UXT

Summary

UXT (ubiquitously expressed prefoldin like chaperone, HGNC:12641) is a protein-coding gene on chromosome Xp11.23, encoding Protein UXT (Q9UBK9). Involved in gene transcription regulation.

The protein encoded by this gene functions as a cofactor that modulates androgen receptor-dependent transcription, and also plays a critical role in tumor necrosis factor-induced apoptosis. Expression of this gene may play a role in tumorigenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 8409 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_004182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12641
Approved symbol	UXT
Name	ubiquitously expressed prefoldin like chaperone
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	ART-27, STAP1, SKP2
Ensembl gene	ENSG00000126756
Ensembl biotype	protein_coding
OMIM	300234
Entrez	8409

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000333119, ENST00000335890, ENST00000376964, ENST00000460840, ENST00000485641, ENST00000936478, ENST00000936479, ENST00000936480, ENST00000936481

RefSeq mRNA: 2 — MANE Select: NM_004182 NM_004182, NM_153477

CCDS: CCDS14284, CCDS14285

Canonical transcript exons

ENST00000333119 — 7 exons

Exon	Start	End
ENSE00000867049	47651796	47651895
ENSE00000867052	47657572	47657639
ENSE00001302861	47659115	47659180
ENSE00003476137	47657782	47657863
ENSE00003480350	47652081	47652144
ENSE00003582928	47658830	47658936
ENSE00003670801	47657183	47657290

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.8435 / max 214.2898, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199142	45.4584	1821
199141	2.3851	1337

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	98.74	gold quality
body of pancreas	UBERON:0001150	98.68	gold quality
granulocyte	CL:0000094	98.58	gold quality
right ovary	UBERON:0002118	98.55	gold quality
ganglionic eminence	UBERON:0004023	98.50	gold quality
skin of abdomen	UBERON:0001416	98.29	gold quality
skin of leg	UBERON:0001511	98.28	gold quality
lymph node	UBERON:0000029	98.26	gold quality
body of stomach	UBERON:0001161	98.20	gold quality
left adrenal gland cortex	UBERON:0035825	98.20	gold quality
ovary	UBERON:0000992	98.18	gold quality
mucosa of transverse colon	UBERON:0004991	98.17	gold quality
right adrenal gland	UBERON:0001233	98.16	gold quality
right adrenal gland cortex	UBERON:0035827	98.15	gold quality
left adrenal gland	UBERON:0001234	98.13	gold quality
endocervix	UBERON:0000458	98.05	gold quality
bone marrow	UBERON:0002371	98.05	gold quality
adrenal cortex	UBERON:0001235	98.00	gold quality
minor salivary gland	UBERON:0001830	98.00	gold quality
spleen	UBERON:0002106	97.98	gold quality
mucosa of stomach	UBERON:0001199	97.95	gold quality
right atrium auricular region	UBERON:0006631	97.94	gold quality
adenohypophysis	UBERON:0002196	97.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.89	gold quality
zone of skin	UBERON:0000014	97.87	gold quality
descending thoracic aorta	UBERON:0002345	97.86	gold quality
left coronary artery	UBERON:0001626	97.85	gold quality
ectocervix	UBERON:0012249	97.85	gold quality
thoracic aorta	UBERON:0001515	97.83	gold quality
ascending aorta	UBERON:0001496	97.82	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-85	no	490.70
E-CURD-11	no	183.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CREB1, E2F1, E2F4, E2F6, MYC

Literature-anchored findings (GeneRIF, showing 29)

