SCNM1

Summary

SCNM1 (sodium channel modifier 1, HGNC:23136) is a protein-coding gene on chromosome 1q21.3, encoding Sodium channel modifier 1 (Q9BWG6). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. It is a selective cancer dependency (DepMap: 25.9% of cell lines).

SCNM1 is a zinc finger protein and putative splicing factor. In mice, Scnm1 modifies phenotypic expression of Scn8a (MIM 600702) mutations (Buchner et al., 2003 [PubMed 12920299]).

Source: NCBI Gene 79005 — RefSeq curated summary.

At a glance

• Gene–disease (curated): orofaciodigital syndrome 19 (Strong, GenCC)
• Clinical variants (ClinVar): 42 total — 3 pathogenic
• Phenotypes (HPO): 42
• Cancer dependency (DepMap): dependent in 25.9% of screened cell lines
• MANE Select transcript: NM_024041

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23136
Approved symbol	SCNM1
Name	sodium channel modifier 1
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC3180
Ensembl gene	ENSG00000163156
Ensembl biotype	protein_coding
OMIM	608095
Entrez	79005

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000368902, ENST00000368905, ENST00000459799, ENST00000461862, ENST00000471039, ENST00000497147, ENST00000602841, ENST00000881392, ENST00000881393, ENST00000881394, ENST00000911421, ENST00000911422

RefSeq mRNA: 3 — MANE Select: NM_024041 NM_001204848, NM_001204856, NM_024041

CCDS: CCDS987

Canonical transcript exons

ENST00000368905 — 7 exons

Exon	Start	End
ENSE00001448245	151166144	151166203
ENSE00001952614	151168986	151170296
ENSE00003589321	151166471	151166541
ENSE00003593198	151166934	151167022
ENSE00003594192	151168144	151168338
ENSE00003612938	151167326	151167414
ENSE00003674697	151167121	151167218

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 97.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.6387 / max 318.8178, expressed in 1816 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5209	33.2016	1815
5207	6.4604	514
5208	0.8977	578
5210	0.5394	299

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.08	gold quality
mononuclear cell	CL:0000842	96.76	gold quality
monocyte	CL:0000576	96.75	gold quality
leukocyte	CL:0000738	96.65	gold quality
gastrocnemius	UBERON:0001388	94.27	gold quality
triceps brachii	UBERON:0001509	94.22	gold quality
tendon of biceps brachii	UBERON:0008188	94.16	gold quality
blood	UBERON:0000178	94.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.09	gold quality
muscle of leg	UBERON:0001383	94.06	gold quality
spleen	UBERON:0002106	93.82	gold quality
descending thoracic aorta	UBERON:0002345	93.58	gold quality
popliteal artery	UBERON:0002250	93.57	gold quality
tibial artery	UBERON:0007610	93.57	gold quality
left coronary artery	UBERON:0001626	93.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.41	gold quality
aorta	UBERON:0000947	93.39	gold quality
muscle organ	UBERON:0001630	93.36	gold quality
mucosa of transverse colon	UBERON:0004991	93.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.29	gold quality
lower esophagus	UBERON:0013473	93.28	gold quality
thoracic aorta	UBERON:0001515	93.27	gold quality
gluteal muscle	UBERON:0002000	93.26	gold quality
ascending aorta	UBERON:0001496	93.21	gold quality
coronary artery	UBERON:0001621	93.06	gold quality
lymph node	UBERON:0000029	92.99	gold quality
ganglionic eminence	UBERON:0004023	92.97	gold quality
right coronary artery	UBERON:0001625	92.85	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	22.19
E-ANND-3	yes	5.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting SCNM1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-4434	99.10	67.01	1984

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Mutations in SCNM1 cause orofaciodigital syndrome due to minor intron splicing defects affecting primary cilia. (PMID:36084634)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	scnm1	ENSDARG00000003027
mus_musculus	Scnm1	ENSMUSG00000092607
rattus_norvegicus	Scnm1	ENSRNOG00000021092

Protein

Protein identifiers

Sodium channel modifier 1 — Q9BWG6 (reviewed: Q9BWG6)

All UniProt accessions (1): Q9BWG6

UniProt curated annotations — full annotation on UniProt →

Function. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. Plays a role in the regulation of primary cilia length and Hedgehog signaling.

Subunit / interactions. Component of the minor spliceosome, which splices U12-type introns. Within this complex, interacts with RNF113A, as well as with SF3B1/SF3b155, SF3B2/SF3b145, SF3B3/SF3b130 and CDC5L. May interact with LUC7L2 and SNRNP70.

Subcellular location. Nucleus. Nucleoplasm. Nucleus speckle.

