CDKN3

Summary

CDKN3 (cyclin dependent kinase inhibitor 3, HGNC:1791) is a protein-coding gene on chromosome 14q22.2, encoding Cyclin-dependent kinase inhibitor 3 (Q16667). May play a role in cell cycle regulation.

The protein encoded by this gene belongs to the dual specificity protein phosphatase family. It was identified as a cyclin-dependent kinase inhibitor, and has been shown to interact with, and dephosphorylate CDK2 kinase, thus prevent the activation of CDK2 kinase. This gene was reported to be deleted, mutated, or overexpressed in several kinds of cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1033 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_005192

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1791
Approved symbol	CDKN3
Name	cyclin dependent kinase inhibitor 3
Location	14q22.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP, CDI1
Ensembl gene	ENSG00000100526
Ensembl biotype	protein_coding
OMIM	123832
Entrez	1033

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000216414, ENST00000335183, ENST00000395577, ENST00000442975, ENST00000458126, ENST00000541304, ENST00000543789, ENST00000555837, ENST00000556102, ENST00000556305, ENST00000891179, ENST00000891180, ENST00000929365, ENST00000929366, ENST00000929367, ENST00000929368, ENST00000929369

RefSeq mRNA: 3 — MANE Select: NM_005192 NM_001130851, NM_001330173, NM_005192

CCDS: CCDS45109, CCDS81804, CCDS9716

Canonical transcript exons

ENST00000335183 — 8 exons

Exon	Start	End
ENSE00001233458	54399894	54399976
ENSE00003540975	54417848	54417951
ENSE00003560296	54401524	54401579
ENSE00003561728	54415899	54415930
ENSE00003571661	54411484	54411706
ENSE00003624252	54419992	54420218
ENSE00003662713	54408745	54408789
ENSE00003847302	54397007	54397077

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5458 / max 531.7996, expressed in 1679 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139636	22.4542	1633
139637	4.7470	1164
139635	1.3446	736

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.65	gold quality
sperm	CL:0000019	98.52	gold quality
right testis	UBERON:0004534	98.49	gold quality
male germ cell	CL:0000015	97.99	gold quality
testis	UBERON:0000473	97.02	gold quality
adult organism	UBERON:0007023	96.76	gold quality
ventricular zone	UBERON:0003053	95.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.11	gold quality
endometrium epithelium	UBERON:0004811	93.37	gold quality
ganglionic eminence	UBERON:0004023	92.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.03	gold quality
buccal mucosa cell	CL:0002336	90.51	gold quality
bone marrow	UBERON:0002371	89.02	gold quality
embryo	UBERON:0000922	88.88	gold quality
trabecular bone tissue	UBERON:0002483	88.63	gold quality
mucosa of transverse colon	UBERON:0004991	87.81	gold quality
rectum	UBERON:0001052	86.74	gold quality
stromal cell of endometrium	CL:0002255	83.89	gold quality
bone marrow cell	CL:0002092	83.31	gold quality
vermiform appendix	UBERON:0001154	83.30	gold quality
lower esophagus mucosa	UBERON:0035834	82.18	gold quality
esophagus mucosa	UBERON:0002469	81.61	gold quality
lymph node	UBERON:0000029	80.94	gold quality
tongue squamous epithelium	UBERON:0006919	80.04	silver quality
caecum	UBERON:0001153	79.66	gold quality
adrenal tissue	UBERON:0018303	77.94	gold quality
gingival epithelium	UBERON:0001949	77.60	gold quality
right atrium auricular region	UBERON:0006631	76.71	gold quality
oral cavity	UBERON:0000167	76.41	gold quality
duodenum	UBERON:0002114	76.12	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	706.35
E-MTAB-6379	yes	504.89
E-MTAB-10290	yes	414.07
E-GEOD-99795	yes	381.19
E-MTAB-7052	yes	316.39
E-HCAD-13	yes	277.52
E-MTAB-8495	yes	241.50
E-MTAB-10855	yes	226.09
E-HCAD-6	yes	203.16
E-HCAD-1	yes	43.05
E-GEOD-134144	yes	30.22
E-HCAD-10	yes	24.33
E-GEOD-125970	yes	23.17
E-MTAB-6678	yes	7.72
E-ANND-3	yes	7.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PAX1, YBX1

miRNA regulators (miRDB)

15 targeting CDKN3, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-4456	97.50	64.88	1678

Literature-anchored findings (GeneRIF, showing 39)

