EXOSC1

Summary

EXOSC1 (exosome component 1, HGNC:17286) is a protein-coding gene on chromosome 10q24.1, encoding Exosome complex component CSL4 (Q9Y3B2). Non-catalytic component of the RNA exosome complex which has 3’->5’ exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. It is a selective cancer dependency (DepMap: 63.5% of cell lines).

This gene encodes a core component of the exosome. The mammalian exosome is required for rapid degradation of AU rich element-containing RNAs but not for poly(A) shortening. The association of this protein with the exosome is mediated by protein-protein interactions with ribosomal RNA-processing protein 42 and ribosomal RNA-processing protein 46. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 51013 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pontocerebellar hypoplasia, type 1F (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 45 total — 1 pathogenic
• Phenotypes (HPO): 21
• Cancer dependency (DepMap): dependent in 63.5% of screened cell lines
• MANE Select transcript: NM_016046

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17286
Approved symbol	EXOSC1
Name	exosome component 1
Location	10q24.1
Locus type	gene with protein product
Status	Approved
Aliases	hCsl4p, Csl4p, CSL4, Ski4p, SKI4, CGI-108, p13
Ensembl gene	ENSG00000171311
Ensembl biotype	protein_coding
OMIM	606493
Entrez	51013

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000370884, ENST00000370885, ENST00000370886, ENST00000370902, ENST00000471049, ENST00000472345, ENST00000474309, ENST00000476234, ENST00000477692, ENST00000485122, ENST00000489158, ENST00000889436, ENST00000889437, ENST00000889438, ENST00000918423, ENST00000918424, ENST00000918425, ENST00000918426, ENST00000918427, ENST00000918428, ENST00000918429, ENST00000918430

RefSeq mRNA: 6 — MANE Select: NM_016046 NM_001318362, NM_001318363, NM_001318364, NM_001318365, NM_001318366, NM_016046

CCDS: CCDS7459, CCDS81492

Canonical transcript exons

ENST00000370902 — 8 exons

Exon	Start	End
ENSE00001821930	97435909	97436551
ENSE00003298481	97438670	97438703
ENSE00003575535	97445732	97445847
ENSE00003588946	97437700	97437750
ENSE00003630778	97443237	97443311
ENSE00003650215	97445955	97446006
ENSE00003659317	97437191	97437275
ENSE00003670371	97441171	97441259

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 93.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.4910 / max 175.6751, expressed in 1820 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110935	36.4910	1820

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.31	gold quality
stromal cell of endometrium	CL:0002255	92.73	gold quality
body of pancreas	UBERON:0001150	92.60	gold quality
leukocyte	CL:0000738	92.19	gold quality
monocyte	CL:0000576	92.10	gold quality
adenohypophysis	UBERON:0002196	91.91	gold quality
body of stomach	UBERON:0001161	91.78	gold quality
prefrontal cortex	UBERON:0000451	91.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.66	gold quality
mucosa of transverse colon	UBERON:0004991	91.57	gold quality
pancreas	UBERON:0001264	91.56	gold quality
spleen	UBERON:0002106	91.18	gold quality
right ovary	UBERON:0002118	91.01	gold quality
lymph node	UBERON:0000029	90.99	gold quality
endocervix	UBERON:0000458	90.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.91	gold quality
ectocervix	UBERON:0012249	90.88	gold quality
pituitary gland	UBERON:0000007	90.85	gold quality
smooth muscle tissue	UBERON:0001135	90.81	gold quality
minor salivary gland	UBERON:0001830	90.81	gold quality
left ovary	UBERON:0002119	90.78	gold quality
body of uterus	UBERON:0009853	90.73	gold quality
stomach	UBERON:0000945	90.71	gold quality
bone marrow cell	CL:0002092	90.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.60	gold quality
mouth mucosa	UBERON:0003729	90.52	gold quality
right adrenal gland	UBERON:0001233	90.51	gold quality
esophagus mucosa	UBERON:0002469	90.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.50	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.78
E-ENAD-20	no	98.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KMT2A, PAX5

miRNA regulators (miRDB)

