	tissue	26.5
Gallbladder	tissue	25.9
Spinal cord	tissue	25.9
Medulla oblongata	tissue	25.4
Superior colliculi	tissue	25.1
Periaqueductal gray	tissue	24.7
Thalamus	tissue	24.6
Midbrain	tissue	24.4
Substantia nigra	tissue	24.1
Corpus callosum	tissue	24.0
Ventral forebrain	tissue	23.6

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Habenula (65.6), Paracentral lobule, anterior (65.1), Arcuate nucleus (64.7), Precentral gyrus, middle (64.5), Lateral hypothalamic area (64.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MRPS21 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

30 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-3664-5P	96.74	66.56	770
HSA-MIR-4790-3P	96.63	67.08	806
HSA-MIR-1298-3P	94.05	64.84	620

Functional genomics

gnomAD constraint: pLI 0.0197, LOEUF 1.61, missense Z 0.498 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000614145 — one region, missense o/e 0.85. DepMap (CRISPR cell-line fitness): dependent in 97.4% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SU-DHL-10 (-2.544), SNU-620 (-2.321), COLO-678 (-2.175), COR-L279 (-2.049), LP-1 (-2.028), HUP-T4 (-1.931), NIH:OVCAR-3 (-1.917), HD-MY-Z (-1.878), G-402 (-1.827), HCC1187 (-1.821), MEL-HO (-1.793), KP-4 (-1.792), SNU-1196 (-1.791), RERF-GC-1B (-1.782), KNS-81 (-1.736).

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mrps21	ENSMUSG00000054312
rattus_norvegicus	Mrps21	ENSRNOG00000024845

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1913542) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P82920	95.4%	Diamond
Acidiphilium cryptum JF-5	A5FVG6	94.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CIART	protein-coding	148523
C1orf54	protein-coding	79630
PRPF3	protein-coding	9129
SNORD13C	snoRNA	109616989
CA14	protein-coding	23632
APH1A	protein-coding	51107
RPRD2	protein-coding	23248
MIR6878	ncRNA	102465529
TARS2	protein-coding	80222

Protein

Protein identifiers

Small ribosomal subunit protein bS21m — P82921 (reviewed: P82921)

Alternative names: 28S ribosomal protein S21, mitochondrial

All UniProt accessions (1): P82921

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Component of the mitochondrial small ribosomal subunit (mt-SSU). 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.

Subcellular location. Mitochondrion.

Similarity. Belongs to the bacterial ribosomal protein bS21 family.

RefSeq proteins (2): NP_061870, NP_114107* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001911	Ribosomal_bS21	Family
IPR038380	Ribosomal_bS21_sf	Homologous_superfamily

Pfam: PF01165

UniProt features (13 total): helix 5, strand 4, sequence variant 2, chain 1, turn 1

Structure

Experimental structures (PDB)

showing 30 of 79 structures by resolution:

PDB	Title	Method	Resolution (Å)
8CSS	Human mitochondrial small subunit assembly intermediate (State D)	ELECTRON MICROSCOPY	2.36
7P2E	Human mitochondrial ribosome small subunit in complex with IF3, GMPPMP and streptomycin	ELECTRON MICROSCOPY	2.4
8RRI	Human mitochondrial ribosome in complex with antibiotic tigecycline	ELECTRON MICROSCOPY	2.4
9OLF	Membrane-associated human mitoribosome in complex with TACO1	ELECTRON MICROSCOPY	2.46
9OJM	Human mitochondrial 28S PIC with tRNA and mtIF2	ELECTRON MICROSCOPY	2.5
8CSQ	Human mitochondrial small subunit assembly intermediate (State B)	ELECTRON MICROSCOPY	2.54
8CSR	Human mitochondrial small subunit assembly intermediate (State C)	ELECTRON MICROSCOPY	2.54
6ZM6	Human mitochondrial ribosome in complex with mRNA, A/A tRNA and P/P tRNA	ELECTRON MICROSCOPY	2.59
8CSP	Human mitochondrial small subunit assembly intermediate (State A)	ELECTRON MICROSCOPY	2.66
7PNX	Assembly intermediate of human mitochondrial ribosome small subunit without mS37 in …	ELECTRON MICROSCOPY	2.76
8ANY	Human mitochondrial ribosome in complex with LRPPRC, SLIRP, A-site, P-site, E-site tRNAs …	ELECTRON MICROSCOPY	2.85
8CST	Human mitochondrial small subunit assembly intermediate (State E)	ELECTRON MICROSCOPY	2.85
6ZM5	Human mitochondrial ribosome in complex with OXA1L, mRNA, A/A tRNA, P/P tRNA and nascent …	ELECTRON MICROSCOPY	2.89
7PO0	Assembly intermediate of human mitochondrial ribosome small subunit without mS37 in …	ELECTRON MICROSCOPY	2.9
8K2A	Cryo-EM structure of the human 55S mitoribosome with Tigecycline	ELECTRON MICROSCOPY	2.9
9PGL	In situ structure of the human mitoribosome in the A-P state with TACO1	ELECTRON MICROSCOPY	2.9
9VXM	Human mitoribosome in a non-rotated state, with multiple neomycin molecules bound …	ELECTRON MICROSCOPY	2.9
7PO1	Initiation complex of human mitochondrial ribosome small subunit with IF3	ELECTRON MICROSCOPY	2.92
7PO3	Human mitochondrial ribosome small subunit	ELECTRON MICROSCOPY	2.92
9PGF	In situ structure of the human mitoribosome in the P state	ELECTRON MICROSCOPY	2.93
6VMI	Structure of the human mitochondrial ribosome-EF-G1 complex (ClassIII)	ELECTRON MICROSCOPY	2.96
6RW4	Structure of human mitochondrial 28S ribosome in complex with mitochondrial IF3	ELECTRON MICROSCOPY	2.97
6VLZ	Structure of the human mitochondrial ribosome-EF-G1 complex (ClassI)	ELECTRON MICROSCOPY	2.97
8QRN	mt-SSU in GTPBP8 knock-out cells, state 4	ELECTRON MICROSCOPY	2.98
9PSM	In situ structure of the human mitoribosome in the A/P-P/E state	ELECTRON MICROSCOPY	2.98
8OIS	28S human mitochondrial small ribosomal subunit with mtRF1 and P-site tRNA	ELECTRON MICROSCOPY	3
9G5C	Assembly intermediate of human mitochondrial ribosome small subunit (State B)	ELECTRON MICROSCOPY	3
9G5D	Assembly intermediate of human mitochondrial ribosome small subunit (State C)	ELECTRON MICROSCOPY	3
9H54	Assembly intermediate of human mitochondrial ribosome small subunit in complex with NOA1 …	ELECTRON MICROSCOPY	3
9HFM	Translation-initiation state of human mitochondrial ribosome small subunit (State D)	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P82921-F1	96.48	0.96