• Identification of a KAP domain that interacts with cyclin-dependent kinase 2. (PMID:12745075)
• In choline-deficient neuroblastoma cells, the promoter of the cyclin-dependent kinase inhibitor 3 gene (CDKN3) was hypomethylated. This was associated with increased expression of CDKN3 gene product kinase-associated phosphatase (KAP) (PMID:15147518)
• HTm4 binding to KAP.Cdk2.cyclin A complex enhances the phosphatase activity of KAP, dissociates cyclin A, and facilitates KAP dephosphorylation of Cdk2 (PMID:15671017)
• Pax3 represses transcription through a novel mechanism involving competition between corepressor KAP1 and the heterochromatin-binding protein HP1gamma (PMID:16945326)
• the reduction of KAP1 levels promotes p53-dependent p21 induction and inhibits cell proliferation in actinomycin D-treated cells. (PMID:17056014)
• IKKalpha, IKKbeta, RANK, Maspin, c-FLIP, Cip2 and cyclinD1 were found to show significant differences between hepatocellular tumor tissue and its corresponding adjacent tissue. (PMID:19728335)
• cyclin-dependent kinase-associated protein phosphatase expression was associated with poorly differentiated Renal cell carcinoma (PMID:21396835)
• analysis of CDKN3 cell cycle networks and the molecular mechanism of non-malignancy associated hepatitis/cirrhosis and HCC transformation (PMID:21535270)
• These results suggest that CDKN3 acts as an oncogene in human hepatocellular carcinoma and antagonism of CDKN3 may be of interest for the treatment of HCC. (PMID:22390936)
• KAP is overexpressed in alcohol-related hepatocellular carcinoma. (PMID:23292002)
• High CDKN3 expression is associated with cervical cancer. (PMID:23405241)
• RelB activation is key for promoting multiple myeloma cell survival through the upregulation of anti-apoptotic proteins, in particular, CIAP2. (PMID:23555623)
• CDKN3 controls mitosis through the CDC2 signaling axis. (PMID:23775190)
• CDKN3 may play an important role in the development and proliferation of epithelial ovarian cancer (PMID:24573179)
• these data identify KAP as a major regulator of cell division via interactions with numerous target proteins. aberrant splicing or miR-26a decreases KAP expression to promote glioblastoma growth and invasion. (PMID:24704824)
• These results highlight the importance of CDKN3 in Bcr-Abl-mediated leukemogenesis. (PMID:25360622)
• High CDKN3 expression is associated with colorectal cancer. (PMID:25735390)
• CDKN3 knockdown reduces cell proliferation, invasion and promotes apoptosis in human ovarian cancer cells. (PMID:26191143)
• CDKN3 mRNA may be a good survival biomarker and potential therapeutic target in cervical cancer (PMID:26372210)
• CDKN3 overexpression in lung adenocarcinoma is not attributed to alternative splicing or mutation but is likely due to increased mitotic activity, arguing against CDKN3 as a tumour suppressor (PMID:26554648)
• Knockdown of Cdkn3 stabilizes Mps1 at centrosomes. (PMID:26586430)
• CDKN3 may act as a tumor suppressor in liver tissues by modulation of the cell survival signal transduction, monitoring carcinogenesis and elimination of abnormal cells. (PMID:27314282)
• CDKN3 is frequently upregulated in gastric cancer tissues and cell lines and is related to advanced clinical stage, recurrence, and poor clinical outcome in gastric cancer. The functional data strongly suggest that CDKN3 behaves as an oncogene in gastric cancer, and downregulation of CDKN3 could inhibit gastric cancer cell proliferation, migration, and invasion, and induce cell cycle arrest and apoptosis. (PMID:27983933)
• Results demonstrate that upregulation of p27 is involved in the knockdown of CDKN3-induced decrease in cell proliferation, increase in cell cycle arrest and apoptosis, decrease in invasion, and increase in radiosensitivity. (PMID:28109073)
• the mechanism of CDKN3 overexpression in human cancer (PMID:28504190)
• The aberrant expression of miR-181d-5p and cyclin-dependent kinase inhibitor 3 (CDKN3) in non-small-cell lung cancer (NSCLC) was screened by microarray analysis. There was a high expression of CDKN3, whereas miR-181d-5p was downregulated in NSCLC. (PMID:30628487)
• NEAT1 may exert a protective effect on HUVECs by regulating the miR-181d-5p/CDKN3A axis (PMID:31352814)
• CDKN3 regulates cisplatin resistance to colorectal cancer through TIPE1. (PMID:32329836)
• CDKN3 expression predicates poor prognosis and regulates adriamycin sensitivity in hepatocellular carcinoma in vitro. (PMID:32721244)
• Integrated transcriptomics explored the cancer-promoting genes CDKN3 in esophageal squamous cell cancer. (PMID:34044866)
• Identification of cell cycle-associated and -unassociated regulators for expression of a hepatocellular carcinoma oncogene cyclin-dependent kinase inhibitor 3. (PMID:35944363)
• GID2 Interacts With CDKN3 and Regulates Pancreatic Cancer Growth and Apoptosis. (PMID:36828188)
• PSMD12 interacts with CDKN3 and facilitates pancreatic cancer progression. (PMID:37037907)
• Identifying key genes related to inflammasome in severe COVID-19 patients based on a joint model with random forest and artificial neural network. (PMID:37113134)
• Cyclin dependent kinase inhibitor 3 (CDKN3) upregulation is associated with unfavorable prognosis in clear cell renal cell carcinoma and shapes tumor immune microenvironment: A bioinformatics analysis. (PMID:37682177)
• MicroRNA-127-3p Inhibits Cardiomyocyte Inflammation and Apoptosis after Acute Myocardial Infarction via Targeting CDKN3. (PMID:38030294)
• Human pan-cancer analysis of the predictive biomarker for the CDKN3. (PMID:38720365)
• N6-Methyladenosine modified circ-NAB1 modulates cell cycle and epithelial-mesenchymal transition via CDKN3 in endometrial cancer. (PMID:38814199)
• Integrative analysis of anoikis-related genes prognostic signature with immunotherapy and identification of CDKN3 as a key oncogene in lung adenocarcinoma. (PMID:39383787)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdkn3	ENSDARG00000039130
mus_musculus	Cdkn3	ENSMUSG00000037628
rattus_norvegicus	Cdkn3	ENSRNOG00000009785

