SNIP1

Summary

SNIP1 (Smad nuclear interacting protein 1, HGNC:30587) is a protein-coding gene on chromosome 1p34.3, encoding Smad nuclear-interacting protein 1 (Q8TAD8). Required for pre-mRNA splicing as component of the spliceosome. It is a selective cancer dependency (DepMap: 81.3% of cell lines).

This gene encodes a protein that contains a coiled-coil motif and C-terminal forkhead-associated (FHA) domain. The encoded protein functions as a transcriptional coactivator that increases c-Myc activity and inhibits transforming growth factor beta (TGF-beta) and nuclear factor kappa-B (NF-kB) signaling. The encoded protein also regulates the stability of cyclin D1 mRNA, and may play a role in cell proliferation and cancer progression. Mutations in this gene are a cause of psychomotor retardation, epilepsy, and craniofacial dysmorphism (PMRED).

Source: NCBI Gene 79753 — RefSeq curated summary.

At a glance

• Gene–disease (curated): psychomotor retardation, epilepsy, and craniofacial dysmorphism (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 128 total
• Phenotypes (HPO): 31
• Cancer dependency (DepMap): dependent in 81.3% of screened cell lines
• MANE Select transcript: NM_024700

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30587
Approved symbol	SNIP1
Name	Smad nuclear interacting protein 1
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	PML1
Ensembl gene	ENSG00000163877
Ensembl biotype	protein_coding
OMIM	608241
Entrez	79753

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 retained_intron, 1 protein_coding, 1 nonsense_mediated_decay

ENST00000296215, ENST00000468040, ENST00000493916, ENST00000638725

RefSeq mRNA: 1 — MANE Select: NM_024700 NM_024700

CCDS: CCDS419

Canonical transcript exons

ENST00000296215 — 4 exons

Exon	Start	End
ENSE00001079222	37540157	37540755
ENSE00001079227	37554006	37554293
ENSE00001885538	37534449	37538012
ENSE00003486891	37552645	37552747

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 88.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.6322 / max 110.6103, expressed in 1809 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11784	16.1267	1808
11783	1.5055	915

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	88.33	gold quality
oocyte	CL:0000023	87.21	gold quality
sural nerve	UBERON:0015488	87.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.95	gold quality
buccal mucosa cell	CL:0002336	85.65	gold quality
calcaneal tendon	UBERON:0003701	84.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.82	gold quality
islet of Langerhans	UBERON:0000006	81.09	gold quality
tendon	UBERON:0000043	80.96	gold quality
bone marrow cell	CL:0002092	80.85	gold quality
bone marrow	UBERON:0002371	80.63	gold quality
stromal cell of endometrium	CL:0002255	80.61	gold quality
leukocyte	CL:0000738	79.40	gold quality
granulocyte	CL:0000094	79.28	gold quality
blood	UBERON:0000178	79.26	gold quality
monocyte	CL:0000576	79.21	gold quality
mononuclear cell	CL:0000842	79.13	gold quality
mucosa of stomach	UBERON:0001199	78.76	gold quality
skin of abdomen	UBERON:0001416	78.11	gold quality
skin of leg	UBERON:0001511	78.01	gold quality
amniotic fluid	UBERON:0000173	77.77	gold quality
descending thoracic aorta	UBERON:0002345	77.57	gold quality
adrenal tissue	UBERON:0018303	77.40	gold quality
left uterine tube	UBERON:0001303	77.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.25	gold quality
lower esophagus	UBERON:0013473	77.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.23	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.16	gold quality
esophagus	UBERON:0001043	77.06	gold quality
pancreas	UBERON:0001264	77.05	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.74

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CCND1	Unknown
MYC	Unknown

miRNA regulators (miRDB)

166 targeting SNIP1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-128-3P	99.95	71.17	2484

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 81.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 20)

