HTATIP2

Summary

HTATIP2 (HIV-1 Tat interactive protein 2, HGNC:16637) is a protein-coding gene on chromosome 11p15.1, encoding Protein HTATIP2 (Q9BUP3). Represses translation by preventing reactivation of elongation factor eEF1A.

Enables protein serine/threonine kinase activity. Involved in import into nucleus and regulation of angiogenesis. Acts upstream of or within positive regulation of programmed cell death; positive regulation of transcription by RNA polymerase II; and protein autophosphorylation. Located in cytosol and nuclear envelope.

Source: NCBI Gene 10553 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 55 total
• Transcription factor: yes — 17 downstream targets (CollecTRI)
• MANE Select transcript: NM_001098522

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16637
Approved symbol	HTATIP2
Name	HIV-1 Tat interactive protein 2
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	TIP30, CC3, FLJ26963, SDR44U1
Ensembl gene	ENSG00000109854
Ensembl biotype	protein_coding
OMIM	605628
Entrez	10553

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000419348, ENST00000421577, ENST00000443524, ENST00000451739, ENST00000530266, ENST00000531058, ENST00000532081, ENST00000532505, ENST00000533914, ENST00000868110, ENST00000917531

RefSeq mRNA: 5 — MANE Select: NM_001098522 NM_001098520, NM_001098521, NM_001098522, NM_001098523, NM_006410

CCDS: CCDS44553, CCDS53613, CCDS7852

Canonical transcript exons

ENST00000451739 — 5 exons

Exon	Start	End
ENSE00000914840	20376580	20376717
ENSE00000988179	20367174	20367281
ENSE00001780980	20363714	20364432
ENSE00002168224	20382980	20383782
ENSE00003691302	20382178	20382239

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.2999 / max 332.3969, expressed in 1707 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113420	25.9713	1706
113423	4.4549	1181
113421	0.5274	324
113422	0.3464	177

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.38	gold quality
colonic mucosa	UBERON:0000317	98.43	gold quality
duodenum	UBERON:0002114	98.42	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.42	gold quality
esophagus squamous epithelium	UBERON:0006920	97.71	gold quality
islet of Langerhans	UBERON:0000006	97.38	gold quality
sperm	CL:0000019	97.33	gold quality
mucosa of transverse colon	UBERON:0004991	97.08	gold quality
epithelium of esophagus	UBERON:0001976	97.03	gold quality
rectum	UBERON:0001052	97.02	gold quality
squamous epithelium	UBERON:0006914	96.70	gold quality
monocyte	CL:0000576	96.16	gold quality
epithelium of nasopharynx	UBERON:0001951	96.10	gold quality
pancreatic ductal cell	CL:0002079	96.02	gold quality
mononuclear cell	CL:0000842	95.92	gold quality
male germ cell	CL:0000015	95.84	gold quality
mammalian vulva	UBERON:0000997	95.84	gold quality
adrenal tissue	UBERON:0018303	95.82	gold quality
leukocyte	CL:0000738	95.74	gold quality
gingiva	UBERON:0001828	95.72	gold quality
nasal cavity epithelium	UBERON:0005384	95.67	gold quality
right adrenal gland	UBERON:0001233	95.66	gold quality
right adrenal gland cortex	UBERON:0035827	95.57	gold quality
gingival epithelium	UBERON:0001949	95.55	gold quality
oral cavity	UBERON:0000167	95.33	gold quality
jejunum	UBERON:0002115	95.19	gold quality
tongue squamous epithelium	UBERON:0006919	95.07	gold quality
left adrenal gland	UBERON:0001234	95.04	gold quality
gall bladder	UBERON:0002110	94.86	gold quality
ileal mucosa	UBERON:0000331	94.83	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-97	yes	1076.08
E-GEOD-100618	yes	125.91
E-MTAB-8142	yes	41.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

17 targets.

