MRPL58

Summary

MRPL58 (mitochondrial ribosomal protein L58, HGNC:5359) is a protein-coding gene on chromosome 17q25.1, encoding Large ribosomal subunit protein mL62 (Q14197). Essential peptidyl-tRNA hydrolase component of the mitochondrial large ribosomal subunit. It is a selective cancer dependency (DepMap: 29.1% of cell lines).

The protein encoded by this gene is a peptidyl-tRNA hydrolase and a vital component of the large mitochondrial ribosome. The encoded protein serves as a ribosome release factor for this ribosome, which translates mitochondrial genes. This protein may be responsible for degrading prematurely-terminated polypeptides and for reusing stalled ribosomes. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3396 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 4 total
• Cancer dependency (DepMap): dependent in 29.1% of screened cell lines
• MANE Select transcript: NM_001545

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5359
Approved symbol	MRPL58
Name	mitochondrial ribosomal protein L58
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	DS-1, mL62
Ensembl gene	ENSG00000167862
Ensembl biotype	protein_coding
OMIM	603000
Entrez	3396

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000301585, ENST00000580800, ENST00000583772, ENST00000584208, ENST00000901229, ENST00000932976, ENST00000932977, ENST00000932978

RefSeq mRNA: 2 — MANE Select: NM_001545 NM_001303265, NM_001545

CCDS: CCDS11711

Canonical transcript exons

ENST00000301585 — 6 exons

Exon	Start	End
ENSE00001117764	75017078	75017114
ENSE00002722173	75012670	75012872
ENSE00003506346	75020313	75020395
ENSE00003566652	75019700	75019759
ENSE00003582497	75020921	75021261
ENSE00003589390	75020488	75020657

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 94.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.7582 / max 286.8428, expressed in 1820 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162685	46.7582	1820

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
triceps brachii	UBERON:0001509	94.88	gold quality
gastrocnemius	UBERON:0001388	94.79	gold quality
muscle of leg	UBERON:0001383	94.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.60	gold quality
gluteal muscle	UBERON:0002000	93.83	gold quality
muscle organ	UBERON:0001630	93.79	gold quality
heart left ventricle	UBERON:0002084	93.78	gold quality
cardiac ventricle	UBERON:0002082	93.62	gold quality
right adrenal gland cortex	UBERON:0035827	93.14	gold quality
apex of heart	UBERON:0002098	93.05	gold quality
left adrenal gland	UBERON:0001234	92.62	gold quality
right adrenal gland	UBERON:0001233	92.58	gold quality
right lobe of liver	UBERON:0001114	92.57	gold quality
mucosa of transverse colon	UBERON:0004991	92.45	gold quality
left adrenal gland cortex	UBERON:0035825	92.34	gold quality
heart	UBERON:0000948	92.10	gold quality
right atrium auricular region	UBERON:0006631	92.00	gold quality
adrenal cortex	UBERON:0001235	91.87	gold quality
skeletal muscle tissue	UBERON:0001134	91.74	gold quality
biceps brachii	UBERON:0001507	91.73	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.70	gold quality
quadriceps femoris	UBERON:0001377	91.53	gold quality
deltoid	UBERON:0001476	91.42	gold quality
adrenal gland	UBERON:0002369	91.32	gold quality
vastus lateralis	UBERON:0001379	91.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.28	gold quality
cardiac atrium	UBERON:0002081	91.27	gold quality
heart right ventricle	UBERON:0002080	90.65	gold quality
muscle tissue	UBERON:0002385	90.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting MRPL58, 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-6134	99.63	65.68	1537
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-6831-3P	97.49	69.29	505
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984
HSA-MIR-5002-3P	95.75	67.04	542

