RBM7

Summary

RBM7 (RNA binding motif protein 7, HGNC:9904) is a protein-coding gene on chromosome 11q23.1-q23.2, encoding RNA-binding protein 7 (Q9Y580). RNA-binding subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation.

Enables 14-3-3 protein binding activity; pre-mRNA intronic binding activity; and snRNA binding activity. Involved in snRNA catabolic process. Located in nucleoplasm.

Source: NCBI Gene 10179 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinal muscular atrophy (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_001286045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9904
Approved symbol	RBM7
Name	RNA binding motif protein 7
Location	11q23.1-q23.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000076053
Ensembl biotype	protein_coding
OMIM	612413
Entrez	10179

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000375490, ENST00000538134, ENST00000540163, ENST00000541475, ENST00000542140, ENST00000544313, ENST00000544582, ENST00000545678, ENST00000956174

RefSeq mRNA: 5 — MANE Select: NM_001286045 NM_001286045, NM_001286046, NM_001286047, NM_001286048, NM_016090

CCDS: CCDS66233, CCDS73395, CCDS8370

Canonical transcript exons

ENST00000375490 — 5 exons

Exon	Start	End
ENSE00002206403	114400666	114400767
ENSE00002287532	114407445	114410607
ENSE00003523277	114401698	114401860
ENSE00003644333	114402828	114402915
ENSE00003658311	114405706	114405799

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 96.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.3537 / max 275.9201, expressed in 1806 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116809	10.1465	1766
116810	6.9259	1714
116811	6.9101	1653
116808	0.8813	592
116807	0.6348	291
116813	0.4806	214
116812	0.3746	160

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	96.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.93	gold quality
calcaneal tendon	UBERON:0003701	93.83	gold quality
colonic mucosa	UBERON:0000317	93.15	gold quality
germinal epithelium of ovary	UBERON:0001304	92.79	gold quality
colonic epithelium	UBERON:0000397	92.64	gold quality
stromal cell of endometrium	CL:0002255	92.42	gold quality
cauda epididymis	UBERON:0004360	91.96	gold quality
islet of Langerhans	UBERON:0000006	91.79	gold quality
skin of hip	UBERON:0001554	91.73	gold quality
ventricular zone	UBERON:0003053	91.53	gold quality
rectum	UBERON:0001052	91.28	gold quality
caput epididymis	UBERON:0004358	91.11	gold quality
gall bladder	UBERON:0002110	90.87	gold quality
palpebral conjunctiva	UBERON:0001812	90.58	gold quality
corpus epididymis	UBERON:0004359	90.56	gold quality
endothelial cell	CL:0000115	90.48	gold quality
endometrium	UBERON:0001295	90.15	gold quality
bone marrow	UBERON:0002371	90.12	gold quality
heart right ventricle	UBERON:0002080	90.07	gold quality
parietal pleura	UBERON:0002400	90.07	gold quality
amniotic fluid	UBERON:0000173	90.02	gold quality
monocyte	CL:0000576	89.92	gold quality
biceps brachii	UBERON:0001507	89.82	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.81	gold quality
smooth muscle tissue	UBERON:0001135	89.64	gold quality
mononuclear cell	CL:0000842	89.63	gold quality
leukocyte	CL:0000738	89.61	gold quality
oral cavity	UBERON:0000167	89.42	gold quality
tendon	UBERON:0000043	89.41	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	1019.39
E-MTAB-7381	no	989.47
E-MTAB-6524	no	164.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting RBM7, 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-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-2110	99.96	66.68	1930
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-30A-3P	99.87	69.74	2928

Literature-anchored findings (GeneRIF, showing 6)