Target	Regulation
ADAMTS7
CCN5
CCND1	Repression
CDH1
EGF
EPHB2
ESR1
FN1
HTATIP2
IGF1
IL1B
MET
MMP2	Repression
MYC
SPP1	Repression
TGFB1
VEGFA	Repression

Upstream regulators (CollecTRI, top): HTATIP2

miRNA regulators (miRDB)

38 targeting HTATIP2, 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-4455	100.00	65.48	1587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-609	99.82	64.26	505
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631

Literature-anchored findings (GeneRIF, showing 40)

• TIP30 interacts with an estrogen receptor alpha-interacting coactivator CIA and regulates ERalpha-mediated c-myc transcription. (PMID:15073177)
• These data indicate that shear-induced VWF binding to platelet GpIb-IX-V activates Pyk2, ERK1/2, p38, and cPLA2. (PMID:15493507)
• TIP30 predisposes hepatoblastoma cells to apoptosis through regulating expression levels of these genes. (PMID:15633220)
• Finally, two inhibitors of cyclin-dependent kinase 9 (a dominant negative CDK9 and flavopiridol) repressed activity from the MR and BMPR2 promoters (PMID:16615932)
• Overexpression of TIP30 might be a promising candidate as a treatment for HCC that would increase sensitivity to chemotherapeutic drugs. (PMID:16799960)
• Data supported the theory that the expression of TIP30/CC3 had a suppressive function on tumor metastasis, and the decrease in expression of TIP30/CC3 is related to metastasis and may represent a new prognosticator in breast carcinoma. (PMID:17097132)
• Translocation of Bax was essential for TIP30-induced apoptosis, whereas overexpression of the anti-apoptotic protein Bcl-xL delayed both second mitochondria-derived activator of caspases (Smac/DIABLO) release and onset of apoptosis. (PMID:17997990)
• results suggest that TIP30 is involved in cellular oxidative stress surveillance and induces apoptosis through stabilization of p53 mRNA in hepatocellular carcinoma cells (PMID:18519672)
• TIP30 plays a role in prostate cancer progression and that TIP30 overexpression may promote prostate cancer cell growth and metastasis. (PMID:18528861)
• Novel pathway by which OPN and possibly other Ets-1 target genes involved in tumor metastasis are regulated by TIP30. Mechanism for metastasis promoted by TIP30 deficiency. (PMID:18537194)
• a novel function of TIP30, which can possibly be used as an independent prognostic factor and a potential therapeutic target for gastric cancer. (PMID:18972434)
• epigenetic silencing of Tip30 gene expression by CpG island DNA hypermethylation is associated with poor prognosis in patients with HCC (PMID:19010857)
• Data suggest that oligodendrocyte precursor cells are pathogenic in multiple sclerosis and their nucleocytoplasmic transport is impaired due to abnormally upregulated TIP30. (PMID:19104151)
• Decreased TIP30 expression promotes tumor metastasis in lung cancer. (PMID:19349353)
• These results demonstrate that promoter methylation is involved in the decreased expression of TIP30 tumor suppressor gene in human colorectal carcinoma. (PMID:19798571)
• we examine the pathophysiological nature of remyelination failure in chronic multiple sclerosis and discuss the role of TIP30 as a novel therapeutic target–review (PMID:19839715)
• Excess of cellular CC3 has a significant negative effect on DNA repair after UV and oxidant exposure, while silencing of endogenous CC3 slightly delays repair of UV-induced damage. (PMID:20374651)
• Data suggest that metabolic flexibility acquired by cells after silencing of CC3 could be directly relevant to the development of metastatic and aggressive human tumors that frequently have low or absent expression of CC3. (PMID:21150275)
