GEMIN8

Summary

GEMIN8 (gem nuclear organelle associated protein 8, HGNC:26044) is a protein-coding gene on chromosome Xp22.2, encoding Gem-associated protein 8 (Q9NWZ8). 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 selective cancer dependency (DepMap: 78.3% of cell lines).

The protein encoded by this gene is part of the SMN complex, which is necessary for spliceosomal snRNP assembly in the cytoplasm and pre-mRNA splicing in the nucleus. The encoded protein binds to both SMN1 and the GEMIN6/GEMIN7 heterodimer, mediating their interaction. This protein is found in nuclear Gemini of Cajal bodies (gems) and in the cytoplasm. Three transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 54960 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 62 total
• Cancer dependency (DepMap): dependent in 78.3% of screened cell lines
• MANE Select transcript: NM_001042479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26044
Approved symbol	GEMIN8
Name	gem nuclear organelle associated protein 8
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20514
Ensembl gene	ENSG00000046647
Ensembl biotype	protein_coding
OMIM	300962
Entrez	54960

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000332885, ENST00000380523, ENST00000398355, ENST00000460203, ENST00000477386, ENST00000680255, ENST00000850642, ENST00000889493, ENST00000889496, ENST00000889498, ENST00000889501, ENST00000889503, ENST00000915202, ENST00000915203, ENST00000915204, ENST00000915205, ENST00000915206, ENST00000965135, ENST00000965136, ENST00000965137, ENST00000965138

RefSeq mRNA: 3 — MANE Select: NM_001042479 NM_001042479, NM_001042480, NM_017856

CCDS: CCDS14159

Canonical transcript exons

ENST00000680255 — 5 exons

Exon	Start	End
ENSE00001485325	14026140	14026221
ENSE00004282434	14021464	14021511
ENSE00004282435	14029777	14029892
ENSE00004282436	14006726	14009169
ENSE00004282439	14020078	14020534

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 95.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5007 / max 74.9323, expressed in 1799 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198509	7.6516	1753
198508	5.0069	1675
198507	0.8421	576

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.79	gold quality
left ovary	UBERON:0002119	92.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.34	gold quality
right ovary	UBERON:0002118	92.33	gold quality
tibial nerve	UBERON:0001323	91.93	gold quality
body of uterus	UBERON:0009853	91.86	gold quality
descending thoracic aorta	UBERON:0002345	90.66	gold quality
left lobe of thyroid gland	UBERON:0001120	90.58	gold quality
right lobe of thyroid gland	UBERON:0001119	90.52	gold quality
left uterine tube	UBERON:0001303	90.34	gold quality
endocervix	UBERON:0000458	90.28	gold quality
adenohypophysis	UBERON:0002196	90.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.97	gold quality
lower esophagus	UBERON:0013473	89.94	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.79	gold quality
spinal cord	UBERON:0002240	89.65	gold quality
body of pancreas	UBERON:0001150	89.58	gold quality
left coronary artery	UBERON:0001626	89.47	gold quality
thoracic aorta	UBERON:0001515	89.46	gold quality
mucosa of stomach	UBERON:0001199	89.43	gold quality
ascending aorta	UBERON:0001496	89.43	gold quality
thyroid gland	UBERON:0002046	89.34	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.31	gold quality
ectocervix	UBERON:0012249	89.18	gold quality
pituitary gland	UBERON:0000007	89.07	gold quality
aorta	UBERON:0000947	89.06	gold quality
tibial artery	UBERON:0007610	89.02	gold quality
popliteal artery	UBERON:0002250	89.01	gold quality
right coronary artery	UBERON:0001625	88.89	gold quality
minor salivary gland	UBERON:0001830	88.76	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1053.44
E-MTAB-8142	yes	16.37
E-ANND-3	yes	4.70
E-MTAB-6524	no	84.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting GEMIN8, 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-8485	100.00	77.57	4731
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-153-5P	99.89	73.86	6317
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-944	99.82	70.85	3042
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-7856-5P	99.75	69.99	2901
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4677-5P	99.70	70.09	1940

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 78.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Gemin8 is a novel integral component of the SMN complex (PMID:16434402)
• 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)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gemin8	ENSDARG00000053496
mus_musculus	Gemin8	ENSMUSG00000040621
rattus_norvegicus	Gemin8	ENSRNOG00000029038
rattus_norvegicus		ENSRNOG00000068876
caenorhabditis_elegans		WBGENE00017357

Protein

Protein identifiers

Gem-associated protein 8 — Q9NWZ8 (reviewed: Q9NWZ8)

Alternative names: Protein FAM51A1

All UniProt accessions (2): Q9NWZ8, H7BYE2

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 GEMIN6; the interaction is direct. Interacts with GEMIN7; the interaction is direct. Interacts with SMN1; the interaction is direct. Interacts with GEMIN4; the interaction is direct.

