EXOSC6

Summary

EXOSC6 (exosome component 6, HGNC:19055) is a protein-coding gene on chromosome 16q22.1, encoding Exosome complex component MTR3 (Q5RKV6). 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 common-essential gene (DepMap: required in 99.1% of cancer cell lines).

This gene product constitutes one of the subunits of the multisubunit particle called exosome, which mediates mRNA degradation. The composition of human exosome is similar to its yeast counterpart. This protein is homologous to the yeast Mtr3 protein. Its exact function is not known, however, it has been shown using a cell-free RNA decay system that the exosome is required for rapid degradation of unstable mRNAs containing AU-rich elements (AREs), but not for poly(A) shortening. The exosome does not recognize ARE-containing mRNAs on its own, but requires ARE-binding proteins that could interact with the exosome and recruit it to unstable mRNAs, thereby promoting their rapid degradation.

Source: NCBI Gene 118460 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 73 total
• Cancer dependency (DepMap): dependent in 99.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_058219

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19055
Approved symbol	EXOSC6
Name	exosome component 6
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MTR3, hMtr3p, Mtr3p, EAP4, p11
Ensembl gene	ENSG00000223496
Ensembl biotype	protein_coding
OMIM	606490
Entrez	118460

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000435634

RefSeq mRNA: 1 — MANE Select: NM_058219 NM_058219

CCDS: CCDS10887

Canonical transcript exons

ENST00000435634 — 1 exons

Exon	Start	End
ENSE00001653290	70246778	70251940

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 96.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.8753 / max 100.1468, expressed in 1763 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157925	16.8753	1763

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.23	gold quality
endothelial cell	CL:0000115	93.90	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.17	gold quality
postcentral gyrus	UBERON:0002581	90.04	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.77	gold quality
primary visual cortex	UBERON:0002436	89.54	gold quality
superior frontal gyrus	UBERON:0002661	89.27	gold quality
middle temporal gyrus	UBERON:0002771	89.07	gold quality
parietal lobe	UBERON:0001872	88.70	gold quality
occipital lobe	UBERON:0002021	87.47	gold quality
calcaneal tendon	UBERON:0003701	87.22	gold quality
entorhinal cortex	UBERON:0002728	86.84	gold quality
pons	UBERON:0000988	86.82	gold quality
cortical plate	UBERON:0005343	86.81	gold quality
lateral globus pallidus	UBERON:0002476	86.79	gold quality
oviduct epithelium	UBERON:0004804	86.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.92	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.72	gold quality
nucleus accumbens	UBERON:0001882	84.53	gold quality
cerebral cortex	UBERON:0000956	84.51	gold quality
cerebellum	UBERON:0002037	84.45	gold quality
caudate nucleus	UBERON:0001873	84.15	gold quality
cerebellar cortex	UBERON:0002129	84.08	gold quality
cerebellar hemisphere	UBERON:0002245	84.06	gold quality
putamen	UBERON:0001874	83.99	gold quality
neocortex	UBERON:0001950	83.95	gold quality
frontal cortex	UBERON:0001870	83.89	gold quality
brain	UBERON:0000955	83.69	gold quality
forebrain	UBERON:0001890	83.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.31	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.70
E-MTAB-6678	yes	4.76
E-GEOD-98556	no	587.49
E-GEOD-70580	no	183.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1

miRNA regulators (miRDB)

50 targeting EXOSC6, 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-8485	100.00	77.57	4731
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-6868-5P	99.06	65.69	1284

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring. (PMID:12419256)
• We have recently identified increased expression of p11 genes that implicate fibrinolysis in ALD progression. (PMID:18289715)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	exosc6	ENSDARG00000036060
mus_musculus	Exosc6	ENSMUSG00000109941
rattus_norvegicus	Exosc6	ENSRNOG00000018582
drosophila_melanogaster	Mtr3	FBGN0036916

Paralogs (2): EXOSC5 (ENSG00000077348), EXOSC4 (ENSG00000178896)

Protein

Protein identifiers

Exosome complex component MTR3 — Q5RKV6 (reviewed: Q5RKV6)

Alternative names: Exosome component 6, mRNA transport regulator 3 homolog, p11

All UniProt accessions (1): Q5RKV6

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.

