MRPS34

Summary

MRPS34 (mitochondrial ribosomal protein S34, HGNC:16618) is a protein-coding gene on chromosome 16p13.3, encoding Small ribosomal subunit protein mS34 (P82930). Required for mitochondrial translation, plays a role in maintaining the stability of the small ribosomal subunit and the 12S rRNA that are required for mitoribosome formation. It is a selective cancer dependency (DepMap: 72.9% 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 28S subunit protein. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 65993 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined oxidative phosphorylation deficiency 32 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 58 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 36
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 72.9% of screened cell lines
• MANE Select transcript: NM_023936

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16618
Approved symbol	MRPS34
Name	mitochondrial ribosomal protein S34
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MRP-S12, MGC2616, mS34
Ensembl gene	ENSG00000074071
Ensembl biotype	protein_coding
OMIM	611994
Entrez	65993

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000177742, ENST00000397375, ENST00000569585, ENST00000890485, ENST00000890486, ENST00000939641, ENST00000939642

RefSeq mRNA: 2 — MANE Select: NM_023936 NM_001300900, NM_023936

CCDS: CCDS10444, CCDS73805

Canonical transcript exons

ENST00000397375 — 3 exons

Exon	Start	End
ENSE00000945911	1771895	1772513
ENSE00001827582	1772799	1773134
ENSE00003340619	1772604	1772646

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 98.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 83.7374 / max 310.2240, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155866	79.1962	1823
155865	1.9155	1009
155864	1.7907	767
155863	0.7332	386
155862	0.1018	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.18	gold quality
right adrenal gland	UBERON:0001233	97.40	gold quality
apex of heart	UBERON:0002098	97.32	gold quality
right adrenal gland cortex	UBERON:0035827	97.31	gold quality
left adrenal gland	UBERON:0001234	97.23	gold quality
left adrenal gland cortex	UBERON:0035825	97.23	gold quality
body of pancreas	UBERON:0001150	96.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.52	gold quality
granulocyte	CL:0000094	96.45	gold quality
adrenal cortex	UBERON:0001235	96.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.08	gold quality
lower esophagus mucosa	UBERON:0035834	95.92	gold quality
right lobe of liver	UBERON:0001114	95.88	gold quality
transverse colon	UBERON:0001157	95.86	gold quality
skin of abdomen	UBERON:0001416	95.86	gold quality
skin of leg	UBERON:0001511	95.84	gold quality
body of stomach	UBERON:0001161	95.59	gold quality
adrenal gland	UBERON:0002369	95.45	gold quality
esophagus mucosa	UBERON:0002469	95.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.40	gold quality
prefrontal cortex	UBERON:0000451	95.36	gold quality
right frontal lobe	UBERON:0002810	95.13	gold quality
gastrocnemius	UBERON:0001388	95.04	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.99	gold quality
muscle of leg	UBERON:0001383	94.98	gold quality
adenohypophysis	UBERON:0002196	94.98	gold quality
cerebellar hemisphere	UBERON:0002245	94.98	gold quality
cerebellar cortex	UBERON:0002129	94.94	gold quality
anterior cingulate cortex	UBERON:0009835	94.92	gold quality
cingulate cortex	UBERON:0003027	94.89	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting MRPS34, 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-4673	100.00	66.64	1490
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-3918	96.13	64.65	1300

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• MRPS34 is required for normal function of the mitoribosome and energy-generating mitochondrial OXPHOS system in humans. (PMID:28777931)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrps34	ENSDARG00000057910
mus_musculus	Mrps34	ENSMUSG00000038880
drosophila_melanogaster	mRpS34	FBGN0285951
caenorhabditis_elegans		WBGENE00010905

Protein

Protein identifiers

Small ribosomal subunit protein mS34 — P82930 (reviewed: P82930)

Alternative names: 28S ribosomal protein S34, mitochondrial

All UniProt accessions (2): P82930, C9JJ19

UniProt curated annotations — full annotation on UniProt →

Function. Required for mitochondrial translation, plays a role in maintaining the stability of the small ribosomal subunit and the 12S rRNA that are required for mitoribosome formation.

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.

Disease relevance. Combined oxidative phosphorylation deficiency 32 (COXPD32) [MIM:617664] An autosomal recessive disorder due to deficiency of mitochondrial respiratory chain complexes, I, III and IV, and characterized by delayed psychomotor development and neurodevelopmental regression. Additional variable symptoms include poor or absent speech, inability to walk, and abnormal movements. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the mitochondrion-specific ribosomal protein mS34 family.