• Phosphorylation of RBM7 by the p38(MAPK)/MK2 axis increases nuclear ncRNA stability by blocking their RBM7-binding and subsequent RNA exosome targeting to allow stress-dependent modulations of the noncoding transcriptome. (PMID:25525152)
• RBM8 and CBP20 RRM-domain crystal structures were used to successfully determine the RBM7 structure by molecular replacement. The structure reveals a ring-shaped pentameric assembly, which is most likely a consequence of crystal packing (PMID:27139832)
• Knock-down of rbm7, exosc8 and exosc3 in zebrafish showed a common pattern of defects in motor neurons and cerebellum. Our data indicate that impaired RNA metabolism may underlie the clinical phenotype by fine tuning gene expression which is essential for correct neuronal differentiation (PMID:27193168)
• a proline-rich segment of ZCCHC8 as the interaction site for the RNA-recognition motif (RRM) of RBM7 and present the crystal structure of the corresponding complex at 2.0 A resolution. (PMID:27905398)
• interfering with the axis of RBM7 and P-TEFb provokes cellular hypersensitivity to DNA-damage-inducing agents due to activation of apoptosis. Our work uncovers the importance of stress-dependent stimulation of Pol II pause release, which enables a pro-survival transcriptional response that is crucial for cell fate upon genotoxic insult. (PMID:30824372)
• Novel insights into the pathogenesis of lung fibrosis: the RBM7-NEAT1-CXCL12-SatM axis at fibrosis onset. (PMID:34165514)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm7	ENSDARG00000020841
mus_musculus	Rbm7	ENSMUSG00000042396
rattus_norvegicus	Rbm7	ENSRNOG00000005710
drosophila_melanogaster	CG11454	FBGN0031224
caenorhabditis_elegans		WBGENE00012558
caenorhabditis_elegans	rnp-8	WBGENE00020091

Paralogs (1): RBM11 (ENSG00000185272)

Protein

Protein identifiers

RNA-binding protein 7 — Q9Y580 (reviewed: Q9Y580)

Alternative names: RNA-binding motif protein 7

All UniProt accessions (7): Q9Y580, F5GXV8, F5GY08, F5H606, F5H674, G3V1T9, J3KPD3

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs. Binds preferentially polyuridine sequences and associates with newly synthesized RNAs, including pre-mRNAs and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and 3’-extended products from small nuclear RNAs (snRNAs). Participates in several biological processes including DNA damage response (DDR) and stress response. During stress response, activation of the p38MAPK-MK2 pathway decreases RBM7-RNA-binding and subsequently the RNA exosome degradation activities, thereby modulating the turnover of non-coding transcriptome. Participates in DNA damage response (DDR), through its interaction with MEPCE and LARP7, the core subunits of 7SK snRNP complex, that release the positive transcription elongation factor b (P-TEFb) complex from the 7SK snRNP. In turn, activation of P-TEFb complex induces the transcription of P-TEFb-dependent DDR genes to promote cell viability.

Subunit / interactions. Component of the nuclear exosome targeting (NEXT) complex composed of MTREX, ZCCHC8, and RBM7 that directs a subset of non-coding short-lived RNAs for exosomal degradation. Interacts with ZCCHC8 and SF3B2/SAP145. Binds to MTREX through ZCCHC8. Interacts with YWHAE and YWHAZ; these interactions are stress-dependent and RBM7 phosphorylation dependent; release RNA from the NEXT complex and may affect RNA targeting to the nuclear RNA exosomome for degradation. Interacts with MEPCE and LARP7, the core subunits of 7SK snRNP; upon genotoxic stress this interaction is enhanced, triggering the release of inactive P-TEFb complex from the core and P-TEFb complex activation.

Subcellular location. Nucleus. Nucleoplasm.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated at Ser-136 by MAPK14/p38-alpha-activated MAPKAPK2/MK2; this phosphorylation is stress-dependent; this phosphorylation decreases its RNA-binding capacity therefore affecting RNA nuclear exosome-mediated degradation. This phosphorylation mediates YWHAE and YWHAZ interactions.

Domain organisation. The RRM domain mediates RNA binding; the RNA must have four nucleotides for efficient binding. Mediates the interaction of NEXT complex with promoter upstream transcripts (PROMPTs) and potentially aberrant forms of other non coding RNAs, such as snRNAs. The RRM domain exhibits specificity for polyuridine sequences.