• define both a new function for SNIP1 and identify a previously unrecognized regulator of the cell cycle and cyclin D1 expression (PMID:15378006)
• Smad-binding peptide aptamers can be developed to selectively inhibit TGF-beta-induced gene expression. (PMID:15750622)
• SNIP1 functions as a regulator of c-Myc activity, binding the N c-Myc N terminus through its C terminus, and that SNIP1 enhances the transcriptional activity of c-Myc by stabilizing it against proteosomal degradation and bridging the c-Myc/p300 complex. (PMID:17157259)
• SNIP1, the human homolog of DDL, is involved in miRNA biogenesis and interacts with Drosha (PMID:18632581)
• Study shows a novel mechanism regulating Cyclin D1 expression and offers new insight into the role of SNIP1 and associated proteins as regulators of proliferation and cancer. (PMID:18794151)
• overexpression of HIF-1alpha, TWIST2 or SNIP1 correlated with poor disease-free survival in patients with tongue squamous cell carcinoma (PMID:21167768)
• SNIP1 in cells strongly activated the heat shock element signaling pathway, and SNIP1 might selectively regulate the transcription of some heat shock proteins through associating with heat shock elements (PMID:22020748)
• Study identified sequence variants in the known disease-causing genes SLC6A3 and FLVCR1, and present evidence to strongly support the pathogenicity of variants identified in TUBGCP6, BRAT1, SNIP1, CRADD, and HARS. (PMID:22279524)
• Involvement of SNIP1 in progression of lung cancer by regulating the RB/HDAC1 interaction. (PMID:23932364)
• SUMOylation of SNIP1 leads to the loss of SNIP1-mediated inhibition on expression of the TGF-beta target genes PAI-1 and MMP2 and eventually enhances TGF-beta-regulated cell migration and invasion. (PMID:27703003)
• these data demonstrated a novel mechanism whereby SNIP1 regulates intestinal inflammation through modulating intestinal epithelial barrier function (PMID:29426045)
• This study also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response. (PMID:30404004)
• Overexpression of miR-335 inhibits the migration and invasion of osteosarcoma by targeting SNIP1 (PMID:30954590)
• MiR-223 promotes pyroptosis of enteritis cells through activating NF-kappaB signalling pathway by targeting SNIP1 in inflammatory bowel disease. (PMID:34151668)
• Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc. (PMID:34168109)
• A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder. (PMID:34570759)
• KMT5A-methylated SNIP1 promotes triple-negative breast cancer metastasis by activating YAP signaling. (PMID:35449131)
• MiR-138-5p suppresses the progression of lung cancer by targeting SNIP1. (PMID:36597175)
• MKRN1 promotes colorectal cancer metastasis by activating the TGF-beta signalling pathway through SNIP1 protein degradation. (PMID:37620897)
• SNIP1 reduces extracellular matrix degradation and inflammation via inhibiting the NF-kappaB signaling pathway in osteoarthritis. (PMID:37739115)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Snip1	ENSMUSG00000050213
rattus_norvegicus	Snip1	ENSRNOG00000024889
drosophila_melanogaster	CG17168	FBGN0039943
caenorhabditis_elegans	pmlr-1	WBGENE00016323

Paralogs (2): PPP1R8 (ENSG00000117751), SLC4A1AP (ENSG00000163798)

Protein

Protein identifiers

Smad nuclear-interacting protein 1 — Q8TAD8 (reviewed: Q8TAD8)

Alternative names: FHA domain-containing protein SNIP1

All UniProt accessions (3): A0A1W2PRA0, B1AK66, Q8TAD8

UniProt curated annotations — full annotation on UniProt →

Function. Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. Down-regulates NF-kappa-B signaling by competing with RELA for CREBBP/EP300 binding. Involved in the microRNA (miRNA) biogenesis. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3’end of the CCND1 gene and its mRNA.

Subunit / interactions. Component of activated spliceosome complexes. Component of the minor spliceosome, which splices U12-type introns. Binds SMAD4 and CREBBP/EP300. Binds the SMAD1/OAZ1/PSMB4 complex. Interacts with DROSHA and SMARCA4. Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous, with highest expression in heart and skeletal muscle.

Post-translational modifications. Degraded by the proteasome upon binding to the SMAD1/OAZ1/PSMB4 complex.

