BOK

Summary

BOK (BCL2 family apoptosis regulator BOK, HGNC:1087) is a protein-coding gene on chromosome 2q37.3, encoding Bcl-2-related ovarian killer protein (Q9UMX3). Apoptosis regulator that functions through different apoptotic signaling pathways.

The protein encoded by this gene belongs to the BCL2 family, members of which form homo- or heterodimers, and act as anti- or proapoptotic regulators that are involved in a wide variety of cellular processes. Studies in rat show that this protein has restricted expression in reproductive tissues, interacts strongly with some antiapoptotic BCL2 proteins, not at all with proapoptotic BCL2 proteins, and induces apoptosis in transfected cells. Thus, this protein represents a proapoptotic member of the BCL2 family.

Source: NCBI Gene 666 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 68 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_032515

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1087
Approved symbol	BOK
Name	BCL2 family apoptosis regulator BOK
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	BCL2L9, BOKL, MGC4631
Ensembl gene	ENSG00000176720
Ensembl biotype	protein_coding
OMIM	605404
Entrez	666

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000318407, ENST00000641230, ENST00000853582, ENST00000853583, ENST00000853584, ENST00000853585, ENST00000853586, ENST00000853587, ENST00000930986, ENST00000930987, ENST00000969135, ENST00000969136

RefSeq mRNA: 1 — MANE Select: NM_032515 NM_032515

CCDS: CCDS2550

Canonical transcript exons

ENST00000318407 — 5 exons

Exon	Start	End
ENSE00001238755	241570125	241570288
ENSE00001238764	241562348	241562476
ENSE00001238774	241558745	241558993
ENSE00001238797	241559455	241559703
ENSE00001304537	241572297	241574131

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 98.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.7586 / max 403.4087, expressed in 1510 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26537	27.5109	1490
26538	3.6084	1273
26541	0.2777	151
26536	0.2766	113
26535	0.0850	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	98.32	gold quality
spinal cord	UBERON:0002240	98.08	gold quality
inferior vagus X ganglion	UBERON:0005363	97.22	gold quality
right lobe of liver	UBERON:0001114	96.75	gold quality
upper arm skin	UBERON:0004263	95.16	gold quality
substantia nigra	UBERON:0002038	94.81	gold quality
midbrain	UBERON:0001891	94.73	gold quality
medulla oblongata	UBERON:0001896	94.28	gold quality
hypothalamus	UBERON:0001898	94.25	gold quality
lower esophagus mucosa	UBERON:0035834	94.12	gold quality
subthalamic nucleus	UBERON:0001906	93.93	gold quality
adipose tissue	UBERON:0001013	93.70	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.52	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.41	gold quality
ventral tegmental area	UBERON:0002691	93.34	gold quality
putamen	UBERON:0001874	93.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.23	gold quality
omental fat pad	UBERON:0010414	93.19	gold quality
peritoneum	UBERON:0002358	93.12	gold quality
amygdala	UBERON:0001876	92.93	gold quality
superior vestibular nucleus	UBERON:0007227	92.86	gold quality
liver	UBERON:0002107	92.53	gold quality
dorsal plus ventral thalamus	UBERON:0001897	92.27	gold quality
corpus callosum	UBERON:0002336	92.27	gold quality
esophagus mucosa	UBERON:0002469	91.94	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.84	gold quality
Ammon’s horn	UBERON:0001954	91.81	gold quality
lower esophagus	UBERON:0013473	91.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.66	gold quality
fundus of stomach	UBERON:0001160	91.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, GTF3A, SRF, TCF7L2

miRNA regulators (miRDB)

51 targeting BOK, 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-4283	100.00	66.42	2097
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023

Literature-anchored findings (GeneRIF, showing 25)

