UBD

Summary

UBD (ubiquitin like modifier D, HGNC:18795) is a protein-coding gene on chromosome 6p22.1, encoding Ubiquitin D (O15205). Ubiquitin-like protein modifier which can be covalently attached to target proteins and subsequently leads to their degradation by the 26S proteasome, in a NUB1-dependent manner.

This gene encodes a protein which contains two ubiquitin-like domains and appears to have similar function to ubiquitin. Through covalent attachment, the encoded protein targets other proteins for 26S proteasome degradation. This protein has been implicated to function in many cellular processes, including caspase-dependent apoptosis, formation of aggresomes, mitotic regulation, and dendritic cell maturation. Upregulation of this gene may promote inflammation in chronic kidney disease and has been observed in many cancer types.

Source: NCBI Gene 10537 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_006398

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18795
Approved symbol	UBD
Name	ubiquitin like modifier D
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	FAT10
Ensembl gene	ENSG00000213886
Ensembl biotype	protein_coding
OMIM	606050
Entrez	10537

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000377050, ENST00000866140

RefSeq mRNA: 1 — MANE Select: NM_006398 NM_006398

CCDS: CCDS4662

Canonical transcript exons

ENST00000377050 — 2 exons

Exon	Start	End
ENSE00001749025	29559675	29559732
ENSE00001897660	29555515	29556350

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 98.46.

FANTOM5 (CAGE): breadth broad, TPM avg 15.4982 / max 930.7772, expressed in 489 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72450	15.4982	489

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	98.46	gold quality
lymph node	UBERON:0000029	98.15	gold quality
islet of Langerhans	UBERON:0000006	94.57	gold quality
rectum	UBERON:0001052	89.84	gold quality
gall bladder	UBERON:0002110	87.93	gold quality
adult mammalian kidney	UBERON:0000082	86.83	gold quality
tonsil	UBERON:0002372	86.60	gold quality
pancreas	UBERON:0001264	86.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.60	gold quality
liver	UBERON:0002107	84.21	gold quality
spleen	UBERON:0002106	83.78	gold quality
metanephros cortex	UBERON:0010533	83.29	gold quality
body of pancreas	UBERON:0001150	82.79	gold quality
kidney	UBERON:0002113	81.38	gold quality
cortex of kidney	UBERON:0001225	80.77	gold quality
saliva-secreting gland	UBERON:0001044	79.64	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.22	gold quality
minor salivary gland	UBERON:0001830	79.02	gold quality
duodenum	UBERON:0002114	78.40	gold quality
right lobe of liver	UBERON:0001114	77.93	gold quality
small intestine	UBERON:0002108	77.76	gold quality
mucosa of transverse colon	UBERON:0004991	76.20	gold quality
calcaneal tendon	UBERON:0003701	74.16	gold quality
colonic epithelium	UBERON:0000397	71.75	gold quality
smooth muscle tissue	UBERON:0001135	71.12	gold quality
esophagus mucosa	UBERON:0002469	71.12	gold quality
prostate gland	UBERON:0002367	70.25	gold quality
thoracic mammary gland	UBERON:0005200	69.76	gold quality
intestine	UBERON:0000160	69.41	gold quality
lung	UBERON:0002048	68.14	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	230.95
E-CURD-122	yes	118.64
E-ANND-3	yes	3.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

14 targeting UBD, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-576-3P	96.14	65.63	773
HSA-MIR-550B-3P	95.43	67.73	599

Literature-anchored findings (GeneRIF, showing 40)

