TNFAIP1

Summary

TNFAIP1 (TNF alpha induced protein 1, HGNC:11894) is a protein-coding gene on chromosome 17q11.2, encoding BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 2 (Q13829). Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in regulation of cytoskeleton structure.

This gene was identified as a gene whose expression can be induced by the tumor necrosis factor alpha (TNF) in umbilical vein endothelial cells. Studies of a similar gene in mouse suggest that the expression of this gene is developmentally regulated in a tissue-specific manner.

Source: NCBI Gene 7126 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_021137

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11894
Approved symbol	TNFAIP1
Name	TNF alpha induced protein 1
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	B61, B12, MGC2317, BTBD34
Ensembl gene	ENSG00000109079
Ensembl biotype	protein_coding
OMIM	191161
Entrez	7126

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000226225, ENST00000544907, ENST00000577535, ENST00000578158, ENST00000582302, ENST00000583213, ENST00000902207, ENST00000902208, ENST00000902209, ENST00000902210, ENST00000928161, ENST00000928162, ENST00000954873, ENST00000954874

RefSeq mRNA: 1 — MANE Select: NM_021137 NM_021137

CCDS: CCDS11227

Canonical transcript exons

ENST00000226225 — 7 exons

Exon	Start	End
ENSE00000866266	28339408	28339726
ENSE00001053464	28344364	28347009
ENSE00002220308	28335761	28335856
ENSE00003537999	28341404	28341456
ENSE00003572637	28341237	28341326
ENSE00003579885	28342247	28342442
ENSE00003786493	28340309	28340478

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 93.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.0466 / max 251.0926, expressed in 1815 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160005	40.0321	1814
160003	1.0436	640
160004	0.5551	273
160006	0.4157	225

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hair follicle	UBERON:0002073	93.42	gold quality
spleen	UBERON:0002106	92.91	gold quality
upper lobe of left lung	UBERON:0008952	92.49	gold quality
omental fat pad	UBERON:0010414	92.33	gold quality
peritoneum	UBERON:0002358	92.30	gold quality
upper lobe of lung	UBERON:0008948	92.10	gold quality
heart left ventricle	UBERON:0002084	92.09	gold quality
cardiac ventricle	UBERON:0002082	91.96	gold quality
right lobe of liver	UBERON:0001114	91.95	gold quality
type B pancreatic cell	CL:0000169	91.93	gold quality
gall bladder	UBERON:0002110	91.92	gold quality
right lung	UBERON:0002167	91.83	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.80	gold quality
islet of Langerhans	UBERON:0000006	91.57	gold quality
body of pancreas	UBERON:0001150	91.56	gold quality
smooth muscle tissue	UBERON:0001135	91.45	gold quality
lower esophagus mucosa	UBERON:0035834	91.39	gold quality
apex of heart	UBERON:0002098	91.38	gold quality
pancreas	UBERON:0001264	91.24	gold quality
esophagus mucosa	UBERON:0002469	91.18	gold quality
stromal cell of endometrium	CL:0002255	90.82	gold quality
olfactory bulb	UBERON:0002264	90.81	gold quality
right frontal lobe	UBERON:0002810	90.69	gold quality
frontal pole	UBERON:0002795	90.68	gold quality
heart	UBERON:0000948	90.63	gold quality
metanephros cortex	UBERON:0010533	90.51	gold quality
lung	UBERON:0002048	90.49	gold quality
left adrenal gland	UBERON:0001234	90.43	gold quality
prefrontal cortex	UBERON:0000451	90.38	gold quality
left adrenal gland cortex	UBERON:0035825	90.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN, SP1, TFAP2A

miRNA regulators (miRDB)

158 targeting TNFAIP1, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
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-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-95-5P	99.89	72.17	3973

Literature-anchored findings (GeneRIF, showing 18)