Disease relevance. Neurodevelopmental disorder with hypotonia, craniofacial abnormalities, and seizures (NEDHCS) [MIM:614501] An autosomal recessive disease characterized by severe psychomotor retardation, intractable seizures, dysmorphic features, and a lumpy skull surface. Patients are hypotonic and have poor feeding in the neonatal period. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_078976* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR050923	Cell_Proc_Reg/RNA_Proc	Family

Pfam: PF00498

UniProt features (41 total): modified residue 10, strand 8, compositionally biased region 6, cross-link 5, region of interest 2, sequence conflict 2, turn 2, chain 1, domain 1, sequence variant 1, mutagenesis site 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
7DVQ	ELECTRON MICROSCOPY	2.89
8I0R	ELECTRON MICROSCOPY	3
8I0P	ELECTRON MICROSCOPY	3.4
6FF7	ELECTRON MICROSCOPY	4.5
7ABH	ELECTRON MICROSCOPY	4.5
5Z58	ELECTRON MICROSCOPY	4.9
5Z56	ELECTRON MICROSCOPY	5.1
5Z57	ELECTRON MICROSCOPY	6.5
7ABG	ELECTRON MICROSCOPY	7.8
7ABI	ELECTRON MICROSCOPY	8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAD8-F1	66.66	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 (15): 35, 49, 52, 54, 57, 58, 99, 153, 202, 394, 30, 30, 30, 108, 223

Mutagenesis-validated functional residues (1):

Position	Phenotype
30	abolishes sumoylation.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 281 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GGAANCGGAANY_UNKNOWN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, chr1p34, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, GOBP_NEGATIVE_REGULATION_OF_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (9): mRNA splicing, via spliceosome (GO:0000398), miRNA processing (GO:0035196), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), positive regulation of transcription by RNA polymerase II (GO:0045944), U2-type prespliceosome assembly (GO:1903241), mRNA processing (GO:0006397), RNA splicing (GO:0008380), regulation of gene expression (GO:0010468), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U2 snRNP (GO:0005686), cytosol (GO:0005829), U2-type precatalytic spliceosome (GO:0071005)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
cellular anatomical structure	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
regulatory ncRNA processing	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
spliceosomal complex assembly	1
mRNA metabolic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
negative regulation of gene expression	1
nucleic acid binding	1
RNA binding	1
regulation of gene expression	1
transcription regulator activity	1
molecular function inhibitor activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
spliceosomal snRNP complex	1
cytoplasm	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1

Protein interactions and networks

STRING

1785 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNIP1	BUD13	Q9BRD0	986
SNIP1	RBMX2	Q9Y388	984
SNIP1	DROSHA	Q9NRR4	891
SNIP1	SNW1	Q13573	825
SNIP1	PPP1R10	Q96QC0	748
SNIP1	SF3B1	O75533	707
SNIP1	TET2	Q6N021	705
SNIP1	EP300	Q09472	698
SNIP1	GLB1	P16278	653
SNIP1	BCLAF1	Q9NYF8	589
SNIP1	SMAD4	Q13485	552
SNIP1	GALC	P54803	548
SNIP1	MYC	P01106	545
SNIP1	CWC22	Q9HCG8	508
SNIP1	SMAD2	Q15796	504

IntAct

209 interactions, top by confidence:

A	B	Type	Score
SNIP1	CLK2	psi-mi:“MI:0915”(physical association)	0.870
CLK2	SNIP1	psi-mi:“MI:0915”(physical association)	0.870
SNIP1	SNW1	psi-mi:“MI:0914”(association)	0.770
SNIP1	SNW1	psi-mi:“MI:0403”(colocalization)	0.770
SNW1	SNIP1	psi-mi:“MI:0915”(physical association)	0.770
SNIP1	CLK3	psi-mi:“MI:0915”(physical association)	0.740
THRAP3	SNIP1	psi-mi:“MI:0914”(association)	0.740
SNIP1	THRAP3	psi-mi:“MI:0403”(colocalization)	0.740
SNIP1	TNIP1	psi-mi:“MI:0915”(physical association)	0.670
TNIP1	SNIP1	psi-mi:“MI:0915”(physical association)	0.670
SRPK2	SNIP1	psi-mi:“MI:0915”(physical association)	0.670
MFAP1	SNIP1	psi-mi:“MI:0915”(physical association)	0.670
SNIP1	RNPS1	psi-mi:“MI:0914”(association)	0.670
SNIP1	SF3B1	psi-mi:“MI:0915”(physical association)	0.670
SNIP1	SRRM2	psi-mi:“MI:0915”(physical association)	0.660
WSB2	SNIP1	psi-mi:“MI:0914”(association)	0.640
BCLAF1	SNW1	psi-mi:“MI:0403”(colocalization)	0.640
MYC	SNIP1	psi-mi:“MI:0915”(physical association)	0.630
SNIP1	MYC	psi-mi:“MI:0915”(physical association)	0.630

