GEMIN6

Summary

GEMIN6 (gem nuclear organelle associated protein 6, HGNC:20044) is a protein-coding gene on chromosome 2p22.1, encoding Gem-associated protein 6 (Q8WXD5). The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. It is a common-essential gene (DepMap: required in 91.6% of cancer cell lines).

GEMIN6 is part of a large macromolecular complex, localized to both the cytoplasm and the nucleus, that plays a role in the cytoplasmic assembly of small nuclear ribonucleoproteins (snRNPs). Other members of this complex include SMN (MIM 600354), GEMIN2 (SIP1; MIM 602595), GEMIN3 (DDX20; MIM 606168), GEMIN4 (MIM 606969), and GEMIN5 (MIM 607005).

Source: NCBI Gene 79833 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 91.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_024775

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20044
Approved symbol	GEMIN6
Name	gem nuclear organelle associated protein 6
Location	2p22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23459
Ensembl gene	ENSG00000152147
Ensembl biotype	protein_coding
OMIM	607006
Entrez	79833

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000281950, ENST00000409011, ENST00000409566, ENST00000911088, ENST00000911089, ENST00000937587, ENST00000937588, ENST00000954658

RefSeq mRNA: 1 — MANE Select: NM_024775 NM_024775

CCDS: CCDS1799

Canonical transcript exons

ENST00000281950 — 3 exons

Exon	Start	End
ENSE00001210471	38778972	38779118
ENSE00001290058	38781517	38785002
ENSE00001586786	38778210	38778281

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 85.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.9039 / max 357.8567, expressed in 1785 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19839	21.9039	1785

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	85.97	silver quality
right testis	UBERON:0004534	84.78	gold quality
left testis	UBERON:0004533	84.66	gold quality
islet of Langerhans	UBERON:0000006	84.59	gold quality
testis	UBERON:0000473	83.84	gold quality
oocyte	CL:0000023	83.35	gold quality
adult organism	UBERON:0007023	83.21	gold quality
mucosa of transverse colon	UBERON:0004991	82.95	gold quality
right adrenal gland	UBERON:0001233	82.52	gold quality
bronchial epithelial cell	CL:0002328	82.30	gold quality
right adrenal gland cortex	UBERON:0035827	81.95	gold quality
right lobe of liver	UBERON:0001114	81.93	gold quality
left adrenal gland	UBERON:0001234	81.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.60	gold quality
left adrenal gland cortex	UBERON:0035825	81.42	gold quality
epithelium of bronchus	UBERON:0002031	81.28	gold quality
biceps brachii	UBERON:0001507	81.10	silver quality
tendon	UBERON:0000043	81.09	gold quality
monocyte	CL:0000576	81.03	gold quality
leukocyte	CL:0000738	81.01	gold quality
granulocyte	CL:0000094	80.92	gold quality
ventricular zone	UBERON:0003053	80.87	gold quality
stromal cell of endometrium	CL:0002255	80.86	gold quality
mononuclear cell	CL:0000842	80.74	gold quality
bronchus	UBERON:0002185	80.49	gold quality
adrenal cortex	UBERON:0001235	80.32	gold quality
adrenal gland	UBERON:0002369	80.24	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	80.14	silver quality
calcaneal tendon	UBERON:0003701	79.92	gold quality
nephron tubule	UBERON:0001231	79.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.28
E-MTAB-6678	no	3.49

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 91.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• Gemin6 is a component of the SMN complex that localizes to gems and interacts with several Sm proteins of the spliceosomal snRNPs. (PMID:11748230)
• Gemin8 has an essential role in the proper structural organization of the SMN complex and the involvement of the heteromeric subunit containing Gemin6, Gemin7, Gemin8, and Unrip in the recruitment of Sm proteins to the snRNP assembly pathway (PMID:17023415)
• Gemin6 promotes c-Myc stabilisation and non-small cell lung cancer progression via accelerating AURKB mRNA maturation. (PMID:35452176)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gemin6	ENSDARG00000105394
mus_musculus	Gemin6	ENSMUSG00000055760
rattus_norvegicus	Gemin6	ENSRNOG00000027332
caenorhabditis_elegans	D1007.4	WBGENE00017002

Protein

Protein identifiers

Gem-associated protein 6 — Q8WXD5 (reviewed: Q8WXD5)

Alternative names: SIP2

All UniProt accessions (3): Q8WXD5, B8ZZ85, B9A037

UniProt curated annotations — full annotation on UniProt →

Function. The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP.

Subunit / interactions. Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG. Interacts with GEMIN7; the interaction is direct. Interacts with GEMIN8; the interaction is direct. Interacts with SNRPB, SNRPD2, SNRPD3 and SNRPE; the interaction is direct.