• TNFAIP1 shows increased transcript levels in Alzheimer’s disease brains (PMID:12600716)
• Expression levels of TNFAIP1 are high in COS7 and NIH3T3 cell lines but low in the cancer cell lines. (PMID:16870576)
• The promoter region of human TNFAIP1 gene was functionally characterized. (PMID:19593659)
• CK2 could phosphorylate TNFAIP1 in vitro and in vivo, which facilitated the distribution of TNFAIP1 in nucleus and enhanced its interaction with PCNA. (PMID:19851886)
• suggest that the TNFAIP1/POLDIP2 complex sense-antisense architecture represents a clinically significant transcriptional structural-functional gene module associated with amplification of the genomic region on 17q11.2 in breast cancer. (PMID:20158880)
• TNFAIP1 inhibited the transcriptional activities of nuclear factor kappa B (NF-kappaB) and activating protein-1 reporters (PMID:22810651)
• Expression of TNFAIP1 is regulated by the transcriptional factor Sp1. (PMID:23912453)
• Results showed that the expression of TNFAIP1 protein was significantly increased in osteosarcoma tissues and associated with distant metastasis. (PMID:24969828)
• MiR-181a played a critical role in regulating pancreatic cancer growth and migration, likely interacting with TNFAIP1. (PMID:26152285)
• TNFAIP1 plays an important role in mediating miR-15a dependent biological functions in osteosarcoma. (PMID:26261520)
• CREB is a negative regulator of the TNFAIP1 gene. (PMID:26398148)
• Tumor necrosis factor alpha-induced protein 1 as a novel tumor suppressor through selective downregulation of CSNK2B blocks nuclear factor-kappaB activation in hepatocellular carcinoma. (PMID:31901862)
• The CRL3(BTBD9) E3 ubiquitin ligase complex targets TNFAIP1 for degradation to suppress cancer cell migration. (PMID:32327643)
• Circ0001320 inhibits lung cancer cell growth and invasion by regulating TNFAIP1 and TPM1 expression through sponging miR-558. (PMID:33128699)
• TNFAIP1 Is Upregulated in APP/PS1 Mice and Promotes Apoptosis in SH-SY5Y Cells by Binding to RhoB. (PMID:33159672)
• The role of TNF-alpha induced protein 1 in the activation of pro-apoptotic proteins. (PMID:33909263)
• Neuronal-specific TNFAIP1 ablation attenuates postoperative cognitive dysfunction via targeting SNAP25 for K48-linked ubiquitination. (PMID:38102610)
• HECTD2/TNFAIP1 Axis Regulating the p38/JNK Pathway to Promote an Inflammatory Response in Renal Cell Carcinoma Cells. (PMID:38688591)

Cross-species orthologs

33 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnfaip1	ENSDARG00000041565
mus_musculus	Tnfaip1	ENSMUSG00000017615
rattus_norvegicus	Tnfaip1	ENSRNOG00000009069
drosophila_melanogaster	CG10465	FBGN0033017
caenorhabditis_elegans		WBGENE00008425
caenorhabditis_elegans		WBGENE00008932
caenorhabditis_elegans		WBGENE00011486
caenorhabditis_elegans		WBGENE00011621
caenorhabditis_elegans		WBGENE00015112
caenorhabditis_elegans		WBGENE00015113
caenorhabditis_elegans		WBGENE00015914
caenorhabditis_elegans		WBGENE00016545
caenorhabditis_elegans		WBGENE00016546
caenorhabditis_elegans		WBGENE00016547
caenorhabditis_elegans		WBGENE00016549
caenorhabditis_elegans		WBGENE00016550
caenorhabditis_elegans		WBGENE00017705
caenorhabditis_elegans		WBGENE00017707
caenorhabditis_elegans		WBGENE00017709
caenorhabditis_elegans		WBGENE00017710
caenorhabditis_elegans		WBGENE00019339
caenorhabditis_elegans		WBGENE00019342
caenorhabditis_elegans		WBGENE00022566
caenorhabditis_elegans		WBGENE00022567
caenorhabditis_elegans		WBGENE00022568
caenorhabditis_elegans		WBGENE00022569
caenorhabditis_elegans		WBGENE00022570
caenorhabditis_elegans		WBGENE00022571
caenorhabditis_elegans		WBGENE00022572
caenorhabditis_elegans		WBGENE00022573
caenorhabditis_elegans		WBGENE00022574
caenorhabditis_elegans		WBGENE00022575
caenorhabditis_elegans		WBGENE00044373

Paralogs (2): KCTD10 (ENSG00000110906), KCTD13 (ENSG00000174943)

Protein

Protein identifiers

BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 2 — Q13829 (reviewed: Q13829)

Alternative names: BTB/POZ domain-containing protein TNFAIP1, Protein B12, Tumor necrosis factor, alpha-induced protein 1, endothelial

All UniProt accessions (4): Q13829, J3QS43, J3QSD4, K7EM01

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in regulation of cytoskeleton structure. The BCR(TNFAIP1) E3 ubiquitin ligase complex mediates the ubiquitination of RHOA, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and cell migration. Its interaction with RHOB may regulate apoptosis. May enhance the PCNA-dependent DNA polymerase delta activity.