Human Protein Atlas

Protein class: Ribosomal proteins, Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IF supported

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

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

MSigDB gene sets: 115 (showing top): PAL_PRMT5_TARGETS_UP, GOBP_MITOCHONDRIAL_TRANSLATION, TGACCTY_ERR1_Q2, SRF_Q5_01, GOBP_TRANSLATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, WANG_LMO4_TARGETS_DN, GGAANCGGAANY_UNKNOWN, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOCC_MITOCHONDRIAL_ENVELOPE, GOCC_RIBOSOME, chr1q21, GOCC_SMALL_RIBOSOMAL_SUBUNIT, GOCC_ORGANELLAR_RIBOSOME, GOCC_MITOCHONDRIAL_MATRIX

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

GO Molecular Function (2): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial small ribosomal subunit (GO:0005763), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Mitochondrial translation	4
Translation	1
Metabolism of proteins	1

GO top-level categories

22 GO namespaces:

Category	Terms
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
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
organellar small ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
intracellular membraneless organelle	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
mitochondrial small ribosomal subunit	CC	direct assay
mitochondrion	CC	direct assay
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 16 of 1,777 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPS21	MRPL51	Q4U2R6	620
MRPS21	MRPS15	P82914	572
MRPS21	MRPL52	Q86TS9	544
MRPS21	MRPL55	Q7Z7F7	530
MRPS21	RBM23	Q86U06	497
MRPS21	MRPS24	P82668	458
MRPS21	MRPL37	Q9BZE1	451
MRPS21	MRPL19	P49406	442
MRPS21	EIF1B	O60739	441
MRPS21	RNF123	Q5XPI4	438
MRPS21	SLC25A29	Q8N8R3	428
MRPS21	RPS21	P35265	427
MRPS21	DAP3	P51398	427
MRPS21	MRPS5	P82675	424
MRPS21	MRPL43	Q8N983	424
MRPS21	MRPL41	Q8IXM3	424

IntAct

BioGRID (145 interactions; top human partners by supporting records): AURKAIP1 (Affinity Capture-MS; 3 records), MRPS31 (Affinity Capture-MS; 3 records), TRMT10B (Affinity Capture-MS; 3 records), CCNF (Affinity Capture-MS; 2 records), MOV10 (Affinity Capture-RNA; 2 records), MRPS11 (Affinity Capture-MS; 2 records), MRPS15 (Affinity Capture-MS; 2 records), MRPS27 (Affinity Capture-MS; 2 records), MRPS34 (Affinity Capture-MS; 2 records), MRPS9 (Affinity Capture-MS; 2 records), RPL6 (Affinity Capture-MS; 2 records), ZC3H3 (Affinity Capture-MS; 2 records), ABT1 (Affinity Capture-MS), ACACA (Negative Genetic), APOBEC3D (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
MRPS21	“form complex”	“28S mitochondrial small ribosomal subunit”	binding