• BOK and NOXA are essential mediators of p53-dependent apoptosis (PMID:15102863)
• A novel Mtd/BOK splice isoform is responsible for trophoblast cell death in pre-eclampsia. (PMID:15775999)
• Studies showed that hBok was distributed in both the cytosol and intracellular membranes of healthy cells. (PMID:15868100)
• a link between the apoptotic activity and nuclear localization of a pro-apoptotic Bok (PMID:16302269)
• Bok represents a cell cycle-regulated pro-apoptotic member of the Bcl-2 family (PMID:16772296)
• BOKAS is a natural antisense transcript that regulates the pro-apoptotic activity of human Bok (PMID:19287972)
• Data conclude that Mtd-L functions to regulate trophoblast cell proliferation during early placentation and that the elevated levels of Mtd found in PE may contribute to increased trophoblast proliferation. (PMID:19942931)
• The results suggest important roles for Bok and Bcl-X(L) in human ovarian development, follicle maturation and apoptosis. (PMID:20673843)
• Bok may govern IP3R cleavage and activity during apoptosis. (PMID:23884412)
• First evidence for a key role of the BOK-MCL1 system in regulating autophagy in the human placenta, whereby an adverse environment as seen in preeclampsia tilts the BOK-MCL1 balance toward the build-up of isoforms that triggers placental autophagy. (PMID:24113155)
• Data suggest that hypoxia-induced expression of BOK in placental cells is regulated via promoter region, hypoxia-response element, and binding of hypoxia-inducible factors (HIF1A, HIF2A/EPAS1, HIF1B/ARNT) but is not affected by its antisense transcript. (PMID:24806027)
• These results not only establish Bok as a Bak- and Bax-independent apoptosis inducer, but also suggest a potential impact of Bok expression in ovarian cancer therapy. (PMID:27076518)
• Data suggest that endoplasmic reticulum (ER) stress-induced apoptosis in hepatoma cells is regulated by highly labile and ER-associated BCL-2 family member BOK, which is controlled at level of protein stability by ER-associated degradation components; DNAJB12 is required in hepatoma cells to maintain BOK at low levels and suppress ER stress. (DNAJB12 = DnaJ (Hsp40) homolog, subfamily B, member 12) (PMID:28536268)
• Loss of BOK is associated with non-small-cell lung carcinoma. (PMID:28744854)
• These data indicate BOK as a prognostic marker in colorectal cancer. (PMID:29374142)
• CER/BOK-induced regulation of mitochondrial fission and its functional consequence for heightened trophoblast cell autophagy in preeclampsia. (PMID:29463805)
• BOK-mediated membrane permeabilization is governed in part by its unique metastability of the hydrophobic groove and helix alpha1 and not through activation by BH3 ligands. (PMID:29768206)
• BOK downregulation may be associated with tumorigenesis of testicular cancer (TC); BOK had the potency to suppress TC cell proliferation and invasion, and BOK also contributes to Cisplatin resistance. (PMID:29985192)
• Bok regulates mitochondrial fusion and morphology. (PMID:30976095)
• Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment. (PMID:31887566)
• Mcl-1 and Bok transmembrane domains: Unexpected players in the modulation of apoptosis. (PMID:33093207)
• The Mysteries around the BCL-2 Family Member BOK. (PMID:33291826)
• Bok binds to a largely disordered loop in the coupling domain of type 1 inositol 1,4,5-trisphosphate receptor. (PMID:33773141)
• The BCL-2 family member BOK promotes KRAS-driven lung cancer progression in a p53-dependent manner. (PMID:35091677)
• BCL-2 and BOK regulate apoptosis by interaction of their C-terminal transmembrane domains. (PMID:39048751)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	bokb	ENSDARG00000008807
danio_rerio	boka	ENSDARG00000052129
mus_musculus	Bok	ENSMUSG00000026278
rattus_norvegicus	Bok	ENSRNOG00000018214
drosophila_melanogaster	Debcl	FBGN0029131
drosophila_melanogaster	Buffy	FBGN0040491

