MRPS31

Summary

MRPS31 (mitochondrial ribosomal protein S31, HGNC:16632) is a protein-coding gene on chromosome 13q14.11, encoding Small ribosomal subunit protein mS31 (Q92665). It is a selective cancer dependency (DepMap: 46.6% 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. The 28S subunit of the mammalian mitoribosome may play a crucial and characteristic role in translation initiation. This gene encodes a 28S subunit protein that has also been associated with type 1 diabetes; however, its relationship to the etiology of this disease remains to be clarified. Pseudogenes corresponding to this gene have been found on chromosomes 3 and 13.

Source: NCBI Gene 10240 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 64 total
• Cancer dependency (DepMap): dependent in 46.6% of screened cell lines
• MANE Select transcript: NM_005830

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16632
Approved symbol	MRPS31
Name	mitochondrial ribosomal protein S31
Location	13q14.11
Locus type	gene with protein product
Status	Approved
Aliases	IMOGN38, mS31
Ensembl gene	ENSG00000102738
Ensembl biotype	protein_coding
OMIM	611992
Entrez	10240

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000323563, ENST00000435009, ENST00000461675, ENST00000498078, ENST00000891372, ENST00000891373, ENST00000891374, ENST00000891375, ENST00000891376, ENST00000891377, ENST00000925417, ENST00000925418

RefSeq mRNA: 1 — MANE Select: NM_005830 NM_005830

CCDS: CCDS9372

Canonical transcript exons

ENST00000323563 — 7 exons

Exon	Start	End
ENSE00001265167	40770985	40771190
ENSE00001676162	40758948	40759106
ENSE00001727660	40756873	40757013
ENSE00001804164	40754019	40754092
ENSE00001928024	40729128	40729601
ENSE00003652212	40749138	40749281
ENSE00003665690	40766746	40767033

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.9311 / max 325.3243, expressed in 1789 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136920	21.9311	1789

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	98.99	gold quality
epithelium of bronchus	UBERON:0002031	98.45	gold quality
bronchus	UBERON:0002185	98.23	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.95	gold quality
epithelium of nasopharynx	UBERON:0001951	95.96	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.37	gold quality
secondary oocyte	CL:0000655	94.98	gold quality
biceps brachii	UBERON:0001507	94.74	gold quality
oocyte	CL:0000023	94.24	gold quality
superior surface of tongue	UBERON:0007371	94.06	gold quality
nasal cavity mucosa	UBERON:0001826	93.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.20	gold quality
calcaneal tendon	UBERON:0003701	93.18	gold quality
nasal cavity epithelium	UBERON:0005384	93.10	gold quality
body of tongue	UBERON:0011876	93.05	gold quality
mammary duct	UBERON:0001765	92.81	gold quality
tongue	UBERON:0001723	92.56	gold quality
pons	UBERON:0000988	92.52	gold quality
heart right ventricle	UBERON:0002080	92.52	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.36	gold quality
caput epididymis	UBERON:0004358	92.30	gold quality
cauda epididymis	UBERON:0004360	92.11	gold quality
triceps brachii	UBERON:0001509	92.08	gold quality
cranial nerve II	UBERON:0000941	91.85	gold quality
epithelium of mammary gland	UBERON:0003244	91.78	gold quality
germinal epithelium of ovary	UBERON:0001304	91.77	gold quality
right lobe of liver	UBERON:0001114	91.66	gold quality
adrenal tissue	UBERON:0018303	91.45	gold quality
jejunum	UBERON:0002115	91.37	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	61.17
E-HCAD-1	yes	29.60
E-ANND-3	yes	11.65
E-MTAB-6379	no	363.08

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 46.6% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrps31	ENSDARG00000057855
mus_musculus	Mrps31	ENSMUSG00000031533
rattus_norvegicus	Mrps31	ENSRNOG00000011839
drosophila_melanogaster	mRpS31	FBGN0036557
caenorhabditis_elegans		WBGENE00007859

Protein

Protein identifiers

Small ribosomal subunit protein mS31 — Q92665 (reviewed: Q92665)

Alternative names: 28S ribosomal protein S31, mitochondrial, Imogen 38

All UniProt accessions (1): Q92665

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 mitochondrion-specific ribosomal protein mS31 family.