• FAT10 may modulate tumorigenesis through its reported interaction with the MAD2 spindle-assembly checkpoint protein. (PMID:12730673)
• FAT10 is degraded by the proteasome in ubiqitin-independent manner. (PMID:15831455)
• high levels of FAT10 protein in cells lead to increased mitotic nondisjunction and chromosome instability, which is mediated by an abbreviated mitotic phase and reduction in the kinetochore localization of MAD2 during prometaphase (PMID:16495226)
• Immunohistochemical studies demonstrated increased FAT10 expression in HIV-associated nephropathy and in autosomal dominant polycystic kidney disease. (PMID:16495380)
• A deletion mutant of NUB1L lacking the UBL domain is still able to bind FAT10 but not the proteasome and no longer accelerates FAT10 degradation (PMID:16707496)
• The identification of an E1-like protein, termed E1-L2, that activates both ubiquitin and another ubiquitin-like protein, FAT10, is reported. (PMID:17889673)
• FAT10 qualifies as a marker for an interferon response in hepatocellular carcinoma and colon carcinoma but is not significantly overexpressed in cancers lacking a proinflammatory environment. (PMID:18574467)
• A new binding partner of HDAC6, the ubiquitin-like modifier FAT10 was identified. (PMID:19033385)
• Structural basis for recognition of diubiquitins by NEMO. (PMID:19185524)
• Study reports the crystal structure of the UBAN motif of NEMO bound to linear diubiquitin chains and provide structural and biochemical evidence for the specificity of this interaction versus interactions with Lys63- or Lys48-linked diubiquitin chains (PMID:19303852)
• Data show that FAT10 and mutant p53 levels in gastric cancer tissue were significantly correlated with lymph node metastasis and tumor, nodes, metastasis staging. (PMID:19437562)
• critical mediator of HIV Vpr-induced apoptosis in renal tubular epithelial cells (PMID:19726511)
• Reverse transcriptase-polymerase chain reaction analysis of intestinal biopsy sample pairs (at diagnosis vs treated) from 30 celiac disease patients confirmed overexpression of UBD in active disease tissue. (PMID:19808075)
• USE1 is not only the first E2 enzyme but also the first known substrate of FAT10 conjugation, as it was efficiently auto-FAT10ylated in cis but not in trans. (PMID:20975683)
• These data reveal that VHS domain of Stam2 enters the hydrophobic pocket of K48-linked diubiquitin and binds the two ubiquitin subunits with different affinities. (PMID:21121635)
• Genetic polymorphism in UBD is associated with colorectal cancer. (PMID:21351261)
• The p53 transcriptional activity was found to be substantially enhanced in FAT10-overexpressing cells. (PMID:21396347)
• Data indicate that the 20,000-bp region is telomeric of the UBD gene and contains LOC729653, a hypothetical gene. (PMID:21631897)
• new role for FAT10 in the pathogenesis of polyglutamine diseases. (PMID:21757738)
• FAT10 plays an important role in mediating the function of TNF-alpha during tumorigenesis by inducing cell cycle deregulation and chromosomal instability. (PMID:22025632)
• Degradation of FAT10 is accelerated after induction of apoptosis, suggesting that it plays a role in prosurvival pathways (PMID:22072791)
• An extract of bark from the tropical rainforest plant Byrsonima crassifolia was screened for inhibition of diubiquitin formation by the human ubiquitin-conjugating enzyme E2-25K. (PMID:22164771)
• In this study a crystal structure of linear diubiquitin at a resolution of 2.2 A degrees is reported. (PMID:22281738)
• Ten SNPs in FAT10 were identified. (PMID:22292662)
• implicate FAT10 in retinal cell biology and Leber congenital amaurosis pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway. (PMID:22347407)
• FAT10 modification of the HCMV-derived antigen pp65 (FAT10-pp65) enhances the presentation of the HLA-A2-restricted pp65495-509 antigenic peptide and provide evidence that FAT10- pp65 differs from Ub-modified pp65 in using the proteasome machinery. (PMID:22349260)
• Immunohistochemistry showed that FAT10 protein was over-expressed in glioma tissues. Expression level of FAT10 increase from grade I to grade IV glioma according to the results of real-time PCR, immunohistochemistry analysis and Western blot. (PMID:22402871)
• Data indicate the potential role of cytokine-induced FAT10 expression in regulating Uba6 pathways. (PMID:22427669)
• findings show how FAT10 and NUB1L dock with the 26S proteasome to initiate proteolysis; identified the 26S proteasome subunit hRpn10/S5a as the receptor for FAT10, whereas NUB1L can bind to both Rpn10 and Rpn1/S2. (PMID:22434192)
• This study identified eEF1A1 as a FAT10-specific binding protein, and when the expression of FAT10 was reduced by siRNA knockdown, this resulted in downregulation of eEF1A1 expression in hepatoma cells. (PMID:22569823)
• p62 becomes covalently mono-FAT10ylated at several lysines, and FAT10 colocalizes with p62 in p62 bodies. (PMID:22797925)
• FATylation of LRRFIP2 occurs on two distinct sites, each being modified by a single FAT10 moiety. (PMID:23036196)
• FAT10 protects cardiac myocytes against apoptosis. (PMID:23416168)
• FAT10 has a central role in regulating diverse aspects of the pathogenesis of hepatocellular carcinoma. (PMID:23812429)
• functional distribution of the FAT10 targets suggests that FAT10 participates in various biological processes, such as translation, protein folding, RNA processing, and macromolecular complex assembly (PMID:23862649)
• FAT10 can induce malignant transformation as evidenced from the anchorage-independent growth as well as in vivo tumor-forming abilities of FAT10-overexpressing NeHepLxHT cells. (PMID:24325913)
• These results suggest that knockdown of FAT10 by adenovirus-delivered siRNA may be a promising therapeutical strategy for treatment of hepatocellular carcinoma. (PMID:24440736)
• FAT10 expression in pancreatic ductal adenocarcinoma (PDAC) was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of PDAC (PMID:24492942)
• STAT3 and NFkappaB synergistically act for maximum induction of FAT10 expression. (PMID:24518302)
• transcription downregulation of the Ufm1 and FAT10 conjugation system in liver Mallory-Denk bodies formation (PMID:24893112)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ubd	ENSMUSG00000035186
rattus_norvegicus	AC112568.1	ENSRNOG00000000767