RefSeq proteins (2): NP_001287829, NP_076425* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032053	Ribosomal_mS34	Family

Pfam: PF16053

UniProt features (29 total): helix 11, strand 9, sequence variant 4, turn 2, chain 1, region of interest 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
9OJM	ELECTRON MICROSCOPY	2.5
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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P82930-F1	82.20	0.28

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: 188 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATION, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOCC_MITOCHONDRIAL_ENVELOPE, BURTON_ADIPOGENESIS_5, GOCC_RIBOSOME, GOCC_SMALL_RIBOSOMAL_SUBUNIT, GOCC_ORGANELLAR_RIBOSOME, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_INNER_MEMBRANE, GOCC_RIBOSOMAL_SUBUNIT, GOCC_RIBONUCLEOPROTEIN_COMPLEX, GOCC_MITOCHONDRIAL_PROTEIN_CONTAINING_COMPLEX

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

GO Molecular Function (1): 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

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
mitochondrion	1
translation	1
mitochondrial gene expression	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

Protein interactions and networks

STRING

6090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPS34	MRPL12	P52815	648
MRPS34	MRPS22	P82650	645
MRPS34	MRPS2	Q9Y399	614
MRPS34	MRPS16	Q9Y3D3	606
MRPS34	MRPL44	Q9H9J2	581
MRPS34	PTCD3	Q96EY7	571
MRPS34	RSPRY1	Q96DX4	528
MRPS34	A8MYK1	A8MYK1	524
MRPS34	CCDC106	Q9BWC9	507
MRPS34	MRPL23	Q16540	506
MRPS34	DLG1	Q12959	484
MRPS34	MAPK8IP3	Q9UPT6	483
MRPS34	NUDT13	Q86X67	472
MRPS34	MRPL11	Q9Y3B7	470
MRPS34	MRPL48	Q96GC5	458

IntAct

159 interactions, top by confidence:

A	B	Type	Score
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ERBB3	PIK3R2	psi-mi:“MI:0914”(association)	0.700
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
MRPS6	STAT5A	psi-mi:“MI:0914”(association)	0.550
RPS6	IPO7	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
TRMT10B	MRPS14	psi-mi:“MI:0914”(association)	0.530
MRPS18B	MRPS14	psi-mi:“MI:0914”(association)	0.530
MRPS34	ZZEF1	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPS34	MRPS12	psi-mi:“MI:0914”(association)	0.530
PSME3	HTRA2	psi-mi:“MI:0914”(association)	0.530
MRPS11	MRPS14	psi-mi:“MI:0914”(association)	0.530
IGF2BP3	PTCD1	psi-mi:“MI:0914”(association)	0.530
MRPS26	MRPS10	psi-mi:“MI:0914”(association)	0.530
STRBP	MAGEB2	psi-mi:“MI:0914”(association)	0.530
DLG1	MRPS34	psi-mi:“MI:0407”(direct interaction)	0.440
PPP2R2B	TCP1	psi-mi:“MI:0914”(association)	0.420
PPP2R2B	TCP1	psi-mi:“MI:2364”(proximity)	0.420
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
Ybx1	MRPS18B	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (423): MRPS34 (Affinity Capture-RNA), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS), MRPS34 (Affinity Capture-MS)

ESM2 similar proteins: B1I1J2, O12160, O70454, O89293, O89942, O91082, P05916, P05917, P05918, P05957, P05958, P08463, P11265, P11266, P12454, P12455, P12514, P12521, P16904, P17664, P18045, P18099, P19508, P19509, P20881, P20891, P21124, P21125, P22385, P27976, P41223, P42075, P82929, P82930, Q1A247, Q567Z7, Q65WT0, Q72ID6, Q74122, Q75004

Diamond homologs: P82929, P82930, Q9JIK9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPS34	“form complex”	“28S mitochondrial small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 185 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 initiation	18	19.0×	5e-16
Mitochondrial translation elongation	18	19.0×	5e-16
Mitochondrial ribosome-associated quality control	18	18.4×	6e-16
Mitochondrial translation	16	18.4×	3e-14
Mitochondrial translation termination	18	16.5×	4e-15
Signaling by ALK in cancer	5	11.3×	4e-03
Signaling by ALK fusions and activated point mutants	9	11.3×	8e-06
Translation	21	10.9×	3e-14

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	19	20.4×	7e-17
positive regulation of fibroblast proliferation	6	10.9×	4e-03
ribosomal small subunit biogenesis	7	9.8×	3e-03
RNA processing	7	9.5×	3e-03
translation	14	8.9×	4e-07
rRNA processing	8	7.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	21
Likely benign	20
Benign	7