Subcellular location. Nucleus. Gem. Cytoplasm.

RefSeq proteins (3): NP_001035944, NP_001035945, NP_060326 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR034754	GEMIN8	Family

Pfam: PF15348

UniProt features (12 total): helix 3, modified residue 3, compositionally biased region 2, chain 1, region of interest 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWZ8-F1	69.28	0.33

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 (3): 117, 124, 126

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: 114 (showing top): GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, P300_01, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_SPLICEOSOMAL_SNRNP_ASSEMBLY, REACTOME_METABOLISM_OF_RNA, GOCC_SMN_COMPLEX, GOCC_GEMINI_OF_CAJAL_BODIES, GOCC_NUCLEAR_BODY, GAVIN_FOXP3_TARGETS_CLUSTER_P6, LEE_RECENT_THYMIC_EMIGRANT, GOCC_SMN_SM_PROTEIN_COMPLEX, chrXp22, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_UP, GOBP_MRNA_PROCESSING

GO Biological Process (3): spliceosomal snRNP assembly (GO:0000387), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), SMN complex (GO:0032797), SMN-Sm protein complex (GO:0034719), Gemini of Cajal bodies (GO:0097504)

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
RNA processing	2
cytoplasm	2
Sm-like protein family complex	2
mRNA splicing, via spliceosome	1
protein-RNA complex assembly	1
mRNA metabolic process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
SMN-Sm protein complex	1
SMN complex	1
nuclear body	1

Protein interactions and networks

STRING

618 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GEMIN8	GEMIN7	Q9H840	968
GEMIN8	GEMIN2	O14893	947
GEMIN8	GEMIN5	Q8TEQ6	894
GEMIN8	GEMIN6	Q8WXD5	880
GEMIN8	STRAP	Q9Y3F4	862
GEMIN8	DDX20	Q9UHI6	815
GEMIN8	GEMIN4	P57678	773
GEMIN8	TCEANC	Q8N8B7	716
GEMIN8	RPS4X	P12631	533
GEMIN8	LSM10	Q969L4	513
GEMIN8	OR4X2	Q8NGF9	506
GEMIN8	SMN1	Q16637	497
GEMIN8	EGFL6	Q8IUX8	493
GEMIN8	SNRPD1	P13641	478
GEMIN8	TOE1	Q96GM8	462
GEMIN8	EIF1AX	P47813	462

IntAct

85 interactions, top by confidence:

A	B	Type	Score
SMN1	GEMIN2	psi-mi:“MI:0914”(association)	0.960
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
SNRNP70	GEMIN2	psi-mi:“MI:0914”(association)	0.640
NCKIPSD	GEMIN2	psi-mi:“MI:0914”(association)	0.640
SMN1	PRMT5	psi-mi:“MI:0914”(association)	0.600
ELAVL2	GEMIN8	psi-mi:“MI:0915”(physical association)	0.560
	GEMIN8	psi-mi:“MI:0915”(physical association)	0.560
PDLIM5	GEMIN8	psi-mi:“MI:0915”(physical association)	0.560
DDX20	GAPDHS	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SNRPF	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
GEMIN7	GEMIN2	psi-mi:“MI:0914”(association)	0.530

BioGRID (117): GEMIN8 (Affinity Capture-MS), GEMIN8 (Affinity Capture-MS), GEMIN8 (Affinity Capture-MS), GEMIN8 (Affinity Capture-MS), GEMIN8 (Affinity Capture-MS), GEMIN8 (Affinity Capture-Western), GEMIN8 (Affinity Capture-Western), GEMIN8 (Affinity Capture-Western), GEMIN8 (Affinity Capture-Western), GEMIN8 (Affinity Capture-MS), STRAP (Affinity Capture-MS), GEMIN7 (Affinity Capture-MS), SNRNP70 (Affinity Capture-MS), GEMIN8 (Affinity Capture-MS), CPNE7 (Affinity Capture-MS)