Disease relevance. Orofaciodigital syndrome 19 (OFD19) [MIM:620107] A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD19 is an autosomal recessive form characterized by tongue nodules, dental and digital anomalies, narrow high-arched or cleft palate, and retrognathia. Some patients have notching of the upper or lower lip. The disease is caused by variants affecting the gene represented in this entry. The genetic variation producing the missense variant p.P51Q, associated with OFD19, has been shown to create a new acceptor splice site, leading to the deletion of 31 nucleotides, resulting in a frameshift and an early termination codon (p.F42YfsTer8). The variant mRNA is predicted to undergo nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BWG6-1	1	yes
Q9BWG6-2	2
Q9BWG6-3	3

RefSeq proteins (3): NP_001191777, NP_001191785, NP_076946* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031622	Znf-SCNM1	Domain
IPR031625	SCNM1_acidic	Domain
IPR033570	SCNM1	Family

Pfam: PF15803, PF15805

UniProt features (30 total): strand 5, compositionally biased region 4, modified residue 4, region of interest 4, helix 4, splice variant 3, chain 1, zinc finger region 1, cross-link 1, sequence variant 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7DVQ	ELECTRON MICROSCOPY	2.89
8Y7E	ELECTRON MICROSCOPY	4.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWG6-F1	70.08	0.15

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, 144, 183, 219, 67

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 240 (showing top): GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, TGACCTY_ERR1_Q2, COUP_01, TCF4_Q5, HNF4_DR1_Q3, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, HNF4_01, PPAR_DR1_Q2, LYF1_01, RFX1_02, ACEVEDO_LIVER_CANCER_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOCC_NUCLEAR_SPECK

GO Biological Process (3): alternative mRNA splicing, via spliceosome (GO:0000380), RNA splicing (GO:0008380), mRNA processing (GO:0006397)

GO Molecular Function (4): zinc ion binding (GO:0008270), enzyme binding (GO:0019899), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), spliceosomal complex (GO:0005681), nuclear speck (GO:0016607), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
mRNA splicing, via spliceosome	1
mRNA metabolic process	1
transition metal ion binding	1
protein binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
nuclear ribonucleoprotein granule	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCNM1	LUC7L2	Q9Y383	926
SCNM1	A0A0A6YYJ8	A0A0A6YYJ8	926
SCNM1	SCN8A	Q9UQD0	889
SCNM1	SCN7A	Q01118	749
SCNM1	SCN3A	Q9NY46	669
SCNM1	SCN1A	P35498	640
SCNM1	SCN2A	Q99250	550
SCNM1	SNRPC	P09234	549
SCNM1	SNRPD2	P43330	548
SCNM1	SNRNP70	P08621	512
SCNM1	SCN4A	P35499	492
SCNM1	MORN5	Q5VZ52	477
SCNM1	LYSMD1	Q96S90	469
SCNM1	RIBC1	Q8N443	451
SCNM1	PHLDB3	Q6NSJ2	445

IntAct

649 interactions, top by confidence:

A	B	Type	Score
KRT38	SCNM1	psi-mi:“MI:0915”(physical association)	0.830
SCNM1	KRT38	psi-mi:“MI:0915”(physical association)	0.830
TRAF1	SCNM1	psi-mi:“MI:0915”(physical association)	0.790
SCNM1	PNMA1	psi-mi:“MI:0915”(physical association)	0.790
SCNM1	TRAF1	psi-mi:“MI:0915”(physical association)	0.790
PNMA1	SCNM1	psi-mi:“MI:0915”(physical association)	0.790
HMG20A	SCNM1	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	SCNM1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	SCNM1	psi-mi:“MI:0915”(physical association)	0.720
SCNM1	CDR2	psi-mi:“MI:0915”(physical association)	0.720
MKRN3	SCNM1	psi-mi:“MI:0915”(physical association)	0.720
KRT31	SCNM1	psi-mi:“MI:0915”(physical association)	0.720
SCNM1	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
SCNM1	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
BLZF1	SCNM1	psi-mi:“MI:0915”(physical association)	0.720
SCNM1	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
SCNM1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (247): SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid), SCNM1 (Two-hybrid)

ESM2 similar proteins: A0A1L8HTT5, A1A5R9, A2RSX4, A4IFR8, A5WUY6, A6QPC0, A7YWH3, B0BNE4, E1BNS6, G3X6E2, Q08BC4, Q0P591, Q0VB26, Q14BB9, Q17RG1, Q1XFL1, Q2NKX9, Q2T9Q3, Q2TA11, Q2TBS4, Q3KQ80, Q3SX64, Q3UFT3, Q3ZBR0, Q4QR77, Q4R5Y0, Q4VXA5, Q562E2, Q6J272, Q6ZQR2, Q7T3U0, Q8C8J0, Q8N1D5, Q8N412, Q8N7X2, Q8N801, Q8TCI5, Q8WW14, Q99932, Q9BWG6

Diamond homologs: Q2YDS5, Q3KQ71, Q3ZBR0, Q8K136, Q9BWG6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
Keratinization	10	13.9×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	34
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1712498	NM_024041.4(SCNM1):c.152C>A (p.Pro51Gln)	Pathogenic
1712499	NM_024041.4:c.301_302ins[N[324];285_301]	Pathogenic
1712500	NM_024041.4(SCNM1):c.187del (p.Arg63fs)	Pathogenic