Subcellular location. Nucleus. Nucleoplasm. Gem. Cytoplasm.

RefSeq proteins (1): NP_079051* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009422	Gemin6	Family
IPR046856	Gemin6_C	Domain
IPR046857	Gemin6_Sm-like_dom	Domain
IPR047574	AD	Domain
IPR047575	Sm	Domain

Pfam: PF06372, PF20417

UniProt features (18 total): helix 5, strand 5, domain 2, turn 2, modified residue 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7BBL	X-RAY DIFFRACTION	1.52
1Y96	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXD5-F1	87.09	0.40

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): 95, 166

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-191859	snRNP Assembly
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery

MSigDB gene sets: 169 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, WEI_MYCN_TARGETS_WITH_E_BOX, MUELLER_PLURINET, ONKEN_UVEAL_MELANOMA_UP, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GARY_CD5_TARGETS_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_SPLICEOSOMAL_SNRNP_ASSEMBLY, GRADE_COLON_AND_RECTAL_CANCER_UP, REACTOME_METABOLISM_OF_RNA

GO Biological Process (5): spliceosomal complex assembly (GO:0000245), spliceosomal snRNP assembly (GO:0000387), mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (8): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604), SMN complex (GO:0032797), SMN-Sm protein complex (GO:0034719), Gemini of Cajal bodies (GO:0097504), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of non-coding RNA	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
mRNA splicing, via spliceosome	2
protein-RNA complex assembly	2
RNA processing	2
cytoplasm	2
Sm-like protein family complex	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
SMN-Sm protein complex	1
SMN complex	1
nuclear body	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GEMIN6	GEMIN2	O14893	994
GEMIN6	DDX20	Q9UHI6	994
GEMIN6	GEMIN7	Q9H840	993
GEMIN6	GEMIN5	Q8TEQ6	988
GEMIN6	STRAP	Q9Y3F4	964
GEMIN6	GEMIN4	P57678	941
GEMIN6	GEMIN8	Q9NWZ8	880
GEMIN6	SNRPE	P08578	668
GEMIN6	PHAX	Q9H814	624
GEMIN6	SNRPD3	P43331	596
GEMIN6	PRKAB1	Q9Y478	588
GEMIN6	SNRPB	P14678	549
GEMIN6	SNUPN	O95149	541
GEMIN6	PRKAG1	P54619	526
GEMIN6	TAX1BP3	O14907	507

IntAct

131 interactions, top by confidence:

A	B	Type	Score
GEMIN6	GEMIN7	psi-mi:“MI:0915”(physical association)	0.960
GEMIN7	GEMIN6	psi-mi:“MI:0915”(physical association)	0.960
GEMIN6	GEMIN7	psi-mi:“MI:0407”(direct interaction)	0.960
SMN1	GEMIN2	psi-mi:“MI:0914”(association)	0.960
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
GEMIN6	SNRPF	psi-mi:“MI:0407”(direct interaction)	0.810
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
GEMIN6	SNRPE	psi-mi:“MI:0407”(direct interaction)	0.760
STRAP	GEMIN6	psi-mi:“MI:0407”(direct interaction)	0.760
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
NCKIPSD	GEMIN2	psi-mi:“MI:0914”(association)	0.640
SNRNP70	GEMIN2	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640

BioGRID (145): GEMIN6 (Two-hybrid), GEMIN6 (Two-hybrid), GEMIN6 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS), GEMIN6 (Two-hybrid), GEMIN6 (Two-hybrid), GEMIN6 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS)

ESM2 similar proteins: A6QPR9, B1H2P5, B5X165, O42611, O95707, P32780, P59764, Q03123, Q08CL8, Q0VCF9, Q0VCL9, Q2KHW8, Q2KIB9, Q2T9V5, Q3MHD2, Q3TTL0, Q498D5, Q502M5, Q5JPI3, Q5M882, Q5PPG7, Q5R7B0, Q5RAT5, Q5RHQ8, Q5XH48, Q5XIA4, Q5ZML5, Q61211, Q66H33, Q6DE97, Q6GP89, Q6NSN1, Q6NU53, Q6P833, Q6PBA2, Q8BH15, Q8CG73, Q8IZC4, Q8N1I0, Q8QFR2

Diamond homologs: Q2KHW8, Q8WXD5, Q9CX53

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FUS	“up-regulates activity”	GEMIN6	relocalization
GEMIN6	“form complex”	“SMN complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
Metabolism of non-coding RNA	9	80.4×	6e-14
snRNP Assembly	14	41.7×	4e-17
SARS-CoV-2 modulates host translation machinery	12	37.9×	4e-14
mRNA Splicing - Minor Pathway	7	22.1×	9e-07
mRNA Splicing	14	21.6×	2e-13
Processing of Capped Intron-Containing Pre-mRNA	15	17.4×	4e-13
RNA Polymerase II Transcription Termination	5	15.5×	3e-04
mRNA Polyadenylation	12	14.8×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	17	111.0×	1e-29
U2-type prespliceosome assembly	7	49.1×	1e-08
spliceosomal complex assembly	6	40.6×	7e-07
mRNA splicing, via spliceosome	17	17.5×	2e-14
RNA splicing	9	8.9×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