Subunit / interactions. Component of the BCR(TNFAIP1) E3 ubiquitin ligase complex, at least composed of CUL3, TNFAIP1/BACURD2 and RBX1. Interacts with RHOA; with a preference for RhoA-GDP. Interacts with RHOB. Interacts with PCNA. Interacts with CSNK2B.

Subcellular location. Cytoplasm. Nucleus. Endosome.

Post-translational modifications. Phosphorylation at Ser-280 by CK2 facilitates the nucleus localization and increases interaction with PCNA.

Induction. By TNF, IL1B/interleukin-1 beta and bacterial lipopolysaccharides (LPS).

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the BACURD family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13829-1	1	yes
Q13829-2	2

RefSeq proteins (1): NP_066960* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR045068	BACURD1-3	Family

Pfam: PF02214

UniProt features (13 total): mutagenesis site 6, modified residue 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13829-F1	81.54	0.63

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): 278, 280

Mutagenesis-validated functional residues (6):

Position	Phenotype
265	does not affect phosphorylation level.
278	slightly impairs phosphorylation level.
280	strongly impairs phosphorylation level.
71–73	abolishes interaction with cul3 and induces abnormal actin stress fibers.
142	does not affect phosphorylation level; when associated with a-237.
237	does not affect phosphorylation level; when associated with a-142.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696270	RND2 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 255 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, ATF_B, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MYOGENIN_Q6, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOMF_GTPASE_BINDING, chr17q11, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (10): apoptotic process (GO:0006915), immune response (GO:0006955), cell migration (GO:0016477), protein ubiquitination (GO:0016567), negative regulation of Rho protein signal transduction (GO:0035024), stress fiber assembly (GO:0043149), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of DNA replication (GO:0045740), protein homooligomerization (GO:0051260), ubiquitin-dependent protein catabolic process (GO:0006511)

GO Molecular Function (5): cyclin binding (GO:0030332), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), endosome (GO:0005768), cytosol (GO:0005829), Cul3-RING ubiquitin ligase complex (GO:0031463)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	2
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
immune system process	1
response to stimulus	1
cell motility	1
protein modification by small protein conjugation	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
contractile actin filament bundle assembly	1
actomyosin structure organization	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
DNA replication	1
regulation of DNA replication	1
positive regulation of DNA metabolic process	1
protein complex oligomerization	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
GTPase binding	1
ubiquitin-like protein transferase activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1
cytoplasm	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

752 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFAIP1	RND2	P52198	752
TNFAIP1	POLD2	P49005	724
TNFAIP1	CUL3	Q13618	712
TNFAIP1	TRIM25	Q14258	655
TNFAIP1	BTBD10	Q9BSF8	600
TNFAIP1	KCTD19	Q17RG1	541
TNFAIP1	KCNRG	Q8N5I3	541
TNFAIP1	RND3	P52199	521
TNFAIP1	KCTD11	Q693B1	520
TNFAIP1	KCTD20	Q7Z5Y7	514
TNFAIP1	MIF4GD	A9UHW6	506
TNFAIP1	PCNX3	Q9H6A9	443
TNFAIP1	AKT1	P31749	440
TNFAIP1	SMAD4	Q13485	438
TNFAIP1	TRAF3	Q13114	435

IntAct

193 interactions, top by confidence:

A	B	Type	Score
LSM3	LSM1	psi-mi:“MI:0914”(association)	0.950
KCTD13	TNFAIP1	psi-mi:“MI:0915”(physical association)	0.900
TNFAIP1	KCTD13	psi-mi:“MI:0915”(physical association)	0.900
TNFAIP1	KCTD13	psi-mi:“MI:0914”(association)	0.900
KCTD13	CUL3	psi-mi:“MI:0914”(association)	0.870
CUL3	TNFAIP1	psi-mi:“MI:0915”(physical association)	0.800
TNFAIP1	CUL3	psi-mi:“MI:0915”(physical association)	0.800
NRP1	CSNK2A2	psi-mi:“MI:0914”(association)	0.790
POLR1C	TNFAIP1	psi-mi:“MI:0915”(physical association)	0.780
TNFAIP1	POLR1C	psi-mi:“MI:0915”(physical association)	0.780
TNFAIP1	ARMC7	psi-mi:“MI:0915”(physical association)	0.720
EXOSC5	TNFAIP1	psi-mi:“MI:0915”(physical association)	0.720
ARMC7	TNFAIP1	psi-mi:“MI:0915”(physical association)	0.720
TNFAIP1	EXOSC5	psi-mi:“MI:0915”(physical association)	0.720
TNFAIP1	TNFAIP1	psi-mi:“MI:0915”(physical association)	0.670
TNFAIP1	KCTD10	psi-mi:“MI:0915”(physical association)	0.670
TNFAIP1	ZMYND19	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (152): TNFAIP1 (Affinity Capture-Western), RHOA (Affinity Capture-Western), TNFAIP1 (Reconstituted Complex), RHOA (Biochemical Activity), TNFAIP1 (Two-hybrid), TNFAIP1 (Two-hybrid), CUL3 (Two-hybrid), HAT1 (Two-hybrid), STK16 (Two-hybrid), POLR1C (Two-hybrid), EPM2AIP1 (Two-hybrid), CAPN7 (Two-hybrid), EXOSC5 (Two-hybrid), CARD9 (Two-hybrid), ARMC7 (Two-hybrid)

ESM2 similar proteins: A0A2R8VHF7, A0JM23, A2QRA0, A4IIA7, A4IIV4, A6NFN9, A6NHR9, A7MBF6, F4IG73, F4JSE7, O17482, O95876, P12540, P21784, P34089, P38899, P55895, P56696, Q08AW4, Q0D2D7, Q12789, Q13829, Q28DC9, Q2WGJ8, Q3E7Y5, Q3UUE9, Q4R907, Q4VXA5, Q5BK83, Q5EA90, Q5F476, Q5HZS2, Q5M9F0, Q5RAX4, Q5RBH4, Q5RD21, Q6AYL6, Q6DGA7, Q6PIY5, Q70XZ2

Diamond homologs: A3KMV1, A4IFB4, A5PKG7, A6H6X4, A9ULR9, B1WC97, B5DEL1, D5SHR0, O70479, P0C5J9, Q03607, Q0VD00, Q0VFV7, Q13829, Q14681, Q28DC9, Q29RJ0, Q2HJ48, Q2T9W0, Q2TUM3, Q3URF8, Q4G0X4, Q50H33, Q54KH0, Q58DF7, Q5DTY9, Q5EAX2, Q5F3E8, Q5M956, Q5RBH4, Q5XJ34, Q5ZJP7, Q68DU8, Q693B1, Q6DC02, Q6DCX3, Q6DG99, Q6DK85, Q6P3P4, Q6P7W2

