SEH1L

Summary

SEH1L (SEH1 like nucleoporin, HGNC:30379) is a protein-coding gene on chromosome 18p11.21, encoding Nucleoporin SEH1 (Q96EE3). Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). It is a common-essential gene (DepMap: required in 96.1% of cancer cell lines).

The protein encoded by this gene is part of a nuclear pore complex, Nup107-160. This protein contains WD repeats and shares 34% amino acid identity with yeast Seh1 and 30% identity with yeast Sec13. All constituents of the Nup107-160 complex, including this protein, specifically localize to kinetochores in mitosis. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 81929 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 68 total
• Cancer dependency (DepMap): dependent in 96.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_001013437

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30379
Approved symbol	SEH1L
Name	SEH1 like nucleoporin
Location	18p11.21
Locus type	gene with protein product
Status	Approved
Aliases	SEH1A, SEH1B, Seh1, SEC13L
Ensembl gene	ENSG00000085415
Ensembl biotype	protein_coding
OMIM	609263
Entrez	81929

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000262124, ENST00000399892, ENST00000585730, ENST00000587761, ENST00000588251, ENST00000589446, ENST00000590032, ENST00000590843, ENST00000592170, ENST00000592582, ENST00000906956, ENST00000906957, ENST00000962384, ENST00000962385, ENST00000962386

RefSeq mRNA: 2 — MANE Select: NM_001013437 NM_001013437, NM_031216

CCDS: CCDS32791, CCDS45832

Canonical transcript exons

ENST00000399892 — 9 exons

Exon	Start	End
ENSE00001496152	12986862	12987531
ENSE00002762808	12948011	12948232
ENSE00003530612	12984040	12984190
ENSE00003533210	12955463	12955609
ENSE00003560232	12982518	12982675
ENSE00003565604	12963160	12963371
ENSE00003646719	12951855	12951905
ENSE00003675989	12978752	12978892
ENSE00003785356	12971153	12971251

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.4894 / max 254.5026, expressed in 1818 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169508	29.8589	1816
208503	1.7919	956
169507	0.7548	478
169509	0.3819	173
169505	0.3031	147
169506	0.2510	79
208502	0.1478	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.53	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.01	gold quality
middle temporal gyrus	UBERON:0002771	97.52	gold quality
germinal epithelium of ovary	UBERON:0001304	96.88	gold quality
parietal pleura	UBERON:0002400	96.39	gold quality
gingival epithelium	UBERON:0001949	96.27	gold quality
secondary oocyte	CL:0000655	96.13	gold quality
esophagus squamous epithelium	UBERON:0006920	96.07	gold quality
squamous epithelium	UBERON:0006914	95.71	gold quality
pleura	UBERON:0000977	95.65	gold quality
visceral pleura	UBERON:0002401	95.62	gold quality
gingiva	UBERON:0001828	95.48	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.03	gold quality
tibia	UBERON:0000979	94.98	gold quality
tongue squamous epithelium	UBERON:0006919	94.98	gold quality
epithelium of esophagus	UBERON:0001976	94.03	gold quality
corpus epididymis	UBERON:0004359	93.95	gold quality
metanephric glomerulus	UBERON:0004736	93.88	gold quality
renal glomerulus	UBERON:0000074	93.76	gold quality
colonic mucosa	UBERON:0000317	93.76	gold quality
skin of hip	UBERON:0001554	93.64	gold quality
oocyte	CL:0000023	93.62	gold quality
primary visual cortex	UBERON:0002436	93.48	gold quality
nephron tubule	UBERON:0001231	93.23	gold quality
hair follicle	UBERON:0002073	93.21	gold quality
upper leg skin	UBERON:0004262	93.16	gold quality
cervix squamous epithelium	UBERON:0006922	92.71	silver quality
cortical plate	UBERON:0005343	92.69	gold quality
cauda epididymis	UBERON:0004360	92.58	gold quality
caput epididymis	UBERON:0004358	92.48	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	225.60
E-ANND-3	yes	6.16
E-MTAB-7303	no	146.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

