SLTM

Summary

SLTM (SAFB like transcription modulator, HGNC:20709) is a protein-coding gene on chromosome 15q22.1, encoding SAFB-like transcription modulator (Q9NWH9). When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis. In precision oncology, MET Exon 14 Skipping Mutation confers sensitivity to Tepotinib in Lung Non-small Cell Carcinoma (CIViC Level A); 46 further curated variant–drug associations are listed below.

Enables RNA binding activity. Predicted to be involved in regulation of mRNA processing and regulation of transcription by RNA polymerase II. Located in nuclear body.

Source: NCBI Gene 79811 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 137 total — 1 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 47 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 7 cancer types
• MANE Select transcript: NM_024755

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20709
Approved symbol	SLTM
Name	SAFB like transcription modulator
Location	15q22.1
Locus type	gene with protein product
Status	Approved
Aliases	Met, FLJ13213
Ensembl gene	ENSG00000137776
Ensembl biotype	protein_coding
OMIM	620992
Entrez	79811

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 26 protein_coding, 10 retained_intron, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000249736, ENST00000380516, ENST00000432750, ENST00000473359, ENST00000474342, ENST00000480144, ENST00000484498, ENST00000492526, ENST00000493062, ENST00000497088, ENST00000557791, ENST00000557924, ENST00000557950, ENST00000558052, ENST00000558486, ENST00000558734, ENST00000558756, ENST00000559261, ENST00000559305, ENST00000559880, ENST00000560012, ENST00000560494, ENST00000560532, ENST00000560682, ENST00000560695, ENST00000628684, ENST00000872290, ENST00000872291, ENST00000872292, ENST00000872293, ENST00000924222, ENST00000924223, ENST00000924224, ENST00000924225, ENST00000924226, ENST00000924227, ENST00000924228, ENST00000924229, ENST00000924230, ENST00000970319, ENST00000970320, ENST00000970321, ENST00000970322

RefSeq mRNA: 2 — MANE Select: NM_024755 NM_001013843, NM_024755

CCDS: CCDS10168

Canonical transcript exons

ENST00000380516 — 21 exons

Exon	Start	End
ENSE00000884973	58899469	58899937
ENSE00001485310	58933404	58933679
ENSE00001687859	58879050	58880107
ENSE00003463671	58897115	58897233
ENSE00003466208	58893821	58893987
ENSE00003489299	58893279	58893364
ENSE00003507273	58932356	58932443
ENSE00003507749	58912563	58912610
ENSE00003510327	58887226	58887540
ENSE00003519075	58892897	58893060
ENSE00003519754	58898803	58898852
ENSE00003528437	58889430	58889554
ENSE00003544072	58888385	58888555
ENSE00003585086	58916935	58916999
ENSE00003609587	58894090	58894193
ENSE00003625753	58883626	58883786
ENSE00003642846	58913499	58913696
ENSE00003644752	58894433	58894582
ENSE00003648734	58890281	58890461
ENSE00003660603	58901260	58901287
ENSE00003671270	58886975	58887119

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.4422 / max 2550.8852, expressed in 1824 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150253	41.8694	1818
150255	12.5131	1798
150248	3.4912	1101
150251	2.7113	889
150247	2.2751	844
150254	1.1208	682
150245	0.6233	251
150252	0.5725	325
150246	0.3922	181
150258	0.3668	135