RefSeq proteins (5): NP_001272974, NP_001272975, NP_001272976, NP_001272977, NP_057174 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034500	RBM7_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR052285	NEXT_complex_subunit	Family

Pfam: PF00076

UniProt features (38 total): mutagenesis site 10, strand 7, modified residue 5, region of interest 4, helix 3, compositionally biased region 3, sequence conflict 2, initiator methionine 1, chain 1, sequence variant 1, domain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5LXR	X-RAY DIFFRACTION	2
5IQQ	X-RAY DIFFRACTION	2.52
5LXY	X-RAY DIFFRACTION	2.85
7S7C	ELECTRON MICROSCOPY	3.62
7S7B	ELECTRON MICROSCOPY	4.06
2M8H	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y580-F1	64.72	0.31

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 (5): 2, 136, 137, 152, 204

Mutagenesis-validated functional residues (10):

Position	Phenotype
13	decreases affinity for rna binding. does not affect the next complex assembly. impairs snrna binding.
25	impaired interaction with zcchc8; when associated with e-29.
29	impaired interaction with zcchc8; when associated with e-25.
50	abrogates the interaction with 7sk small nuclear rna (7sk); when associated with a-52 and a-54. does not affect interact
52	decreases affinity for rna binding. abrogates the interaction with 7sk small nuclear rna (7sk); when associated with a-5
54	abrogates the interaction with 7sk small nuclear rna (7sk); when associated with a-50 and a-52. does not affect interact
65	reduced interaction with zcchc8, and impaired interaction with sf3b2/sap145; when associated with e-69.
69	reduced interaction with zcchc8, and impaired interaction with sf3b2/sap145; when associated with a-65.
136	impairs phosphorylation. impairs phosphorylation; when associated with s-204. prevents prompts accumulation to >50%.
204	impairs phosphorylation. impairs phosphorylation; when associated with s-136.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9843970	Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex
R-HSA-9930044	Nuclear RNA decay

MSigDB gene sets: 210 (showing top): TGCGCANK_UNKNOWN, MODULE_255, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_317, TERAMOTO_OPN_TARGETS_CLUSTER_3, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, HIF1_Q3, REACTOME_MRNA_SPLICING, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_REGULATION_OF_MRNA_SPLICING_VIA_SPLICEOSOME, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN

GO Biological Process (3): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), snRNA catabolic process (GO:0016076), meiotic cell cycle (GO:0051321)

GO Molecular Function (7): RNA binding (GO:0003723), single-stranded RNA binding (GO:0003727), snRNA binding (GO:0017069), 14-3-3 protein binding (GO:0071889), pre-mRNA intronic binding (GO:0097157), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	1
Regulation of endogenous retroelements	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	2
binding	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
RNA catabolic process	1
snRNA metabolic process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
nucleic acid binding	1
protein binding	1
pre-mRNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

908 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM7	ZCCHC8	Q6NZY4	998
RBM7	MTREX	P42285	996
RBM7	SF3B2	Q13435	916
RBM7	ZCCHC7	Q8N3Z6	860
RBM7	ZFC3H1	O60293	821
RBM7	SRSF3	P23152	807
RBM7	EXOSC3	Q9NQT5	804
RBM7	PHAX	Q9H814	695
RBM7	DIS3	Q9Y2L1	674
RBM7	EXOSC8	Q96B26	672
RBM7	EXOSC10	Q01780	665
RBM7	TENT4B	Q8NDF8	661
RBM7	EXOSC2	Q13868	641
RBM7	EXOSC9	Q06265	620
RBM7	PABPN1	Q86U42	614
RBM7	TENT4A	Q5XG87	614

IntAct

126 interactions, top by confidence:

A	B	Type	Score
PPP2R2A	PPP2R1A	psi-mi:“MI:2364”(proximity)	0.970
ZCCHC8	RBM7	psi-mi:“MI:0915”(physical association)	0.890
ZCCHC8	RBM7	psi-mi:“MI:0407”(direct interaction)	0.890
RBM7	ZCCHC8	psi-mi:“MI:0915”(physical association)	0.890
RBM7	ZCCHC8	psi-mi:“MI:0914”(association)	0.890
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
RBM7	SF3B2	psi-mi:“MI:0915”(physical association)	0.780
RBM7	SF3B2	psi-mi:“MI:0914”(association)	0.780
SF3B2	RBM7	psi-mi:“MI:0915”(physical association)	0.780
PRMT9	SF3B2	psi-mi:“MI:0914”(association)	0.750
PPP2R2D	YEATS4	psi-mi:“MI:0914”(association)	0.730
PPP2R2C	PPP2R1A	psi-mi:“MI:0914”(association)	0.730
RBM7	MTREX	psi-mi:“MI:0914”(association)	0.730
RBM7	PPP2R1A	psi-mi:“MI:0914”(association)	0.730
HAUS6	HAUS5	psi-mi:“MI:0914”(association)	0.710
MPHOSPH6	MTREX	psi-mi:“MI:0914”(association)	0.690
C1D	ZFC3H1	psi-mi:“MI:0914”(association)	0.640
EXOSC3	MTREX	psi-mi:“MI:0914”(association)	0.640
EXOSC5	ZFC3H1	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640

