GEMIN2

Summary

GEMIN2 (gem nuclear organelle associated protein 2, HGNC:10884) is a protein-coding gene on chromosome 14q21.1, encoding Gem-associated protein 2 (O14893). 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: 78.0% of cell lines).

This gene encodes one of the proteins found in the SMN complex, which consists of several gemin proteins and the protein known as the survival of motor neuron protein. The SMN complex is localized to a subnuclear compartment called gems (gemini of coiled bodies) and is required for assembly of spliceosomal snRNPs and for pre-mRNA splicing. This protein interacts directly with the survival of motor neuron protein and it is required for formation of the SMN complex. A knockout mouse targeting the mouse homolog of this gene exhibited disrupted snRNP assembly and motor neuron degeneration.

Source: NCBI Gene 8487 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 64 total
• Cancer dependency (DepMap): dependent in 78.0% of screened cell lines
• MANE Select transcript: NM_003616

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10884
Approved symbol	GEMIN2
Name	gem nuclear organelle associated protein 2
Location	14q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000092208
Ensembl biotype	protein_coding
OMIM	602595
Entrez	8487

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 20 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000250379, ENST00000308317, ENST00000396249, ENST00000412033, ENST00000524781, ENST00000524980, ENST00000525153, ENST00000525430, ENST00000527381, ENST00000529365, ENST00000531684, ENST00000534684, ENST00000650481, ENST00000873080, ENST00000873081, ENST00000873082, ENST00000873083, ENST00000917042, ENST00000917043, ENST00000917044, ENST00000917045, ENST00000917046, ENST00000917047, ENST00000917048, ENST00000917049, ENST00000967542, ENST00000967543

RefSeq mRNA: 3 — MANE Select: NM_003616 NM_001009182, NM_001009183, NM_003616

CCDS: CCDS32068, CCDS41946, CCDS9669

Canonical transcript exons

ENST00000308317 — 10 exons

Exon	Start	End
ENSE00002196338	39114323	39114475
ENSE00003480445	39124992	39125036
ENSE00003494487	39136440	39136973
ENSE00003547976	39118540	39118599
ENSE00003569080	39122430	39122543
ENSE00003645233	39128280	39128348
ENSE00003667129	39114829	39114913
ENSE00003671537	39117999	39118088
ENSE00003676689	39133661	39133719
ENSE00003788202	39131958	39132068

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 94.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8590 / max 169.1686, expressed in 1712 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139341	8.8590	1712

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.81	gold quality
secondary oocyte	CL:0000655	91.50	gold quality
sperm	CL:0000019	91.28	gold quality
oocyte	CL:0000023	90.27	gold quality
ventricular zone	UBERON:0003053	88.57	gold quality
male germ cell	CL:0000015	88.30	gold quality
ganglionic eminence	UBERON:0004023	86.83	gold quality
cortical plate	UBERON:0005343	86.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.41	gold quality
embryo	UBERON:0000922	85.78	gold quality
right testis	UBERON:0004534	85.37	gold quality
left testis	UBERON:0004533	85.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.11	gold quality
gastrocnemius	UBERON:0001388	85.09	gold quality
muscle of leg	UBERON:0001383	85.01	gold quality
islet of Langerhans	UBERON:0000006	84.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.53	gold quality
testis	UBERON:0000473	84.38	gold quality
cerebellar hemisphere	UBERON:0002245	84.30	gold quality
cerebellar cortex	UBERON:0002129	84.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.57	gold quality
calcaneal tendon	UBERON:0003701	83.44	gold quality
right ovary	UBERON:0002118	83.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.32	gold quality
granulocyte	CL:0000094	83.23	gold quality
left ovary	UBERON:0002119	82.83	gold quality
endocervix	UBERON:0000458	82.71	gold quality
cerebellum	UBERON:0002037	82.61	gold quality
mucosa of transverse colon	UBERON:0004991	82.48	gold quality
ectocervix	UBERON:0012249	82.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting GEMIN2, 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-4481	100.00	66.42	1669
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4319	99.76	69.83	2586