• TIP30 complex regulates EGFR endocytosis by facilitating the transport of V-ATPases from trans-Golgi network to early endosomes. (PMID:21252234)
• overexpression of MCM2 or loss of expression of Tat-interacting protein 30 is closely related to carcinogenesis, progression, biological behavior, and prognosis of gallbladder adenocarcinoma. (PMID:21543106)
• The TIP30 complex facilitates biological membrane fusion through modification of phosphatidic acid on membranes. (PMID:21731680)
• The loss of CC3/TIP30 is related to occurrence and development in breast cancer, suggesting early onset of metastasis and recurrence. (PMID:22490293)
• TIP30 acts as a crucial regulator in suppressing cytoplasmic and nuclear EGFR signaling in the lung.TIP30 functions as a tumor suppressor to inhibit EGFR cytoplasmic and nuclear signaling and suppress adenocarcinogenesis in the lung. (PMID:22733137)
• TIP30 binds to the DNA-binding domain and the C-terminal domain of p53 (PMID:23178973)
• We demonstrated the potential role of HTATIP2/TIP30 in ovarian cancer for the first time, thereby enlightening future studies targeting HTATIP2/TIP30 in ovarian cancer treatment, diagnosis, and prevention. (PMID:23800048)
• Decreased TIP30 expression is associated with pancreatic cancer. (PMID:24037692)
• miR-10b promotes pancreatic cancer cell proliferation and invasion by suppressing TIP30. (PMID:24096486)
• The results suggest a novel and critical role of TIP30 involved in hepatocellular carcinoma progression and aggressiveness. (PMID:24681951)
• The combination of HTATIP2 and MVD predicts the converse survival of HCC with or without sorafenib intervention. (PMID:25008315)
• TIP30-induced downregulation of cyclin D1 transcription antagonizes EGFR signaling and suppresses tumorigenesis (PMID:25135222)
• Data iindicate TIP30 was a marker in predicting the prognosis of esophageal squamous cell carcinoma (ESCC). (PMID:25544767)
• the present study showed that loss of HTATIP2 expression was a frequent event in glioma and is associated with poor prognosis. (PMID:25617528)
• Meta-analysis suggests that the rs2230199 C/G, rs1047286 C/T, rs11569536 G/A and rs2250656 A/G SNPs in the CC3 gene may be associated with age-related macular degeneration risk. (PMID:25688879)
• Increased HMGB1 and cleaved caspase-3 stimulate the proliferation of tumor cells and are correlated with the poor prognosis in colorectal cancer (PMID:25986235)
• The results of the present study indicated that TIP30 may suppress oncogenesis and glioma progression, thereby improving the prognosis of patients with glioma. (PMID:26718891)
• combination of sorafenib and metformin inhibits proliferation and invasion in vitro, prolongs median survival, and reduces lung metastasis of HCC in vivo. This effect is closely associated with the upregulation of TIP30 (PMID:26752068)
• the results suggest that downregulation of TIP30 may result from HBV infection, and subsequently promotes the progression of HCC. (PMID:27418384)
• these data suggest that positive MCM2 and negative TIP30 expression are closely correlated with the clinical, pathological and biological parameters, in addition to poor prognosis in patients with gallbladder cancer. (PMID:27748889)
• TIP30 expression is associated with a good prognosis in patients with tumors. (PMID:28036326)
• Cholangiocarcinoma patients who had high methylation of HTATIP2 and low methylation of UCHL1 showed longer overall survival than those with low HTATIP2 methylation and high UCHL1 methylation. (PMID:29359783)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	htatip2	ENSDARG00000028386
mus_musculus	Htatip2	ENSMUSG00000039745
rattus_norvegicus	Htatip2	ENSRNOG00000022189
caenorhabditis_elegans		WBGENE00050941