467 predictions. Top by Δscore:

Variant	Effect	Δscore
2:38779114:GCCAA:G	donor_gain	1.0000
2:38779116:CAA:C	donor_gain	1.0000
2:38779116:CAAG:C	donor_loss	1.0000
2:38779119:GTGA:G	donor_gain	1.0000
2:38779120:T:A	donor_loss	1.0000
2:38781515:A:AG	acceptor_gain	1.0000
2:38781516:G:GG	acceptor_gain	1.0000
2:38781516:GTATT:G	acceptor_gain	1.0000
2:38778243:GTTGC:G	donor_gain	0.9900
2:38778244:TTGCT:T	donor_gain	0.9900
2:38778247:C:G	donor_gain	0.9900
2:38778267:G:GT	donor_gain	0.9900
2:38778311:T:G	donor_gain	0.9900
2:38778967:TTCA:T	acceptor_loss	0.9900
2:38778968:TCA:T	acceptor_loss	0.9900
2:38778968:TCAGA:T	acceptor_gain	0.9900
2:38778971:GATTT:G	acceptor_gain	0.9900
2:38779085:G:GT	donor_gain	0.9900
2:38779115:CCAA:C	donor_gain	0.9900
2:38779117:AA:A	donor_gain	0.9900
2:38779121:GAGT:G	donor_loss	0.9900
2:38779122:AGTA:A	donor_loss	0.9900
2:38779123:G:GG	donor_gain	0.9900
2:38781514:A:G	acceptor_gain	0.9900
2:38781516:GT:G	acceptor_gain	0.9900
2:38778311:T:TG	donor_gain	0.9800
2:38778967:TTCAG:T	acceptor_gain	0.9800
2:38778969:CA:C	acceptor_gain	0.9800
2:38778970:A:AG	acceptor_gain	0.9800
2:38778970:AG:A	acceptor_gain	0.9800

AlphaMissense

1108 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:38781824:A:C	S146R	0.990
2:38781826:C:A	S146R	0.990
2:38781826:C:G	S146R	0.990
2:38781849:G:C	R154P	0.988
2:38781717:T:C	L110P	0.984
2:38781861:T:C	L158P	0.984
2:38781792:T:A	I135K	0.981
2:38781843:T:C	L152P	0.980
2:38781852:T:A	V155D	0.979
2:38781522:T:A	V45D	0.976
2:38779024:T:A	W12R	0.973
2:38779024:T:C	W12R	0.973
2:38781786:T:C	L133P	0.973
2:38779084:G:A	G32R	0.972
2:38779084:G:C	G32R	0.972
2:38781705:T:C	L106P	0.972
2:38781792:T:G	I135R	0.970
2:38779000:T:A	W4R	0.969
2:38779000:T:C	W4R	0.969
2:38781818:T:C	C144R	0.969
2:38781848:C:A	R154S	0.969
2:38781840:T:A	I151N	0.968
2:38779091:T:A	V34D	0.964
2:38781774:T:A	V129E	0.964
2:38781525:T:C	L46P	0.963
2:38781837:T:C	I150T	0.963
2:38781820:C:G	C144W	0.962
2:38781786:T:A	L133Q	0.961
2:38781832:T:A	N148K	0.959
2:38781832:T:G	N148K	0.959

dbSNP variants (sampled 300 via entrez): RS1000035576 (2:38779692 C>A,G,T), RS1000159051 (2:38783252 A>G), RS1000538065 (2:38784789 G>A,C), RS1000981782 (2:38780958 A>G), RS1001099585 (2:38777879 G>A,T), RS1002085530 (2:38782683 G>C), RS1002415141 (2:38782986 A>C,G), RS1002828986 (2:38776417 T>G), RS1002866432 (2:38777857 T>A), RS1002919998 (2:38783556 G>A), RS1002970812 (2:38783255 T>G), RS1003022945 (2:38783061 G>A), RS1003227876 (2:38778084 A>G,T), RS1003775186 (2:38779380 GCCA>G), RS1004033154 (2:38784279 G>A,T)

Disease associations

OMIM: gene MIM:607006 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	5
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	4
Valproic Acid	increases expression, affects expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, decreases expression	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	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_B1ST	Abcam HeLa GEMIN6 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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