SpliceAI

1955 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151161017:TACC:T	acceptor_gain	1.0000
1:151161019:CC:C	acceptor_gain	1.0000
1:151161020:CC:C	acceptor_gain	1.0000
1:151161729:GACTC:G	donor_loss	1.0000
1:151161730:ACTCA:A	donor_loss	1.0000
1:151161731:CTCAC:C	donor_loss	1.0000
1:151161732:TCACC:T	donor_loss	1.0000
1:151161733:CACCC:C	donor_loss	1.0000
1:151161734:A:AC	donor_gain	1.0000
1:151161734:AC:A	donor_gain	1.0000
1:151161735:C:CC	donor_gain	1.0000
1:151161735:C:T	donor_loss	1.0000
1:151161735:CC:C	donor_gain	1.0000
1:151162097:CCAT:C	acceptor_gain	1.0000
1:151162098:CAT:C	acceptor_gain	1.0000
1:151162098:CATC:C	acceptor_gain	1.0000
1:151162101:C:CC	acceptor_gain	1.0000
1:151162102:T:C	acceptor_gain	1.0000
1:151162102:T:TC	acceptor_gain	1.0000
1:151166168:G:T	donor_gain	1.0000
1:151166204:G:GG	donor_gain	1.0000
1:151166828:G:GT	donor_gain	1.0000
1:151166933:GCTTT:G	acceptor_gain	1.0000
1:151167018:GTCCA:G	donor_gain	1.0000
1:151167023:G:GG	donor_gain	1.0000
1:151167119:A:AG	acceptor_gain	1.0000
1:151167119:AG:A	acceptor_gain	1.0000
1:151167120:G:A	acceptor_gain	1.0000
1:151167120:G:GC	acceptor_gain	1.0000
1:151167120:GGC:G	acceptor_gain	1.0000

AlphaMissense

1485 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151166159:T:C	F3L	0.997
1:151166161:C:A	F3L	0.997
1:151166161:C:G	F3L	0.997
1:151169041:T:C	F217L	0.997
1:151169043:T:A	F217L	0.997
1:151169043:T:G	F217L	0.997
1:151166941:T:C	C44R	0.996
1:151166950:T:C	C47R	0.996
1:151166164:G:C	K4N	0.993
1:151166164:G:T	K4N	0.993
1:151166490:T:C	L24P	0.992
1:151166995:C:G	H62D	0.992
1:151166999:G:C	R63P	0.992
1:151168993:T:A	W201R	0.992
1:151168993:T:C	W201R	0.992
1:151166167:G:C	R5S	0.991
1:151166167:G:T	R5S	0.991
1:151166987:T:C	L59P	0.991
1:151166942:G:A	C44Y	0.990
1:151167015:T:A	H68Q	0.990
1:151167015:T:G	H68Q	0.990
1:151169017:T:A	W209R	0.990
1:151169017:T:C	W209R	0.990
1:151166541:G:C	R41P	0.989
1:151166943:T:G	C44W	0.989
1:151166998:C:A	R63S	0.989
1:151166160:T:C	F3S	0.988
1:151166479:A:C	R20S	0.988
1:151166479:A:T	R20S	0.988
1:151166939:C:A	A43D	0.988

dbSNP variants (sampled 300 via entrez): RS1000901120 (1:151164922 T>G), RS1001354526 (1:151168461 T>G), RS1001465731 (1:151170622 G>A,T), RS1002178677 (1:151165932 C>T), RS1003029571 (1:151166721 A>C), RS1003168458 (1:151166414 C>T), RS1005109400 (1:151168022 A>G,T), RS1005708847 (1:151169424 T>G), RS1006150449 (1:151170714 C>G), RS1006830415 (1:151167323 C>G), RS1007162551 (1:151169716 A>G,T), RS1008445141 (1:151164876 A>G), RS1008505741 (1:151165893 T>C), RS1010181961 (1:151164455 A>G), RS1010212865 (1:151164741 C>T)

Disease associations

OMIM: gene MIM:608095 | disease phenotypes: MIM:620107

GenCC curated gene-disease

Disease	Classification	Inheritance
orofaciodigital syndrome 19	Strong	Autosomal recessive

Mondo (1): orofaciodigital syndrome 19 (MONDO:0859310)

Orphanet (0):

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000160	Narrow mouth
HP:0000180	Lobulated tongue
HP:0000185	Cleft soft palate
HP:0000189	Narrow palate
HP:0000191	Accessory oral frenulum
HP:0000199	Tongue nodules
HP:0000218	High palate
HP:0000268	Dolichocephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000378	Cupped ear
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000456	Bifid nasal tip
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000582	Upslanted palpebral fissure
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000691	Microdontia
HP:0000750	Delayed speech and language development
HP:0001162	Postaxial hand polydactyly
HP:0001249	Intellectual disability
HP:0001770	Toe syndactyly
HP:0001830	Postaxial foot polydactyly

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
salinomycin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects binding, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Cyclosporine	increases expression	1
Copper Sulfate	increases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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