Protein

Protein identifiers

Protein HTATIP2 — Q9BUP3 (reviewed: Q9BUP3)

Alternative names: 30 kDa HIV-1 TAT-interacting protein, HIV-1 TAT-interactive protein 2

All UniProt accessions (2): Q9BUP3, E9PI87

UniProt curated annotations — full annotation on UniProt →

Function. Represses translation by preventing reactivation of elongation factor eEF1A. May also inhibit nuclear import by competing with nuclear import substrates for binding to a subset of nuclear transport receptors. Has additionally been proposed to act as a redox sensor involved in cellular oxidative stress surveillance.

Subunit / interactions. Monomer. Forms homodimers during oxidative stress. Interacts (via N-terminus) with elongation factor EEF1A1 (via middle-region); the interaction is direct and competes with EEF1A1 binding to guanyl-nucleotide exchange factor EEF1B2, thereby inhibiting GDP for GTP exchange and reactivation of EEF1A1. Interacts with nuclear transport receptors XPO4, IPO5/RANBP5, IPO7, IPO9 and KPNB1 as well as GCN1L1/GCN1 and LRPPRC probably through their HEAT repeats. Binds NCOA5/CIA. Interacts (via N-terminus) with proteasome subunit PSMD4/s5a. (Microbial infection) Interacts with HIV-1 Tat (via activation domain).

Subcellular location. Cytoplasm.

Tissue specificity. High levels in liver, lung, skeletal muscle, pancreas and placenta. Moderate levels in heart and kidney. Low levels in brain. Not expressed or low levels in variant small cell lung carcinomas, 33% of hepatocellular carcinomas and neuroblastomas. Levels are reduced in the heart of patients with hypertrophic cardiomyopathy and failing hearts.

Domain organisation. Unique C-terminus confers high proteasome-dependent instability to isoform 2.

Miscellaneous. Mutagenesis of Leu-154 and Leu-157 or Cys-158, Cys-160 and Cys-161 abolishes antiapoptotic effect.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BUP3-1	1, CC3	yes
Q9BUP3-2	2, TC3
Q9BUP3-3	3

RefSeq proteins (5): NP_001091990, NP_001091991, NP_001091992, NP_001091993, NP_006401 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016040	NAD(P)-bd_dom	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF13460

UniProt features (55 total): binding site 12, helix 12, strand 9, sequence variant 6, sequence conflict 4, splice variant 3, mutagenesis site 2, active site 2, initiator methionine 1, chain 1, modified residue 1, disulfide bond 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2BKA	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUP3-F1	89.05	0.77

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 (2): 143 (proton acceptor); 147

Ligand- & substrate-binding residues (12): 53; 92; 93; 143; 147; 170; 178; 27; 28; 29; 30; 52

Post-translational modifications (1): 2

Disulfide bonds (1): 172

Mutagenesis-validated functional residues (2):

Position	Phenotype
28–31	loss of proapoptotic and metastatis-inhibiting effect.
106	loss of association with nucleus.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 211 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, RODRIGUES_NTN1_TARGETS_DN, PATIL_LIVER_CANCER, GOBP_TRANSLATION, GTGCCTT_MIR506, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GERY_CEBP_TARGETS, ONKEN_UVEAL_MELANOMA_UP, UEDA_PERIFERAL_CLOCK, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, KOYAMA_SEMA3B_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, MARTIN_VIRAL_GPCR_SIGNALING_UP

GO Biological Process (5): regulation of translation (GO:0006417), positive regulation of programmed cell death (GO:0043068), positive regulation of transcription by RNA polymerase II (GO:0045944), protein autophosphorylation (GO:0046777), angiogenesis (GO:0001525)

GO Molecular Function (3): protein serine/threonine kinase activity (GO:0004674), catalytic activity (GO:0003824), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
programmed cell death	1
regulation of programmed cell death	1
positive regulation of cellular process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
protein phosphorylation	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
protein kinase activity	1
molecular_function	1
binding	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTATIP2	ROBO3	Q96MS0	795
HTATIP2	TUBA3E	Q6PEY2	761
HTATIP2	TUBAL3	A6NHL2	761
HTATIP2	TUBA1C	Q9BQE3	761
HTATIP2	TUBA3C	P0DPH7	714
HTATIP2	TUBA8	Q9NY65	714
HTATIP2	NDUFA9	Q16795	698
HTATIP2	BICD2	Q8TD16	613
HTATIP2	NTN1	O95631	544
HTATIP2	SH3GLB1	Q9Y371	531
HTATIP2	ST20	Q9HBF5	520
HTATIP2	ACSL4	O60488	518
HTATIP2	SCGB1A1	P11684	506
HTATIP2	DYNLL1	P63167	493
HTATIP2	TUBA4A	P05215	491