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 29.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• ICT1 may be essential for hydrolysis of prematurely terminated peptidyl-tRNA moieties in stalled mitoribosomes. (PMID:20186120)
• ICT1 knockdown significantly inhibited cell proliferation and migration, led to G2/M phase cell-cycle arrest, and triggered apoptosis via the intracellular AMPKa, SAPK/JNK, and PARP signaling pathways. (PMID:27411551)
• our preliminary study reveals the important role of ICT1 in NSCLC cells that knockdown of ICT1 significantly suppressed cell proliferation, arrested cell cycle though altering expression cell cycle regulators, and promoted cell apoptosis. (PMID:27413166)
• ICT1 knockdown altered the expression of apoptosis- or cell cyclerelated proteins such as Bcl-2, caspase-3, CDK1, CDK2 and cyclin B. (PMID:28290601)
• ICT1 was significantly upregulated in diffuse large B-cell lymphoma tissues (DLBCL) and correlated with poor survival. Knockdown of ICT1 remarkably induced cell cycle G0/G phase arrest and apoptosis in DLBCL cells. (PMID:28629825)
• The results provide direct evidence that localized feedbacks on Fat4-Ds1 complexes can give rise to planar cell polarity. (PMID:28826487)
• ICT1 overexpression notably predicted poor prognosis of gastric cancer patients. (PMID:28987942)
• ICT1 may play a crucial role in promoting gastric cancer proliferation in vitro. (PMID:29036264)
• Study demonstrates that ICT1 overexpression correlates with malignant clinical features and poor prognosis of hepatocellular carcinoma (HCC) patients. Functionally, ICT1 promotes proliferation, cell cycle progression and inhibits apoptosis of HCC cells. ICT1 regulates the expressions of CDK1, cyclin B1, Bcl-2 and Bax, and is directly targeted by microRNA-134 (miR-134) in HCC cells. (PMID:29130100)
• High ICT1 expression is associated with leukemia. (PMID:29328466)
• miR-1301-3p inhibits cell proliferation via inducing cell cycle arrest and apoptosis through targeting ICT1, and might be a therapeutic target for BC. (PMID:29951881)
• ICT1 Promotes Osteosarcoma Cell Proliferation and Inhibits Apoptosis via STAT3/BCL-2 Pathway. (PMID:33585660)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mrpl58	ENSMUSG00000018858
rattus_norvegicus	Mrpl58	ENSRNOG00000032780
drosophila_melanogaster	CG6094	FBGN0032261

Paralogs (2): MTRF1L (ENSG00000112031), MTRF1 (ENSG00000120662)

Protein

Protein identifiers

Large ribosomal subunit protein mL62 — Q14197 (reviewed: Q14197)

Alternative names: 39S ribosomal protein L58, mitochondrial, Digestion substraction 1, Immature colon carcinoma transcript 1 protein, Peptidyl-tRNA hydrolase ICT1, mitochondrial

All UniProt accessions (3): Q14197, J3KS15, J3QRF8

UniProt curated annotations — full annotation on UniProt →

Function. Essential peptidyl-tRNA hydrolase component of the mitochondrial large ribosomal subunit. Acts as a codon-independent translation release factor that has lost all stop codon specificity and directs the termination of translation in mitochondrion, possibly in case of abortive elongation. Involved in the hydrolysis of peptidyl-tRNAs that have been prematurely terminated and thus in the recycling of stalled mitochondrial ribosomes.

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.

Subcellular location. Mitochondrion.

Tissue specificity. Down-regulated during the in vitro differentiation of HT29-D4 colon carcinoma cells.

Post-translational modifications. Methylation of glutamine in the GGQ triplet by HEMK1.

Similarity. Belongs to the prokaryotic/mitochondrial release factor family. Mitochondrion-specific ribosomal protein mL62 subfamily.

RefSeq proteins (2): NP_001290194, NP_001536* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000352	Pep_chain_release_fac_I	Domain
IPR052104	Mito_Release_Factor_mL62	Family

Pfam: PF00472

Enzyme classification (BRENDA):

• EC 3.1.1.29 — peptidyl-tRNA hydrolase (BRENDA: 24 organisms, 89 substrates, 19 inhibitors, 50 Km, 45 kcat entries)

Substrate kinetics (BRENDA)

22 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DIACETYL-LYSYL-TRNALYS	—	14
DIACETYL-LYS-TRNALYS	—	9
DIACETYL-LYSINE-TRNA	—	5
N-ACETYL-ALA-TRNA(ALA)	0.0047–0.0269	4
FORMYL-METHIONYL-TRNAFMET	—	2
ACETYL-HIS-TRNAHIS	—	1
ACETYL-HISTIDYL-TRNA	—	1
ACETYL-HISTIDYL-TRNAHIS	—	1
BULK PEPTIDYL-TRNA	0.008	1
DEPHOSPHORYLATED DIACYL-LYSINE-TRNA	—	1
DEPHOSPHORYLATED FORMYL-MET-TRNAFMET	—	1
DEPHOSPHORYLATED FORMYL-METHIONINYL-TRNA	—	1
FORMYL-MET-TRNAFMET	—	1
FORMYL-METHIONYL-TRNA	—	1
N-ACETYL-MET-TRNA	0.0022	1

Catalyzed reactions (Rhea), 1 shown:

• an N-acyl-L-alpha-aminoacyl-tRNA + H2O = an N-acyl-L-amino acid + a tRNA + H(+) (RHEA:54448)

UniProt features (21 total): helix 6, strand 5, sequence variant 3, mutagenesis site 2, transit peptide 1, chain 1, turn 1, modified residue 1, sequence conflict 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
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
9PSM	ELECTRON MICROSCOPY	2.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14197-F1	84.81	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 90

Mutagenesis-validated functional residues (2):