Paralogs (10): UBL4A (ENSG00000102178), NEDD8 (ENSG00000129559), RPS27A (ENSG00000143947), UBC (ENSG00000150991), UBB (ENSG00000170315), ZFAND4 (ENSG00000172671), UBL4B (ENSG00000186150), ISG15 (ENSG00000187608), ANKUB1 (ENSG00000206199), UBA52 (ENSG00000221983)

Protein

Protein identifiers

Ubiquitin D — O15205 (reviewed: O15205)

Alternative names: Diubiquitin, Ubiquitin-like protein FAT10

All UniProt accessions (2): A0A1U9X8S6, O15205

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-like protein modifier which can be covalently attached to target proteins and subsequently leads to their degradation by the 26S proteasome, in a NUB1-dependent manner. Conjugation to the target protein is activated by UBA6 via adenylation of its C-terminal glycine. Promotes the expression of the proteasome subunit beta type-9 (PSMB9/LMP2). Regulates TNF-induced and LPS-mediated activation of the central mediator of innate immunity NF-kappa-B by promoting TNF-mediated proteasomal degradation of ubiquitinated-I-kappa-B-alpha. Required for TNF-induced p65 nuclear translocation in renal tubular epithelial cells (RTECs). May be involved in dendritic cell (DC) maturation, the process by which immature dendritic cells differentiate into fully competent antigen-presenting cells that initiate T-cell responses. Mediates mitotic non-disjunction and chromosome instability, in long-term in vitro culture and cancers, by abbreviating mitotic phase and impairing the kinetochore localization of MAD2L1 during the prometaphase stage of the cell cycle. May be involved in the formation of aggresomes when proteasome is saturated or impaired. Mediates apoptosis in a caspase-dependent manner, especially in renal epithelium and tubular cells during renal diseases such as polycystic kidney disease and Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN).

Subunit / interactions. Interacts directly with the 26S proteasome. Interacts with NUB1; this interaction facilitates the linking of UBD-conjugated target protein to the proteasome complex and accelerates its own degradation and that of its conjugates. Interacts (via ubiquitin-like 1 domain) with the spindle checkpoint protein MAD2L1 during mitosis. Present in aggresomes of proteasome inhibited cells. Interacts with HDAC6 under proteasome impairment conditions. Forms a thioester with UBA6 in cells stimulated with tumor necrosis factor-alpha (TNFa) and interferon-gamma (IFNg). Interacts with SQSTM1 and TP53/p53.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Constitutively expressed in mature dendritic cells and B-cells. Mostly expressed in the reticuloendothelial system (e.g. thymus, spleen), the gastrointestinal system, kidney, lung and prostate gland.