Paralogs (8): BAK1 (ENSG00000030110), BAX (ENSG00000087088), BCL2L2 (ENSG00000129473), BCL2L10 (ENSG00000137875), BCL2A1 (ENSG00000140379), MCL1 (ENSG00000143384), BCL2L1 (ENSG00000171552), BCL2 (ENSG00000171791)

Protein

Protein identifiers

Bcl-2-related ovarian killer protein — Q9UMX3 (reviewed: Q9UMX3)

Alternative names: Bcl-2-like protein 9

All UniProt accessions (2): Q9UMX3, A0A024R4A8

UniProt curated annotations — full annotation on UniProt →

Function. Apoptosis regulator that functions through different apoptotic signaling pathways. Plays a roles as pro-apoptotic protein that positively regulates intrinsic apoptotic process in a BAX- and BAK1-dependent manner or in a BAX- and BAK1-independent manner. In response to endoplasmic reticulum stress promotes mitochondrial apoptosis through downstream BAX/BAK1 activation and positive regulation of PERK-mediated unfolded protein response. Activates apoptosis independently of heterodimerization with survival-promoting BCL2 and BCL2L1 through induction of mitochondrial outer membrane permeabilization, in a BAX- and BAK1-independent manner, in response to inhibition of ERAD-proteasome degradation system, resulting in cytochrome c release. In response to DNA damage, mediates intrinsic apoptotic process in a TP53-dependent manner. Plays a role in granulosa cell apoptosis by CASP3 activation. Plays a roles as anti-apoptotic protein during neuronal apoptotic process, by negatively regulating poly ADP-ribose polymerase-dependent cell death through regulation of neuronal calcium homeostasis and mitochondrial bioenergetics in response to NMDA excitation. In addition to its role in apoptosis, may regulate trophoblast cell proliferation during the early stages of placental development, by acting on G1/S transition through regulation of CCNE1 expression. May also play a role as an inducer of autophagy by disrupting interaction between MCL1 and BECN1. Pro-apoptotic molecule exerting its function through the mitochondrial pathway.

Subunit / interactions. Monomer; positively regulates apoptotic process. Homodimer. Heterodimer. Oligomer; promoted by apoptotic stimuli and BH3-only proteins; mediates constitutive activation. Interacts (via BH4 domain) with ITPR1; enhances BOK expression and stabilization; limits apoptosis and prevents ubiquitination and then degradation; protects ITPR1 from proteolysis by CASP3 during apoptosis. Interacts with ITPR2 and ITPR3; binds most strongly to ITPR2, and barely to ITPR3; regulates their expression. Interacts with XPO1; translocates to the cytoplasm. Interacts with BNIP3; promotes oligomerization.

Subcellular location. Mitochondrion membrane. Endoplasmic reticulum membrane. Mitochondrion inner membrane. Cytoplasm. Nucleus. Mitochondrion. Endoplasmic reticulum. Mitochondrion outer membrane. Early endosome membrane. Recycling endosome membrane. Nucleus outer membrane. Golgi apparatus. cis-Golgi network membrane. trans-Golgi network membrane. Membrane Membrane.

Tissue specificity. Expressed mainly in oocytes; weak expression in granulosa cells of the developing follicles. In adult human ovaries, expressed in granulosa cells at all follicular stages, but expression in primordial/primary follicles granulosa cell is stronger than in secondary and antral follicles.

Post-translational modifications. Ubiquitinated by AMFR/gp78 E3 ubiquitin ligase complex; mediates degradation by ubiquitin-proteasome pathway in a VCP/p97-dependent manner; prevents from pro-apoptotic activity; promotes degradation of newly synthesized proteins that are not ITPR1 associated.

Domain organisation. BH4 domain mediates interaction with ITPR1.

Induction. Up-regulated by DNA damage.