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	TNFAIP1	phosphorylation
CUL3	“up-regulates activity”	TNFAIP1	binding
TNFAIP1	“down-regulates quantity”	RHOA	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
SPOP-mediated proteasomal degradation of PD-L1(CD274)	6	20.8×	3e-04
Degradation of DVL	5	18.0×	2e-03
Hedgehog ‘on’ state	5	12.0×	6e-03
Neddylation	9	6.5×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	11	6.2×	2e-03
protein ubiquitination	11	5.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1359 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28341225:T:TA	acceptor_gain	1.0000
17:28341227:T:TA	acceptor_gain	1.0000
17:28341230:C:A	acceptor_gain	1.0000
17:28341233:A:AG	acceptor_gain	1.0000
17:28341233:ACAG:A	acceptor_gain	1.0000
17:28341234:C:G	acceptor_gain	1.0000
17:28341234:CA:C	acceptor_loss	1.0000
17:28341235:A:AG	acceptor_gain	1.0000
17:28341235:A:AT	acceptor_loss	1.0000
17:28341235:AG:A	acceptor_gain	1.0000
17:28341236:G:GC	acceptor_gain	1.0000
17:28341236:GG:G	acceptor_gain	1.0000
17:28341236:GGA:G	acceptor_gain	1.0000
17:28341236:GGAC:G	acceptor_gain	1.0000
17:28341236:GGACA:G	acceptor_gain	1.0000
17:28341322:CCAAG:C	donor_loss	1.0000
17:28341323:CAAG:C	donor_loss	1.0000
17:28341324:AAGGT:A	donor_loss	1.0000
17:28341325:AG:A	donor_loss	1.0000
17:28341326:GGT:G	donor_loss	1.0000
17:28341327:G:A	donor_loss	1.0000
17:28341328:T:G	donor_loss	1.0000
17:28342234:AT:A	acceptor_gain	1.0000
17:28342235:T:G	acceptor_gain	1.0000
17:28342245:A:AG	acceptor_gain	1.0000
17:28342246:G:GC	acceptor_gain	1.0000
17:28342246:GC:G	acceptor_gain	1.0000
17:28342246:GCA:G	acceptor_gain	1.0000
17:28342246:GCAA:G	acceptor_gain	1.0000
17:28342246:GCAAC:G	acceptor_gain	1.0000

AlphaMissense

2076 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28340425:G:C	A108P	1.000
17:28341417:T:C	L160P	1.000
17:28341429:G:C	R164T	1.000
17:28341430:A:C	R164S	1.000
17:28341430:A:T	R164S	1.000
17:28341439:C:A	N167K	1.000
17:28341439:C:G	N167K	1.000
17:28341440:A:G	K168E	1.000
17:28341443:T:C	Y169H	1.000
17:28341449:T:C	Y171H	1.000
17:28342252:C:T	S175F	1.000
17:28342267:T:C	L180P	1.000
17:28342274:C:A	N182K	1.000
17:28342274:C:G	N182K	1.000
17:28342282:T:C	L185P	1.000
17:28342353:T:C	C209R	1.000
17:28342355:C:G	C209W	1.000
17:28342359:T:A	W211R	1.000
17:28342359:T:C	W211R	1.000
17:28342361:G:C	W211C	1.000
17:28342361:G:T	W211C	1.000
17:28342401:T:C	C225R	1.000
17:28342402:G:A	C225Y	1.000
17:28342403:T:G	C225W	1.000
17:28342407:T:C	S227P	1.000
17:28342411:T:A	I228N	1.000
17:28342411:T:G	I228S	1.000
17:28342416:T:C	Y230H	1.000
17:28344370:T:C	F241L	1.000
17:28344372:C:A	F241L	1.000

dbSNP variants (sampled 300 via entrez): RS1000930560 (17:28342312 G>A), RS1001100615 (17:28335720 C>G,T), RS1001151565 (17:28335513 C>A), RS1001377599 (17:28342696 G>A,T), RS1001382808 (17:28342094 T>A), RS1002839028 (17:28345582 G>A), RS1002944819 (17:28339470 G>A), RS1003335224 (17:28337494 G>A), RS1003397223 (17:28338030 T>C), RS1003407890 (17:28339174 G>T), RS1003727788 (17:28344080 G>A), RS1004174209 (17:28336017 T>A), RS1004290869 (17:28336305 C>G,T), RS1004469098 (17:28335144 A>C), RS1004521897 (17:28334850 G>A)

Disease associations

OMIM: gene MIM:191161 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002546_2	Osteoprotegerin levels	1.000000e-09
GCST006004_6	Low density lipoprotein cholesterol levels	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects expression, affects cotreatment, increases expression, decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
potassium perchlorate	decreases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
K 7174	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Biological Factors	increases expression	1
Citrinin	decreases expression, increases expression, affects cotreatment	1
Coumestrol	decreases expression, affects cotreatment	1
Diazinon	increases methylation	1
Estradiol	increases expression, affects cotreatment	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Menthol	decreases expression	1
Nickel	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Oils	decreases expression	1
Polycyclic Aromatic Hydrocarbons	increases expression, affects cotreatment, increases abundance	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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