Post-translational modifications. Can be acetylated.

Induction. Rapidly degraded by the proteasome. Cell-cycle regulation with highest expression during the S-phase (at protein level). Induced during dendritic cell maturation. Negatively regulated by p53/TP53. High levels in various gastrointestinal and gynecological cancer cells. Induced in RTECs in common renal diseases including diabetic nephropathy (DN), IgA nephropathy (IgAN), and hypertensive nephrosclerosis (HN), as well as in hepatocellular carcinoma (HCC) and during HIVAN. Inducible by the pro-inflammatory cytokines IFNG/IFN-gamma and TNF in cancers of liver and colon. Repressed by NUB1 (at protein level).

Miscellaneous. Common types of chronic kidney disease are associated with tubulointerstitial up-regulation of FAT10. FAT10 may mediate NF-kappa-B activation and may promote tubulointerstitial inflammation in chronic kidney diseases.

Similarity. Belongs to the ubiquitin D family.

RefSeq proteins (1): NP_006389* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR019956	Ubiquitin_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR042969	Ubiquitin_D	Family

Pfam: PF00240

UniProt features (32 total): strand 9, sequence variant 7, mutagenesis site 6, helix 5, domain 2, chain 1, turn 1, site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6GF1	X-RAY DIFFRACTION	1.93
9E8O	ELECTRON MICROSCOPY	3.1
7PYV	X-RAY DIFFRACTION	3.27
2MBE	SOLUTION NMR
6GF2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15205-F1	85.60	0.41

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): 164–165 (activation by thioester intermediate formation with uba6)

Mutagenesis-validated functional residues (6):

Position	Phenotype
11	decreases interaction with mad2l1, no effect on the interaction with hdac6, uba6, nub1 and sqstm1 and moderately attenua
13	decreases interaction with mad2l1, no effect on the interaction with hdac6, uba6, nub1 and sqstm1 and moderately attenua
75	decreases interaction with mad2l1, no effect on the interaction with hdac6, uba6, nub1 and sqstm1 and moderately attenua
77	decreases interaction with mad2l1, no effect on the interaction with hdac6, uba6, nub1 and sqstm1 and moderately attenua
79	decreases interaction with mad2l1, no effect on the interaction with hdac6, uba6, nub1 and sqstm1 and moderately attenua
164–165	impaired thioester formation-mediated activation by uba6. loss of interaction with uba6 and sqstm1. no effect on its int

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 171 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, MODULE_172, CREL_01, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_PEPTIDE, MODULE_545, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, PATIL_LIVER_CANCER, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, MODULE_75, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1

GO Biological Process (12): proteolysis (GO:0006508), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), protein modification by small protein conjugation (GO:0032446), response to type II interferon (GO:0034341), response to tumor necrosis factor (GO:0034612), myeloid dendritic cell differentiation (GO:0043011), positive regulation of apoptotic process (GO:0043065), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), aggresome assembly (GO:0070842), regulation of mitotic cell cycle phase transition (GO:1901990), response to stress (GO:0006950)

GO Molecular Function (2): proteasome binding (GO:0070628), protein binding (GO:0005515)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), aggresome (GO:0016235)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
response to cytokine	2
protein metabolic process	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
protein modification by small protein conjugation or removal	1
innate immune response	1
myeloid dendritic cell activation	1
myeloid leukocyte differentiation	1
dendritic cell differentiation	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
inclusion body assembly	1
regulation of mitotic cell cycle	1
mitotic cell cycle phase transition	1
regulation of cell cycle phase transition	1
response to stimulus	1
protein-containing complex binding	1
binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
inclusion body	1

Protein interactions and networks

STRING

4102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBD	UBA6	A0AVT1	955
UBD	UBE2R2	Q712K3	806
UBD	NEDD8	Q15843	785
UBD	NUB1	Q9Y5A7	771
UBD	UBA1	P22314	741
UBD	HLA-F	P30511	728
UBD	PSMD4	P55036	715
UBD	UFM1	P61960	694
UBD	URM1	Q9BTM9	673
UBD	GABARAPL2	P60520	672
UBD	PHF20	Q9BVI0	663
UBD	F5GZY7	F5GZY7	656
UBD	SUMO2	P55855	643
UBD	ZUP1	Q96AP4	627
UBD	ISG15	P05161	597