IntAct

15 interactions, top by confidence:

A	B	Type	Score
MACROD1	PARP1	psi-mi:“MI:0914”(association)	0.620
EMP3	HTATIP2	psi-mi:“MI:0915”(physical association)	0.540
EMP3	HTATIP2	psi-mi:“MI:2364”(proximity)	0.540
CFTR	HTATIP2	psi-mi:“MI:0915”(physical association)	0.370
PB2		psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
OTOA	SLC27A2	psi-mi:“MI:0914”(association)	0.350
HTATIP2	NCOA5	psi-mi:“MI:0914”(association)	0.350
SLC9A9	PODXL	psi-mi:“MI:0914”(association)	0.350

BioGRID (81): HTATIP2 (Proximity Label-MS), HTATIP2 (Affinity Capture-MS), RAB5A (Affinity Capture-Western), ACSL4 (Affinity Capture-Western), SH3GLB1 (Affinity Capture-Western), HTATIP2 (Affinity Capture-Western), HTATIP2 (Affinity Capture-Western), HTATIP2 (Affinity Capture-Western), HTATIP2 (PCA), HTATIP2 (PCA), HTATIP2 (PCA), ACSL4 (Reconstituted Complex), SH3GLB1 (Reconstituted Complex), NCOA5 (Affinity Capture-MS), AMOTL2 (Affinity Capture-MS)

ESM2 similar proteins: A1YER2, A1YFX9, A2T7G9, A6NNS2, B0BN93, B0BNF8, O22718, O35331, O35678, O75911, O77769, O80526, O88876, O95154, P11172, P14755, P15904, P84169, Q06136, Q15738, Q1RMJ5, Q28DS0, Q2KIJ5, Q2QNG7, Q2QZ86, Q3SZM9, Q3T067, Q3ZBE9, Q5E964, Q5I0K3, Q5PPL3, Q5R514, Q5R5C9, Q5RDZ2, Q6AY30, Q6UWP2, Q811X6, Q86WA6, Q8JGT5, Q8K183

Diamond homologs: A1CTL5, A1CYD8, A1DMU2, A1YER2, A1YFX9, A2QWW3, A2T7G9, A3LQJ9, A3LSB6, A3LUX6, A5DEZ6, A5DSN1, B0BNF8, P0C5D8, P40008, Q0CI32, Q0CZ00, Q1E7Y1, Q2TXI3, Q2UMY4, Q4WMS0, Q5AP65, Q5BCH7, Q6BLA6, Q6CQW6, Q6FRC1, Q75AB3, Q9BUP3, Q9P5L2, Q9Z2G9, P45469, P0CB81, P0CB82, Q0MQB3, Q0MQB4, Q16795, B6JHG4, A0A0H3C8X7, Q5BK63, Q9DC69

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

945 predictions. Top by Δscore:

Variant	Effect	Δscore
11:20364415:G:GT	donor_gain	1.0000
11:20364430:GTG:G	donor_gain	1.0000
11:20367277:GGGCG:G	donor_gain	1.0000
11:20367278:GGCGG:G	donor_gain	1.0000
11:20367287:G:GT	donor_gain	1.0000
11:20376713:T:G	donor_gain	1.0000
11:20382238:GG:G	donor_gain	1.0000
11:20382239:GG:G	donor_gain	1.0000
11:20382240:G:GG	donor_gain	1.0000
11:20364235:A:AG	acceptor_gain	0.9900
11:20364235:AGCAT:A	acceptor_gain	0.9900
11:20364236:G:GG	acceptor_gain	0.9900
11:20364236:GC:G	acceptor_gain	0.9900
11:20364236:GCAT:G	acceptor_gain	0.9900
11:20364236:GCATG:G	acceptor_gain	0.9900
11:20364396:G:GT	donor_gain	0.9900
11:20367172:A:AG	acceptor_gain	0.9900
11:20367173:G:GG	acceptor_gain	0.9900
11:20367278:GGCG:G	donor_gain	0.9900
11:20367279:GCGG:G	donor_gain	0.9900
11:20367288:A:T	donor_gain	0.9900
11:20367291:GCA:G	donor_gain	0.9900
11:20376429:GGTC:G	donor_gain	0.9900
11:20376578:AGGAG:A	acceptor_gain	0.9900
11:20376579:GGAGG:G	acceptor_gain	0.9900
11:20382177:G:A	acceptor_loss	0.9900
11:20382240:G:GC	donor_loss	0.9900
11:20382241:TAAGT:T	donor_loss	0.9900
11:20382242:AAGTA:A	donor_loss	0.9900
11:20382243:AGTA:A	donor_loss	0.9900

