RPL13

Summary

RPL13 (ribosomal protein L13, HGNC:10303) is a protein-coding gene on chromosome 16q24.3, encoding Large ribosomal subunit protein eL13 (P26373). Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L13E family of ribosomal proteins. It is located in the cytoplasm. This gene is expressed at significantly higher levels in benign breast lesions than in breast carcinomas. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6137 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondyloepimetaphyseal dysplasia, Isidor-Toutain type (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 50 total — 6 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 13
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000977

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10303
Approved symbol	RPL13
Name	ribosomal protein L13
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Aliases	D16S444E, BBC1, L13, eL13
Ensembl gene	ENSG00000167526
Ensembl biotype	protein_coding
OMIM	113703
Entrez	6137

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 22 protein_coding, 7 retained_intron, 1 nonsense_mediated_decay

ENST00000311528, ENST00000393099, ENST00000399461, ENST00000452368, ENST00000467736, ENST00000472354, ENST00000484610, ENST00000487034, ENST00000491523, ENST00000562879, ENST00000563270, ENST00000563749, ENST00000565571, ENST00000567815, ENST00000570149, ENST00000902246, ENST00000902247, ENST00000902248, ENST00000902249, ENST00000935772, ENST00000935773, ENST00000935774, ENST00000935775, ENST00000935776, ENST00000935777, ENST00000935778, ENST00000935779, ENST00000935780, ENST00000971042, ENST00000971043

RefSeq mRNA: 3 — MANE Select: NM_000977 NM_000977, NM_001243131, NM_033251

CCDS: CCDS10979, CCDS58492

Canonical transcript exons

ENST00000311528 — 6 exons

Exon	Start	End
ENSE00001189530	89560682	89560712
ENSE00001834571	89562884	89564542
ENSE00003493808	89561578	89561751
ENSE00003505594	89562335	89562391
ENSE00003644914	89561227	89561368
ENSE00003673277	89560940	89561063

Expression profiles

Bgee: expression breadth ubiquitous, 311 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 481.0067 / max 5710.5790, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155600	478.4606	1827
155601	2.1217	1083
155607	0.2615	136
155604	0.1004	15
155603	0.0437	5
155602	0.0188	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.96	gold quality
right ovary	UBERON:0002118	99.96	gold quality
left ovary	UBERON:0002119	99.96	gold quality
skin of abdomen	UBERON:0001416	99.95	gold quality
endocervix	UBERON:0000458	99.94	gold quality
skin of leg	UBERON:0001511	99.94	gold quality
left uterine tube	UBERON:0001303	99.93	gold quality
adenohypophysis	UBERON:0002196	99.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.93	gold quality
body of uterus	UBERON:0009853	99.93	gold quality
ectocervix	UBERON:0012249	99.93	gold quality
granulocyte	CL:0000094	99.92	gold quality
pituitary gland	UBERON:0000007	99.92	gold quality
peritoneum	UBERON:0002358	99.92	gold quality
left testis	UBERON:0004533	99.92	gold quality
right testis	UBERON:0004534	99.92	gold quality
omental fat pad	UBERON:0010414	99.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.92	gold quality
lower esophagus mucosa	UBERON:0035834	99.92	gold quality
peripheral nervous system	UBERON:0000010	99.91	gold quality
nerve	UBERON:0001021	99.91	gold quality
right lobe of thyroid gland	UBERON:0001119	99.91	gold quality
mucosa of stomach	UBERON:0001199	99.91	gold quality
tibial nerve	UBERON:0001323	99.91	gold quality
right lung	UBERON:0002167	99.91	gold quality
mucosa of transverse colon	UBERON:0004991	99.91	gold quality
lower esophagus	UBERON:0013473	99.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.91	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.91	gold quality
ovary	UBERON:0000992	99.90	gold quality

Single-cell (SCXA)

Detected in 53 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	11687.07
E-CURD-122	yes	9992.10
E-MTAB-6678	yes	2802.97
E-GEOD-111727	yes	2555.86
E-GEOD-180759	yes	2089.99
E-HCAD-35	yes	1658.16
E-MTAB-7037	yes	935.47
E-MTAB-9543	yes	32.87
E-MTAB-10042	yes	17.18
E-MTAB-9801	yes	6.68
E-GEOD-137537	yes	5.64
E-CURD-46	no	15815.05
E-GEOD-149689	no	15618.26
E-MTAB-6653	no	14890.96
E-GEOD-139324	no	14176.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting RPL13, 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-4775	99.98	75.00	6394
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-4717-3P	99.06	66.34	1072