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 78.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• Spinal muscular atrophy and amyotropic lateral sclerosis patients have decreased SIP 1-alpha and increased SIP 1-beta expression levels compared to normal tissues. (PMID:11943600)
• SIP1 determines the capacity for snRNP assembly: biochemical deficiency in spinal muscular atrophy. (PMID:15964810)
• binds to HIV-1 integrase and facilitates viral cDNA synthesis and subsequent steps that precede integration in vivo (PMID:16731905)
• Gemin2 plays an important role in small nuclear ribonucleoprotein assembly through the stabilization of the survival of motor neuron oligomer/complex via novel self-interaction (PMID:17308308)
• relationship between the feature of gene mutations and single nucleotide polymorphisms of SIP1 gene and HSCR (PMID:18247312)
• SIP1 appears to stabilize functional multimer forms of IN, thereby promoting the assembly of IN and RT on viral RNA to allow efficient reverse transcription, which is a prerequisite for efficient HIV-1 infection (PMID:19915660)
• purified SMN-GEMIN2 fusion protein enhanced the RAD51-mediated homologous pairing much more efficiently than GEMIN2 alone (PMID:21732698)
• Study identified Gemin2 as the protein that binds a pentamer of Sm proteins comprised of SmD1/D2 and SmF/E/G; the crystal structure of this complex bound to SMN’s Gemin2 binding domain to 2.5 A was determined. (PMID:21816274)
• Overexpression of SIP1 and downregulation of E-cadherin is associated with delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy (PMID:21913013)
• several conserved SMN residues, including the sites of two SMA patient mutations, are not required for binding to Gemin2. Instead, they form a conserved SMN/Gemin2 surface that may be functionally important for snRNP assembly. (PMID:22607171)
• Two monoclonal antibodies against SMN (survival-of-motor-neurons) protein bind to its site of interaction with gemin2. (PMID:23939045)
• investigate the oligomeric nature of the SMN.Gemin2 complexes from humans and fission yeast (hSMN.Gemin2 and ySMN.Gemin2) (PMID:26092730)
• The authors propose that Gemin2 is a versatile hub for ribonucleoprotein exchange that functions broadly in RNA metabolism. (PMID:26828962)
• Specific mutations in the yeast Sm protein ring expose a requirement for assembly factor Brr1, a homolog of human Gemin2. (PMID:27974620)
• Here we show, using crystallographic and biochemical approaches, that Gemin2 of the SMN complex enhances RNA specificity of SmD1/D2/F/E/G via a negative cooperativity between Gemin2 and RNA in binding SmD1/D2/F/E/G. (PMID:31799625)
• Interaction between MARK3 (rs11623869), PLCB4 (rs6086746) and GEMIN2 (rs2277458) variants with bone mineral density and serum 25-hidroxivitamin D levels in Mexican Mestizo women. (PMID:38715801)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gemin2	ENSDARG00000015638
mus_musculus	Gemin2	ENSMUSG00000060121
rattus_norvegicus	Gemin2	ENSRNOG00000004360
drosophila_melanogaster	Gem2	FBGN0036850
caenorhabditis_elegans		WBGENE00004886

Protein

Protein identifiers

Gem-associated protein 2 — O14893 (reviewed: O14893)

Alternative names: Component of gems 2, Survival of motor neuron protein-interacting protein 1

All UniProt accessions (10): O14893, A0A3B3IU42, A0A8J9FJK1, A0A8J9FN78, A0A8J9FTZ9, G5EA29, H0YCF4, H0YDP6, H0YEL0, S4R421

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 (5Sm) 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. Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. Within the SMN complex, GEMIN2 constrains the conformation of 5Sm, thereby promoting 5Sm binding to snRNA containing the snRNP code (a nonameric Sm site and a 3’-adjacent stem-loop), thus preventing progression of assembly until a cognate substrate is bound.

Subunit / interactions. Monomer. 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 GEMIN5; the interaction is direct. Interacts (via C-terminus) with SMN1; the interaction is direct. Interacts with SNRPD1; the interaction is direct. Interacts with SNRPD2; the interaction is direct. Interacts (via N-terminus) with SNRPF; the interaction is direct. Interacts (via N-terminus) with SNRPE; the interaction is direct. Interacts (via N-terminus) with SNRPG; the interaction is direct.

Subcellular location. Nucleus. Gem. Cytoplasm.

Similarity. Belongs to the gemin-2 family.

Isoforms (5)

UniProt ID	Names	Canonical?
O14893-1	1, SIP1-alpha	yes
O14893-2	2, SIP1-beta
O14893-3	3, SIP1-gamma
O14893-4	4, SIP1-delta
O14893-5	5

RefSeq proteins (3): NP_001009182, NP_001009183, NP_003607* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017364	GEMIN2	Family
IPR035426	Gemin2/Brr1	Family

Pfam: PF04938

UniProt features (29 total): helix 11, splice variant 6, turn 4, mutagenesis site 2, strand 2, modified residue 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5XJL	X-RAY DIFFRACTION	2.5
5XJU	X-RAY DIFFRACTION	2.58
5XJT	X-RAY DIFFRACTION	2.92
5XJR	X-RAY DIFFRACTION	3.12
5XJQ	X-RAY DIFFRACTION	3.28
5XJS	X-RAY DIFFRACTION	3.38
2LEH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14893-F1	81.45	0.43

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): 81, 166

Mutagenesis-validated functional residues (2):

Position	Phenotype
52	impairs binding to sm complex proteins.
213	impairs binding to smn1.