ESM2 similar proteins: A0JNN6, A2A9F4, A7MB40, A8MQ03, B5X7E4, D2HS03, E2QSX5, O60927, O95817, O95886, P07733, P97837, P97838, P97839, Q08DN6, Q13522, Q14209, Q2KJ10, Q5RD34, Q5REU9, Q5RFW2, Q5SYE7, Q5TM51, Q5VUB5, Q6AW68, Q6AY88, Q6BCB4, Q6DJE5, Q6MFY6, Q6PEI3, Q6PFD5, Q75NY9, Q7YR30, Q8BG87, Q8BHE1, Q8BJ42, Q8CAF4, Q8CBR1, Q8K3Q3, Q8NAX2

Diamond homologs: Q1LZ79, Q8BHE1, Q9NWZ8, P34399

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 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	7	83.8×	6e-11
snRNP Assembly	14	55.9×	2e-19
SARS-CoV-2 modulates host translation machinery	12	50.7×	3e-16
mRNA Splicing - Minor Pathway	5	21.1×	5e-05
mRNA Splicing	10	20.7×	1e-09
Processing of Capped Intron-Containing Pre-mRNA	11	17.1×	1e-09
mRNA Polyadenylation	10	16.6×	9e-09
SARS-CoV-2-host interactions	6	13.5×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	16	134.8×	3e-29
spliceosomal complex assembly	6	52.3×	2e-07
U2-type prespliceosome assembly	5	45.2×	8e-06
mRNA splicing, via spliceosome	14	18.6×	5e-12
RNA splicing	7	8.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

774 predictions. Top by Δscore:

Variant	Effect	Δscore
X:14009165:CCGCC:C	acceptor_gain	1.0000
X:14009166:CGCC:C	acceptor_gain	1.0000
X:14009166:CGCCC:C	acceptor_gain	1.0000
X:14009167:GCC:G	acceptor_gain	1.0000
X:14009168:CC:C	acceptor_gain	1.0000
X:14009168:CCC:C	acceptor_gain	1.0000
X:14009168:CCCTG:C	acceptor_loss	1.0000
X:14009169:CC:C	acceptor_gain	1.0000
X:14009170:C:CC	acceptor_gain	1.0000
X:14009170:C:T	acceptor_gain	1.0000
X:14009170:CT:C	acceptor_loss	1.0000
X:14009177:C:CT	acceptor_gain	1.0000
X:14020071:AACTT:A	donor_loss	1.0000
X:14020072:ACTT:A	donor_loss	1.0000
X:14020073:CTTAC:C	donor_loss	1.0000
X:14020074:TTAC:T	donor_loss	1.0000
X:14020075:T:TG	donor_loss	1.0000
X:14020076:A:AC	donor_gain	1.0000
X:14020077:C:CC	donor_gain	1.0000
X:14020077:CG:C	donor_gain	1.0000
X:14020077:CGT:C	donor_gain	1.0000
X:14020077:CGTCG:C	donor_gain	1.0000
X:14009178:A:T	acceptor_gain	0.9900
X:14009181:C:CT	acceptor_gain	0.9900
X:14020072:A:C	donor_gain	0.9900
X:14020076:ACGT:A	donor_gain	0.9900
X:14020077:CGTC:C	donor_gain	0.9900
X:14020532:TGC:T	acceptor_gain	0.9900
X:14020533:GCC:G	acceptor_loss	0.9900
X:14020535:C:CC	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008808 (X:14025345 A>C), RS1000024501 (X:14015445 G>C), RS1000077990 (X:13993702 G>A), RS1000088241 (X:14013512 T>C), RS1000196480 (X:14006939 G>A), RS1000521588 (X:14016024 T>C), RS1000669353 (X:14026280 C>G,T), RS1000710537 (X:13991644 A>G), RS1000763042 (X:13998512 A>G), RS1000982555 (X:13999715 G>A), RS1000999378 (X:14001535 C>T), RS1001039806 (X:14025637 G>A), RS1001053613 (X:13990177 T>C), RS1001082744 (X:13991060 T>C), RS1001139378 (X:14006219 G>C)

Disease associations

OMIM: gene MIM:300962 | 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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	2
Cisplatin	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
sodium arsenite	decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	increases expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Dihydrotestosterone	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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