BioGRID (247): SF3B1 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), HTATSF1 (Affinity Capture-MS), SKIV2L2 (Affinity Capture-MS), SLC4A1AP (Affinity Capture-MS), ZCCHC8 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), SF3A3 (Affinity Capture-MS), EXOSC7 (Affinity Capture-MS), RBM7 (Affinity Capture-MS), RBM7 (Affinity Capture-MS), RBM7 (Affinity Capture-MS), RBM7 (Affinity Capture-MS), CCDC85B (Two-hybrid), RBM7 (Two-hybrid)

ESM2 similar proteins: A1A6K6, B9DFV2, F4HWF9, F4JCU0, F4JP52, F4KDN0, G7ID19, O22812, O80567, O80678, Q08A72, Q0D3J9, Q0P5D2, Q0VBL3, Q10M00, Q16630, Q3MHY8, Q5NVH8, Q5XI29, Q5ZL34, Q6ATR0, Q6DDW4, Q6JB11, Q6NWC6, Q6ZK57, Q7KMJ6, Q7Z5Q1, Q812E0, Q8BTV2, Q8H0P8, Q8LPQ9, Q8N684, Q8W4I9, Q940D0, Q94CJ8, Q96T37, Q9CQT2, Q9LES2, Q9LKA4, Q9LKA5

Diamond homologs: A2SW84, A6PVI3, A8NS61, A8Y1R8, B0W939, B1WC40, B3LYP1, B3P0D7, B4GLK8, B4IBA4, B4JUT1, B4KCD5, B4LZ88, B4M205, B4NB54, B4PL68, B4QV17, B5DGI7, B5G279, B7P877, C0H859, C1BY64, O89086, P08621, P27476, P31483, P33240, P40561, P52298, P52299, P52912, P60824, P60825, P60826, P62995, P62996, P62997, P78795, P98179, Q01085

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RBM7	“up-regulates activity”	P-TEFb	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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
Activation of BAD and translocation to mitochondria	6	59.3×	2e-08
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA	7	57.7×	1e-09
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	7	57.7×	1e-09
Nuclear RNA decay	14	56.1×	3e-19
mRNA decay by 3’ to 5’ exoribonuclease	6	55.6×	3e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	52.4×	4e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	52.4×	4e-08
KSRP (KHSRP) binds and destabilizes mRNA	6	49.4×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
maturation of 5.8S rRNA	5	54.3×	2e-06
RNA catabolic process	9	42.3×	1e-10
RNA processing	15	33.8×	1e-16
mRNA splicing, via spliceosome	17	16.1×	1e-13
regulation of alternative mRNA splicing, via spliceosome	6	15.1×	1e-04
rRNA processing	8	11.7×	2e-05
positive regulation of cell growth	5	9.4×	5e-03
intracellular protein localization	7	7.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

630 predictions. Top by Δscore:

Variant	Effect	Δscore
11:114400763:ACCAG:A	donor_gain	1.0000
11:114400764:CCAG:C	donor_gain	1.0000
11:114400765:CAG:C	donor_gain	1.0000
11:114400766:AG:A	donor_gain	1.0000
11:114400767:GG:G	donor_gain	1.0000
11:114400768:G:GG	donor_gain	1.0000
11:114401693:TGTA:T	acceptor_loss	1.0000
11:114401694:GTA:G	acceptor_loss	1.0000
11:114401695:TA:T	acceptor_loss	1.0000
11:114401696:A:AG	acceptor_gain	1.0000
11:114401696:AG:A	acceptor_gain	1.0000
11:114401696:AGGCT:A	acceptor_gain	1.0000
11:114401697:G:GT	acceptor_gain	1.0000
11:114401697:GG:G	acceptor_gain	1.0000
11:114401697:GGC:G	acceptor_gain	1.0000
11:114401697:GGCT:G	acceptor_gain	1.0000
11:114401697:GGCTG:G	acceptor_gain	1.0000
11:114401831:G:GT	donor_gain	1.0000
11:114401857:TCAGG:T	donor_loss	1.0000
11:114401858:CAG:C	donor_loss	1.0000
11:114401858:CAGG:C	donor_loss	1.0000
11:114401859:AGG:A	donor_loss	1.0000
11:114401861:G:C	donor_loss	1.0000
11:114401861:G:GC	donor_loss	1.0000
11:114402821:A:AG	acceptor_gain	1.0000
11:114402822:TTTTA:T	acceptor_loss	1.0000
11:114402823:TTTA:T	acceptor_loss	1.0000
11:114402826:A:AG	acceptor_gain	1.0000
11:114402826:A:T	acceptor_loss	1.0000
11:114402826:AG:A	acceptor_gain	1.0000

AlphaMissense

1769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:114400708:T:C	F13L	1.000
11:114400710:T:A	F13L	1.000
11:114400710:T:G	F13L	1.000
11:114401702:G:A	G34E	1.000
11:114401755:T:C	F52L	1.000
11:114401757:T:A	F52L	1.000
11:114401757:T:G	F52L	1.000
11:114401759:C:A	A53E	1.000
11:114401761:T:C	F54L	1.000
11:114401763:T:A	F54L	1.000
11:114401763:T:G	F54L	1.000
11:114401771:T:C	F57S	1.000
11:114400706:T:A	L12H	0.999
11:114400706:T:C	L12P	0.999
11:114400709:T:C	F13S	0.999
11:114400715:G:A	G15D	0.999
11:114400721:T:A	L17H	0.999
11:114400721:T:C	L17P	0.999
11:114400748:T:A	L26H	0.999
11:114400757:T:C	L29P	0.999
11:114401701:G:A	G34R	0.999
11:114401701:G:C	G34R	0.999
11:114401701:G:T	G34W	0.999
11:114401751:G:C	K50N	0.999
11:114401751:G:T	K50N	0.999
11:114401756:T:C	F52S	0.999
11:114401758:G:C	A53P	0.999
11:114401762:T:C	F54S	0.999
11:114401762:T:G	F54C	0.999
11:114401765:T:A	V55E	0.999

dbSNP variants (sampled 300 via entrez): RS1000122162 (11:114400453 G>A,C), RS1000142686 (11:114399283 G>A), RS1000345090 (11:114406788 T>C), RS1000352717 (11:114405129 T>A), RS1000794307 (11:114401256 G>A), RS1000932282 (11:114407184 T>G), RS1000951812 (11:114409556 A>G), RS1001143431 (11:114400507 A>G), RS1001717616 (11:114406269 A>G), RS1001732093 (11:114407389 A>G), RS1002168380 (11:114405923 T>G), RS1002183171 (11:114406977 C>T), RS1002235581 (11:114402458 C>T), RS1002289919 (11:114402185 T>G), RS1002783140 (11:114410024 C>T)

Disease associations

OMIM: gene MIM:612413 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
spinal muscular atrophy	Moderate	Autosomal recessive

Mondo (1): spinal muscular atrophy (MONDO:0001516)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004131_119	Inflammatory bowel disease	2.000000e-06
GCST004133_61	Ulcerative colitis	2.000000e-09