21 targeting EXOSC1, 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-3924	100.00	72.09	2394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-1278	97.75	67.55	628
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-103B	95.51	66.85	441

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 63.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• association of hCsl4p with the exosome is mediated by protein-protein interactions with hRrp42p and hRrp46p (PMID:11812149)
• Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring. (PMID:12419256)
• Human exosome hCsl4p participates in RNA degradation. (PMID:22068837)
• The combined p16- and p53-expression status in cervical metastases of CUP may represent a simple method for risk stratification. Further validation of these biomarkers in large prospective trials is essential to design rational trials for CUP treatment optimization. (PMID:28144684)
• Post-transcriptional control of cellular differentiation by the RNA exosome complex. (PMID:33119769)
• Bi-allelic missense variant, p.Ser35Leu in EXOSC1 is associated with pontocerebellar hypoplasia. (PMID:33463720)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	exosc1	ENSDARG00000059841
mus_musculus	Exosc1	ENSMUSG00000034321
rattus_norvegicus	Exosc1	ENSRNOG00000048708
drosophila_melanogaster	Csl4	FBGN0032346
caenorhabditis_elegans		WBGENE00012966

Protein

Protein identifiers

Exosome complex component CSL4 — Q9Y3B2 (reviewed: Q9Y3B2)

Alternative names: Exosome component 1

All UniProt accessions (6): B1AMU3, B1AMU4, B1AMU7, Q9Y3B2, R4GMQ7, R4GNH9

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic component of the RNA exosome complex which has 3’->5’ exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding ‘pervasive’ transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3’ untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC1 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC6 and EXOSC8.

Subunit / interactions. Component of the RNA exosome core complex (Exo-9), composed of EXOSC1, EXOSC2, EXOSC3, EXOSC4, EXOSC5, EXOSC6, EXOSC7, EXOSC8 and EXOSC9; within the complex interacts with EXOSC6. The catalytically inactive RNA exosome core complex (Exo-9) associates with the catalytic subunit EXOSC10/RRP6. Exo-9 may associate with DIS3 to form the nucleolar exosome complex, or DIS3L to form the cytoplasmic exosome complex. Exo-9 is formed by a hexameric base ring consisting of the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and a cap ring consisting of EXOSC1, EXOSC2 and EXOSC3. The RNA exosome complex associates with cofactors C1D/RRP47, MPHOSPH6/MPP6 and MTREX/MTR4. Interacts with DDX60.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Disease relevance. Pontocerebellar hypoplasia 1F (PCH1F) [MIM:619304] A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH1F is an autosomal recessive form characterized by hypotonia, global developmental delay, poor overall growth, and dysmorphic facial features. Brain imaging shows pontocerebellar hypoplasia, thin corpus callosum, cerebral atrophy, and delayed myelination. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CSL4 family.

RefSeq proteins (6): NP_001305291, NP_001305292, NP_001305293, NP_001305294, NP_001305295, NP_057130* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003029	S1_domain	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR019495	EXOSC1_C	Domain
IPR025721	Exosome_cplx_N_dom	Domain
IPR039771	Csl4	Family

Pfam: PF10447, PF14382

UniProt features (27 total): strand 17, helix 3, modified residue 2, turn 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
9G8M	ELECTRON MICROSCOPY	3.3
2NN6	X-RAY DIFFRACTION	3.35
9G8O	ELECTRON MICROSCOPY	3.4
6D6Q	ELECTRON MICROSCOPY	3.45
6D6R	ELECTRON MICROSCOPY	3.45
9G8N	ELECTRON MICROSCOPY	3.7
6H25	ELECTRON MICROSCOPY	3.8
9G8P	ELECTRON MICROSCOPY	7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3B2-F1	78.40	0.02

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 (2): 21, 98

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-429958	mRNA decay by 3’ to 5’ exoribonuclease
R-HSA-450385	Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
R-HSA-450513	Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA
R-HSA-450604	KSRP (KHSRP) binds and destabilizes mRNA
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-9930044	Nuclear RNA decay