Literature-anchored findings (GeneRIF, showing 5)

• Ribosomal protein L13 plays an essential role in the progression of some gastrointestinal malignancies. (PMID:16786168)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• Using a combination of human genetics and cardiac model systems, RPL13 gene was identified as a new candidate for congenital heart pathogenesis. (PMID:31625562)
• The identified RPL13 variants cause a human ribosomopathy defined by a rare skeletal dysplasia. (PMID:31630789)
• Novel RPL13 Variants and Variable Clinical Expressivity in a Human Ribosomopathy With Spondyloepimetaphyseal Dysplasia. (PMID:32916022)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl13	ENSDARG00000099380
mus_musculus	Rpl13	ENSMUSG00000000740
rattus_norvegicus	Rpl13	ENSRNOG00000015335
rattus_norvegicus	LOC100361259	ENSRNOG00000055911
rattus_norvegicus	LOC100360491	ENSRNOG00000061438
rattus_norvegicus		ENSRNOG00000077833
drosophila_melanogaster	RpL13	FBGN0011272
caenorhabditis_elegans	rpl-13	WBGENE00004425

Protein

Protein identifiers

Large ribosomal subunit protein eL13 — P26373 (reviewed: P26373)

Alternative names: 60S ribosomal protein L13, Breast basic conserved protein 1

All UniProt accessions (6): A8K4C8, P26373, H3BTH3, H3BUK8, J3KS98, J3QSB4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. As part of the LSU, it is probably required for its formation and the maturation of rRNAs. Plays a role in bone development.

Subunit / interactions. Component of the 60S large ribosomal subunit (LSU).

Subcellular location. Cytoplasm.

Tissue specificity. Higher levels of expression in benign breast lesions than in carcinomas.

Disease relevance. Spondyloepimetaphyseal dysplasia, Isidor-Toutain type (SEMDIST) [MIM:618728] An autosomal dominant bone disease characterized by early postnatal growth deficiency, severe short stature, genu varum, platyspondyly and severe epiphyseal and metaphyseal changes in the lower limbs. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the eukaryotic ribosomal protein eL13 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P26373-1	1	yes
P26373-2	2

RefSeq proteins (3): NP_000968, NP_001230060, NP_150254 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001380	Ribosomal_eL13	Family
IPR018256	Ribosomal_eL13_CS	Conserved_site

Pfam: PF01294

UniProt features (16 total): modified residue 5, cross-link 5, sequence variant 3, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

191 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8A3D	ELECTRON MICROSCOPY	1.67
8GLP	ELECTRON MICROSCOPY	1.67
8QYX	ELECTRON MICROSCOPY	1.78
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8QFD	ELECTRON MICROSCOPY	2.2
8YOP	ELECTRON MICROSCOPY	2.2
9GUL	ELECTRON MICROSCOPY	2.2
9O3V	ELECTRON MICROSCOPY	2.2
9O3Y	ELECTRON MICROSCOPY	2.2
8JDK	ELECTRON MICROSCOPY	2.26
8G5Y	ELECTRON MICROSCOPY	2.29
9S3D	ELECTRON MICROSCOPY	2.32
9RPV	ELECTRON MICROSCOPY	2.35
9S3B	ELECTRON MICROSCOPY	2.38
7OW7	ELECTRON MICROSCOPY	2.4
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9SPF	ELECTRON MICROSCOPY	2.4
9SPI	ELECTRON MICROSCOPY	2.4
8JDL	ELECTRON MICROSCOPY	2.42
9S3C	ELECTRON MICROSCOPY	2.42
8FKV	ELECTRON MICROSCOPY	2.47
9QLO	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
9P8B	ELECTRON MICROSCOPY	2.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26373-F1	95.47	0.95

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 (10): 16, 177, 52, 77, 106, 177, 123, 145, 174, 174

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-156902	Peptide chain elongation
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-192823	Viral mRNA Translation
R-HSA-2408557	Selenocysteine synthesis
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-72764	Eukaryotic Translation Termination
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA

MSigDB gene sets: 311 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_CYTOPLASMIC_TRANSLATION, HORIUCHI_WTAP_TARGETS_DN, GRUETZMANN_PANCREATIC_CANCER_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, MODULE_151, MORF_UBE2I, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, GOBP_BONE_DEVELOPMENT

GO Biological Process (4): blastocyst development (GO:0001824), cytoplasmic translation (GO:0002181), translation (GO:0006412), bone development (GO:0060348)