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: 153 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IWANAGA_E2F1_TARGETS_INDUCED_BY_SERUM, PUJANA_CHEK2_PCC_NETWORK, MUELLER_PLURINET, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, AAAGACA_MIR511, GOBP_RNA_SPLICING, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, DING_LUNG_CANCER_EXPRESSION_BY_COPY_NUMBER, HAN_SATB1_TARGETS_DN, DANG_BOUND_BY_MYC, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS

GO Biological Process (6): spliceosomal complex assembly (GO:0000245), RNA splicing, via transesterification reactions (GO:0000375), spliceosomal snRNP assembly (GO:0000387), mRNA processing (GO:0006397), RNA splicing (GO:0008380), protein-containing complex assembly (GO:0065003)

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

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), nucleolus (GO:0005730), cytosol (GO:0005829), nuclear body (GO:0016604), SMN complex (GO:0032797), SMN-Sm protein complex (GO:0034719), Gemini of Cajal bodies (GO:0097504), cytoplasm (GO:0005737)

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
nuclear lumen	2
intracellular membraneless organelle	2
cytoplasm	2
Sm-like protein family complex	2
RNA splicing	1
mRNA metabolic process	1
cellular component assembly	1
protein-containing complex organization	1
binding	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
nucleoplasm	1
SMN-Sm protein complex	1
SMN complex	1
nuclear body	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GEMIN2	DDX20	Q9UHI6	999
GEMIN2	GEMIN5	Q8TEQ6	998
GEMIN2	GEMIN4	P57678	998
GEMIN2	STRAP	Q9Y3F4	998
GEMIN2	GEMIN6	Q8WXD5	994
GEMIN2	GEMIN7	Q9H840	993
GEMIN2	GEMIN8	Q9NWZ8	947
GEMIN2	SMN1	Q16637	931
GEMIN2	SNRPB	P14678	823
GEMIN2	HNRNPR	O43390	816
GEMIN2	SNRPD1	P13641	782
GEMIN2	COIL	P38432	779
GEMIN2	SNRPE	P08578	767
GEMIN2	SYNCRIP	O60506	714
GEMIN2	SNRPD2	P43330	707

IntAct

154 interactions, top by confidence:

A	B	Type	Score
GEMIN2	SMN1	psi-mi:“MI:0915”(physical association)	0.960
SMN1	GEMIN2	psi-mi:“MI:0914”(association)	0.960
GEMIN2	SMN1	psi-mi:“MI:0407”(direct interaction)	0.960
SMN1	GEMIN2	psi-mi:“MI:0915”(physical association)	0.960
GEMIN2	SNRPF	psi-mi:“MI:0915”(physical association)	0.910
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
GEMIN2	SNRPE	psi-mi:“MI:0914”(association)	0.770
GEMIN2	SNRPE	psi-mi:“MI:0915”(physical association)	0.770
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
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
SMN1	GEMIN2	psi-mi:“MI:0407”(direct interaction)	0.650

BioGRID (223): GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS)

ESM2 similar proteins: A0A5F9C6I2, A1L3F5, A2RT67, A4IIA7, A6NHR9, A7MBJ1, A8K855, D3ZXK7, F4JSE7, O08658, O14893, O75165, P0C8M4, P49021, Q0P410, Q3UD82, Q4R5A4, Q568D5, Q5F3F2, Q5R9R1, Q5RC14, Q5VVJ2, Q5XI20, Q5XPI3, Q5XPI4, Q5ZJK1, Q66J91, Q66KJ5, Q69Z66, Q6GPL9, Q7TMY8, Q7TNH6, Q7Z494, Q7Z6Z7, Q7ZX36, Q8BHR8, Q8CDG3, Q8CEC0, Q8CF97, Q8CGA4

Diamond homologs: O14893, O42260, Q9CQQ4, Q9QZP1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GEMIN2	“form complex”	“SMN complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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	8	70.5×	5e-12
snRNP Assembly	14	41.1×	5e-17
SARS-CoV-2 modulates host translation machinery	11	34.2×	1e-12
mRNA Splicing	15	22.9×	1e-14
mRNA Splicing - Minor Pathway	7	21.8×	1e-06
RNA Polymerase II Transcription Termination	6	18.3×	2e-05
Processing of Capped Intron-Containing Pre-mRNA	16	18.3×	2e-14
mRNA Polyadenylation	13	15.9×	7e-11