Paralogs (8): CDC14A (ENSG00000079335), CDC14B (ENSG00000081377), PALD1 (ENSG00000107719), PTP4A1 (ENSG00000112245), PTPDC1 (ENSG00000158079), PTP4A2 (ENSG00000184007), PTP4A3 (ENSG00000184489), CDC14C (ENSG00000218305)

Protein

Protein identifiers

Cyclin-dependent kinase inhibitor 3 — Q16667 (reviewed: Q16667)

Alternative names: CDK2-associated dual-specificity phosphatase, Cyclin-dependent kinase interactor 1, Cyclin-dependent kinase-interacting protein 2, Kinase-associated phosphatase

All UniProt accessions (7): Q16667, F5H232, F8WD24, G3V1K6, G3V2J7, H7C0S3, Q86SK8

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in cell cycle regulation. Dual specificity CC phosphatase active toward substrates containing either phosphotyrosine or phosphoserine residues. Dephosphorylates CDK2 at ‘Thr-160’ in a cyclin-dependent manner.

Subunit / interactions. Interacts with cyclin-dependent kinases such as CDK1, CDK2 and CDK3. Does not interact with CDK4. Interacts (via C-terminus) with phosphorylated CDK2 (via C-terminal helix). Interacts with MS4A3 (via C-terminus); the interaction enhances CDKN3 enzymatic activity.

Subcellular location. Cytoplasm. Perinuclear region.

Disease relevance. Hepatocellular carcinoma (HCC) [MIM:114550] A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. The gene represented in this entry may be involved in disease pathogenesis.

Induction. Up-regulated in breast and prostate cancer cells.

Similarity. Belongs to the protein-tyrosine phosphatase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16667-1	1	yes
Q16667-2	2

RefSeq proteins (3): NP_001124323, NP_001317102, NP_005183* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR008425	CDK_inhib_3	Family
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR022778	CDKN3	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR050561	PTP	Family

Pfam: PF05706

Catalyzed reactions (Rhea), 3 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (36 total): sequence variant 10, helix 9, strand 7, sequence conflict 2, region of interest 2, chain 1, domain 1, turn 1, compositionally biased region 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1FPZ	X-RAY DIFFRACTION	2
1FQ1	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16667-F1	91.18	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 140 (phosphocysteine intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 308 (showing top): MODULE_52, HORIUCHI_WTAP_TARGETS_DN, BROWNE_HCMV_INFECTION_6HR_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, GOBP_REGULATION_OF_PHOSPHORYLATION, CROONQUIST_NRAS_SIGNALING_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, PRAMOONJAGO_SOX4_TARGETS_DN

GO Biological Process (6): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), G1/S transition of mitotic cell cycle (GO:0000082), negative regulation of cell population proliferation (GO:0008285), regulation of cell cycle (GO:0051726), protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311)