IntAct

20 interactions, top by confidence:

A	B	Type	Score
MAPK8IP2	UBD	psi-mi:“MI:0915”(physical association)	0.570
UBD	MAPK8IP2	psi-mi:“MI:0915”(physical association)	0.570
UBD	PDE9A	psi-mi:“MI:0915”(physical association)	0.560
PRKN	UBD	psi-mi:“MI:0915”(physical association)	0.560
UBD	SNCA	psi-mi:“MI:0915”(physical association)	0.560
UBD	UBE2Z	psi-mi:“MI:0915”(physical association)	0.520
UBD	NUB1	psi-mi:“MI:0915”(physical association)	0.500
SRPK2	UBD	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
UBD	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
UBD	RABGGTA	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350
UBD	PDE9A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (95): TOR1AIP2 (Affinity Capture-Western), UBD (Two-hybrid), UBD (Affinity Capture-Luminescence), DDX58 (Affinity Capture-Western), UBD (Affinity Capture-Western), MAD2L1 (Reconstituted Complex), MAD2L1 (Affinity Capture-Western), UBA6 (Affinity Capture-Western), NUB1 (Affinity Capture-Western), HDAC6 (Affinity Capture-Western), SQSTM1 (Affinity Capture-Western), MAD2L1 (Co-localization), UBA6 (Co-localization), NUB1 (Co-localization), HDAC6 (Co-localization)

ESM2 similar proteins: A0A1I1P2K9, A0AUS0, A4QND0, D3ZHP7, O02741, O15205, O55222, O65381, O97628, P05161, P0C2F1, P34934, P52333, P55812, P62865, P62868, P63072, Q03919, Q05474, Q0D261, Q2KI24, Q2NKY8, Q38SD2, Q3EBD3, Q3U3Q1, Q3UHC2, Q54TK0, Q5BJS0, Q5BK10, Q5FWY5, Q5R607, Q5ZI74, Q5ZJH6, Q60435, Q62137, Q63272, Q64339, Q6I7R3, Q6K881, Q6MZZ7

Diamond homologs: B9DHA6, C4YP88, O15205, P0C273, P0CG47, P0CG48, P0CG49, P0CG50, P0CG51, P0CG53, P0CG54, P0CG55, P0CG60, P0CG61, P0CG62, P0CG63, P0CG64, P0CG65, P0CG66, P0CG67, P0CG68, P0CG69, P0CG70, P0CG71, P0CG72, P0CG73, P0CG74, P0CG75, P0CG76, P0CG77, P0CG78, P0CG79, P0CG80, P0CG81, P0CG82, P0CG83, P0CG84, P0CG85, P0CG86, P0CG87

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

341 predictions. Top by Δscore:

Variant	Effect	Δscore
6:29556346:TGCAC:T	acceptor_gain	1.0000
6:29556348:CAC:C	acceptor_gain	1.0000
6:29556351:C:A	acceptor_loss	1.0000
6:29556352:T:G	acceptor_loss	1.0000
6:29556347:GCAC:G	acceptor_gain	0.9900
6:29556348:CACC:C	acceptor_gain	0.9900
6:29556351:C:CC	acceptor_gain	0.9900
6:29556358:G:C	acceptor_gain	0.9900
6:29556358:G:GC	acceptor_gain	0.9900
6:29556349:AC:A	acceptor_gain	0.9800
6:29556350:CC:C	acceptor_gain	0.9800
6:29559674:CA:C	donor_gain	0.9800
6:29558561:CGG:C	donor_gain	0.9700
6:29559673:A:AC	donor_gain	0.9700
6:29559674:C:CC	donor_gain	0.9700
6:29558561:CGGCT:C	donor_gain	0.9600
6:29558490:C:CA	donor_gain	0.9500
6:29558560:A:AC	donor_gain	0.9300
6:29558561:C:CC	donor_gain	0.9300
6:29559674:CACA:C	donor_gain	0.9300
6:29558706:C:A	acceptor_gain	0.9200
6:29559674:CACAG:C	donor_gain	0.9200
6:29558584:G:A	donor_gain	0.9100
6:29558707:T:A	acceptor_gain	0.9100
6:29559668:AACTT:A	donor_loss	0.9100
6:29559669:ACTTA:A	donor_loss	0.9100
6:29559670:CTT:C	donor_loss	0.9100
6:29559671:TT:T	donor_loss	0.9100
6:29558631:T:TA	donor_gain	0.8900
6:29559672:TAC:T	donor_gain	0.8800