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

GO Cellular Component (11): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), synapse (GO:0045202), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Ribosome-associated quality control	3
Translation	2
Cap-dependent Translation Initiation	2
Nonsense-Mediated Decay (NMD)	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
rRNA processing in the nucleus and cytosol	1
Signaling by ROBO receptors	1
Cellular response to starvation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
ribosome	2
intracellular membrane-bounded organelle	2
intracellular membraneless organelle	2
cytoplasm	2
in utero embryonic development	1
anatomical structure development	1
translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
skeletal system development	1
animal organ development	1
nucleic acid binding	1
structural molecule activity	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
cell junction	1
protein-containing complex	1

Protein interactions and networks

STRING

3146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL13	ZNF112	Q9UJU3	582
RPL13	RPL13A	P40429	561
RPL13	MYO5A	Q9Y4I1	553
RPL13	GAPDH	P00354	542
RPL13	RPS18	P25232	539
RPL13	RPS7	P23821	536
RPL13	RPL8	P25120	534
RPL13	RPS29	P30054	505
RPL13	EEF1A2	P54266	504
RPL13	EEF1A1	P04719	504
RPL13	SLA	Q13239	495
RPL13	TBP	P20226	493
RPL13	RPS19	P39019	493
RPL13	RPL23	P23131	486
RPL13	RPL35	P42766	481

IntAct

395 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DCC	NTN1	psi-mi:“MI:0914”(association)	0.700
RPL13	HTT	psi-mi:“MI:0915”(physical association)	0.670
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
CEP70	RPL13	psi-mi:“MI:0915”(physical association)	0.560
KMT2A	RPL13	psi-mi:“MI:0915”(physical association)	0.560
MRPL38	RPL13	psi-mi:“MI:0915”(physical association)	0.560
BRIX1	RPL13	psi-mi:“MI:0915”(physical association)	0.560
NOM1	RPLP0	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MAGEB10	GTPBP10	psi-mi:“MI:0914”(association)	0.530

BioGRID (1071): RPL13 (Affinity Capture-MS), CEP70 (Two-hybrid), RPL13 (Affinity Capture-RNA), RPL13 (Affinity Capture-RNA), RPL13 (Affinity Capture-MS), RPL13 (Affinity Capture-MS), RPL13 (Affinity Capture-MS), GTF3C2 (Affinity Capture-MS), MRPS9 (Affinity Capture-MS), PTCD3 (Affinity Capture-MS), GTF3C3 (Affinity Capture-MS), RANBP6 (Affinity Capture-MS), IPO5 (Affinity Capture-MS), MRPS27 (Affinity Capture-MS), MRPL9 (Affinity Capture-MS)

ESM2 similar proteins: A1RRN8, A2BN55, A2STI9, A3DNH3, A3MUU4, A4G029, A4WLS6, A4YH79, A6URE0, A6UVQ6, A6VIE9, A9A8D5, B1YAF1, B6YWY4, B8GEU4, C5A7H4, C6A264, G1TKB3, O16130, O27650, O28212, O96269, P04650, P05767, P0CX33, P0CX34, P26373, P52814, P54056, P59472, P59473, Q43292, Q46FA3, Q56JZ1, Q5JGT6, Q6BHV8, Q6F482, Q6L2L2, Q6M0V9, Q758D8

Diamond homologs: G1TKB3, O46157, O48513, O59931, O74175, P0DJ58, P26373, P40212, P41123, P41125, P41126, P41127, P41128, P41129, P47963, P49627, P91128, Q12690, Q54E20, Q56JZ1, Q876B2, Q90YV5, Q90Z10, Q95043, Q962U1, Q9FF90, Q9SMT4, Q9YEN9, Q9Z313, C3MKC0, C3MU90, C3N178, C3N968, C3NMT7, C4KKE5, P58469, Q97W05

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL13	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 206 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
Signaling by ALK	5	19.6×	2e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	17	13.7×	4e-12
Peptide chain elongation	15	13.0×	4e-11
Viral mRNA Translation	15	13.0×	4e-11
Downstream signal transduction	5	13.0×	1e-03
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	15	12.9×	4e-11
Selenocysteine synthesis	15	12.3×	7e-11
Eukaryotic Translation Termination	15	12.3×	7e-11

