RNF128

Summary

RNF128 (ring finger protein 128, HGNC:21153) is a protein-coding gene on chromosome Xq22.3, encoding E3 ubiquitin-protein ligase RNF128 (Q8TEB7). E3 ubiquitin-protein ligase that catalyzes ‘Lys-27’, ‘Lys-48’- or ‘Lys-63’-linked polyubiquitin chains formation and plays a role in different biological processes such as modulation of immune response, cytoskeletal dynamics or protein homeostasis.

The protein encoded by this gene is a type I transmembrane protein that localizes to the endocytic pathway. This protein contains a RING zinc-finger motif and has been shown to possess E3 ubiquitin ligase activity. Expression of this gene in retrovirally transduced T cell hybridoma significantly inhibits activation-induced IL2 and IL4 cytokine production. Induced expression of this gene was observed in anergic CD4(+) T cells, which suggested a role in the induction of anergic phenotype. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 79589 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 152 total
• MANE Select transcript: NM_194463

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21153
Approved symbol	RNF128
Name	ring finger protein 128
Location	Xq22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23516, GRAIL
Ensembl gene	ENSG00000133135
Ensembl biotype	protein_coding
OMIM	300439
Entrez	79589

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000255499, ENST00000324342, ENST00000418562, ENST00000862728, ENST00000862729

RefSeq mRNA: 2 — MANE Select: NM_194463 NM_024539, NM_194463

CCDS: CCDS14520, CCDS14521

Canonical transcript exons

ENST00000255499 — 7 exons

Exon	Start	End
ENSE00001039449	106785065	106785136
ENSE00001165460	106726701	106727397
ENSE00001266131	106772913	106773160
ENSE00001266162	106787918	106788000
ENSE00001754849	106791066	106791234
ENSE00002036539	106790186	106790282
ENSE00003849166	106795580	106797016

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 99.12.

FANTOM5 (CAGE): breadth broad, TPM avg 4.9315 / max 178.8393, expressed in 760 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197165	3.2057	633
197164	1.1550	475
197162	0.1830	67
197163	0.1348	64
197166	0.1124	59
197161	0.0577	26
197167	0.0369	10
209772	0.0361	12
197160	0.0099	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.12	gold quality
parotid gland	UBERON:0001831	97.47	gold quality
nephron tubule	UBERON:0001231	97.02	gold quality
duodenum	UBERON:0002114	96.37	gold quality
colonic mucosa	UBERON:0000317	95.57	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.22	gold quality
epithelial cell of pancreas	CL:0000083	94.88	gold quality
liver	UBERON:0002107	94.25	gold quality
kidney epithelium	UBERON:0004819	93.95	gold quality
right lobe of liver	UBERON:0001114	93.12	gold quality
islet of Langerhans	UBERON:0000006	92.80	gold quality
renal glomerulus	UBERON:0000074	92.80	gold quality
jejunum	UBERON:0002115	92.70	gold quality
metanephric glomerulus	UBERON:0004736	92.58	gold quality
pancreatic ductal cell	CL:0002079	92.56	gold quality
gall bladder	UBERON:0002110	92.53	gold quality
adrenal tissue	UBERON:0018303	92.15	gold quality
ileal mucosa	UBERON:0000331	91.79	gold quality
right adrenal gland cortex	UBERON:0035827	91.12	gold quality
left adrenal gland	UBERON:0001234	91.07	gold quality
adrenal cortex	UBERON:0001235	91.06	gold quality
left adrenal gland cortex	UBERON:0035825	90.81	gold quality
esophagus squamous epithelium	UBERON:0006920	90.59	gold quality
right adrenal gland	UBERON:0001233	90.37	gold quality
renal medulla	UBERON:0000362	90.32	gold quality
adrenal gland	UBERON:0002369	89.44	gold quality
lower lobe of lung	UBERON:0008949	89.35	gold quality
upper leg skin	UBERON:0004262	89.19	gold quality
rectum	UBERON:0001052	89.01	gold quality
mucosa of transverse colon	UBERON:0004991	88.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

155 targeting RNF128, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 18)