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009134	Muscular Atrophy, Spinal	C10.228.854.468; C10.574.562.500; C10.668.467.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	4
Air Pollutants	decreases expression, increases abundance	2
Smoke	decreases expression, increases abundance	2
Cyclosporine	increases expression, increases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
coumarin	increases phosphorylation	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Gefitinib	affects response to substance	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Coal	decreases expression, increases abundance	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Phenobarbital	affects expression	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2IQ	HAP1 RBM7 (-) 1	Cancer cell line	Male
CVCL_E2IR	HAP1 RBM7 (-) 2	Cancer cell line	Male
CVCL_E2IS	HAP1 RBM7 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01422200	PHASE4	COMPLETED	Flu Vaccine Study in Neuromuscular Patients 2011
NCT05232929	PHASE4	ACTIVE_NOT_RECRUITING	Long-term Follow-up Study of Risdiplam in Participants With Spinal Muscular Atrophy (SMA)
NCT05522361	PHASE4	ACTIVE_NOT_RECRUITING	Risdiplam in Patients With Spinal Muscular Atrophy Previously Treated With Nusinersen
NCT07448610	PHASE4	NOT_YET_RECRUITING	ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (OAV101B) (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM)
NCT01671384	PHASE3	UNKNOWN	Valproate and Levocarnitine in Children With Spinal Muscular Atrophy
NCT02193074	PHASE3	TERMINATED	A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy
NCT02292537	PHASE3	COMPLETED	A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Participants With Later-onset Spinal Muscular Atrophy (SMA)
NCT02594124	PHASE3	COMPLETED	A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies
NCT03505099	PHASE3	COMPLETED	Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2
NCT03837184	PHASE3	COMPLETED	Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies
NCT04042025	PHASE3	ACTIVE_NOT_RECRUITING	Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi
NCT04851873	PHASE3	COMPLETED	Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
NCT05067790	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn About the Effect of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Risdiplam (ASCEND)
NCT05156320	PHASE3	COMPLETED	Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
NCT05335876	PHASE3	RECRUITING	Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials
NCT05337553	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
NCT05386680	PHASE3	COMPLETED	Phase IIIb, Open-label, Multi-center Study to Evaluate Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally to Participants With SMA Who Discontinued Treatment With Nusinersen or Risdiplam
NCT05626855	PHASE3	ACTIVE_NOT_RECRUITING	Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab
NCT07265232	PHASE3	RECRUITING	Real World Clinical Effectiveness & Safety of Vesemnogene Lantuparvovec for Spinal Muscular Atrophy (SMA) in Low-middle Income Countries (LMIC).
NCT07444476	PHASE3	RECRUITING	A Study to Learn About Salanersen’s (BIIB115) Effects on Movement and Its Safety in Participants Aged 15 to 60 Years With Spinal Muscular Atrophy (SMA) Who Are Either New to SMA Treatment or Were Previously Treated With Risdiplam
NCT00004771	PHASE2	COMPLETED	Phase II Study of Leuprolide and Testosterone for Men With Kennedy’s Disease or Other Motor Neuron Disease
NCT00227266	PHASE2	COMPLETED	Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy
NCT00481013	PHASE2	COMPLETED	Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy
NCT01028833	PHASE2	COMPLETED	Effects of Power Mobility on Young Children With Severe Motor Impairments
NCT01302600	PHASE2	COMPLETED	Safety and Efficacy of Olesoxime (TRO19622) in 3-25 Years SMA Patients.
NCT01839656	PHASE2	COMPLETED	A Study to Assess the Efficacy, Safety and Pharmacokinetics of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (SMA)
NCT02386553	PHASE2	COMPLETED	A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
NCT02462759	PHASE2	TERMINATED	A Study to Assess the Safety and Tolerability of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA).
NCT02644668	PHASE2	COMPLETED	A Study of CK-2127107 in Patients With Spinal Muscular Atrophy
NCT02876094	PHASE2	TERMINATED	Effect of Low-Dose Celecoxib on SMN2 in Patients With Spinal Muscular Atrophy
NCT02941328	PHASE2	COMPLETED	SPACE Trial: Pyridostigmine vs Placebo in SMA Types 2, 3 and 4
NCT03032172	PHASE2	COMPLETED	A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy
NCT03921528	PHASE2	COMPLETED	An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy
NCT05794139	PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of NMD670 in Ambulatory Adult Patients With Type 3 Spinal Muscular Atrophy
NCT07047144	PHASE2	RECRUITING	A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy
NCT07287982	PHASE2	RECRUITING	A Study to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of Intravenous Administration of ARGX-119 in Pediatric Participants Aged 5 to Less Than 18 Years With Spinal Muscular Atrophy
NCT00374075	PHASE1	COMPLETED	Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy
NCT01494701	PHASE1	COMPLETED	An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA)
NCT01780246	PHASE1	COMPLETED	An Open-label Safety and Tolerability Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1 (NCT01494701)
NCT02052791	PHASE1	COMPLETED	An Open-label Safety and Tolerability Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in ISIS 396443-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246)