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	17	17.7×	5e-14
mRNA stabilization	6	12.3×	1e-03
translation	21	12.1×	5e-14
ribosomal small subunit biogenesis	8	10.2×	4e-04
translational initiation	5	10.1×	1e-02
negative regulation of translation	8	8.8×	8e-04
rRNA processing	10	8.0×	3e-04
insulin receptor signaling pathway	6	7.5×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	3
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
2671824	NM_000977.4(RPL13):c.478-1G>T	Pathogenic
689800	NM_000977.4(RPL13):c.477+1G>T	Pathogenic
689801	NM_000977.4(RPL13):c.477+2T>C	Pathogenic
689803	NM_000977.4(RPL13):c.548G>T (p.Arg183Leu)	Pathogenic
813853	NM_000977.4(RPL13):c.533C>A (p.Ala178Asp)	Pathogenic
813854	NM_000977.4(RPL13):c.553G>C (p.Ala185Pro)	Pathogenic
1696793	NM_000977.4(RPL13):c.569G>T (p.Arg190Leu)	Likely pathogenic
3362462	NM_000977.4(RPL13):c.516dup (p.Glu173fs)	Likely pathogenic
4056463	NM_003119.4(SPG7):c.2182-1011A>G	Likely pathogenic

SpliceAI

512 predictions. Top by Δscore:

Variant	Effect	Δscore
16:89561061:CAG:C	donor_loss	1.0000
16:89561062:AG:A	donor_loss	1.0000
16:89561063:GG:G	donor_loss	1.0000
16:89561065:T:A	donor_loss	1.0000
16:89561224:CAG:C	acceptor_loss	1.0000
16:89561225:A:AG	acceptor_gain	1.0000
16:89561225:AGAC:A	acceptor_gain	1.0000
16:89561226:G:GT	acceptor_gain	1.0000
16:89561226:GAC:G	acceptor_gain	1.0000
16:89561226:GACG:G	acceptor_gain	1.0000
16:89561226:GACGT:G	acceptor_gain	1.0000
16:89561367:GG:G	donor_gain	1.0000
16:89561368:GG:G	donor_gain	1.0000
16:89561564:T:TA	acceptor_gain	1.0000
16:89561570:T:TA	acceptor_gain	1.0000
16:89561685:G:GT	donor_gain	1.0000
16:89561718:G:GT	donor_gain	1.0000
16:89561740:G:GT	donor_gain	1.0000
16:89561747:GTTCT:G	donor_gain	1.0000
16:89561748:TTCT:T	donor_gain	1.0000
16:89561749:TCT:T	donor_gain	1.0000
16:89561750:CTG:C	donor_loss	1.0000
16:89561751:TGT:T	donor_loss	1.0000
16:89561752:G:GG	donor_gain	1.0000
16:89562327:A:AG	acceptor_gain	1.0000
16:89562330:A:AG	acceptor_gain	1.0000
16:89562332:CAGG:C	acceptor_loss	1.0000
16:89562333:A:AG	acceptor_gain	1.0000
16:89562333:AG:A	acceptor_gain	1.0000
16:89562334:G:GA	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000041999 (16:89563015 A>G), RS1000505502 (16:89566178 G>A), RS1000677952 (16:89567139 A>G), RS1000776510 (16:89564140 T>A,C), RS1000993157 (16:89563803 G>C), RS1001195052 (16:89558732 A>G), RS1001467406 (16:89566372 T>C), RS1001626695 (16:89558896 T>C), RS1001653395 (16:89563589 G>C), RS1001666319 (16:89562107 G>C,T), RS1001996737 (16:89564465 T>C), RS1002510848 (16:89561881 G>A,C,T), RS1002601979 (16:89559636 G>C,T), RS1002609496 (16:89558701 T>C,G), RS1003342248 (16:89561229 G>A,T)

Disease associations

OMIM: gene MIM:113703 | disease phenotypes: MIM:618728, MIM:607259

GenCC curated gene-disease

Disease	Classification	Inheritance
spondyloepimetaphyseal dysplasia, Isidor-Toutain type	Strong	Autosomal dominant
spondyloepiphyseal dysplasia	Moderate	Autosomal dominant

Mondo (4): spondyloepimetaphyseal dysplasia, Isidor-Toutain type (MONDO:0032885), hereditary spastic paraplegia 7 (MONDO:0011803), spondyloepimetaphyseal dysplasia (MONDO:0100510), spondyloepiphyseal dysplasia (MONDO:0016761)

Orphanet (1): Spastic paraplegia type 7 (Orphanet:99013)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000926	Platyspondyly
HP:0001903	Anemia
HP:0002650	Scoliosis
HP:0002812	Coxa vara
HP:0002970	Genu varum
HP:0003026	Short long bone
HP:0003051	Enlarged metaphyses
HP:0003510	Severe short stature
HP:0003850	Upper-limb metaphyseal irregularity
HP:0006361	Irregular femoral epiphysis
HP:0008897	Postnatal growth retardation
HP:0030291	Lower-limb metaphyseal irregularity

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007486_17	Hair morphology traits	8.000000e-11
GCST012465_13	Bipolar disorder	7.000000e-09

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564599	Spastic Paraplegia 7, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066931 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds).