MSigDB gene sets: 158 (showing top): GOBP_RIBOSOME_BIOGENESIS, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GROSS_HYPOXIA_VIA_HIF1A_UP, GOMF_EXONUCLEASE_ACTIVITY, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, REACTOME_METABOLISM_OF_RNA, GOCC_NUCLEAR_EXOSOME_RNASE_COMPLEX, GOCC_CYTOPLASMIC_EXOSOME_RNASE_COMPLEX, SANSOM_APC_MYC_TARGETS

GO Biological Process (3): rRNA processing (GO:0006364), RNA processing (GO:0006396), RNA catabolic process (GO:0006401)

GO Molecular Function (3): RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (9): nuclear exosome (RNase complex) (GO:0000176), cytoplasmic exosome (RNase complex) (GO:0000177), exosome (RNase complex) (GO:0000178), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), nucleolar exosome (RNase complex) (GO:0101019)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Regulation of mRNA stability by proteins that bind AU-rich elements	3
PERK regulates gene expression	1
Deadenylation-dependent mRNA decay	1
rRNA processing in the nucleus and cytosol	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	3
cellular anatomical structure	3
binding	2
exosome (RNase complex)	2
cytoplasm	2
intracellular anatomical structure	2
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA metabolic process	1
nucleic acid catabolic process	1
nucleic acid binding	1
nucleus	1
nuclear protein-containing complex	1
exoribonuclease complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
nuclear exosome (RNase complex)	1
nucleolus	1

Protein interactions and networks

STRING

2125 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EXOSC1	EXOSC5	Q9NQT4	999
EXOSC1	EXOSC7	Q15024	999
EXOSC1	EXOSC4	Q9NPD3	999
EXOSC1	EXOSC3	Q9NQT5	999
EXOSC1	EXOSC6	Q5RKV6	999
EXOSC1	EXOSC8	Q96B26	999
EXOSC1	EXOSC9	Q06265	997
EXOSC1	EXOSC2	Q13868	996
EXOSC1	EXOSC10	Q01780	945
EXOSC1	DIS3	Q9Y2L1	905
EXOSC1	SKIC2	Q15477	891
EXOSC1	MPHOSPH6	Q99547	874
EXOSC1	MTREX	P42285	863
EXOSC1	C1D	Q13901	855
EXOSC1	DIS3L	Q8TF46	778

IntAct

142 interactions, top by confidence:

A	B	Type	Score
EXOSC5	EXOSC1	psi-mi:“MI:0915”(physical association)	0.970
EXOSC1	EXOSC5	psi-mi:“MI:0915”(physical association)	0.970
EXOSC1	EXOSC5	psi-mi:“MI:0407”(direct interaction)	0.970
EXOSC1	EXOSC7	psi-mi:“MI:0915”(physical association)	0.910
EXOSC1	EXOSC7	psi-mi:“MI:0407”(direct interaction)	0.910
EXOSC7	EXOSC1	psi-mi:“MI:0915”(physical association)	0.910
EXOSC8	EXOSC1	psi-mi:“MI:0915”(physical association)	0.890
EXOSC1	EXOSC2	psi-mi:“MI:0914”(association)	0.850
EXOSC4	EXOSC10	psi-mi:“MI:0914”(association)	0.840
EXOSC1	EXOSC10	psi-mi:“MI:0915”(physical association)	0.810
EXOSC1	EXOSC10	psi-mi:“MI:0914”(association)	0.810

BioGRID (239): EXOSC1 (Two-hybrid), EXOSC1 (Two-hybrid), EXOSC5 (Two-hybrid), PAK7 (Two-hybrid), KCTD1 (Two-hybrid), EXOSC1 (Affinity Capture-MS), EXOSC1 (Affinity Capture-MS), EXOSC1 (Affinity Capture-MS), EXOSC1 (Co-fractionation), EXOSC1 (Co-fractionation), EXOSC1 (Co-fractionation), EXOSC1 (Co-fractionation), EXOSC1 (Co-fractionation), EXOSC10 (Co-fractionation), EXOSC2 (Co-fractionation)