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.24	gold quality
sural nerve	UBERON:0015488	98.02	gold quality
tibia	UBERON:0000979	97.64	gold quality
left lobe of thyroid gland	UBERON:0001120	97.32	gold quality
tonsil	UBERON:0002372	97.29	gold quality
right lobe of thyroid gland	UBERON:0001119	97.27	gold quality
monocyte	CL:0000576	97.20	gold quality
skin of abdomen	UBERON:0001416	97.20	gold quality
parietal pleura	UBERON:0002400	97.14	gold quality
mononuclear cell	CL:0000842	97.13	gold quality
thyroid gland	UBERON:0002046	97.13	gold quality
visceral pleura	UBERON:0002401	97.08	gold quality
ventricular zone	UBERON:0003053	97.07	gold quality
leukocyte	CL:0000738	96.97	gold quality
lower esophagus mucosa	UBERON:0035834	96.97	gold quality
pleura	UBERON:0000977	96.96	gold quality
mucosa of stomach	UBERON:0001199	96.93	gold quality
metanephros cortex	UBERON:0010533	96.93	gold quality
skin of leg	UBERON:0001511	96.92	gold quality
palpebral conjunctiva	UBERON:0001812	96.82	gold quality
peripheral nervous system	UBERON:0000010	96.81	gold quality
tibial nerve	UBERON:0001323	96.81	gold quality
colonic epithelium	UBERON:0000397	96.76	gold quality
minor salivary gland	UBERON:0001830	96.75	gold quality
esophagus mucosa	UBERON:0002469	96.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.67	gold quality
right uterine tube	UBERON:0001302	96.63	gold quality
vagina	UBERON:0000996	96.56	gold quality
right ovary	UBERON:0002118	96.55	gold quality
body of uterus	UBERON:0009853	96.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-89	no	1523.32
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting SLTM, 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-4425	100.00	67.59	1049
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-377-3P	99.37	70.18	1905

Literature-anchored findings (GeneRIF, showing 11)

• Inhibition of a Chromatin and Transcription Modulator, SLTM, Increases HIV-1 Reactivation Identified by a CRISPR Inhibition Screen. (PMID:35730977)
• Plexin-B3 expression stimulates MET signaling, breast cancer stem cell specification, and lung metastasis. (PMID:36857181)
• Circular RNA SLTM as a miR-421-competing endogenous RNA to mediate HMGB2 expression stimulates apoptosis and inflammation in arthritic chondrocytes. (PMID:36935520)
• Long noncoding RNA FTX promotes epithelial-mesenchymal transition of epithelial ovarian cancer through modulating miR-7515/TPD52 and activating Met/Akt/mTOR. (PMID:37140169)
• Lack of correlation between MET and PD-L1 expression in non-small cell lung cancer revealed by comparative study of matched biopsies and surgical resection samples. (PMID:37150140)
• A DNA-PK phosphorylation site on MET regulates its signaling interface with the DNA damage response. (PMID:37188738)
• Impact of SMAD2 and MET Expression on Lymph Node Metastasis of HER2-positive Gastric Cancer Cells. (PMID:37772583)
• SPOP promotes CREB5 ubiquitination to inhibit MET signaling in liver cancer. (PMID:37996058)
• MET exon 14 skipping mutation drives cancer progression and recurrence via activation of SMAD2 signalling. (PMID:38110666)
• Deubiquitinase BRCC3 promotes the migration, invasion and EMT progression of colon adenocarcinoma by stabilizing MET expression. (PMID:38470543)
• circSLTM knockdown attenuates chondrocyte inflammation, apoptosis and ECM degradation in osteoarthritis by regulating the miR-515-5p/VAPB axis. (PMID:38981227)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sltm	ENSDARG00000052728
mus_musculus	Sltm	ENSMUSG00000032212
rattus_norvegicus	Sltm	ENSRNOG00000054446
drosophila_melanogaster	Saf-B	FBGN0039229
caenorhabditis_elegans	phm-2	WBGENE00009314

Paralogs (2): SAFB2 (ENSG00000130254), SAFB (ENSG00000160633)

Protein

Protein identifiers

SAFB-like transcription modulator — Q9NWH9 (reviewed: Q9NWH9)

Alternative names: Modulator of estrogen-induced transcription

All UniProt accessions (12): Q9NWH9, H0YKH2, H0YKU6, H0YL55, H0YLE6, H0YLW7, H0YMM0, H0YMR6, H0YMW8, H0YNF3, H7BXE3, H7C3F4

UniProt curated annotations — full annotation on UniProt →

Function. When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NWH9-1	1	yes
Q9NWH9-3	2

RefSeq proteins (2): NP_001013865, NP_079031* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR003034	SAP_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036361	SAP_dom_sf	Homologous_superfamily
IPR051738	SAF_Modulators	Family

Pfam: PF00076, PF02037

UniProt features (65 total): modified residue 26, compositionally biased region 21, region of interest 4, cross-link 4, sequence conflict 3, domain 2, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWH9-F1	52.38	0.11