• Forced expression of GRAIL in a T cell line from a T-cell receptor transgenic mouse is sufficient for conversion of these cells to a regulatory phenotype. (PMID:17259178)
• Inhibition of T cell activation is not due to apoptosis or disruption of proximal T- cell receptor signaling, but is associated with up-regulation of GRAIL in CD4+ T cells, with modest effects on other E3 ubiquitin ligases. (PMID:17475842)
• GRAIL expression was significantly higher in patients with ulcerative colitis in remission than in patients with active disease and in healthy volunteers. (PMID:18467499)
• GRAIL captures and then ubiquitinates transmembrane proteins across the cell membrane (PMID:18713730)
• endogenous GRAIL regulates general cell cycle and proliferation of primary naive CD4 T cells. (PMID:19414743)
• GRAIL can down-modulate the expression of CD83 antigen on CD4 T cells. (PMID:19542455)
• study shows that Grail has a novel, p53-dependent role in regulating the cell cycle and apoptosis (PMID:23370271)
• results show that expression of GRAIL is uniquely regulated by the specific miRNA in intestinal mucosa, and suggest that GRAIL may associate with the pathophysiology of Crohn’s disease (PMID:24356810)
• Results demonstrate that Grail acts as a negative regulator of influenza A virus infection and replication by degrading viral nucleoprotein. (PMID:30467324)
• RNF128 downregulation was shown to correlate with the malignant phenotype of melanoma, and further functional assays demonstrated that low levels of RNF128 promoted melanoma progression via inducing cell epithelial-mesenchymal transition (EMT) and the acquisition of stemness. (PMID:30832692)
• We found that isoform 2 of RNF128 is decreased in BE cells, resulting in increased levels of mutant p53, whereas isoform 1 of RNF128 is increased in BE cells, further promoting the stabilization of mutant p53. (PMID:31715145)
• E3 ubiquitin ligase Grail promotes hepatic steatosis through Sirt1 inhibition. (PMID:33771967)
• GRAIL inhibits the growth, migration and invasion of lung adenocarcinoma cells by modulating STAT3/C-MYC signaling pathways. (PMID:34076979)
• UBCH5 Family Members Differentially Impact Stabilization of Mutant p53 via RNF128 Iso1 During Barrett’s Progression to Esophageal Adenocarcinoma. (PMID:34416429)
• RING finger protein 128 (RNF128) regulates malignant biological behaviors of colorectal cancer cells via PI3K/AKT signaling pathway. (PMID:35723244)
• RNF128 expression in lung adenocarcinoma is a favorable prognostic factor associated with decreased tumor-associated macrophages. (PMID:37186218)
• Mechanism of tumor-derived extracellular vesicles in prostatic cancer progression through the circFMN2/KLF2/RNF128 axis. (PMID:37452271)
• GRAIL1 Stabilizes Misfolded Mutant p53 through a Ubiquitin Ligase-Independent, Chaperone Regulatory Function. (PMID:39018356)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf128a	ENSDARG00000016867
mus_musculus	Rnf128	ENSMUSG00000031438
rattus_norvegicus	Rnf128	ENSRNOG00000055721

Paralogs (9): RNF13 (ENSG00000082996), RNF215 (ENSG00000099999), ZNRF4 (ENSG00000105428), RNF167 (ENSG00000108523), RNF130 (ENSG00000113269), RNF149 (ENSG00000163162), RNF150 (ENSG00000170153), RNF133 (ENSG00000188050), RNF148 (ENSG00000235631)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF128 — Q8TEB7 (reviewed: Q8TEB7)

Alternative names: Gene related to anergy in lymphocytes protein, RING finger protein 128, RING-type E3 ubiquitin transferase RNF128