Similarity. Belongs to the Bcl-2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UMX3-1	1, Mtd-L	yes
Q9UMX3-2	2, Mtd-P

RefSeq proteins (1): NP_115904* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002475	Bcl2-like	Family
IPR026298	Bcl-2_fam	Family
IPR036834	Bcl-2-like_sf	Homologous_superfamily
IPR046371	Bcl-2_BH1-3	Domain

Pfam: PF00452

UniProt features (24 total): helix 8, cross-link 4, short sequence motif 4, region of interest 2, chain 1, transmembrane region 1, splice variant 1, mutagenesis site 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6CKV	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMX3-F1	83.33	0.54

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 (5): 32, 159, 176, 7, 25

Mutagenesis-validated functional residues (1):

Position	Phenotype
71–73	significantly accumulates in the nucleus. increases apoptotic activity. does not interact with xpo1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 263 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, HNF3ALPHA_Q6, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_MEMBRANE_DEPOLARIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (27): release of cytochrome c from mitochondria (GO:0001836), apoptotic process (GO:0006915), cellular component disassembly involved in execution phase of apoptosis (GO:0006921), male gonad development (GO:0008584), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), regulation of autophagy (GO:0010506), positive regulation of apoptotic process (GO:0043065), negative regulation of neuron apoptotic process (GO:0043524), oligodendrocyte differentiation (GO:0048709), protein complex oligomerization (GO:0051259), neuron apoptotic process (GO:0051402), regulation of cytosolic calcium ion concentration (GO:0051480), negative regulation of mitochondrial depolarization (GO:0051902), negative regulation of necroptotic process (GO:0060546), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), response to cisplatin (GO:0072718), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), positive regulation of execution phase of apoptosis (GO:1900119), negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway (GO:1901029), positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway (GO:1901030), regulation of chorionic trophoblast cell proliferation (GO:1901382), positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway (GO:1902237), positive regulation of PERK-mediated unfolded protein response (GO:1903899), regulation of granulosa cell apoptotic process (GO:1904708), positive regulation of intrinsic apoptotic signaling pathway (GO:2001244), regulation of apoptotic process (GO:0042981), transmembrane transport (GO:0055085)

GO Molecular Function (9): signaling receptor binding (GO:0005102), channel activity (GO:0015267), ubiquitin protein ligase binding (GO:0031625), protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), protein heterodimerization activity (GO:0046982), BH domain binding (GO:0051400), protein binding (GO:0005515), protein dimerization activity (GO:0046983)

GO Cellular Component (16): nucleus (GO:0005634), nuclear outer membrane (GO:0005640), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial inner membrane (GO:0005743), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), membrane (GO:0016020), early endosome membrane (GO:0031901), mitochondrial membrane (GO:0031966), trans-Golgi network membrane (GO:0032588), cis-Golgi network membrane (GO:0033106), recycling endosome membrane (GO:0055038), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	4
execution phase of apoptosis	3
cytoplasm	3
endomembrane system	3
organelle membrane	3
apoptotic signaling pathway	2
intrinsic apoptotic signaling pathway	2
apoptotic process	2
mitochondrial outer membrane permeabilization	2
regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	2
protein binding	2
protein dimerization activity	2
binding	2
organelle outer membrane	2
nuclear outer membrane-endoplasmic reticulum membrane network	2
cellular anatomical structure	2
mitochondrial membrane	2
endosome membrane	2
apoptotic mitochondrial changes	1
programmed cell death	1
cellular component disassembly	1
gonad development	1
development of primary male sexual characteristics	1
DNA damage response	1
autophagy	1
regulation of catabolic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
central nervous system development	1
glial cell differentiation	1
protein-containing complex assembly	1
intracellular calcium ion homeostasis	1
mitochondrial depolarization	1
regulation of mitochondrial depolarization	1
negative regulation of membrane depolarization	1
regulation of necroptotic process	1
negative regulation of programmed necrotic cell death	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BOK	MCL1	Q07820	982
BOK	BCL2	P10415	841
BOK	BCL2L10	Q9HD36	750
BOK	BIK	Q13323	721
BOK	HRK	O00198	709
BOK	PMAIP1	Q13794	667
BOK	BCL2L11	O43521	663
BOK	CASP3	P42574	629
BOK	CYCS	P00001	624
BOK	BCL2A1	Q16548	620
BOK	BCL2L14	Q9BZR8	587
BOK	BAK1	Q16611	582
BOK	BCL2L1	Q07817	564
BOK	APAF1	O14727	543
BOK	BID	P55957	516