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 (30): 2, 93, 97, 139, 144, 289, 401, 421, 550, 551, 553, 748, 789, 800, 815, 909, 923, 929, 944, 998 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 660 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, CHOI_ATL_ACUTE_STAGE, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, WANG_CLIM2_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_CHEMOTAXIS, GOBP_CELL_CHEMOTAXIS, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_EPITHELIAL_CELL_DEVELOPMENT, PAL_PRMT5_TARGETS_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), apoptotic process (GO:0006915), regulation of mRNA processing (GO:0050684)

GO Molecular Function (4): RNA binding (GO:0003723), sequence-specific DNA binding (GO:0043565), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
mRNA processing	1
regulation of mRNA metabolic process	1
nucleic acid binding	1
DNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2285 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLTM	COMMD2	Q86X83	448
SLTM	HNRNPA1	P09651	413
SLTM	HNRNPH1	P31943	404
SLTM	VMA12	Q8N511	398
SLTM	ERMP1	Q7Z2K6	394
SLTM	WDR81	Q562E7	386
SLTM	STPG4	Q8N801	378
SLTM	DPM3	Q9P2X0	357
SLTM	COMMD4	Q9H0A8	348
SLTM	ATP6V0B	Q99437	323
SLTM	CHST14	Q8NCH0	311
SLTM	LARP4	Q71RC2	306
SLTM	PIGS	Q96S52	305
SLTM	MANBAL	Q9NQG1	297
SLTM	ATP6V1H	Q9UI12	295

IntAct

123 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
FANCC	FANCA	psi-mi:“MI:0914”(association)	0.680
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
MCC	SLTM	psi-mi:“MI:0915”(physical association)	0.560
GGPS1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
LTBR	ZNF724	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
GHITM	CCNB2	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
EXOSC4	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
IFNA14	IFIT1	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
CCDC65	SLTM	psi-mi:“MI:0915”(physical association)	0.400
MBL2	SLTM	psi-mi:“MI:0915”(physical association)	0.400
CYLC1	SLTM	psi-mi:“MI:0915”(physical association)	0.400
SMC1B	SLTM	psi-mi:“MI:0915”(physical association)	0.400
PRKACA	SLTM	psi-mi:“MI:0915”(physical association)	0.400
JAKMIP2	SLTM	psi-mi:“MI:0915”(physical association)	0.400
REV3L	SLTM	psi-mi:“MI:0915”(physical association)	0.400
NELL1	SLTM	psi-mi:“MI:0915”(physical association)	0.400
Taf15	BTBD10	psi-mi:“MI:0914”(association)	0.350
MATR3	BCLAF3	psi-mi:“MI:0914”(association)	0.350
Fus	DDX3X	psi-mi:“MI:0914”(association)	0.350
Srsf1	SRRM1	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
NBEAL2	HAX1	psi-mi:“MI:0914”(association)	0.350
HMGB1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (190): SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS), SLTM (Biochemical Activity), SLTM (Proximity Label-MS), SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS), SLTM (Affinity Capture-MS)

ESM2 similar proteins: A0A1I8MUL8, A0A2R6X6S3, A9D2P7, D3YXK2, E9Q5K9, G5EGK6, O44548, O62203, O88453, P22293, P26017, P30414, P30415, P30651, Q08D57, Q15424, Q18221, Q1LUE5, Q1LY77, Q27450, Q3KPW4, Q3TLH4, Q3UC65, Q498L2, Q4IL82, Q5R452, Q5RAA7, Q5T200, Q5U317, Q5XJD3, Q66J90, Q6AXY7, Q6KC79, Q6KCD5, Q6PCT5, Q6UN15, Q7Z6E9, Q80SY5, Q872I5, Q8CH25

Diamond homologs: A0A0D1C8Z4, A1A5R1, A1D4K4, A2A5N3, A2Q848, A3LXL0, A4F5G6, A5DW14, A6NFN3, A6QPR6, F1QB54, F4HT49, O04319, O43251, P04147, P0CB38, P11940, P15771, P19682, P19683, P20965, P23246, P28644, P29341, P42731, P49313, P60824, P60825, P60826, P61286, P62995, P62996, P62997, P82277, Q04836, Q08935, Q08937, Q09511, Q0CR95, Q0VD23