GO Molecular Function (6): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	3
cellular anatomical structure	3
cytoplasm	2
cyclin-dependent protein serine/threonine kinase activity	1
regulation of protein serine/threonine kinase activity	1
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell cycle	1
regulation of cellular process	1
dephosphorylation	1
protein modification process	1
phosphate-containing compound metabolic process	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3290 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDKN3	CDK2	P24941	984
CDKN3	CDKN1A	P38936	947
CDKN3	CDK6	Q00534	877
CDKN3	TP53	P04637	850
CDKN3	CDKN2A	P42771	835
CDKN3	CCNL2	Q96S94	794
CDKN3	CDK4	P11802	790
CDKN3	CDKN1B	P46527	782
CDKN3	MDM2	Q00987	771
CDKN3	CDKN1C	P49918	749
CDKN3	TCHP	Q9BT92	729
CDKN3	CCNA2	P20248	726
CDKN3	CDKN2B	P42772	714
CDKN3	CCNA1	P78396	704
CDKN3	CDK1	P06493	688

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CDK2	CCNE2	psi-mi:“MI:0914”(association)	0.940
CDK2	CDKN3	psi-mi:“MI:0407”(direct interaction)	0.930
CDKN3	CDK2	psi-mi:“MI:0915”(physical association)	0.930
CDKN3	CDK2	psi-mi:“MI:0203”(dephosphorylation reaction)	0.930
CDK2	CCNB1	psi-mi:“MI:0914”(association)	0.890
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
CDK2	GMNN	psi-mi:“MI:0914”(association)	0.640
CDKN3	CDK1	psi-mi:“MI:0915”(physical association)	0.550
CDKN3	CDK3	psi-mi:“MI:0915”(physical association)	0.550
CDKN3	ARK2N	psi-mi:“MI:0915”(physical association)	0.500
CDKN3	CDC28	psi-mi:“MI:0915”(physical association)	0.370
CDKN3	CST8	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): CDKN3 (Affinity Capture-MS), CDKN3 (Affinity Capture-MS), CDKN3 (Affinity Capture-MS), CDKN3 (Affinity Capture-Western), ROCK2 (Affinity Capture-Western), ROCK1 (Affinity Capture-Western), CDC42BPB (Affinity Capture-Western), ROCK2 (Reconstituted Complex), ROCK2 (Co-localization), PPP1R12A (Biochemical Activity), CDKN3 (Affinity Capture-MS), RAD23B (Affinity Capture-MS), CLPB (Affinity Capture-MS), GOPC (Affinity Capture-MS), RAD23A (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, B2RZ50, E9Q4Z2, G4LTX4, O08586, O42099, O54857, O60733, O82656, O88712, O94806, P29074, P60483, P60484, P97570, P97819, Q02384, Q07832, Q07890, Q16667, Q1PET6, Q4R678, Q5BIP9, Q5F361, Q5F480, Q5IH13, Q5IH14, Q5RF15, Q5VNW5, Q641K1, Q66H63, Q6AXW7, Q6NRC7, Q6NU47, Q6NU98, Q810P3, Q8BM85, Q8K1Y2, Q8NEJ0, Q8TEA7

Diamond homologs: B2RZ50, Q16667, Q810P3, Q9MYN5, Q91FX3, A1L1R5, A2A3K4, A7E379, O94526, Q196Z3, Q6NZK8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDKN3	“down-regulates activity”	CDK2	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1379 predictions. Top by Δscore:

Variant	Effect	Δscore
14:54397074:GCCG:G	donor_gain	1.0000
14:54399892:A:AG	acceptor_gain	1.0000
14:54399893:G:GG	acceptor_gain	1.0000
14:54399893:GCCCA:G	acceptor_gain	1.0000
14:54417837:T:G	acceptor_gain	1.0000
14:54417837:T:TA	acceptor_gain	1.0000
14:54417843:A:AG	acceptor_gain	1.0000
14:54417844:T:G	acceptor_gain	1.0000
14:54417846:A:AG	acceptor_gain	1.0000
14:54417847:G:GG	acceptor_gain	1.0000
14:54417847:GT:G	acceptor_gain	1.0000
14:54417847:GTA:G	acceptor_gain	1.0000
14:54417847:GTAGC:G	acceptor_gain	1.0000
14:54397075:CCGG:C	donor_loss	0.9900
14:54397077:GGT:G	donor_loss	0.9900
14:54397078:G:GG	donor_gain	0.9900
14:54397078:GT:G	donor_loss	0.9900
14:54397079:T:A	donor_loss	0.9900
14:54397080:GA:G	donor_loss	0.9900
14:54399889:T:TA	acceptor_gain	0.9900
14:54399893:GCC:G	acceptor_gain	0.9900
14:54411449:T:G	acceptor_gain	0.9900
14:54411466:ATCCT:A	acceptor_gain	0.9900
14:54411470:T:TA	acceptor_gain	0.9900
14:54411660:G:GT	donor_gain	0.9900
14:54411707:G:GG	donor_gain	0.9900
14:54417836:AT:A	acceptor_gain	0.9900
14:54417842:CATTA:C	acceptor_loss	0.9900
14:54417843:ATTAG:A	acceptor_loss	0.9900
14:54417844:TTAGT:T	acceptor_loss	0.9900