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	15	90.8×	3e-24
U2-type prespliceosome assembly	6	39.0×	8e-07
spliceosomal complex assembly	6	37.6×	8e-07
mRNA splicing, via spliceosome	18	17.2×	3e-15
RNA splicing	12	11.0×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1441 predictions. Top by Δscore:

Variant	Effect	Δscore
14:39114418:A:T	donor_gain	1.0000
14:39114446:G:GT	donor_gain	1.0000
14:39114456:G:GT	donor_gain	1.0000
14:39114457:A:T	donor_gain	1.0000
14:39114471:GTCCA:G	donor_gain	1.0000
14:39114476:G:GG	donor_gain	1.0000
14:39114892:G:GT	donor_gain	1.0000
14:39114910:TTCT:T	donor_gain	1.0000
14:39114914:G:GG	donor_gain	1.0000
14:39117989:T:TA	acceptor_gain	1.0000
14:39117997:A:AG	acceptor_gain	1.0000
14:39117998:G:GG	acceptor_gain	1.0000
14:39117998:GC:G	acceptor_gain	1.0000
14:39118084:GACAG:G	donor_gain	1.0000
14:39118085:ACAG:A	donor_gain	1.0000
14:39118086:CAG:C	donor_gain	1.0000
14:39118087:AG:A	donor_gain	1.0000
14:39118087:AGGT:A	donor_loss	1.0000
14:39118088:GG:G	donor_gain	1.0000
14:39118088:GGTA:G	donor_loss	1.0000
14:39118089:G:GG	donor_gain	1.0000
14:39118089:GTA:G	donor_loss	1.0000
14:39122428:A:AG	acceptor_gain	1.0000
14:39122429:G:GG	acceptor_gain	1.0000
14:39122481:T:G	donor_gain	1.0000
14:39122518:A:T	donor_gain	1.0000
14:39122544:G:GG	donor_gain	1.0000
14:39132066:GTG:G	donor_gain	1.0000
14:39114417:G:GT	donor_gain	0.9900
14:39114900:GT:G	donor_gain	0.9900

AlphaMissense

1821 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:39114459:T:C	Y52H	1.000
14:39114463:T:C	L53P	1.000
14:39118047:T:A	W102R	1.000
14:39118047:T:C	W102R	1.000
14:39118071:T:C	F110L	1.000
14:39118072:T:C	F110S	1.000
14:39118073:T:A	F110L	1.000
14:39118073:T:G	F110L	1.000
14:39122454:T:A	W144R	1.000
14:39122454:T:C	W144R	1.000
14:39122456:G:C	W144C	1.000
14:39122456:G:T	W144C	1.000
14:39124996:G:A	G175D	1.000
14:39125005:C:A	P178H	1.000
14:39125020:T:A	V183D	1.000
14:39131964:T:A	W214R	1.000
14:39131964:T:C	W214R	1.000
14:39131966:G:C	W214C	1.000
14:39131966:G:T	W214C	1.000
14:39136444:T:C	F270L	1.000
14:39136446:T:A	F270L	1.000
14:39136446:T:G	F270L	1.000
14:39136452:A:C	Q272H	1.000
14:39136452:A:T	Q272H	1.000
14:39114460:A:G	Y52C	0.999
14:39114469:G:C	R55P	0.999
14:39114836:G:C	A60P	0.999
14:39114855:T:A	V66D	0.999
14:39114864:C:A	A69D	0.999
14:39118049:G:C	W102C	0.999

dbSNP variants (sampled 300 via entrez): RS1000078149 (14:39116045 C>T), RS1000161232 (14:39125977 G>A), RS1000220973 (14:39115531 A>C,G), RS1000260442 (14:39131645 G>A,C), RS1000299776 (14:39119139 C>T), RS1000330499 (14:39119424 G>T), RS1000554926 (14:39113058 G>T), RS1000789668 (14:39127474 C>T), RS1000819481 (14:39133963 A>T), RS1000926961 (14:39112875 G>C), RS1000944517 (14:39127828 G>A,C), RS1001010976 (14:39120469 C>G), RS1001128286 (14:39137052 C>T), RS1001151447 (14:39126214 C>A,T), RS1001224601 (14:39115978 T>A)

Disease associations

OMIM: gene MIM:602595 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004726_7	Vitamin D levels	6.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cadmium Chloride	decreases expression	2
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	affects cotreatment, decreases expression	1
Cisplatin	decreases response to substance, increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Valproic Acid	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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