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 170 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
mRNA 3’-end processing	7	12.6×	1e-04
mRNA Splicing	12	12.1×	4e-08
Processing of Capped Intron-Containing Pre-mRNA	14	10.6×	1e-08
mRNA Polyadenylation	13	10.5×	4e-08
rRNA processing in the nucleus and cytosol	7	10.3×	4e-04
RNA Polymerase II Transcription Termination	5	10.1×	6e-03
rRNA processing	7	9.4×	5e-04
mRNA Splicing - Major Pathway	17	8.5×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	7	11.7×	1e-03
mRNA splicing, via spliceosome	16	10.0×	5e-09
ribosomal small subunit biogenesis	6	9.4×	6e-03
rRNA processing	8	7.8×	2e-03
RNA splicing	10	6.0×	2e-03
mRNA processing	10	5.4×	3e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

Mesenchymal Epithelial Transition MET is a prototypical receptor tyrosine kinase. Its ligand is Hepatocyte Growth Factor (HGF). MET alterations are drivers of human cancer. Amplification and resulting overexpression has been reported in several cancers, and make the receptor’s activity independent of HGF. Gene fusions also decouple kinase activity from the cell membrane and render it constitutively active. Finally, exclusion of the juxtamembrane (JM) domain of the kinase by ““skipping”” of exon 14 activates the kinase. FDA-approved selective MET inhibitors, including tepotinib and capmatinib, have shown efficacy in cancers with exon 14 skipping mutations or MET amplification.

From intOGen — cancer-driver classification: activating (oncogene-like) across 7 cancer types — CCRCC, LGGNOS, LUAD, NSCLC, OS, PRCC, RCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	109
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
617857	NM_024755.4(SLTM):c.2600C>A (p.Pro867His)	Likely pathogenic

SpliceAI

6549 predictions. Top by Δscore:

Variant	Effect	Δscore
15:58880108:C:CC	acceptor_gain	1.0000
15:58883621:TTTA:T	donor_loss	1.0000
15:58883622:TTAC:T	donor_loss	1.0000
15:58883623:TA:T	donor_loss	1.0000
15:58883625:C:CT	donor_loss	1.0000
15:58883782:TAGTG:T	acceptor_gain	1.0000
15:58883783:AGTG:A	acceptor_gain	1.0000
15:58883784:GTG:G	acceptor_gain	1.0000
15:58883784:GTGC:G	acceptor_loss	1.0000
15:58883785:TG:T	acceptor_gain	1.0000
15:58883785:TGC:T	acceptor_loss	1.0000
15:58883786:GC:G	acceptor_loss	1.0000
15:58883787:C:A	acceptor_loss	1.0000
15:58883787:C:CC	acceptor_gain	1.0000
15:58883788:T:G	acceptor_loss	1.0000
15:58886971:TTA:T	donor_loss	1.0000
15:58886973:A:AC	donor_gain	1.0000
15:58886973:AC:A	donor_gain	1.0000
15:58886974:C:CA	donor_loss	1.0000
15:58886974:C:CC	donor_gain	1.0000
15:58886974:CC:C	donor_gain	1.0000
15:58886974:CCT:C	donor_gain	1.0000
15:58887115:CAACT:C	acceptor_gain	1.0000
15:58887116:AACT:A	acceptor_gain	1.0000
15:58887117:ACT:A	acceptor_gain	1.0000
15:58887118:CT:C	acceptor_gain	1.0000
15:58887118:CTC:C	acceptor_gain	1.0000
15:58887119:TCT:T	acceptor_gain	1.0000
15:58887119:TCTGT:T	acceptor_loss	1.0000
15:58887120:C:CC	acceptor_gain	1.0000