RefSeq proteins (1): NP_005821* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026299	MRP-S31	Family

Pfam: PF15433

UniProt features (24 total): helix 8, strand 6, region of interest 2, sequence variant 2, sequence conflict 2, transit peptide 1, chain 1, turn 1, compositionally biased region 1

Structure

Experimental structures (PDB)

76 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7QI4	ELECTRON MICROSCOPY	2.21
8CSS	ELECTRON MICROSCOPY	2.36
7P2E	ELECTRON MICROSCOPY	2.4
8RRI	ELECTRON MICROSCOPY	2.4
9OLF	ELECTRON MICROSCOPY	2.46
8CSQ	ELECTRON MICROSCOPY	2.54
8CSR	ELECTRON MICROSCOPY	2.54
6ZM6	ELECTRON MICROSCOPY	2.59
7QI5	ELECTRON MICROSCOPY	2.63
8CSP	ELECTRON MICROSCOPY	2.66
7PNX	ELECTRON MICROSCOPY	2.76
8ANY	ELECTRON MICROSCOPY	2.85
8CST	ELECTRON MICROSCOPY	2.85
6ZM5	ELECTRON MICROSCOPY	2.89
7PO0	ELECTRON MICROSCOPY	2.9
8K2A	ELECTRON MICROSCOPY	2.9
9PGL	ELECTRON MICROSCOPY	2.9
7PO1	ELECTRON MICROSCOPY	2.92
7PO3	ELECTRON MICROSCOPY	2.92
9PGF	ELECTRON MICROSCOPY	2.93
6VMI	ELECTRON MICROSCOPY	2.96
6RW4	ELECTRON MICROSCOPY	2.97
6VLZ	ELECTRON MICROSCOPY	2.97
7QI6	ELECTRON MICROSCOPY	2.98
8QRN	ELECTRON MICROSCOPY	2.98
9PSM	ELECTRON MICROSCOPY	2.98
8OIS	ELECTRON MICROSCOPY	3
9G5C	ELECTRON MICROSCOPY	3
9G5D	ELECTRON MICROSCOPY	3
9H54	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92665-F1	66.44	0.29

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: 194 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_MITOCHONDRIAL_TRANSLATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_TRANSLATION, WANG_LMO4_TARGETS_DN, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, BROWNE_HCMV_INFECTION_14HR_DN, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOCC_MITOCHONDRIAL_ENVELOPE, AACTTT_UNKNOWN, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, ZHANG_BREAST_CANCER_PROGENITORS_UP, AML1_01, MODULE_48, MODULE_95

GO Biological Process (1): mitochondrial translation (GO:0032543)

GO Molecular Function (4): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), protein domain specific binding (GO:0019904), protein binding (GO:0005515)

GO Cellular Component (6): nucleolus (GO:0005730), 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

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
intracellular membraneless organelle	2
mitochondrion	1
translation	1
mitochondrial gene expression	1
nucleic acid binding	1
structural molecule activity	1
ribosome	1
protein binding	1
binding	1
nuclear lumen	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
protein-containing complex	1

Protein interactions and networks

STRING

1736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPS31	FASTKD3	Q14CZ7	651
MRPS31	MRPL45	Q9BRJ2	607
MRPS31	MRPL39	Q9NYK5	588
MRPS31	MRPS33	Q9Y291	574
MRPS31	PTCD3	Q96EY7	540
MRPS31	MRPL53	Q96EL3	539
MRPS31	WBP4	O75554	534
MRPS31	AURKAIP1	Q9NWT8	524
MRPS31	MRPS18B	Q9Y676	519
MRPS31	MTRF1	O75570	507
MRPS31	NUP42	O15504	505
MRPS31	CYB5D1	Q6P9G0	489
MRPS31	NUP88	Q99567	476
MRPS31	COG6	Q9Y2V7	474
MRPS31	ZFPM2	Q8WW38	466

IntAct

239 interactions, top by confidence:

A	B	Type	Score
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
ESR1	TRIM24	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF707	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF331	USP9Y	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
MRPS24	ZZEF1	psi-mi:“MI:0914”(association)	0.530
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530
MRPS15	MRPS14	psi-mi:“MI:0914”(association)	0.530
TRMT10B	MRPS14	psi-mi:“MI:0914”(association)	0.530
PDGFB	DKC1	psi-mi:“MI:0914”(association)	0.530
BHLHA15	RPLP0	psi-mi:“MI:0914”(association)	0.530
MRPS18B	MRPS14	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
SNRNP70	GTPBP1	psi-mi:“MI:0914”(association)	0.530
ZNF689	ZNF593	psi-mi:“MI:0914”(association)	0.530
CCDC59	GAPDHS	psi-mi:“MI:0914”(association)	0.530
ZC3HAV1	KHNYN	psi-mi:“MI:0914”(association)	0.530

BioGRID (448): MRPS31 (Affinity Capture-MS), MRPS31 (Affinity Capture-MS), MRPS31 (Affinity Capture-MS), MRPS31 (Affinity Capture-MS), MRPS31 (Affinity Capture-MS), MRPS31 (Affinity Capture-MS), MRPS31 (Affinity Capture-MS), MRPS31 (Affinity Capture-MS), MRPS31 (Affinity Capture-MS), MRPS31 (Affinity Capture-MS), MRPS35 (Affinity Capture-MS), MRPS9 (Affinity Capture-MS), MRPS26 (Affinity Capture-MS), PTCD3 (Affinity Capture-MS), MRPS15 (Affinity Capture-MS)

ESM2 similar proteins: A0A1N7SYS3, A1A619, A3LP48, A9ULX8, B0BN56, D4A2Y9, F1NVK6, F6UF99, O04326, P40508, P82908, P82925, P92204, Q02854, Q04935, Q0P5B1, Q1LVV0, Q28GQ3, Q28HF6, Q28X44, Q2UDY8, Q3SYY7, Q3V0J1, Q56VL3, Q5I030, Q5R891, Q5XI29, Q61733, Q659C4, Q66IE4, Q68EU0, Q6AZH0, Q6BI17, Q6CHT7, Q6CJX5, Q6DFB7, Q6DFJ8, Q6NYD7, Q6PFM4, Q75D23

Diamond homologs: B0BN56, P82925, Q09261, Q61733, Q92665

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPS31	“form complex”	“28S mitochondrial small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 221 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	17	16.5×	5e-14
Mitochondrial ribosome-associated quality control	18	15.6×	4e-14
Mitochondrial translation initiation	17	15.2×	1e-13
Mitochondrial translation elongation	17	15.2×	1e-13
Mitochondrial translation termination	17	13.2×	1e-12
Translation	22	9.6×	1e-13
Influenza Infection	7	8.7×	9e-04
rRNA modification in the nucleus and cytosol	6	7.9×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	19	17.1×	2e-15
peptidyl-tyrosine phosphorylation	6	13.1×	1e-03
cytoplasmic translation	10	9.6×	4e-05
RNA processing	8	9.1×	8e-04
translation	17	9.1×	4e-09
ribosomal small subunit biogenesis	7	8.3×	4e-03
protein import into nucleus	8	6.0×	8e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	11	4.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

975 predictions. Top by Δscore:

Variant	Effect	Δscore
13:40729599:AACC:A	acceptor_loss	1.0000
13:40729600:ACCTA:A	acceptor_loss	1.0000
13:40729603:T:A	acceptor_loss	1.0000
13:40749133:CTTA:C	donor_loss	1.0000
13:40749134:TTA:T	donor_loss	1.0000
13:40749135:TACC:T	donor_loss	1.0000
13:40749136:ACCTG:A	donor_gain	1.0000
13:40749137:CCTG:C	donor_gain	1.0000
13:40749137:CCTGC:C	donor_gain	1.0000
13:40749277:TGTGT:T	acceptor_gain	1.0000
13:40749278:GTGT:G	acceptor_gain	1.0000
13:40749279:TGT:T	acceptor_gain	1.0000
13:40749280:GT:G	acceptor_gain	1.0000
13:40749280:GTCTA:G	acceptor_loss	1.0000
13:40749281:TC:T	acceptor_loss	1.0000
13:40749282:C:CC	acceptor_gain	1.0000
13:40756867:TGATA:T	donor_loss	1.0000
13:40756868:GATAC:G	donor_loss	1.0000
13:40756869:ATACC:A	donor_loss	1.0000
13:40756870:TA:T	donor_loss	1.0000
13:40756871:A:AT	donor_loss	1.0000
13:40757009:TGAAA:T	acceptor_gain	1.0000
13:40757010:GAAA:G	acceptor_gain	1.0000
13:40757011:AAA:A	acceptor_gain	1.0000
13:40757012:AA:A	acceptor_gain	1.0000
13:40757012:AAC:A	acceptor_loss	1.0000
13:40757014:C:CC	acceptor_gain	1.0000
13:40757019:A:AC	acceptor_gain	1.0000
13:40758944:TCAC:T	donor_loss	1.0000
13:40758945:CAC:C	donor_loss	1.0000

AlphaMissense

2607 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:40729576:A:C	F328L	0.989
13:40729576:A:T	F328L	0.989
13:40729578:A:G	F328L	0.989
13:40729510:G:C	F350L	0.987
13:40729510:G:T	F350L	0.987
13:40729512:A:G	F350L	0.987
13:40729487:A:G	L358P	0.986
13:40729502:A:G	L353P	0.986
13:40729511:A:G	F350S	0.986
13:40729432:A:C	F376L	0.985
13:40729432:A:T	F376L	0.985
13:40729434:A:G	F376L	0.985
13:40729437:A:G	W375R	0.983
13:40729437:A:T	W375R	0.983
13:40729453:C:A	K369N	0.983
13:40729453:C:G	K369N	0.983
13:40729477:G:C	N361K	0.983
13:40729477:G:T	N361K	0.983
13:40729421:A:G	F380S	0.979
13:40729435:C:A	W375C	0.977
13:40729435:C:G	W375C	0.977
13:40729577:A:G	F328S	0.976
13:40729485:A:G	S359P	0.975
13:40729487:A:T	L358H	0.975
13:40729490:C:T	G357D	0.975
13:40729469:A:G	L364P	0.974
13:40729433:A:G	F376S	0.973
13:40749157:G:C	F313L	0.972
13:40749157:G:T	F313L	0.972
13:40749159:A:G	F313L	0.972

dbSNP variants (sampled 300 via entrez): RS1000013067 (13:40729792 G>A,C,T), RS1000028686 (13:40755321 G>A), RS1000063242 (13:40729206 T>C), RS1000190471 (13:40741738 A>G), RS1000200297 (13:40741939 G>C), RS1000225667 (13:40762170 C>T), RS1000465842 (13:40765277 G>A,T), RS1000516499 (13:40764886 T>C), RS1000638812 (13:40767988 G>A,C), RS1000826088 (13:40760689 A>G), RS1001029310 (13:40753745 T>C), RS1001185383 (13:40768452 G>T), RS1001342031 (13:40754329 C>A,T), RS1001434866 (13:40754590 G>A), RS1001503845 (13:40746894 C>T)

Disease associations

OMIM: gene MIM:611992 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004623_63	Neutrophil percentage of granulocytes	5.000000e-11
GCST006627_8	Diastolic blood pressure	9.000000e-11
GCST90000032_14	Myeloproliferative neoplasms	3.000000e-08
GCST90013442_21	Keratoconus	6.000000e-35

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007994	neutrophil percentage of granulocytes
EFO:0006336	diastolic blood pressure
EFO:0004251	myeloproliferative disorder

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Leflunomide	decreases expression	2
Acetaminophen	affects cotreatment, increases expression, decreases expression	2
Valproic Acid	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
deoxynivalenol	increases expression	1
sodium arsenite	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
bisphenol B	increases expression	1
abrine	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Doxorubicin	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Haloperidol	increases expression	1
Ivermectin	decreases expression	1
Ketoconazole	increases expression	1
Lipopolysaccharides	increases expression, affects cotreatment	1
Nickel	decreases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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