AlphaMissense

1357 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:54411527:C:G	C79W	0.997
14:54417938:T:A	I180K	0.997
14:54408745:G:A	G50D	0.996
14:54408753:T:C	F53L	0.996
14:54408755:T:A	F53L	0.996
14:54408755:T:G	F53L	0.996
14:54415910:G:A	G143E	0.996
14:54415926:T:G	C148W	0.996
14:54401579:G:C	G50R	0.995
14:54411541:T:C	L84P	0.995
14:54415900:T:C	C140R	0.995
14:54415920:A:C	R146S	0.995
14:54415920:A:T	R146S	0.995
14:54415922:C:T	S147F	0.995
14:54417938:T:G	I180R	0.995
14:54411525:T:C	C79R	0.994
14:54411526:G:A	C79Y	0.994
14:54417851:C:A	A151D	0.994
14:54401562:G:A	G44D	0.993
14:54401574:T:A	L48H	0.993
14:54408770:A:C	R58S	0.993
14:54408770:A:T	R58S	0.993
14:54411667:T:C	L126P	0.993
14:54411703:T:A	I138K	0.993
14:54415916:G:A	G145E	0.993
14:54415916:G:T	G145V	0.993
14:54417860:T:C	L154P	0.993
14:54417914:G:C	R172P	0.993
14:54408745:G:T	G50V	0.992
14:54415919:G:C	R146T	0.992

dbSNP variants (sampled 300 via entrez): RS1000135183 (14:54396336 G>A), RS1000215363 (14:54415152 C>A,T), RS1000243950 (14:54408547 C>T), RS1000692666 (14:54410166 A>G), RS1000819465 (14:54403535 T>A), RS1000828314 (14:54414740 G>A,T), RS1000880809 (14:54414960 T>G), RS1001189578 (14:54403769 A>G), RS1001195138 (14:54413490 A>C), RS1001317999 (14:54407626 G>A), RS1001360317 (14:54401901 A>G), RS1001640136 (14:54395854 A>G), RS1001925805 (14:54395909 T>C), RS1002381096 (14:54397166 T>C), RS1002391572 (14:54414674 T>G)

Disease associations

OMIM: gene MIM:123832 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000883_3	Response to antipsychotic treatment in schizophrenia (working memory)	3.000000e-06
GCST001786_22	Dental caries	2.000000e-07
GCST001786_33	Dental caries	2.000000e-06
GCST002119_25	Metabolite levels (X-11787)	9.000000e-06
GCST003477_3	Monobrow thickness	4.000000e-07
GCST003997_38	Myopia	5.000000e-17
GCST006466_7	Endometrial cancer (Non-endometrioid histology)	7.000000e-07
GCST009391_465	Metabolite levels	9.000000e-06
GCST009962_16	High myopia	3.000000e-08
GCST010002_151	Refractive error	2.000000e-59
GCST011616_18	Cortical volume	2.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004335	short-term memory
EFO:0005276	hydroxy-leucine measurement
EFO:0010522	phosphoenolpyruvic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
bisphenol A	decreases expression, increases expression	3
sodium arsenite	increases expression	3
Arsenic Trioxide	increases expression	3
Cyclosporine	affects expression, decreases expression	3
Acetaminophen	affects expression, increases expression	2
Cisplatin	affects cotreatment, decreases expression, affects expression	2
Coumestrol	affects cotreatment, increases expression, increases reaction	2
Estradiol	decreases expression, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tretinoin	decreases expression	2
Aflatoxin B1	affects expression, increases expression	2
Particulate Matter	decreases expression, decreases reaction, increases abundance	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
quercitrin	decreases expression	1
trichostatin A	increases expression	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
boron nitride	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
cryptolepine	decreases expression	1
manganese chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1

Clinical trials (associated diseases)

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