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
430586	NM_023936.1(MRPS34):c.321+1G>T	Pathogenic
438633	NM_023936.2(MRPS34):c.322-10G>A	Pathogenic
1527902	NM_023936.2(MRPS34):c.562G>A (p.Glu188Lys)	Likely pathogenic
2441484	NM_023936.2(MRPS34):c.532C>T (p.Arg178Ter)	Likely pathogenic
3012930	NM_023936.2(MRPS34):c.322-1G>A	Likely pathogenic

SpliceAI

162 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1772598:CCTTA:C	donor_loss	1.0000
16:1772599:CTTAC:C	donor_loss	1.0000
16:1772600:TTA:T	donor_loss	1.0000
16:1772601:TA:T	donor_loss	1.0000
16:1772602:ACC:A	donor_loss	1.0000
16:1772794:CGCA:C	donor_loss	1.0000
16:1772795:GCACC:G	donor_loss	1.0000
16:1772797:ACCTG:A	donor_loss	1.0000
16:1772798:C:CT	donor_loss	1.0000
16:1772509:CTTCC:C	acceptor_gain	0.9900
16:1772511:TCCCT:T	acceptor_loss	0.9900
16:1772512:CC:C	acceptor_gain	0.9900
16:1772513:CC:C	acceptor_gain	0.9900
16:1772513:CCTGA:C	acceptor_loss	0.9900
16:1772514:C:CC	acceptor_gain	0.9900
16:1772514:CT:C	acceptor_loss	0.9900
16:1772515:T:C	acceptor_loss	0.9900
16:1772647:C:CC	acceptor_gain	0.9900
16:1772510:TTCC:T	acceptor_gain	0.9800
16:1772517:A:AC	acceptor_gain	0.9800
16:1772517:A:C	acceptor_gain	0.9800
16:1772602:A:AC	donor_gain	0.9800
16:1772603:C:CC	donor_gain	0.9800
16:1772643:AGTTC:A	acceptor_loss	0.9800
16:1772644:GTTCT:G	acceptor_loss	0.9800
16:1772645:TT:T	acceptor_gain	0.9800
16:1772645:TTC:T	acceptor_loss	0.9800
16:1772646:TCTG:T	acceptor_loss	0.9800
16:1772647:C:T	acceptor_loss	0.9800
16:1772648:T:G	acceptor_loss	0.9800

AlphaMissense

1397 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1772463:A:G	W139R	0.991
16:1772463:A:T	W139R	0.991
16:1772461:C:A	W139C	0.980
16:1772461:C:G	W139C	0.980
16:1772459:C:G	R140P	0.978
16:1772881:A:T	V80D	0.977
16:1772364:C:G	A172P	0.976
16:1772622:C:G	G116R	0.975
16:1772867:A:G	W85R	0.971
16:1772867:A:T	W85R	0.971
16:1772462:C:G	W139S	0.962
16:1772837:A:G	W95R	0.961
16:1772837:A:T	W95R	0.961
16:1772366:C:G	R171P	0.953
16:1772633:C:T	G112E	0.953
16:1772382:A:C	Y166D	0.952
16:1772865:C:A	W85C	0.952
16:1772865:C:G	W85C	0.952
16:1772621:C:T	G116D	0.949
16:1772634:C:A	G112W	0.947
16:1773076:G:T	A15D	0.945
16:1772841:G:C	C93W	0.944
16:1772840:A:C	Y94D	0.943
16:1772608:G:C	F120L	0.942
16:1772608:G:T	F120L	0.942
16:1772610:A:G	F120L	0.942
16:1772513:C:A	G122V	0.939
16:1772465:T:A	D138V	0.937
16:1772830:A:T	L97H	0.936
16:1772466:C:G	D138H	0.934

dbSNP variants (sampled 300 via entrez): RS1000988298 (16:1773005 C>G,T), RS1002180875 (16:1771576 C>G,T), RS1003213252 (16:1772269 G>A), RS1003222824 (16:1774798 G>A), RS1003252289 (16:1774929 C>A,T), RS1004356275 (16:1773174 C>A,G,T), RS1005072779 (16:1774542 G>A,C), RS1005102461 (16:1774446 G>A,C), RS1005595041 (16:1771837 C>T), RS1006459180 (16:1771604 G>A,C,T), RS1007227328 (16:1771867 CAG>C), RS1007434620 (16:1772070 C>T), RS1007631125 (16:1771446 C>A), RS1009618634 (16:1774915 G>A,C), RS1009810615 (16:1771546 G>A,C,T)

Disease associations

OMIM: gene MIM:611994 | disease phenotypes: MIM:617664

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation deficiency 32	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Leigh syndrome	Moderate	AR