Position	Phenotype
88	strongly impairs peptide release activity.
89	strongly impairs peptide release activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 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

MSigDB gene sets: 155 (showing top): MATTIOLI_MGUS_VS_PCL, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MITOCHONDRIAL_TRANSLATION, TAL1ALPHAE47_01, GOBP_TRANSLATIONAL_TERMINATION, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOCC_MITOCHONDRIAL_ENVELOPE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_TRANSLATIONAL_ELONGATION, GUO_HEX_TARGETS_DN, SCHLOSSER_SERUM_RESPONSE_AUGMENTED_BY_MYC, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON

GO Biological Process (5): mitochondrial translation (GO:0032543), mitochondrial translational termination (GO:0070126), rescue of stalled cytosolic ribosome (GO:0072344), translation (GO:0006412), translational termination (GO:0006415)

GO Molecular Function (4): peptidyl-tRNA hydrolase activity (GO:0004045), translation release factor activity, codon nonspecific (GO:0016150), translation release factor activity (GO:0003747), hydrolase activity (GO:0016787)

GO Cellular Component (8): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), mitochondrial large ribosomal subunit (GO:0005762), plasma membrane (GO:0005886), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitochondrial translation	4

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
translation	2
translational termination	2
mitochondrial gene expression	1
mitochondrial translation	1
cytoplasmic translational elongation	1
ribosome disassembly	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
protein-containing complex disassembly	1
carboxylic ester hydrolase activity	1
catalytic activity, acting on a tRNA	1
translation release factor activity	1
translation termination factor activity	1
catalytic activity	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
organellar large ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
membrane	1
cell periphery	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

3220 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL58	MTRFR	Q9H3J6	966
MRPL58	MRPL12	P52815	949
MRPL58	ADSL	P30566	823
MRPL58	NDUFB8	O95169	799
MRPL58	MTRF1L	Q9UGC7	763
MRPL58	YIPF2	Q9BWQ6	761
MRPL58	MTRF1	O75570	732
MRPL58	KIR2DL4	P78400	723
MRPL58	SPECC1	Q5M775	712
MRPL58	PRSS57	Q6UWY2	695
MRPL58	MT-ATP6	P00846	663
MRPL58	SH2D3A	Q9BRG2	658
MRPL58	MRRF	Q96E11	649
MRPL58	MALSU1	Q96EH3	643
MRPL58	SH2D3C	Q8N5H7	614

IntAct

117 interactions, top by confidence:

A	B	Type	Score
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
MRPL50	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL10	ZZEF1	psi-mi:“MI:0914”(association)	0.530
MRPL42	GATC	psi-mi:“MI:0914”(association)	0.530
MRPL28	MRPL3	psi-mi:“MI:0914”(association)	0.530
MRPL41	MRPL3	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL13	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL18	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL27	MRPL33	psi-mi:“MI:0914”(association)	0.530
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
MRPL58	MRPL3	psi-mi:“MI:0403”(colocalization)	0.460
MRPL58	MRPL3	psi-mi:“MI:0914”(association)	0.460
ZNF226	MRPL58	psi-mi:“MI:0915”(physical association)	0.400
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
NP	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
MRPL4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350

BioGRID (625): ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), ICT1 (Co-fractionation), ICT1 (Co-fractionation)

ESM2 similar proteins: A4IHS0, A5WUX7, A6ZND9, B1P1W2, B3LIY9, B4KPG8, B5XAM2, D2HD32, E7EXT2, O44568, O94443, P25642, P34511, P82673, Q05863, Q08230, Q08DT6, Q08DU1, Q09691, Q12322, Q14197, Q2KI45, Q3T116, Q3UFY8, Q497V5, Q498P2, Q5RDI0, Q5U2R4, Q60R52, Q7JUX9, Q80VP5, Q8C1Z8, Q8K2Y7, Q8MT06, Q8N5C6, Q8R035, Q8VCE1, Q95Q11, Q9BRU9, Q9BVP2

Diamond homologs: B5XAM2, D2HD32, P40711, P45388, Q12322, Q14197, Q3T116, Q8R035, Q9HDZ3, A6LDR9, A9W1A4, B0JYC5, B1M766, B7K0A6, B7L246, B8EI32, C5BSZ6, Q087I4, Q31L36, Q5LH11, Q5N0T6, Q64XW5, Q7U3W6, Q8A011

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPL58	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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 ribosome-associated quality control	27	48.8×	1e-37
Mitochondrial translation	23	46.5×	2e-31
Mitochondrial translation initiation	24	44.8×	2e-32
Mitochondrial translation elongation	24	44.8×	2e-32
Mitochondrial translation termination	24	38.8×	6e-31
Translation	24	21.9×	1e-24
Peptide chain elongation	5	9.3×	8e-03
Viral mRNA Translation	5	9.3×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	26	57.9×	2e-37
translation	19	25.0×	2e-19
cytoplasmic translation	5	11.9×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