IntAct

26 interactions, top by confidence:

A	B	Type	Score
ATP1A3	BOK	psi-mi:“MI:0915”(physical association)	0.560
DNM2	BOK	psi-mi:“MI:0915”(physical association)	0.560
ATN1	BOK	psi-mi:“MI:0915”(physical association)	0.560
HSPD1	BOK	psi-mi:“MI:0915”(physical association)	0.560
BOK	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
GDAP1	BOK	psi-mi:“MI:0915”(physical association)	0.560
NOA1	BOK	psi-mi:“MI:0915”(physical association)	0.370
TESPA1	ITPRID2	psi-mi:“MI:0914”(association)	0.350
IRAG1	ITPRID2	psi-mi:“MI:0914”(association)	0.350
BBOX1	PPL	psi-mi:“MI:0914”(association)	0.350
IRAG1	ITPR2	psi-mi:“MI:0914”(association)	0.350
TESPA1	COL1A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): BOK (Affinity Capture-MS), BCL2A1 (Two-hybrid), BOK (Affinity Capture-MS), BOK (Affinity Capture-MS), BOK (Two-hybrid), BOK (Affinity Capture-RNA), BOK (Affinity Capture-MS), BOK (Affinity Capture-MS), BOK (Affinity Capture-MS), M (Affinity Capture-Western), BOK (Affinity Capture-Western), BOK (Negative Genetic), BOK (Negative Genetic), BOK (Negative Genetic), BOK (Negative Genetic)

ESM2 similar proteins: A2AWP8, A6QL63, A6QQ47, B1AZA5, D3Z291, D3ZXD8, E1BD52, F1LQY6, O02718, O35425, P10415, P10417, Q0GA42, Q1LVW0, Q29RM4, Q32PF0, Q3B7L5, Q3UMR5, Q3UVL4, Q5E943, Q5E9V6, Q5R5M3, Q5R812, Q62784, Q68FF6, Q6GQW0, Q6IEE6, Q6IEE7, Q6ZPY2, Q792S6, Q7Z6G3, Q8IU99, Q8IW40, Q8NE86, Q8R1T1, Q8TBN0, Q8WUX9, Q91ZP9, Q96JH8, Q9BZ71

Diamond homologs: O35425, Q6DC66, Q792S6, Q7T381, Q9I8I2, Q9UMX3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	52
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
562659	GRCh37/hg19 2q37.3(chr2:239884390-242783384)x1	Pathogenic
442540	GRCh37/hg19 2q37.3(chr2:240141439-242783384)x3	Likely pathogenic

SpliceAI

856 predictions. Top by Δscore:

Variant	Effect	Δscore
2:241562343:CACA:C	acceptor_loss	1.0000
2:241562344:A:AG	acceptor_gain	1.0000
2:241562344:ACAG:A	acceptor_gain	1.0000
2:241562345:C:G	acceptor_gain	1.0000
2:241562345:CAGG:C	acceptor_loss	1.0000
2:241562346:A:AC	acceptor_loss	1.0000
2:241562346:A:AG	acceptor_gain	1.0000
2:241562346:AG:A	acceptor_gain	1.0000
2:241562346:AGGC:A	acceptor_gain	1.0000
2:241562347:G:GG	acceptor_gain	1.0000
2:241562347:G:GT	acceptor_loss	1.0000
2:241562347:GG:G	acceptor_gain	1.0000
2:241562347:GGC:G	acceptor_gain	1.0000
2:241562347:GGCG:G	acceptor_gain	1.0000
2:241562347:GGCGA:G	acceptor_gain	1.0000
2:241562473:GCAG:G	donor_gain	1.0000
2:241562475:AGG:A	donor_loss	1.0000
2:241562478:T:G	donor_loss	1.0000
2:241570120:T:TA	acceptor_gain	1.0000
2:241570122:CAG:C	acceptor_loss	1.0000
2:241570123:A:AG	acceptor_gain	1.0000
2:241570123:A:C	acceptor_loss	1.0000
2:241570123:AG:A	acceptor_gain	1.0000
2:241570124:G:GA	acceptor_gain	1.0000
2:241570124:GG:G	acceptor_gain	1.0000
2:241570124:GGC:G	acceptor_gain	1.0000
2:241570124:GGCA:G	acceptor_gain	1.0000
2:241570124:GGCAT:G	acceptor_gain	1.0000
2:241570287:GGGTG:G	donor_loss	1.0000
2:241570289:G:GA	donor_loss	1.0000