All UniProt accessions (2): Q8TEB7, Q5JSK4

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that catalyzes ‘Lys-27’, ‘Lys-48’- or ‘Lys-63’-linked polyubiquitin chains formation and plays a role in different biological processes such as modulation of immune response, cytoskeletal dynamics or protein homeostasis. Inhibits IL2 and IL4 transcription, thereby playing an important role in the induction of the anergic phenotype, a long-term stable state of T-lymphocyte unresponsiveness to antigenic stimulation associated with the blockade of interleukin production. Ubiquitinates ARPC5 with ‘Lys-48’ linkages and COR1A with ‘Lys-63’ linkages leading to their degradation, down-regulation of these cytoskeletal components results in impaired lamellipodium formation and reduced accumulation of F-actin at the immunological synapse. Functions in the patterning of the dorsal ectoderm; sensitizes ectoderm to respond to neural-inducing signals. Plays a positive role in innate immune response by promoting ‘Lys-63’-linked ubiquitination of TBK1 after RNA- or DNA-virus infection. Regulates alveolar macrophage activation and neutrophil infiltration by interacting with TLR4, targeting it for degradation, and inhibiting NF-kappa-B activation, hence decreasing pro-inflammatory cytokines. Negatively regulates the IL-3/STAT5 signaling pathway by facilitating ‘Lys-27’-linked polyubiquitination of IL3RA leading to its degradation via lysosomal pathway. Directly regulates the N-glycosylation process in the endoplasmic reticulum by targeting the glycosyl-transferase RPN1 for ubiquitination and degradation. Other substrates targeted for degradation by RNF128 include transmembrane proteins CD40L, CD83 or the tetraspanin CD151.

Subcellular location. Cytoplasm. Endomembrane system. Cytoskeleton. Perinuclear region.

Post-translational modifications. Auto-ubiquitinated. Controls the development of T-cell clonal anergy by ubiquitination.

Domain organisation. Binding to E2 ubiquitin-conjugating enzyme requires an intact RING finger domain.

Induction. Induced under anergic conditions. Up-regulated during T-cell anergy induction following signaling through the T-cell antigen receptor. Upon viral infection.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TEB7-1	1	yes
Q8TEB7-2	2

RefSeq proteins (2): NP_078815, NP_919445* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR003137	PA_domain	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR046450	PA_dom_sf	Homologous_superfamily
IPR051073	ZNRF3_Arkadia_E3_ligases	Family

Pfam: PF02225, PF13639

UniProt features (27 total): sequence conflict 7, strand 7, glycosylation site 3, helix 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, domain 1, zinc finger region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3ICU	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TEB7-F1	76.10	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.

Glycosylation sites (3): 48, 59, 101

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5689896	Ovarian tumor domain proteases
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 233 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, AAGCAAT_MIR137, BENPORATH_ES_WITH_H3K27ME3, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_PROTEIN_LOCALIZATION_TO_LYSOSOME, FOXD3_01, PAX2_01, GTGCCTT_MIR506, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, KOYAMA_SEMA3B_TARGETS_UP

GO Biological Process (6): negative regulation of cytokine production (GO:0001818), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), regulation of protein stability (GO:0031647), protein localization to lysosome (GO:0061462), positive regulation of protein catabolic process in the vacuole (GO:1904352)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (9): cytoplasm (GO:0005737), late endosome (GO:0005770), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoskeleton (GO:0005856), perinuclear region of cytoplasm (GO:0048471), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Deubiquitination	2
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
endomembrane system	2
intracellular membrane-bounded organelle	2
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
regulation of biological quality	1
protein localization to vacuole	1
protein catabolic process in the vacuole	1
positive regulation of protein catabolic process	1
regulation of protein catabolic process in the vacuole	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
endosome	1
intracellular membraneless organelle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF128	OTUB1	Q96FW1	769
RNF128	USP8	P40818	721
RNF128	ZUP1	Q96AP4	697
RNF128	STX5	Q13190	669
RNF128	OTUB2	Q96DC9	653
RNF128	TBK1	Q9UHD2	592
RNF128	UBE2N	P61088	550
RNF128	RNF168	Q8IYW5	547
RNF128	IL2	P01585	515
RNF128	UBE3A	P78355	480
RNF128	RNF41	Q9H4P4	480
RNF128	USP38	Q8NB14	444
RNF128	HSPA5	P11021	424
RNF128	DTX4	Q9Y2E6	418
RNF128	CALU	O43852	418

IntAct

25 interactions, top by confidence:

A	B	Type	Score
RNF128	CEP76	psi-mi:“MI:0915”(physical association)	0.720
CEP76	RNF128	psi-mi:“MI:0915”(physical association)	0.720
APPBP2	RNF128	psi-mi:“MI:0915”(physical association)	0.560
RNF128	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
RNF128	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
SNX17	RNF128	psi-mi:“MI:0915”(physical association)	0.560
RNF128	UBE2I	psi-mi:“MI:0915”(physical association)	0.370
RNF128	UBE2T	psi-mi:“MI:0915”(physical association)	0.370
RNF128	rep	psi-mi:“MI:0915”(physical association)	0.370
RNF149	CCDC85C	psi-mi:“MI:0914”(association)	0.350
TMEM59	GPR89A	psi-mi:“MI:0914”(association)	0.350
HFE	PODXL	psi-mi:“MI:0914”(association)	0.350
SLC37A1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC37A2	WWP2	psi-mi:“MI:0914”(association)	0.350
SLC4A1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
RNF128	CEP76	psi-mi:“MI:0915”(physical association)	0.000
RNF128	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
SNX17	RNF128	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (486): RNF128 (Two-hybrid), CEP76 (Two-hybrid), RNF128 (Affinity Capture-Western), TBK1 (Reconstituted Complex), TBK1 (Biochemical Activity), CD83 (Affinity Capture-Western), RNF128 (Affinity Capture-Western), OTUB1 (Two-hybrid), RNF128 (Affinity Capture-Western), OTUB1 (Reconstituted Complex), RNF128 (Affinity Capture-Western), RNF128 (Reconstituted Complex), RNF128 (Two-hybrid), RNF128 (Two-hybrid), RNF128 (Two-hybrid)

ESM2 similar proteins: A2AR95, A4IHY6, B7ZWI3, D3ZF92, O15165, O43278, O75509, O88204, P98153, P98154, Q0VBF2, Q1L8G6, Q29RU0, Q4KMG9, Q566M8, Q5DTZ6, Q5HZW5, Q5R662, Q5R8E0, Q5RD34, Q5RF74, Q5VUB5, Q61003, Q68FU0, Q6AXS2, Q6NRX0, Q6UWW9, Q6ZPS6, Q6ZUJ8, Q7TQH7, Q86YD5, Q8BGN6, Q8BLD6, Q8BUJ9, Q8R182, Q8TEB7, Q8WUU8, Q91ZV2, Q91ZV3, Q96PD2

Diamond homologs: A5WWA0, E9QAU8, G3X9R7, O22197, O22755, O43567, O54965, O64763, P0C034, P0CH30, P0DPR2, Q06003, Q07G42, Q08D68, Q0II22, Q0VD51, Q10R93, Q14B02, Q29RU0, Q2TA44, Q3U2C5, Q4KLR8, Q4R6Y5, Q5NCP0, Q5RCV8, Q5RF74, Q5SPX3, Q5SSZ7, Q5XF85, Q641J8, Q66HG0, Q68DV7, Q69U49, Q6AY01, Q6DIP3, Q6IRP0, Q6NML0, Q6NQG7, Q6NRX0, Q6Y290

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF128	ubiquitination
RNF128	“up-regulates quantity by stabilization”	ARHGDIB	polyubiquitination
RNF128	“up-regulates quantity by stabilization”	ARHGDIA	polyubiquitination
RNF128	“down-regulates quantity by destabilization”	CD83	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

906 predictions. Top by Δscore:

Variant	Effect	Δscore
X:106727396:GG:G	donor_gain	1.0000
X:106727397:GG:G	donor_gain	1.0000
X:106785061:A:AG	acceptor_gain	1.0000
X:106785062:CA:C	acceptor_loss	1.0000
X:106785063:A:AG	acceptor_gain	1.0000
X:106785063:AGAG:A	acceptor_gain	1.0000
X:106785064:G:A	acceptor_loss	1.0000
X:106785064:G:GA	acceptor_gain	1.0000
X:106785064:GA:G	acceptor_gain	1.0000
X:106785064:GAGG:G	acceptor_gain	1.0000
X:106785064:GAGGC:G	acceptor_gain	1.0000
X:106785132:ACAAG:A	donor_loss	1.0000
X:106785133:CAAG:C	donor_loss	1.0000
X:106785134:AAG:A	donor_loss	1.0000
X:106785135:AGGT:A	donor_loss	1.0000
X:106785137:GT:G	donor_loss	1.0000
X:106785138:T:G	donor_loss	1.0000
X:106788001:G:GG	donor_gain	1.0000
X:106791053:AT:A	acceptor_gain	1.0000
X:106791054:T:G	acceptor_gain	1.0000
X:106791064:A:AT	acceptor_loss	1.0000
X:106791064:AGGT:A	acceptor_gain	1.0000
X:106791065:GGTG:G	acceptor_gain	1.0000
X:106791233:AAG:A	donor_loss	1.0000
X:106791234:AG:A	donor_loss	1.0000
X:106791235:G:GA	donor_loss	1.0000
X:106791235:G:GG	donor_gain	1.0000
X:106791236:TA:T	donor_loss	1.0000
X:106791237:AA:A	donor_loss	1.0000
X:106795578:A:AG	acceptor_gain	1.0000