708 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75012882:G:GT	donor_gain	1.0000
17:75012882:G:T	donor_gain	1.0000
17:75020308:CACA:C	acceptor_loss	1.0000
17:75020309:ACAGT:A	acceptor_gain	1.0000
17:75020310:CA:C	acceptor_loss	1.0000
17:75020311:A:AG	acceptor_gain	1.0000
17:75020311:AG:A	acceptor_loss	1.0000
17:75020311:AGT:A	acceptor_gain	1.0000
17:75020312:G:GT	acceptor_gain	1.0000
17:75020312:GT:G	acceptor_gain	1.0000
17:75020312:GTG:G	acceptor_gain	1.0000
17:75020312:GTGA:G	acceptor_gain	1.0000
17:75020312:GTGAA:G	acceptor_gain	1.0000
17:75020393:ACGG:A	donor_loss	1.0000
17:75020394:CGGTA:C	donor_loss	1.0000
17:75020395:GGTAA:G	donor_loss	1.0000
17:75020396:G:GG	donor_gain	1.0000
17:75020397:T:A	donor_loss	1.0000
17:75020483:TGCA:T	acceptor_loss	1.0000
17:75020485:CAGC:C	acceptor_loss	1.0000
17:75020486:A:AG	acceptor_gain	1.0000
17:75020486:A:T	acceptor_loss	1.0000
17:75020487:G:A	acceptor_loss	1.0000
17:75020487:G:GA	acceptor_gain	1.0000
17:75020487:GC:G	acceptor_gain	1.0000
17:75020487:GCA:G	acceptor_gain	1.0000
17:75020487:GCAT:G	acceptor_gain	1.0000
17:75020487:GCATA:G	acceptor_gain	1.0000
17:75020916:TTCA:T	acceptor_loss	1.0000
17:75020918:CAGG:C	acceptor_loss	1.0000

AlphaMissense

1358 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75020357:T:A	W110R	0.997
17:75020357:T:C	W110R	0.997
17:75020571:C:G	C150W	0.994
17:75020331:T:A	V101D	0.992
17:75020337:T:C	F103S	0.992
17:75019746:G:C	Q90H	0.990
17:75019746:G:T	Q90H	0.990
17:75020319:C:T	S97F	0.989
17:75020323:G:C	K98N	0.989
17:75020323:G:T	K98N	0.989
17:75020359:G:C	W110C	0.989
17:75020359:G:T	W110C	0.989
17:75020519:T:C	L133S	0.989
17:75019726:A:C	S84R	0.987
17:75019728:T:A	S84R	0.987
17:75019728:T:G	S84R	0.987
17:75020573:T:C	L151P	0.987
17:75020570:G:A	C150Y	0.986
17:75020530:T:C	S137P	0.985
17:75020559:T:A	N146K	0.985
17:75020559:T:G	N146K	0.985
17:75020557:A:G	N146D	0.984
17:75020376:G:C	R116P	0.982
17:75020561:T:C	L147P	0.981
17:75019706:T:C	L77S	0.980
17:75020513:G:T	G131V	0.979
17:75020569:T:C	C150R	0.979
17:75020318:T:C	S97P	0.978
17:75020324:G:C	A99P	0.977
17:75020558:A:C	N146T	0.976

dbSNP variants (sampled 300 via entrez): RS1000228315 (17:75011651 T>C), RS1000305013 (17:75017272 C>T), RS1000333716 (17:75012557 G>A,C), RS1000601715 (17:75011353 A>C), RS1000670033 (17:75013691 T>A), RS1001546819 (17:75012241 A>G), RS1001679985 (17:75017831 C>T), RS1001808745 (17:75011830 G>A,C), RS1001883955 (17:75013251 C>G), RS1001924346 (17:75016740 A>T), RS1002031302 (17:75010948 T>C), RS1002052938 (17:75019534 C>G,T), RS1002119254 (17:75018105 G>A,C,T), RS1002145576 (17:75013052 G>C,T), RS1002423448 (17:75019215 A>T)

Disease associations

OMIM: gene MIM:603000 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003423_1	Alzheimer’s disease or small vessel stroke	2.000000e-08
GCST008103_113	Bipolar disorder	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001504	small vessel stroke

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
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
1,6-hexamethylene diisocyanate	increases methylation	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
deguelin	increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
pyrachlostrobin	affects expression	1
bisphenol S	increases expression	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Doxorubicin	affects expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Ozone	increases abundance, affects cotreatment, increases oxidation	1
Smoke	decreases expression	1
T-2 Toxin	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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