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
55S ribosome, mitochondrial	78	MRPS30, MRPL1, MRPL14, MRPL41, MRPL45, MRPL50, MRPL54, MRPS18B, MRPS2, MRPS21, MRPS34, MRPL17, MRPS6, MRPS17, MRPS31, MRPS33, MRPL21, MRPL24, MRPS10, MRPS11, MRPL12, MRPL22, MRPL47, MRPL49, MRPS35, MRPS7, MRPL28, MRPL37, MRPL40, MRPL48, MRPS18A, MRPS22, MRPS23, MRPL13, MRPL46, MRPS28, MRPL16, MRPL23, MRPL39, MRPL52, MRPL53, MRPL19, MRPL42, MRPL44, MRPL11, MRPL2, MRPL27, MRPL33, MRPL34, MRPL35, MRPS25, MRPS26, DAP3, MRPL18, MRPL38, MRPL9, MRPS12, MRPS27, MRPS5, MRPS9, MRPL20, MRPL30, MRPL36, MRPL43, MRPS14, KGD4, MRPL32, MRPL4, MRPL51, MRPS15, MRPS16, MRPL3, MRPL55, MRPS18C, LACTB, MRPL10, MRPL15, MRPS24
28S ribosomal subunit, mitochondrial	30	MRPS18A, MRPS28, MRPS30, MRPS7, DAP3, MRPS11, MRPS18C, MRPS16, MRPS17, MRPS18B, MRPS23, MRPS25, MRPS9, MRPS34, MRPS31, MRPS6, KGD4, MRPS15, MRPS2, MRPS27, MRPS35, MRPS10, MRPS12, MRPS21, MRPS26, MRPS33, MRPS22, MRPS24, MRPS5, MRPS14

Disease & clinical

Genetic variants

Variant evidence for MRPS21: 25 ClinVar records (0 pathogenic / likely pathogenic); 19 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 15 predictions of 189):

Position(s)	Effect	Δscore	Sites
1:150294450–150294451	donor_loss	1.0000	5
1:150308045	acceptor_gain	1.0000
1:150308047	acceptor_loss	1.0000
1:150308043	acceptor_gain	0.9900
1:150308047	acceptor_loss	0.9900
1:150308046–150308047	acceptor_loss	0.9800	2
1:150294451	donor_loss	0.9700
1:150308046	acceptor_loss	0.9700
1:150308046	acceptor_loss	0.9600
1:150295543	donor_gain	0.9500

AlphaMissense

65 missense substitutions predicted likely pathogenic (of 578 scored), across 31 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M68	6	0.658	0.714
F7	4	0.864	0.935
F74	4	0.815	0.867
W84	4	0.716	0.742
R54	4	0.698	0.783
R10	4	0.692	0.741
E46	4	0.666	0.750
K71	3	0.719	0.779
K47	3	0.698	0.734
L30	3	0.689	0.789
A22	2	0.699	0.804
T11	2	0.644	0.713
C60	2	0.643	0.675
E67	2	0.642	0.661
L26	2	0.627	0.677
V12	1	0.777	0.777
R52	1	0.758	0.758
R70	1	0.718	0.718
R62	1	0.716	0.716
A9	1	0.641	0.641

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000164

Disease associations

OMIM: gene MIM:611984 | disease phenotypes:

GWAS associations

19 associations:

Study	Trait	p-value
GCST010700_28	Cortical thickness (MOSTest)	8e-38
GCST010696_2	Cortical thickness (min-P)	2e-23
GCST008059_87	Estimated glomerular filtration rate	3e-19
GCST010002_27	Refractive error	3e-15
GCST010701_57	Cortical surface area (MOSTest)	9e-12
GCST010703_294	Brain morphology (MOSTest)	9e-12
GCST90020028_1240	Hip circumference adjusted for BMI	9e-11
GCST012332_7	Multisite chronic pain	1e-10
GCST008747_38	Estimated glomerular filtration rate	3e-10
GCST005038_66	Allergic disease (asthma, hay fever or eczema)	1e-9
GCST010702_101	Subcortical volume (MOSTest)	4e-9
GCST003184_16	Atopic dermatitis	5e-9
GCST004946_34	Schizophrenia	5e-9
GCST008745_3	Estimated glomerular filtration rate in non-diabetics	5e-9
GCST010697_28	Cortical surface area (min-P)	9e-9
GCST010698_54	Subcortical volume (min-P)	2e-8
GCST011352_36	Alanine aminotransferase levels	2e-8
GCST010699_28	Brain morphology (min-P)	3e-8
GCST003184_26	Atopic dermatitis	1e-7

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0010100	multisite chronic pain
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
chloropicrin	affects expression, decreases expression	2
Leflunomide	decreases expression	2
Acetaminophen	decreases expression, increases expression, affects cotreatment	2
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
sodium arsenite	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
jinfukang	increases expression	1
Temozolomide	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Estradiol	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Phthalic Acids	increases methylation	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Lactic Acid	decreases expression	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.