ESM2 similar proteins: A6QRA1, B0VZR4, B3MGZ0, B4HQJ2, F4IFF3, J9VR81, O13867, O14459, O23617, O59821, O65041, O65595, O94285, P05198, P18562, P20459, P20460, P22200, P34087, P35718, P46228, P56286, P68101, P68102, Q16974, Q16WA6, Q1JPL4, Q2T9X1, Q32NH8, Q54P04, Q55GQ6, Q5R493, Q5ZLX2, Q6GL89, Q6ZWX6, Q7QJW7, Q7ZTK4, Q8BLR2, Q8LE42, Q96A23

Diamond homologs: O59821, P53859, Q9DAA6, Q9Y3B2, Q9XXD2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EXOSC1	“form complex”	Exosome_Complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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 decay by 3’ to 5’ exoribonuclease	8	93.6×	7e-13
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA	8	83.2×	1e-12
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	8	83.2×	1e-12
KSRP (KHSRP) binds and destabilizes mRNA	8	83.2×	1e-12
Nuclear RNA decay	15	75.9×	4e-23
ATF4 activates genes in response to endoplasmic reticulum stress	8	53.5×	7e-11
Major pathway of rRNA processing in the nucleolus and cytosol	17	17.2×	1e-14
rRNA processing in the nucleus and cytosol	6	15.8×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
rRNA catabolic process	7	102.0×	1e-11
maturation of 5.8S rRNA	5	77.4×	2e-07
RNA catabolic process	11	73.7×	8e-16
nuclear-transcribed mRNA catabolic process	5	56.3×	8e-07
RNA processing	11	35.4×	1e-12
mitophagy	6	28.1×	2e-06
rRNA processing	13	27.1×	2e-13
autophagosome maturation	5	25.8×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	23
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1068761	NM_016046.5(EXOSC1):c.104C>T (p.Ser35Leu)	Pathogenic

SpliceAI

1321 predictions. Top by Δscore:

Variant	Effect	Δscore
10:97430649:G:GG	donor_gain	1.0000
10:97430649:GTAAG:G	donor_loss	1.0000
10:97430651:AAG:A	donor_loss	1.0000
10:97430653:GG:G	donor_loss	1.0000
10:97430654:G:GA	donor_loss	1.0000
10:97430953:A:AG	acceptor_gain	1.0000
10:97430953:AG:A	acceptor_gain	1.0000
10:97430954:G:GC	acceptor_loss	1.0000
10:97430954:G:GG	acceptor_gain	1.0000
10:97430954:GG:G	acceptor_gain	1.0000
10:97430954:GGATC:G	acceptor_gain	1.0000
10:97431131:GGAGG:G	donor_gain	1.0000
10:97431132:GAGG:G	donor_gain	1.0000
10:97431132:GAGGG:G	donor_gain	1.0000
10:97431134:GG:G	donor_gain	1.0000
10:97431135:GG:G	donor_gain	1.0000
10:97431136:GTAT:G	donor_gain	1.0000
10:97432353:A:AG	acceptor_gain	1.0000
10:97432354:G:GG	acceptor_gain	1.0000
10:97437185:TCTCA:T	donor_loss	1.0000
10:97437187:TCAC:T	donor_loss	1.0000
10:97437190:C:G	donor_loss	1.0000
10:97437292:G:T	acceptor_gain	1.0000
10:97441168:TACCG:T	donor_loss	1.0000
10:97441169:A:AC	donor_gain	1.0000
10:97441169:A:C	donor_loss	1.0000
10:97441170:C:CC	donor_gain	1.0000
10:97441258:ACC:A	acceptor_loss	1.0000
10:97441260:C:CC	acceptor_gain	1.0000
10:97441260:CTGCG:C	acceptor_loss	1.0000