AlphaMissense

1338 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:241570133:T:A	W120R	0.999
2:241570133:T:C	W120R	0.999
2:241570135:G:C	W120C	0.999
2:241570135:G:T	W120C	0.999
2:241570286:T:A	W171R	0.999
2:241570286:T:C	W171R	0.999
2:241570288:G:C	W171C	0.999
2:241570288:G:T	W171C	0.999
2:241562456:C:A	A110D	0.998
2:241559574:G:C	A31P	0.997
2:241570287:G:C	W171S	0.997
2:241562357:T:C	L77P	0.996
2:241562380:T:G	Y85D	0.996
2:241570176:C:A	A134D	0.996
2:241559611:T:C	L43P	0.995
2:241559703:G:C	G74R	0.995
2:241570173:T:C	L133P	0.995
2:241570265:T:A	W164R	0.995
2:241570265:T:C	W164R	0.995
2:241570175:G:C	A134P	0.994
2:241559575:C:A	A31D	0.993
2:241559586:G:C	G35R	0.993
2:241562455:G:C	A110P	0.993
2:241570134:G:C	W120S	0.993
2:241570136:G:C	G121R	0.993
2:241570137:G:A	G121D	0.993
2:241570152:T:C	L126P	0.993
2:241570154:T:G	Y127D	0.993
2:241570164:C:A	A130D	0.993
2:241570267:G:C	W164C	0.993

dbSNP variants (sampled 300 via entrez): RS1000052399 (2:241562743 C>T), RS1000504861 (2:241556007 G>A,C), RS1000510401 (2:241557852 T>A), RS1000510541 (2:241565109 C>T), RS1000643349 (2:241555800 G>A), RS1000681073 (2:241551350 C>A,T), RS1000905832 (2:241565812 G>A), RS1000929515 (2:241571188 A>G), RS1000947670 (2:241561420 G>A), RS1000999794 (2:241561953 C>A,G), RS1001047874 (2:241567545 C>A,G,T), RS1001052175 (2:241561718 G>A), RS1001111948 (2:241566282 C>T), RS1001137924 (2:241561215 G>A), RS1001248313 (2:241556704 C>T)

Disease associations

OMIM: gene MIM:605404 | 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
GCST000597_2	Brain structure	6.000000e-07
GCST001942_6	Prostate cancer	5.000000e-09
GCST008839_274	Height	5.000000e-13
GCST009459_1	Planum temporale asymmetry index	8.000000e-10
GCST010653_8	Thyroid stimulating hormone levels	1.000000e-11
GCST012490_360	Femur bone mineral density x serum urate levels interaction	2.000000e-12
GCST90000025_718	Appendicular lean mass	2.000000e-19
GCST90020028_765	Hip circumference adjusted for BMI	7.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	6
bisphenol A	decreases expression, decreases methylation, affects expression	4
sodium arsenite	increases expression, decreases expression, increases abundance	2
Acetaminophen	decreases expression	2
Arsenic	increases expression, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cadmium	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
propylparaben	increases expression	1
diepoxybutane	increases expression	1
trichostatin A	increases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
usnic acid	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
buprofezin	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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