AlphaMissense

6835 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:58889508:A:G	L709P	1.000
15:58889532:C:G	R701P	1.000
15:58889547:C:G	R696P	1.000
15:58889550:C:G	R695P	1.000
15:58890297:C:G	R688P	1.000
15:58890298:G:T	R688S	1.000
15:58890309:A:G	L684S	1.000
15:58890312:C:G	R683P	1.000
15:58890318:C:G	R681P	1.000
15:58890339:A:G	L674P	1.000
15:58894440:A:T	V457D	1.000
15:58894461:A:G	L450P	1.000
15:58894487:A:C	C441W	1.000
15:58894489:A:G	C441R	1.000
15:58894521:A:T	V430E	1.000
15:58894527:C:A	G428V	1.000
15:58894527:C:T	G428D	1.000
15:58894528:C:G	G428R	1.000
15:58894534:A:G	C426R	1.000
15:58894554:G:T	A419D	1.000
15:58894563:A:T	V416D	1.000
15:58894566:A:T	V415E	1.000
15:58894572:G:T	A413E	1.000
15:58894581:A:T	V410D	1.000
15:58897119:C:A	G408V	1.000
15:58897119:C:T	G408E	1.000
15:58897120:C:G	G408R	1.000
15:58897120:C:T	G408R	1.000
15:58897134:A:G	L403P	1.000
15:58897139:C:A	K401N	1.000

dbSNP variants (sampled 300 via entrez): RS1000406541 (15:58901578 C>T), RS1000495887 (15:58913428 G>C,T), RS1000827465 (15:58923379 A>G), RS1000910711 (15:58917956 G>A), RS1000914761 (15:58934011 G>C,T), RS1000984233 (15:58886736 C>G,T), RS1001182515 (15:58919818 C>G), RS1001209647 (15:58913847 T>A,C,G), RS1001354599 (15:58908535 T>A), RS1001426810 (15:58908763 C>T), RS1001678043 (15:58894946 C>T), RS1001742147 (15:58934698 A>G), RS1001796275 (15:58929419 G>T), RS1001827636 (15:58929589 T>C), RS1001915706 (15:58882189 A>C)

Disease associations

OMIM: gene MIM:620992 | disease phenotypes: MIM:208500

GenCC curated gene-disease

Mondo (1): Jeune syndrome (MONDO:0018770)

Orphanet (1): Jeune syndrome (Orphanet:474)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000767	Pectus excavatum
HP:0001395	Hepatic fibrosis
HP:0001402	Hepatocellular carcinoma
HP:0001413	Micronodular cirrhosis
HP:0001442	Typified by somatic mosaicism
HP:0001762	Talipes equinovarus
HP:0001838	Rocker bottom foot
HP:0001840	Metatarsus adductus
HP:0001848	Calcaneovalgus deformity
HP:0002013	Vomiting
HP:0002027	Abdominal pain
HP:0002240	Hepatomegaly
HP:0002605	Hepatic necrosis
HP:0002756	Pathologic fracture
HP:0003038	Fibular hypoplasia
HP:0003577	Congenital onset
HP:0003829	Typified by incomplete penetrance
HP:0005864	Pseudoarthrosis
HP:0006077	Absent proximal finger flexion creases
HP:0006254	Elevated circulating alpha-fetoprotein concentration
HP:0006394	Limited pronation/supination of forearm
HP:0006572	Subacute progressive viral hepatitis
HP:0006766	Papillary renal cell carcinoma
HP:0012378	Fatigue
HP:0012385	Camptodactyly
HP:0030242	Portal vein thrombosis
HP:0410019	Epigastric pain

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000904_2	Asperger disorder	7.000000e-06
GCST012309_2	Schizophrenia	2.000000e-08
GCST012311_22	Schizophrenia x sex interaction	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537571	Jeune syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523469 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 11,177 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2105717	CABOZANTINIB	4	11,177

Clinical evidence (CIViC)

Drug × variant × indication: 47 predictive associations from 74 curated evidence items; also 2 prognostic, 1 diagnostic, 1 functional.