AlphaMissense

1260 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:97437217:C:T	G152E	1.000
10:97437713:A:T	V128D	1.000
10:97436476:G:T	A186D	0.999
10:97436481:T:A	K184N	0.999
10:97436481:T:G	K184N	0.999
10:97436485:C:G	R183P	0.999
10:97436486:G:C	R183G	0.999
10:97437205:G:T	A156D	0.999
10:97437217:C:A	G152V	0.999
10:97437218:C:G	G152R	0.999
10:97437218:C:T	G152R	0.999
10:97437707:G:T	A130D	0.999
10:97437708:C:G	A130P	0.999
10:97437719:T:A	D126V	0.999
10:97438689:C:G	R109P	0.999
10:97438692:A:T	V108D	0.999
10:97441174:A:T	I103N	0.999
10:97441180:C:T	G101E	0.999
10:97441181:C:G	G101R	0.999
10:97441181:C:T	G101R	0.999
10:97441234:G:T	A83D	0.999
10:97441258:A:T	V75D	0.999
10:97443240:A:C	C73W	0.999
10:97443242:A:G	C73R	0.999
10:97443247:A:T	V71E	0.999
10:97436483:T:C	K184E	0.998
10:97436528:A:G	W169R	0.998
10:97436528:A:T	W169R	0.998
10:97437214:A:T	V153E	0.998
10:97437220:A:G	L151P	0.998

dbSNP variants (sampled 300 via entrez): RS1000058773 (10:97446901 T>A,C), RS1000433704 (10:97438159 C>A,T), RS1000519724 (10:97443213 G>A,C), RS1000572108 (10:97443546 G>A), RS1000675822 (10:97437415 A>G), RS1001484941 (10:97447304 G>A), RS1001985859 (10:97442942 C>T), RS1002045274 (10:97437003 G>A), RS1002183876 (10:97437057 T>A,C), RS1002642834 (10:97437358 T>G), RS1002654808 (10:97439829 T>G), RS1002859793 (10:97446997 C>T), RS1003028043 (10:97441397 T>C), RS1003081941 (10:97441605 C>T), RS1003117071 (10:97440142 T>C)

Disease associations

OMIM: gene MIM:606493 | disease phenotypes: MIM:619304

GenCC curated gene-disease

Disease	Classification	Inheritance
pontocerebellar hypoplasia, type 1F	Limited	Autosomal recessive

Mondo (1): pontocerebellar hypoplasia, type 1F (MONDO:0030261)

Orphanet (0):

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000506	Telecanthus
HP:0000592	Blue sclerae
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001321	Cerebellar hypoplasia
HP:0001510	Growth delay
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0002188	Delayed CNS myelination
HP:0005280	Depressed nasal bridge
HP:0012110	Hypoplasia of the pons
HP:0012471	Thick vermilion border

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_863	Blood protein levels	6.000000e-06
GCST008178_10	Early spontaneous preterm birth	3.000000e-06
GCST008180_6	Spontaneous preterm birth with premature rupture of membranes	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006917	spontaneous preterm birth

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
deoxynivalenol	increases expression	1
beta-lapachone	increases expression	1
arsenite	increases reaction, affects binding	1
methylparaben	decreases expression, affects cotreatment	1
mono-(2-ethylhexyl)phthalate	affects expression, affects cotreatment	1
sodium arsenite	increases expression	1
monobutyl phthalate	affects cotreatment, affects expression	1
coumarin	increases phosphorylation	1
2-ethyl-5-carboxypentyl phthalate	affects cotreatment, affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
mono(2-ethyl-5-oxohexyl)phthalate	affects expression, affects cotreatment	1
mono-benzyl phthalate	affects cotreatment, affects expression, decreases expression	1
mono(2-ethyl-5-hydroxyhexyl) phthalate	affects expression, affects cotreatment, decreases expression	1
mono-isobutyl phthalate	affects cotreatment, affects expression, decreases expression	1
monoethyl phthalate	affects expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Valproic Acid	increases expression	1
Zinc	decreases expression	1
Aflatoxin B1	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1RQ	Abcam HeLa EXOSC1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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