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 EXOSC1, EXOSC7 and EXOSC8. The catalytically inactive Exo-9 may associate 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 EXOSC10/RRP6, C1D/RRP47, MPHOSPH6/MPP6 and MTREX/MTR4.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Similarity. Belongs to the RNase PH family.

RefSeq proteins (1): NP_478126* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001247	ExoRNase_PH_dom1	Domain
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR027408	PNPase/RNase_PH_dom_sf	Homologous_superfamily
IPR036345	ExoRNase_PH_dom2_sf	Homologous_superfamily
IPR050080	RNase_PH	Family

Pfam: PF01138

UniProt features (24 total): strand 13, helix 5, turn 4, chain 1, region of interest 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-Q5RKV6-F1	80.97	0.42

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: 169 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_REGULATION_OF_DNA_RECOMBINATION, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, chr16q22, GOBP_B_CELL_ACTIVATION, GOMF_NUCLEASE_ACTIVITY, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_SNO_S_RNA_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_B_CELL_MEDIATED_IMMUNITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_B_CELL_MEDIATED_IMMUNITY

GO Biological Process (11): rRNA processing (GO:0006364), RNA processing (GO:0006396), RNA catabolic process (GO:0006401), rRNA catabolic process (GO:0016075), U4 snRNA 3’-end processing (GO:0034475), DNA deamination (GO:0045006), isotype switching (GO:0045190), positive regulation of isotype switching (GO:0045830), nuclear mRNA surveillance (GO:0071028), poly(A)-dependent snoRNA 3’-end processing (GO:0071051), DNA metabolic process (GO:0006259)

GO Molecular Function (1): RNA binding (GO:0003723)

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), cytosol (GO:0005829), nucleolar exosome (RNase complex) (GO:0101019), cytoplasm (GO:0005737)

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
rRNA metabolic process	2
exosome (RNase complex)	2
cytoplasm	2
intracellular anatomical structure	2
RNA processing	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA metabolic process	1
nucleic acid catabolic process	1
RNA catabolic process	1
snRNA 3’-end processing	1
DNA modification	1
somatic recombination of immunoglobulin genes involved in immune response	1
B cell activation involved in immune response	1
positive regulation of immunoglobulin production	1
positive regulation of immunoglobulin mediated immune response	1
isotype switching	1
regulation of isotype switching	1
positive regulation of DNA recombination	1
positive regulation of B cell activation	1
positive regulation of developmental process	1
nuclear-transcribed mRNA catabolic process	1
nuclear RNA surveillance	1
sno(s)RNA 3’-end processing	1
nucleic acid metabolic 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

2031 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EXOSC6	EXOSC7	Q15024	999
EXOSC6	EXOSC3	Q9NQT5	999
EXOSC6	EXOSC1	Q9Y3B2	999
EXOSC6	EXOSC9	Q06265	999
EXOSC6	EXOSC8	Q96B26	999
EXOSC6	EXOSC5	Q9NQT4	992
EXOSC6	EXOSC4	Q9NPD3	991
EXOSC6	EXOSC2	Q13868	984
EXOSC6	EXOSC10	Q01780	912
EXOSC6	SKIC2	Q15477	847
EXOSC6	MTREX	P42285	836
EXOSC6	DIS3	Q9Y2L1	823
EXOSC6	C1D	Q13901	748
EXOSC6	MPHOSPH6	Q99547	743
EXOSC6	DIS3L	Q8TF46	740

IntAct

79 interactions, top by confidence:

A	B	Type	Score
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
EXOSC3	EXOSC10	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	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
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
EXOSC7	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
EXOSC4	MTREX	psi-mi:“MI:0914”(association)	0.530
PHF10	ACTL6A	psi-mi:“MI:0914”(association)	0.530
EXOSC2	MTREX	psi-mi:“MI:0914”(association)	0.530
EXOSC4	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
EXOSC7	MTREX	psi-mi:“MI:0914”(association)	0.530
MPHOSPH6	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
DIS3L	EIF4E2	psi-mi:“MI:0914”(association)	0.530
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350

BioGRID (191): EXOSC6 (Affinity Capture-RNA), EXOSC6 (Affinity Capture-MS), EXOSC6 (Affinity Capture-MS), EXOSC6 (Affinity Capture-MS), EXOSC6 (Co-fractionation), EXOSC6 (Co-fractionation), EXOSC6 (Co-fractionation), EXOSC6 (Co-fractionation), EXOSC6 (Co-fractionation), EXOSC6 (Co-fractionation), EXOSC6 (Co-fractionation), EXOSC6 (Co-fractionation), EXOSC6 (Co-fractionation), EXOSC6 (Co-fractionation), EXOSC6 (Co-fractionation)

ESM2 similar proteins: A0A061IR73, A0A7N9VSG0, A6QQ74, D3ZX08, D4A2B7, O08644, O43542, P11086, P41226, P52785, P54777, Q002B5, Q02846, Q08DH8, Q08DM2, Q13608, Q14CH7, Q28F19, Q2KIR4, Q2KJ24, Q2V057, Q3SZ07, Q3UQ84, Q3ZBE0, Q4KM32, Q568Y2, Q5JTZ9, Q5RE82, Q5RKV6, Q5ST30, Q5TM74, Q68FW7, Q6MG21, Q6P0I8, Q767M3, Q86U10, Q8BTW3, Q8N5L8, Q8N8Q3, Q8TDZ2

Diamond homologs: A0RXU1, A1AHH4, A1KID0, A1RST0, A1TY30, A2BKC0, A2RVK7, A3MUP1, A4QGQ6, A4WM67, A4Y0L7, A5G3S1, A5IMM8, A5N2V9, A5U240, A5WB10, A6VLF1, A7ZTJ4, A8WQQ5, A9A5C9, B0KQ94, B1J4L4, B1LBY0, B1LK80, B1Y978, B1YI57, B2TJ05, B2TTV7, B2UZ31, B5YEU4, B5YWE1, B6I3M0, B6YSI2, B7IE23, B7UM50, B8E0G7, B8ZR59, B9DWL2, B9K8Y9, C1A1V2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EXOSC6	“form complex”	Exosome_Complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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	7	102.0×	2e-11
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA	7	90.6×	3e-11
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	7	90.6×	3e-11
KSRP (KHSRP) binds and destabilizes mRNA	7	90.6×	3e-11
Nuclear RNA decay	14	88.2×	2e-22
ATF4 activates genes in response to endoplasmic reticulum stress	8	66.6×	2e-11
Major pathway of rRNA processing in the nucleolus and cytosol	15	18.9×	2e-13
rRNA processing in the nucleus and cytosol	5	16.4×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
maturation of 5.8S rRNA	5	92.4×	8e-08
rRNA catabolic process	5	87.0×	1e-07
RNA catabolic process	10	79.9×	1e-14
nuclear-transcribed mRNA catabolic process	5	67.2×	4e-07
RNA processing	10	38.4×	1e-11
rRNA processing	12	29.8×	1e-12
mRNA splicing, via spliceosome	5	8.0×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

197 predictions. Top by Δscore:

Variant	Effect	Δscore
16:70250978:T:TA	donor_gain	0.9900
16:70250889:G:A	donor_gain	0.9500
16:70250957:C:CT	donor_gain	0.9500
16:70250979:C:A	donor_gain	0.9200
16:70250907:AGTC:A	donor_gain	0.9100
16:70251290:T:TA	donor_gain	0.9100
16:70250852:TC:T	donor_gain	0.9000
16:70250853:CC:C	donor_gain	0.9000
16:70250998:A:AC	donor_gain	0.8900
16:70250999:C:CC	donor_gain	0.8900
16:70247232:T:TG	acceptor_gain	0.8800
16:70250910:C:CA	donor_gain	0.8800
16:70250970:AGGGC:A	donor_gain	0.8700
16:70248053:T:TG	acceptor_gain	0.8600
16:70248054:C:G	acceptor_gain	0.8500
16:70250856:C:CT	donor_gain	0.8500
16:70250932:CCAT:C	donor_gain	0.8500
16:70247233:C:G	acceptor_gain	0.8400
16:70250955:A:AT	donor_gain	0.8400
16:70250968:T:C	donor_gain	0.8400
16:70251234:C:CT	donor_gain	0.8300
16:70251235:C:CT	donor_gain	0.8200
16:70248055:A:T	acceptor_gain	0.8100
16:70249397:C:CT	acceptor_gain	0.8000
16:70250958:C:CT	donor_gain	0.7900
16:70250917:CCAG:C	donor_gain	0.7800
16:70250952:T:TA	donor_gain	0.7800
16:70248054:C:CT	acceptor_gain	0.7700
16:70250854:C:CT	donor_gain	0.7700
16:70250900:T:TA	donor_gain	0.7700

AlphaMissense

1671 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:70251718:C:A	K61N	0.996
16:70251718:C:G	K61N	0.996
16:70251586:G:C	F105L	0.993
16:70251586:G:T	F105L	0.993
16:70251588:A:G	F105L	0.993
16:70251368:T:A	D178V	0.992
16:70251743:G:T	A53D	0.992
16:70251750:C:G	G51R	0.992
16:70251157:G:C	C248W	0.991
16:70251158:C:T	C248Y	0.991
16:70251171:C:G	G244R	0.991
16:70251387:C:G	A172P	0.991
16:70251407:G:T	A165D	0.990
16:70251750:C:A	G51C	0.990
16:70251709:A:C	C64W	0.989
16:70251170:C:T	G244D	0.988
16:70251357:C:G	G182R	0.988
16:70251710:C:T	C64Y	0.988
16:70251747:A:G	S52P	0.988
16:70251398:G:T	A168D	0.986
16:70251159:A:G	C248R	0.985
16:70251260:G:T	A214E	0.985
16:70251369:C:A	D178Y	0.985
16:70251369:C:G	D178H	0.985
16:70251744:C:G	A53P	0.985
16:70251749:C:T	G51D	0.985
16:70251251:G:T	P217H	0.984
16:70251741:A:C	Y54D	0.984
16:70251356:C:T	G182D	0.983
16:70251392:G:T	A170D	0.982

dbSNP variants (sampled 300 via entrez): RS1000072923 (16:70252699 T>C), RS1000234239 (16:70248139 C>T), RS1000402983 (16:70251990 G>A,T), RS1001697904 (16:70248730 G>A), RS1002150088 (16:70248522 G>A), RS1002341112 (16:70252087 T>C), RS1002861882 (16:70253531 C>A,T), RS1004036997 (16:70247866 C>G), RS1004142196 (16:70250537 C>T), RS1004161471 (16:70252125 G>A), RS1004215271 (16:70252429 T>C), RS1004288370 (16:70251695 G>C), RS1005699847 (16:70252487 C>T), RS1006290269 (16:70253737 T>C), RS1006596694 (16:70249311 T>A,C,G)

Disease associations

OMIM: gene MIM:606490 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010703_100	Brain morphology (MOSTest)	2.000000e-40
GCST010725_47	Malaria	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects cotreatment, increases abundance, increases expression	5
Cyclosporine	decreases expression, increases expression	4
Cadmium Chloride	increases expression	2
methylmercuric chloride	decreases expression	1
sodium arsenate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
hydroquinone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
2-palmitoylglycerol	increases expression	1
entinostat	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Naphthoquinones	increases expression	1
Ribonucleotides	affects binding	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1WQ	HAP1 EXOSC6 (-) 1	Cancer cell line	Male
CVCL_E1WR	HAP1 EXOSC6 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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