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

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

ChEMBL bioactivities

48 potent at pChembl≥5 of 54 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.71	Kd	19.57	nM	CHEMBL5653589
7.71	ED50	19.57	nM	CHEMBL5653589
6.52	IC50	300	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4574496
6.41	IC50	390	nM	CHEMBL4126894
6.39	IC50	410	nM	CHEMBL4114159
6.35	IC50	450	nM	CHEMBL4126496
6.30	IC50	500	nM	CHEMBL4574496
6.30	IC50	500	nM	CHEMBL4560206
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	IC50	1730	nM	CHEMBL4534859
5.69	IC50	2050	nM	CHEMBL4566239
5.68	IC50	2080	nM	CHEMBL4446635
5.66	IC50	2210	nM	CHEMBL4446635
5.66	EC50	2200	nM	CHEMBL4464929
5.64	IC50	2270	nM	CHEMBL4533299
5.63	IC50	2330	nM	CHEMBL4566239
5.62	IC50	2380	nM	CHEMBL4128388
5.58	IC50	2630	nM	CHEMBL4128250
5.55	IC50	2820	nM	CHEMBL4127458
5.53	IC50	2970	nM	CHEMBL4127311
5.51	IC50	3080	nM	CHEMBL4126072
5.46	IC50	3500	nM	CHEMBL4525277
5.44	IC50	3630	nM	CHEMBL4469712
5.39	IC50	4100	nM	CHEMBL4128560
5.37	IC50	4300	nM	CHEMBL4127016
5.36	IC50	4380	nM	CHEMBL4527910
5.16	IC50	7000	nM	CHEMBL4109308
5.13	IC50	7400	nM	CHLORAMPHENICOL SULFATE SALT
5.09	IC50	8040	nM	CHEMBL4128250
5.08	IC50	8370	nM	CHEMBL4128250
5.03	IC50	9320	nM	CHEMBL4127016
5.03	IC50	9240	nM	CHEMBL4128560

PubChem BioAssay actives

47 with measured affinity, of 209 total; 27 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149243: Binding affinity to human RPL13 incubated for 45 mins by Kinobead based pull down assay	kd	0.0196	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1585498: Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method	ic50	0.3000	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3800	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3900	uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4100	uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4500	uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.5000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.6900	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.7100	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.9200	uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	1.0600	uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	1.5400	uM
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.0500	uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	2.0800	uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretion	ec50	2.2000	uM
N-isoquinolin-1-yl-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.6300	uM
N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.8200	uM
N-(3-chloro-2-pyridinyl)-4-[6-(dimethylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.9700	uM
N-(3-chloro-2-pyridinyl)-4-[6-(methylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	3.0800	uM
N-isoquinolin-1-yl-4-(6-methyl-1,2-benzoxazol-3-yl)-N-[(3R)-piperidin-3-yl]piperazine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	3.5000	uM
N-(3-methylpyrazin-2-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	3.6300	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-6-(triazolo[4,5-b]pyridin-3-yl)pyridine-3-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.1000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazin-2-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.3000	uM
4-(2-fluorophenyl)-N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	4.3800	uM
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide;sulfuric acid	717551: Inhibition of mitochondrial ribosome-mediated protein synthesis in human HeLa cells assessed as {35S]methionine incorporation by autoradiography	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	4
sodium arsenite	decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
perfluorooctanoic acid	decreases expression, increases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
epigallocatechin gallate	decreases expression, affects cotreatment, increases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
Cadmium Chloride	increases expression, increases methylation	2
Particulate Matter	affects cotreatment, increases abundance, increases expression, decreases expression	2
FR900359	decreases phosphorylation	1
TAK-243	affects sumoylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation	1
vanadyl sulfate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CD 437	decreases expression	1

ChEMBL screening assays

90 unique, capped per target: 90 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1920845	Binding	Induction of ribosome to readthrough in human A-T lymphoblastoid cells assessed as ATM ser1981 autophosphorylation at 30 uM after 4 days by PTT-ELISA assay	Synthesis and evaluation of compounds that induce readthrough of premature termination codons. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05127967	Not specified	COMPLETED	Consequences of Mutations in the SPG7 Gene at the Heterozygous State
NCT06261424	Not specified	RECRUITING	Effects of a Supervised Rehabilitation Program on Disease Severity in Spastic Ataxias