AlphaMissense

2781 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:106727199:T:A	C96S	1.000
X:106727200:G:A	C96Y	1.000
X:106727200:G:C	C96S	1.000
X:106727218:T:C	F102S	1.000
X:106727218:T:G	F102C	1.000
X:106727289:T:A	C126S	1.000
X:106727289:T:C	C126R	1.000
X:106727290:G:C	C126S	1.000
X:106727295:T:C	F128L	1.000
X:106727296:T:G	F128C	1.000
X:106727297:C:A	F128L	1.000
X:106727297:C:G	F128L	1.000
X:106727306:G:C	K131N	1.000
X:106727306:G:T	K131N	1.000
X:106727344:T:A	V144D	1.000
X:106727354:C:A	N147K	1.000
X:106727354:C:G	N147K	1.000
X:106772954:G:C	G176R	1.000
X:106772955:G:A	G176D	1.000
X:106787942:T:A	C277S	1.000
X:106787942:T:C	C277R	1.000
X:106787943:G:A	C277Y	1.000
X:106787943:G:C	C277S	1.000
X:106787943:G:T	C277F	1.000
X:106787944:T:G	C277W	1.000
X:106787946:C:A	A278D	1.000
X:106787951:T:A	C280S	1.000
X:106787951:T:C	C280R	1.000
X:106787952:G:A	C280Y	1.000
X:106787952:G:C	C280S	1.000

dbSNP variants (sampled 300 via entrez): RS1000000987 (X:106752849 G>T), RS1000069058 (X:106778694 C>G,T), RS1000081511 (X:106708198 C>G), RS1000098252 (X:106778041 AAC>A), RS1000179292 (X:106743753 G>T), RS1000187733 (X:106730882 G>C), RS1000216499 (X:106734267 C>T), RS1000247127 (X:106715395 C>T), RS1000251799 (X:106762871 G>T), RS1000252987 (X:106791993 A>C,G), RS1000277725 (X:106768003 A>G,T), RS1000317613 (X:106737718 A>C), RS1000345122 (X:106768684 T>C), RS1000491251 (X:106787181 C>G), RS1000496670 (X:106748777 G>T)

Disease associations

OMIM: gene MIM:300439 | disease phenotypes: MIM:601086

GenCC curated gene-disease

Mondo (1): laterality defects, autosomal dominant (MONDO:0010991)

Orphanet (1): Visceral heterotaxy (Orphanet:450)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004860_2	Alcoholic chronic pancreatitis	2.000000e-09
GCST004860_63	Alcoholic chronic pancreatitis	3.000000e-06
GCST004860_66	Alcoholic chronic pancreatitis	6.000000e-20
GCST004860_97	Alcoholic chronic pancreatitis	1.000000e-24
GCST007876_36	Estimated glomerular filtration rate	2.000000e-20
GCST007877_25	Creatinine levels	8.000000e-20

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563391	Laterality Defects, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Particulate Matter	decreases expression, increases abundance	3
bisphenol A	affects expression, decreases expression, increases methylation	2
Air Pollutants	decreases expression, increases abundance	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
ciglitazone	affects binding, increases expression	1
dinophysistoxin 1	decreases expression	1
2-palmitoylglycerol	increases expression	1
nickel acetate	affects expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
prothioconazole	increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Doxorubicin	increases expression	1
Melphalan	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Isotretinoin	decreases expression	1

Clinical trials (associated diseases)

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