AlphaMissense

1572 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:20376717:G:C	K147N	0.992
11:20376717:G:T	K147N	0.992
11:20367251:C:G	C91W	0.989
11:20367246:T:C	C90R	0.985
11:20376602:G:C	R109P	0.984
11:20376631:G:C	A119P	0.984
11:20367241:G:A	G88E	0.983
11:20376586:T:C	F104L	0.982
11:20376588:T:A	F104L	0.982
11:20376588:T:G	F104L	0.982
11:20367244:T:C	F89S	0.979
11:20367248:T:G	C90W	0.979
11:20364311:G:A	G25D	0.978
11:20364320:G:A	G28E	0.978
11:20364329:G:A	G31D	0.978
11:20367223:T:C	F82S	0.978
11:20367256:G:A	G93D	0.978
11:20367222:T:C	F82L	0.977
11:20367224:T:A	F82L	0.977
11:20367224:T:G	F82L	0.977
11:20367249:T:C	C91R	0.977
11:20367255:G:C	G93R	0.977
11:20376668:C:T	S131F	0.977
11:20364316:A:C	S27R	0.976
11:20364318:C:A	S27R	0.976
11:20364318:C:G	S27R	0.976
11:20376598:G:C	D108H	0.975
11:20382997:G:T	R174M	0.975
11:20382211:T:C	F159L	0.974
11:20382213:T:A	F159L	0.974

dbSNP variants (sampled 300 via entrez): RS1000044665 (11:20374231 T>G), RS1000087055 (11:20371614 T>C), RS1000261671 (11:20378305 G>A), RS1000316876 (11:20365047 G>A), RS1000434740 (11:20367519 A>G), RS1000587591 (11:20366813 C>G,T), RS1001569882 (11:20378070 T>C), RS1001790599 (11:20372779 A>G), RS1001797186 (11:20384029 G>A,T), RS1001943450 (11:20379209 T>C), RS1002095222 (11:20374583 A>G), RS1002274473 (11:20381388 C>T), RS1002312371 (11:20379525 A>G), RS1002334306 (11:20367998 C>G), RS1002377830 (11:20380691 A>G)

Disease associations

OMIM: gene MIM:605628 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001762_234	Obesity-related traits	3.000000e-06
GCST001762_908	Obesity-related traits	7.000000e-06
GCST002754_2	Response to inhaled glucocorticoid treatment in asthma (change in FEV1)	6.000000e-11
GCST006029_3	Fractional shortening	4.000000e-08
GCST011354_2	Bell’s palsy	8.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement
EFO:0003940	physical activity
EFO:0005921	FEV change measurement
EFO:0009285	fractional shortening

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	4
sodium arsenite	increases abundance, increases expression, affects methylation	4
Arsenic Trioxide	increases expression, decreases response to substance	4
Valproic Acid	affects expression, increases expression	4
decabromobiphenyl ether	affects expression, decreases expression	2
arsenite	affects binding, increases reaction, increases abundance, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
epigallocatechin gallate	decreases expression, affects cotreatment	2
entinostat	decreases expression, increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Etoposide	affects response to substance, increases activity, increases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Cadmium Chloride	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
chloroacetaldehyde	increases expression	1
triphenyl phosphate	affects expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, increases expression	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
trichostatin A	decreases expression	1
cinnamaldehyde	increases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1

Clinical trials (associated diseases)

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