187 targeting SEH1L, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4789-5P	99.98	70.76	2721
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-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• Sec13 stably interacts with Nup96 at the NPC during interphase and the shuttling of Sec13 between the nucleus and the cytoplasm may couple and regulate functions between these two compartments (PMID:14517296)
• The assembly of soluble Nup107-160 complexes into higher order structures occurs only at sites on the chromatin surface that are already covered with the nuclear envelope. (PMID:21825076)
• Analysis reveals a role for Seh1 at human centromeres, where it is required for efficient localisation of the chromosomal passenger complex (CPC). (PMID:29618633)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	seh1l	ENSDARG00000004280
mus_musculus	Seh1l	ENSMUSG00000079614
rattus_norvegicus	Seh1l	ENSRNOG00000081107
drosophila_melanogaster	Nup44A	FBGN0033247
caenorhabditis_elegans		WBGENE00003804

Paralogs (1): SEC13 (ENSG00000157020)

Protein

Protein identifiers

Nucleoporin SEH1 — Q96EE3 (reviewed: Q96EE3)

Alternative names: GATOR2 complex protein SEH1, Nup107-160 subcomplex subunit SEH1, SEC13-like protein

All UniProt accessions (5): Q96EE3, K7ELV2, K7ENI5, K7EP88, K7EPZ5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation. This subunit plays a role in recruitment of the Nup107-160 subcomplex to the kinetochore. As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway. The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex. GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1. In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation. In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex. Within the GATOR2 complex, SEC13 and SEH1L are required to stabilize the complex.

Subunit / interactions. Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex includes NUP160, NUP133, NUP107, NUP98, NUP85, NUP43, NUP37, SEH1 and SEC13. The SEH1 subunit appears to be only weakly associated with the Nup107-160 subcomplex. Component of the GATOR2 subcomplex, composed of MIOS, SEC13, SEH1L, WDR24 and WDR59. The GATOR2 complex interacts with CASTOR1 and CASTOR2; the interaction is negatively regulated by arginine. The GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction is negatively regulated by amino acids. SESN1, SESN2 and SESN3 convey leucine availability via direct interaction with SEH1L and WDR24.

Subcellular location. Chromosome. Centromere. Kinetochore. Nucleus. Nuclear pore complex. Lysosome membrane.

Activity regulation. The GATOR2 complex is negatively regulated by the upstream amino acid sensors CASTOR1 and SESN2, which sequester the GATOR2 complex in absence of amino acids. In the presence of abundant amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated.

Similarity. Belongs to the WD repeat SEC13 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96EE3-2	A, SEH1A	yes
Q96EE3-1	B, SEH1B

RefSeq proteins (2): NP_001013455, NP_112493 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR037363	Sec13/Seh1_fam	Family

Pfam: PF00400

UniProt features (16 total): repeat 6, modified residue 3, chain 1, cross-link 1, splice variant 1, sequence variant 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
9LWF	ELECTRON MICROSCOPY	3.41
9OTI	ELECTRON MICROSCOPY	3.5
9LVK	ELECTRON MICROSCOPY	3.59
7UHY	ELECTRON MICROSCOPY	3.66
9LVJ	ELECTRON MICROSCOPY	3.82
7R5K	ELECTRON MICROSCOPY	12
5A9Q	ELECTRON MICROSCOPY	23
7PEQ	ELECTRON MICROSCOPY	35
7R5J	ELECTRON MICROSCOPY	50

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EE3-F1	87.74	0.75

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 (4): 190, 12, 365, 179

Function

Pathways and Gene Ontology

Reactome pathways

42 pathways

ID	Pathway
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-159227	Transport of the SLBP independent Mature mRNA
R-HSA-159230	Transport of the SLBP Dependant Mature mRNA
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-165054	Rev-mediated nuclear export of HIV RNA
R-HSA-168271	Transport of Ribonucleoproteins into the Host Nucleus
R-HSA-168276	NS1 Mediated Effects on Host Pathways
R-HSA-168325	Viral Messenger RNA Synthesis
R-HSA-168333	NEP/NS2 Interacts with the Cellular Export Machinery
R-HSA-170822	Regulation of Glucokinase by Glucokinase Regulatory Protein
R-HSA-180746	Nuclear import of Rev protein
R-HSA-180910	Vpr-mediated nuclear import of PICs
R-HSA-191859	snRNP Assembly
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-3301854	Nuclear Pore Complex (NPC) Disassembly
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-4085377	SUMOylation of SUMOylation proteins
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4615885	SUMOylation of DNA replication proteins
R-HSA-5578749	Transcriptional regulation by small RNAs
R-HSA-5619107	Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6784531	tRNA processing in the nucleus

MSigDB gene sets: 336 (showing top): GOBP_CHROMOSOME_ORGANIZATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_VACUOLAR_MEMBRANE, TTTGTAG_MIR520D, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, GOBP_CHROMOSOME_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR

GO Biological Process (14): nucleocytoplasmic transport (GO:0006913), nuclear pore organization (GO:0006999), mitotic metaphase chromosome alignment (GO:0007080), protein transport (GO:0015031), protein-containing complex localization (GO:0031503), cellular response to nutrient levels (GO:0031669), cellular response to amino acid starvation (GO:0034198), defense response to Gram-positive bacterium (GO:0050830), mRNA transport (GO:0051028), cell division (GO:0051301), attachment of mitotic spindle microtubules to kinetochore (GO:0051315), negative regulation of TORC1 signaling (GO:1904262), positive regulation of TORC1 signaling (GO:1904263), chromosome segregation (GO:0007059)

GO Molecular Function (2): structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (13): kinetochore (GO:0000776), nuclear envelope (GO:0005635), nuclear pore (GO:0005643), lysosomal membrane (GO:0005765), cytosol (GO:0005829), nuclear pore outer ring (GO:0031080), Seh1-associated complex (GO:0035859), GATOR2 complex (GO:0061700), chromosome, centromeric region (GO:0000775), nucleus (GO:0005634), chromosome (GO:0005694), lysosome (GO:0005764), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
Interactions of Rev with host cellular proteins	2
Influenza Infection	2
SUMO E3 ligases SUMOylate target proteins	2
Cellular response to starvation	1
Antimicrobial mechanism of IFN-stimulated genes	1
Amplification of signal from the kinetochores	1
Transport of Mature Transcript to Cytoplasm	1
Late Phase of HIV Life Cycle	1
Influenza Viral RNA Transcription and Replication	1
Export of Viral Ribonucleoproteins from Nucleus	1
Glycolysis	1
Interactions of Vpr with host cellular proteins	1
Metabolism of non-coding RNA	1
Mitotic Anaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle process	2
TORC1 signaling	2
regulation of TORC1 signaling	2
intracellular membraneless organelle	2
nuclear protein-containing complex	2
cellular anatomical structure	2
protein-containing complex	2
nuclear transport	1
nucleus organization	1
protein-containing complex organization	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
macromolecule localization	1
response to nutrient levels	1
cellular response to stimulus	1
cellular response to starvation	1
response to amino acid starvation	1
defense response to bacterium	1
RNA transport	1
cellular process	1
mitotic metaphase chromosome alignment	1
attachment of spindle microtubules to kinetochore	1
negative regulation of TOR signaling	1
positive regulation of TOR signaling	1
cell cycle process	1
molecular_function	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear envelope	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1

Protein interactions and networks

STRING

1872 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEH1L	NUP107	P57740	999
SEH1L	NUP85	Q9BW27	999
SEH1L	WDR59	Q6PJI9	998
SEH1L	NUP133	Q8WUM0	997
SEH1L	WDR24	Q96S15	997
SEH1L	MIOS	Q9NXC5	997
SEH1L	NUP43	Q8NFH3	997
SEH1L	NUP160	Q12769	997
SEH1L	NUP98	P52948	996
SEH1L	NUP37	Q8NFH4	996
SEH1L	SEC13	P55735	991
SEH1L	AHCTF1	Q8WYP5	944
SEH1L	NPRL2	Q8WTW4	866
SEH1L	NUP93	Q8N1F7	835
SEH1L	NUP205	Q92621	827

IntAct

76 interactions, top by confidence:

A	B	Type	Score
TAB1	MAP3K7	psi-mi:“MI:0914”(association)	0.900
NUP43	SEH1L	psi-mi:“MI:0915”(physical association)	0.800
MIOS	SEC13	psi-mi:“MI:0914”(association)	0.790
SEC13	SEH1L	psi-mi:“MI:0915”(physical association)	0.770
SEH1L	SEC13	psi-mi:“MI:0915”(physical association)	0.770
BECN1	ZWINT	psi-mi:“MI:0914”(association)	0.750
TAB1	HSPA8	psi-mi:“MI:0914”(association)	0.740
NUP133	NUP98	psi-mi:“MI:0914”(association)	0.730
NUP85	SEH1L	psi-mi:“MI:0407”(direct interaction)	0.700
WDR24	CASTOR1	psi-mi:“MI:0914”(association)	0.690
SEC13	SEC16A	psi-mi:“MI:0914”(association)	0.640
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
NUP43	NUP98	psi-mi:“MI:0914”(association)	0.640
Nup107	NUP98	psi-mi:“MI:0915”(physical association)	0.560
SZT2	DEPDC5	psi-mi:“MI:0914”(association)	0.530
PDGFD	DCTN6	psi-mi:“MI:0914”(association)	0.530
ADIPOQ	C1QL1	psi-mi:“MI:0914”(association)	0.530
NUP43	KIF5B	psi-mi:“MI:0914”(association)	0.530
CXCL1	TRAF2	psi-mi:“MI:0914”(association)	0.530
AHCTF1	NUP98	psi-mi:“MI:0915”(physical association)	0.490
env	PGRMC1	psi-mi:“MI:0914”(association)	0.460
Nup98	NUP98	psi-mi:“MI:0915”(physical association)	0.400
NUP85	NUP98	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (226): SEH1L (Affinity Capture-MS), SEH1L (Affinity Capture-MS), SEH1L (Affinity Capture-MS), SEH1L (Affinity Capture-MS), NUP98 (Co-fractionation), SEH1L (Affinity Capture-MS), SEH1L (Proximity Label-MS), SEH1L (Proximity Label-MS), BUB1 (Affinity Capture-MS), GLE1 (Affinity Capture-MS), NUP88 (Affinity Capture-MS), NUP98 (Affinity Capture-MS), RANBP2 (Affinity Capture-MS), RANGAP1 (Affinity Capture-MS), SEC13 (Affinity Capture-MS)

ESM2 similar proteins: A7YY75, C1BK83, O60907, O89050, P17427, P18484, P61962, P61963, P97834, Q05048, Q08211, Q1JP79, Q28141, Q28D01, Q4FZW5, Q4R8H1, Q58E77, Q5BJQ6, Q5R874, Q5R8K2, Q5RAN6, Q5RB35, Q5U4Y8, Q5ZHN3, Q5ZMV7, Q640J6, Q6GL39, Q6GNF1, Q6GPC6, Q6NV31, Q6TGU2, Q6UXN9, Q7SZM9, Q8BFQ4, Q8BHJ5, Q8C6G8, Q8R2U0, Q92747, Q96EE3, Q99LC2

Diamond homologs: A1CGS0, A2QHM1, A3LNW3, A4REK3, A5DHD9, A5DXE2, A6ZQL5, A7EZJ5, A7THX0, A7YY75, A8XJ40, B0XAF3, B6H7A3, C1BK83, C1GB49, C5FWH1, G0S8H7, G0SA60, O54929, O64740, O80990, O94319, P0CS50, P0CS51, P47025, P53024, P55735, Q04491, Q0CHM0, Q0UNA9, Q0V8J1, Q0VC24, Q1DZQ0, Q2GSM6, Q2UG43, Q32LP9, Q3ZCC9, Q4FZW5, Q4PCB8, Q4WNK7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SEH1L	“form complex”	GATOR2	binding
SEH1L	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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
IPs transport between nucleus and cytosol	8	47.6×	5e-10
IP3 and IP4 transport between cytosol and nucleus	8	47.6×	5e-10
IP6 and IP7 transport between cytosol and nucleus	8	47.6×	5e-10
Transport of Ribonucleoproteins into the Host Nucleus	8	44.6×	5e-10
Regulation of Glucokinase by Glucokinase Regulatory Protein	8	44.6×	5e-10
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	8	44.6×	5e-10
Postmitotic nuclear pore complex (NPC) reformation	7	44.6×	3e-09
NEP/NS2 Interacts with the Cellular Export Machinery	8	43.3×	5e-10

GO biological processes:

GO term	Partners	Fold	FDR
nucleocytoplasmic transport	8	41.2×	1e-08
negative regulation of TORC1 signaling	6	25.6×	3e-05
cellular response to amino acid starvation	6	25.1×	3e-05
mRNA transport	6	20.8×	8e-05
protein import into nucleus	7	13.3×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1989 predictions. Top by Δscore:

Variant	Effect	Δscore
18:12948228:T:G	donor_gain	1.0000
18:12948231:AGG:A	donor_loss	1.0000
18:12948233:G:GA	donor_loss	1.0000
18:12951849:TTATA:T	acceptor_loss	1.0000
18:12951850:TATAG:T	acceptor_loss	1.0000
18:12951851:ATAGG:A	acceptor_loss	1.0000
18:12951852:TAGGT:T	acceptor_loss	1.0000
18:12951853:A:AC	acceptor_loss	1.0000
18:12951854:GGTCT:G	acceptor_gain	1.0000
18:12951906:G:GC	donor_loss	1.0000
18:12951906:G:GG	donor_gain	1.0000
18:12955452:T:TA	acceptor_gain	1.0000
18:12963155:TTTA:T	acceptor_loss	1.0000
18:12963156:TTA:T	acceptor_loss	1.0000
18:12963158:A:AG	acceptor_gain	1.0000
18:12963158:AGGT:A	acceptor_loss	1.0000
18:12963159:G:GC	acceptor_loss	1.0000
18:12963159:G:GG	acceptor_gain	1.0000
18:12964411:T:G	acceptor_gain	1.0000
18:12971148:TCTA:T	acceptor_loss	1.0000
18:12971150:TAGCT:T	acceptor_loss	1.0000
18:12971151:A:AG	acceptor_gain	1.0000
18:12971151:AGC:A	acceptor_loss	1.0000
18:12971152:G:GA	acceptor_gain	1.0000
18:12971152:GC:G	acceptor_gain	1.0000
18:12971152:GCT:G	acceptor_gain	1.0000
18:12971152:GCTC:G	acceptor_gain	1.0000
18:12971152:GCTCT:G	acceptor_gain	1.0000
18:12971249:CAGG:C	donor_loss	1.0000
18:12971250:AGG:A	donor_loss	1.0000

AlphaMissense

2780 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:12948158:G:C	D13H	1.000
18:12948159:A:T	D13V	1.000
18:12948162:T:C	L14P	1.000
18:12948165:T:A	I15N	1.000
18:12948165:T:G	I15S	1.000
18:12948167:C:G	H16D	1.000
18:12948171:A:T	D17V	1.000
18:12948174:T:A	V18D	1.000
18:12948183:A:T	D21V	1.000
18:12948191:G:A	G24R	1.000
18:12948191:G:C	G24R	1.000
18:12948191:G:T	G24W	1.000
18:12948192:G:A	G24E	1.000
18:12948192:G:T	G24V	1.000
18:12948198:G:C	R26P	1.000
18:12948203:G:C	A28P	1.000
18:12948204:C:A	A28E	1.000
18:12948207:C:T	T29I	1.000
18:12948209:T:C	C30R	1.000
18:12948210:G:A	C30Y	1.000
18:12948211:C:G	C30W	1.000
18:12948212:T:C	S31P	1.000
18:12948213:C:A	S31Y	1.000
18:12948213:C:T	S31F	1.000
18:12948215:A:C	S32R	1.000
18:12948217:C:A	S32R	1.000
18:12948217:C:G	S32R	1.000
18:12948218:G:C	D33H	1.000
18:12948218:G:T	D33Y	1.000
18:12948219:A:C	D33A	1.000

dbSNP variants (sampled 300 via entrez): RS1000020009 (18:12953172 G>T), RS1000069438 (18:12952717 T>C), RS1000114582 (18:12975110 A>C,G), RS1000153155 (18:12982405 G>A), RS1000166883 (18:12974823 C>G), RS1000176236 (18:12987544 T>C), RS1000212510 (18:12965214 G>A,T), RS1000365173 (18:12960921 G>T), RS1000429450 (18:12968358 T>C), RS1000441329 (18:12982063 G>A,T), RS1000630903 (18:12948655 G>T), RS1000668972 (18:12947178 C>A,G), RS1000683060 (18:12948847 T>A,C), RS1000980823 (18:12954602 G>A,T), RS1001048710 (18:12965747 A>G,T)

Disease associations

OMIM: gene MIM:609263 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002831_12	Lead levels in blood	2.000000e-07
GCST004525_7	Subclinical trait of interstitial lung disease (basilar peel-core ratio of high attentuation areas on CT scan)	5.000000e-08
GCST005141_27	Cognitive ability (MTAG)	7.000000e-09
GCST005142_58	Cognitive ability	3.000000e-08
GCST005316_218	Intelligence (MTAG)	2.000000e-08
GCST006979_263	Heel bone mineral density	1.000000e-09
GCST008595_215	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	1.000000e-08
GCST009207_17	Lateral ventricle volume	2.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007627	airway imaging measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009270	heel bone mineral density
EFO:0008487	lateral ventricle volume measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects expression, decreases expression	4
Nickel	decreases expression, increases expression	3
bisphenol A	decreases expression, increases methylation	2
sodium arsenite	affects binding, increases reaction, decreases expression	2
cobaltous chloride	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1

Clinical trials (associated diseases)

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