BioGRID (577): SNIP1 (Two-hybrid), SNIP1 (Two-hybrid), BCLAF1 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), ZC3H14 (Affinity Capture-MS), PNN (Affinity Capture-MS), GPATCH8 (Affinity Capture-MS), NCBP1 (Affinity Capture-MS), CRNKL1 (Affinity Capture-MS), RBM22 (Affinity Capture-MS), AQR (Affinity Capture-MS), GPALPP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IZ84, B0BN49, B2KF05, B2RRD7, B5DE93, E1BB52, E9Q5K9, F1LP90, F1Q8W0, O95819, P30414, P30415, P97820, Q0P678, Q0WX00, Q14004, Q27450, Q5EA28, Q5M9G6, Q5U3H2, Q62504, Q69ZA1, Q6P1G2, Q6TQE1, Q86UR5, Q86VM9, Q8BIZ6, Q8K3A9, Q8N4C8, Q8NHM5, Q8R0F5, Q8TAD8, Q8UVR5, Q8W4D8, Q96KQ7, Q96MU7, Q96T58, Q99NE5, Q9CSP9, Q9CWW7

Diamond homologs: A0JM08, Q498L0, Q5M9G6, Q5SW79, Q6A065, Q80U49, Q8BIZ6, Q8TAD8, Q96L14, Q9BWU0, Q9Y4F5, Q07930, B7SY83, Q54VU4, Q8W4D8, B1AJZ9, A0QNG6, P34648, Q12972, Q28147, Q8R3G1, Q9FIK2

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SNIP1	down-regulates	CBP/p300	binding
SNIP1	“form complex”	“U2 snRNP complex”	binding
SNIP1	down-regulates	SMAD4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 159 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
SUMOylation of intracellular receptors	5	15.7×	1e-03
SUMOylation of transcription cofactors	6	13.6×	4e-04
mRNA Splicing	13	13.3×	4e-09
mRNA 3’-end processing	6	11.0×	1e-03
Processing of Capped Intron-Containing Pre-mRNA	14	10.8×	9e-09
mRNA Splicing - Major Pathway	21	10.7×	2e-13
mRNA Polyadenylation	12	9.8×	5e-07
SUMOylation of DNA damage response and repair proteins	7	9.6×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing, via transesterification reactions	5	22.6×	3e-04
protein sumoylation	8	18.8×	3e-06
mRNA splicing, via spliceosome	20	13.3×	4e-14
regulation of alternative mRNA splicing, via spliceosome	7	12.4×	2e-04
RNA splicing	15	9.6×	2e-08
mRNA processing	11	6.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	42
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

648 predictions. Top by Δscore:

Variant	Effect	Δscore
1:37537743:G:C	donor_gain	1.0000
1:37537764:T:TA	donor_gain	1.0000
1:37537767:T:TA	donor_gain	1.0000
1:37537872:T:TA	donor_gain	1.0000
1:37538008:CAAGC:C	acceptor_gain	1.0000
1:37538011:GC:G	acceptor_gain	1.0000
1:37538011:GCCTA:G	acceptor_loss	1.0000
1:37538012:CC:C	acceptor_gain	1.0000
1:37538012:CCTAG:C	acceptor_loss	1.0000
1:37538013:C:CA	acceptor_loss	1.0000
1:37538013:C:CC	acceptor_gain	1.0000
1:37538014:T:C	acceptor_loss	1.0000
1:37540154:TAC:T	donor_loss	1.0000
1:37540155:A:AC	donor_gain	1.0000
1:37540155:ACC:A	donor_loss	1.0000
1:37540156:C:CC	donor_gain	1.0000
1:37540753:CTC:C	acceptor_gain	1.0000
1:37554002:TTA:T	donor_loss	1.0000
1:37554003:TAC:T	donor_loss	1.0000
1:37554004:A:AC	donor_gain	1.0000
1:37554004:AC:A	donor_gain	1.0000
1:37554005:C:CA	donor_gain	1.0000
1:37554005:CC:C	donor_gain	1.0000
1:37554005:CCGG:C	donor_gain	1.0000
1:37537795:T:A	donor_gain	0.9900
1:37538009:AAGC:A	acceptor_gain	0.9900
1:37538010:AGC:A	acceptor_gain	0.9900
1:37538017:C:CT	acceptor_gain	0.9900
1:37538018:A:T	acceptor_gain	0.9900
1:37539253:T:TA	donor_gain	0.9900