AlphaMissense

1075 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:29555907:G:C	F157L	0.876
6:29555907:G:T	F157L	0.876
6:29555909:A:G	F157L	0.876
6:29556268:A:T	V37D	0.832
6:29556030:T:A	K116N	0.824
6:29556030:T:G	K116N	0.824
6:29556208:A:G	L57S	0.816
6:29556343:A:T	V12D	0.813
6:29556312:A:C	F22L	0.799
6:29556312:A:T	F22L	0.799
6:29556314:A:G	F22L	0.799
6:29555983:A:T	V132E	0.793
6:29556151:A:G	L76P	0.784
6:29555944:A:T	M145K	0.720
6:29555971:C:A	G136V	0.713
6:29556034:A:T	V115E	0.712
6:29555944:A:C	M145R	0.710
6:29556043:A:T	V112E	0.705
6:29556235:T:G	Q48P	0.705
6:29556229:A:T	L50H	0.700
6:29556265:C:G	R38P	0.700
6:29556280:A:G	I33T	0.693
6:29556229:A:C	L50R	0.690
6:29556234:C:A	Q48H	0.686
6:29556234:C:G	Q48H	0.686
6:29556031:T:A	K116I	0.681
6:29556280:A:C	I33S	0.677
6:29556229:A:G	L50P	0.676
6:29555988:C:A	Q130H	0.675
6:29555988:C:G	Q130H	0.675

dbSNP variants (sampled 300 via entrez): RS1000246981 (6:29558868 G>A), RS1000612349 (6:29557520 G>A), RS1000622253 (6:29557873 A>G), RS1000923103 (6:29558332 C>A), RS1000958775 (6:29558580 G>A,T), RS1001302137 (6:29560512 A>G), RS1002149720 (6:29557371 T>G), RS1002923547 (6:29561047 G>C,T), RS1002993707 (6:29561362 G>A,C), RS1003461075 (6:29555476 G>A,C), RS1003527125 (6:29556962 T>C), RS1003983473 (6:29555153 C>G,T), RS1006141215 (6:29557329 C>T), RS1006317179 (6:29556910 T>C), RS1006431596 (6:29556620 C>A,T)

Disease associations

OMIM: gene MIM:606050 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST001438_6	Crohn’s disease	2.000000e-10
GCST002702_7	Height	2.000000e-24
GCST004521_112	Autism spectrum disorder or schizophrenia	3.000000e-26
GCST004521_171	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_263	Autism spectrum disorder or schizophrenia	7.000000e-17
GCST004521_268	Autism spectrum disorder or schizophrenia	7.000000e-12
GCST004521_295	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_56	Autism spectrum disorder or schizophrenia	1.000000e-22
GCST004521_58	Autism spectrum disorder or schizophrenia	1.000000e-17
GCST010002_46	Refractive error	2.000000e-20
GCST010083_91	Hemoglobin levels	1.000000e-19
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16
GCST90011900_181	Serum alkaline phosphatase levels	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	6
Cyclosporine	decreases expression, increases expression	4
Estradiol	decreases expression, increases expression, affects cotreatment	3
Tetrachlorodibenzodioxin	increases expression	3
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tretinoin	increases expression	2
Valproic Acid	affects expression, decreases expression	2
TL8-506	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
methylparaben	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
1,2,5,6-dibenzanthracene	increases expression	1
nickel sulfate	increases expression	1
butylparaben	decreases expression	1
octa-2,4,6-trienoic acid	increases expression	1
gadodiamide	increases expression	1
CGP 52608	affects binding, increases reaction	1
LG 100815	increases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	decreases expression	1
Arsenic	affects methylation	1
Azathioprine	decreases expression	1
Diethylhexyl Phthalate	increases methylation, increases abundance	1

Clinical trials (associated diseases)

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