Mondo (2): combined oxidative phosphorylation deficiency 32 (MONDO:0054654), hereditary neoplastic syndrome (MONDO:0015356)

Orphanet (1): Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000085	Horseshoe kidney
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000577	Exotropia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001522	Death in infancy
HP:0002015	Dysphagia
HP:0002019	Constipation
HP:0002020	Gastroesophageal reflux
HP:0002151	Increased circulating lactate concentration
HP:0002376	Developmental regression
HP:0002490	Increased CSF lactate
HP:0002540	Inability to walk
HP:0002751	Kyphoscoliosis
HP:0003128	Lactic acidosis
HP:0003593	Infantile onset

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067264 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.55	Kd	27.91	nM	CHEMBL3752910
7.55	ED50	27.91	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149890: Binding affinity to human MRPS34 incubated for 45 mins by Kinobead based pull down assay	kd	0.0279	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression, increases expression	4
Valproic Acid	decreases expression, increases expression, increases methylation, affects expression	4
Acetaminophen	affects cotreatment, decreases expression	3
TAK-243	increases sumoylation	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
jinfukang	increases expression	1
Diazinon	increases methylation	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Sodium Selenite	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652932	Binding	Binding affinity to human MRPS34 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001496	Not specified	COMPLETED	Establishment of Normal Breast Epithelial Cell Lines From Patients at High Risk for Breast Cancer
NCT00001898	Not specified	COMPLETED	Microarray Analysis for Human Genetic Disease
NCT00026884	Not specified	RECRUITING	Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease
NCT02289326	Not specified	COMPLETED	Biomarker Monitoring in TP53 Mutation Carriers
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03160274	Not specified	RECRUITING	Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
NCT03426878	Not specified	COMPLETED	Cancer Health Assessments Reaching Many
NCT03857594	Not specified	ACTIVE_NOT_RECRUITING	Integrative Sequencing In Germline and Hereditary Tumours
NCT03973450	Not specified	UNKNOWN	Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04261972	Not specified	ACTIVE_NOT_RECRUITING	Cell-free DNA in Hereditary And High-Risk Malignancies 1
NCT04494945	Not specified	RECRUITING	Identifying and Caring for Individuals With Inherited Cancer Syndrome
NCT04541654	Not specified	RECRUITING	Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress
NCT04763915	Not specified	ACTIVE_NOT_RECRUITING	Improving Care After Inherited Cancer Testing
NCT05562778	Not specified	RECRUITING	Chatbot to Maximize Hereditary Cancer Genetic Risk Assessment
NCT05664867	Not specified	RECRUITING	Implementation of Population Cancer Genetic Services in Federally Qualified Health Centers (FQHC)
NCT05721326	Not specified	COMPLETED	Sequential EHR Based Interventions to Increase Genetic Testing for Breast and Ovarian Cancer Predisposition
NCT06096688	Not specified	RECRUITING	Discovering New Targets for Colorectal and Endometrial Cancer Risk Reduction
NCT06654466	Not specified	RECRUITING	Closing the GAPS: Guideline Adherence, Prevention and Surveillance in Hereditary Cancer
NCT06708429	Not specified	RECRUITING	Lynch Syndrome X-Talk of Enteral Mucosa With Immune System
NCT06726642	Not specified	RECRUITING	CfDNA in Hereditary And High-risk Malignancies 2
NCT06914726	Not specified	ENROLLING_BY_INVITATION	Patient Centered Clinical Decision Support for Hereditary Cancer Syndromes
NCT06927947	Not specified	RECRUITING	Navigation Interventions to Improve Cascade Genetic Testing Among Relatives of Patients With Hereditary Cancer Syndromes
NCT06999954	Not specified	RECRUITING	Shwachman-Diamond Syndrome Global Patient Survey and Partnering Platform
NCT07052266	Not specified	RECRUITING	Trial of Combined Obstetric Carrier Screening and Hereditary Cancer Screening
NCT07195071	Not specified	RECRUITING	Feasibility Trial of Combination of Obstetrical Carrier Screening and Hereditary Cancer Screening
NCT07378423	Not specified	RECRUITING	Questionnaire on Congenital Cancer Signs Through Self-Assessment
NCT07381985	Not specified	ENROLLING_BY_INVITATION	Strategy for Management of Patients With Hereditary Cancer Syndromes (HCS) in a Rural Environment
NCT07542405	Not specified	NOT_YET_RECRUITING	A Web-Based Program (Kindred) to Improve the Understanding of Genetic Cancer Risk and Cancer Genetic Testing in African American Families