AlphaMissense

2580 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:37537830:A:G	L370P	1.000
1:37537830:A:T	L370H	1.000
1:37537836:A:T	V368D	1.000
1:37537840:A:C	Y367D	1.000
1:37537840:A:G	Y367H	1.000
1:37537844:T:A	R365S	1.000
1:37537844:T:G	R365S	1.000
1:37537845:C:A	R365I	1.000
1:37537845:C:G	R365T	1.000
1:37537846:T:C	R365G	1.000
1:37537850:A:C	S363R	1.000
1:37537850:A:T	S363R	1.000
1:37537851:C:A	S363I	1.000
1:37537851:C:T	S363N	1.000
1:37537852:T:G	S363R	1.000
1:37537853:G:C	F362L	1.000
1:37537853:G:T	F362L	1.000
1:37537855:A:G	F362L	1.000
1:37537857:C:A	G361V	1.000
1:37537857:C:T	G361E	1.000
1:37537858:C:G	G361R	1.000
1:37537858:C:T	G361R	1.000
1:37537859:A:C	F360L	1.000
1:37537859:A:T	F360L	1.000
1:37537860:A:G	F360S	1.000
1:37537861:A:G	F360L	1.000
1:37537866:A:G	L358P	1.000
1:37537866:A:T	L358H	1.000
1:37537871:A:C	D356E	1.000
1:37537871:A:T	D356E	1.000

dbSNP variants (sampled 300 via entrez): RS1000022294 (1:37553781 A>C), RS1000091083 (1:37547035 T>C), RS1000526355 (1:37547257 G>T), RS1000557377 (1:37541831 T>A), RS1000590025 (1:37542153 T>G), RS1000772228 (1:37545455 A>C,G), RS1000789861 (1:37535524 G>A), RS1000876352 (1:37536624 A>C), RS1001075109 (1:37535259 A>T), RS1001131512 (1:37548720 C>T), RS1001226317 (1:37554019 G>C), RS1001619203 (1:37535146 C>A,T), RS1001817595 (1:37554748 A>C), RS1002090131 (1:37536239 C>T), RS1002330401 (1:37547923 G>A,C)

Disease associations

OMIM: gene MIM:608241 | disease phenotypes: MIM:614501

GenCC curated gene-disease

Disease	Classification	Inheritance
psychomotor retardation, epilepsy, and craniofacial dysmorphism	Moderate	Autosomal recessive

Mondo (1): psychomotor retardation, epilepsy, and craniofacial dysmorphism (MONDO:0013787)

Orphanet (0):

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000218	High palate
HP:0000347	Micrognathia
HP:0000414	Bulbous nose
HP:0000486	Strabismus
HP:0000666	Horizontal nystagmus
HP:0001182	Tapered finger
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001518	Small for gestational age
HP:0001537	Umbilical hernia
HP:0001601	Laryngomalacia
HP:0001607	Subglottic stenosis
HP:0001647	Bicuspid aortic valve
HP:0001650	Aortic valve stenosis
HP:0001762	Talipes equinovarus
HP:0001943	Hypoglycemia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002263	Exaggerated cupid’s bow
HP:0002353	EEG abnormality
HP:0002500	Abnormal cerebral white matter morphology
HP:0003429	CNS hypomyelination
HP:0004279	Short palm
HP:0011304	Broad thumb
HP:0011344	Severe global developmental delay
HP:0011968	Feeding difficulties

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002115_4	Axial length	4.000000e-13
GCST003476_2	Eyebrow thickness	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects cotreatment, increases abundance, increases expression	3
Arsenic	increases expression, affects methylation, affects cotreatment, increases abundance	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	affects cotreatment, increases expression	1
pyrimidin-2-one beta-ribofuranoside	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression, increases expression	1
neodymium oxide	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arbutin	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, decreases expression	1

Clinical trials (associated diseases)

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