Variant	Therapy	Indication	Effect	Level	CIViC
MET Exon 14 Skipping Mutation	Tepotinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11766 +3
MET Exon 14 Skipping Mutation	Capmatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID8847 +2
MET Amplification	Crizotinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID7502 +4
MET Exon 14 Skipping Mutation	Crizotinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID11416 +3
MET Amplification	Crizotinib	Gastrointestinal System Cancer	Sensitivity/Response	CIViC B	EID11454
MET Amplification	Savolitinib	Stomach Cancer	Sensitivity/Response	CIViC B	EID7729
MET Amplification	Capmatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID8849
MET Exon 14 Skipping Mutation	Crizotinib	Stomach Cancer	Sensitivity/Response	CIViC B	EID11377
MET Exon 14 Skipping Mutation	SAIT301	Stomach Cancer	Sensitivity/Response	CIViC B	EID11378
MET Exon 14 Skipping Mutation	Crizotinib	Colorectal Cancer	Sensitivity/Response	CIViC B	EID11379
MET Exon 14 Skipping Mutation	SAIT301	Colorectal Cancer	Sensitivity/Response	CIViC B	EID11380
MET Mutation	Foretinib	Papillary Renal Cell Carcinoma	Sensitivity/Response	CIViC B	EID796
MET Overexpression	Rilotumumab	Stomach Carcinoma	Sensitivity/Response	CIViC B	EID5835
MET Overexpression	Vemurafenib	Skin Melanoma	Resistance	CIViC B	EID1581 +1
MET Exon 14 Skipping Mutation	Crizotinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID11384 +8
MET Exon 14 Skipping Mutation	Tepotinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID11464 +3
MET Amplification	Crizotinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID11383 +2
MET Exon 14 Skipping Mutation	Capmatinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID11417 +1
MET Amplification	Crizotinib	Glioblastoma	Sensitivity/Response	CIViC C	EID1565
MET Amplification	Crizotinib + Vemurafenib	Colorectal Cancer	Sensitivity/Response	CIViC C	EID1588
MET Amplification	Crizotinib	Cancer	Sensitivity/Response	CIViC C	EID1714
MET Amplification	Onartuzumab	Gastric Adenocarcinoma	Sensitivity/Response	CIViC C	EID689
MET Amplification	Crizotinib	Lung Squamous Cell Carcinoma	Sensitivity/Response	CIViC C	EID890
MET Amplification AND MET Splice Site (c.3028G>A)	Crizotinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID1095
MET D1228V	Cabozantinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID1864
MET Exon 14 Skipping Mutation	Cabozantinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID11400
MET Exon 14 Skipping Mutation	Cabozantinib + Crizotinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID11410
MET Exon 14 Skipping Mutation	Savolitinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID11474
MET Exon 14 Skipping Mutation	Pembrolizumab + Carboplatin/Pemetrexed Regimen	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID11487
MET Exon 14 Skipping Mutation	Crizotinib	Histiocytic And Dendritic Cell Cancer	Sensitivity/Response	CIViC C	EID7796

+17 more predictive associations (showing top 30 by evidence level).

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.89	IC50	1.3	nM	CABOZANTINIB

PubChem BioAssay actives

1 with measured affinity, of 15 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
Cabozantinib	1895682: Inhibition of human recombinant full length c-Met in presence of ATP by alphascreen assay	ic50	0.0013	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression, affects cotreatment, decreases expression	4
sodium arsenite	decreases expression, increases expression	2
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment, increases oxidation	2
Acrolein	increases oxidation, decreases expression, increases abundance, affects cotreatment	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Ozone	affects cotreatment, increases oxidation, decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
potassium perchlorate	increases expression	1
titanium dioxide	decreases methylation	1
butyraldehyde	decreases expression	1
bleomycetin	decreases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	decreases phosphorylation	1
nivalenol	increases expression	1
celastrol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
gedunin	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
Rosiglitazone	decreases reaction, increases expression	1
Pioglitazone	decreases reaction, increases expression	1
Sunitinib	increases expression	1
Troglitazone	decreases expression, decreases reaction, increases expression, affects cotreatment	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4341402	Binding	Binding affinity to SLTM in human A549 cells lysates grown on SILAC media at 10 uM incubated for 1 hr by LC-MS/MS analysis relative to untreated control	Profiling withanolide A for therapeutic targets in neurodegenerative diseases. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00948376	Not specified	COMPLETED	Natural History of Asphyxiating Thoracic Dystrophy (DTJ)
NCT04143841	Not specified	TERMINATED	Viveye Ocular Magnetic Neurostimulation System (OMNS) for the Management of Severe Dry Eye Disease
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)