• UXT was identified in a screen for proteins that interact with the Androgen Receptor N-terminal activation domain. We termed the protein Androgen Receptor Trapped clone 27 (ART-27). ART-27 appears to function as a transcriptional coactivator protein. (PMID:11854421)
• decreased levels of ART-27 protein in prostate cancer tissue may occur as a result of de-differentiation, and indicate that ART-27 is likely to regulate a subset of AR-responsive genes important to prostate growth suppression and differentiation. (PMID:14711828)
• UXT is a component of centrosome and is essential for cell viability and may facilitate transformation by corrupting regulated centrosome functions. (PMID:16221885)
• Increasing concentrations of UXT contributes to progressive aggregation of mitochondria. (PMID:17554592)
• UXT is a novel and essential cofactor in the NF-kappa B transcriptional enhanceosome. (PMID:17620405)
• UXT suppresses cell transformation and might mediate this function by interaction and inhibition of the biological activity of cell proliferation and survival stimulatory factors like ecotropic viral integration site 1 (PMID:17635584)
• propose a transcriptional regulatory circuit for the developmental expression of ART-27 that includes repression by chromatin modification through a trichostatin A-sensitive factor and activation upon growth factor stimulation via CREB (PMID:17761951)
• Loss of ART-27 enhances expression of many androgen-regulated genes, suggesting that ART-27 inhibits gene expression, and nuclear ART-27 expression was lost in the majority of AR-positive recurrent prostate cancers. (PMID:19318562)
• Is part of an RNA polymerase II-associated complex with possible chaperone activity. (PMID:19450687)
• Ubiquitously expressed transcript, UXT-V1, is a novel regulator of TNF-induced apoptosis. It protects cells against TNF-induced apoptosis through modulating complex II formation. (PMID:21307340)
• Data show that while Art-27 can bind AR directly, URI is bound to chromatin prior to hormone-dependent recruitment of AR, suggesting a role for URI in modulating AR recruitment to target genes. (PMID:21730289)
• these results suggest that Als2 is a binding partner of Uxt and Als2/Uxt interaction could be important for the activation of Nf-kappaB pathway. (PMID:21907703)
• UXT-V1 represents a novel integral component of the MAVS signalosome on mitochondria, mediating the innate antiviral signal transduction. (PMID:22131337)
• Epstein-Barr virus BGLF4 kinase downregulates NF-kappaB transactivation through phosphorylation of coactivator UXT (PMID:22933289)
• VHL-UXT interaction and VHL-induced ubiquitination of androgen receptor(AR) regulate transcriptional activation of the AR. (PMID:23961993)
• Data found that the UXT isoforms elicit dual opposing regulatory effects on SARM-induced apoptosis. (PMID:24021647)
• Knockdown of UXT expression in Treg cells results in a less-suppressive phenotype. (PMID:24136450)
• Art27 interacts with GATA4, FOG2 and NKX2.5 and is a novel co-repressor of cardiac genes. (PMID:24743694)
• UXT is a binding protein of PIAS2, and interaction between PIAS2 and UXT may be important for the transcriptional activation of AR. (PMID:25434787)
• we describe the identification of UXT as a novel MDMX-interacting protein (PMID:25974965)
• EZH1, SUZ12 and UXT work synergistically to regulate pathway activation in the nucleus. (PMID:27127229)
• UXT Is a LOX-PP Interacting Protein That Modulates Estrogen Receptor Alpha Activity in Breast Cancer Cells. (PMID:28106301)
• The ubiquitous expressed transcript (UXT) interacts with the polycomb repressive complex 2 (PRC2) through directly binding to the enhancer of zeste homolog 2 (EZH2) and suppressor of zeste 12 homolog (SUZ12) in the nucleus. Knockdown of UXT inhibits proliferation, colony formation, migration and invasion of renal cancer cells, in an EZH2-dependent manner. UXT expression is upregulated in clear cell renal cell carcinoma. (PMID:31481081)
• Mice deficient in UXT exhibit retinitis pigmentosa-like features via aberrant autophagy activation. (PMID:32744119)
• The E3 ubiquitin ligase SCF(Fbxo7) mediates proteasomal degradation of UXT isoform 2 (UXT-V2) to inhibit the NF-kappaB signaling pathway. (PMID:33010352)
• UXT chaperone prevents proteotoxicity by acting as an autophagy adaptor for p62-dependent aggrephagy. (PMID:33782410)
• HOXD9 transcriptionally induced UXT facilitate breast cancer progression via epigenetic modification of RND3. (PMID:34767964)
• Prefoldin and prefoldin-like complex subunits as predictive biomarkers for hepatocellular carcinoma immunotherapy. (PMID:35217267)
• MYB regulates the SUMO protease SENP1 and its novel interaction partner UXT, modulating MYB target genes and the SUMO landscape. (PMID:37468105)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	uxt	ENSDARG00000019339
mus_musculus	Uxt	ENSMUSG00000001134
rattus_norvegicus	Uxt	ENSRNOG00000085857

Protein

Protein identifiers

Protein UXT — Q9UBK9 (reviewed: Q9UBK9)

Alternative names: Androgen receptor trapped clone 27 protein, Ubiquitously expressed transcript protein

All UniProt accessions (2): Q9UBK9, S4R2Z4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in gene transcription regulation. Acts in concert with the corepressor URI1 to regulate androgen receptor AR-mediated transcription. Together with URI1, associates with chromatin to the NKX3-1 promoter region. Negatively regulates the transcriptional activity of the estrogen receptor ESR1 by inducing its translocation into the cytoplasm. May act as nuclear chaperone that facilitates the formation of the NF-kappa-B enhanceosome and thus positively regulates NF-kappa-B transcription activity. Potential component of mitochondrial-associated LRPPRC, a multidomain organizer that potentially integrates mitochondria and the microtubular cytoskeleton with chromosome remodeling. Increasing concentrations of UXT contributes to progressive aggregation of mitochondria and cell death potentially through its association with LRPPRC. Suppresses cell transformation and it might mediate this function by interaction and inhibition of the biological activity of cell proliferation and survival stimulatory factors like MECOM. Plays a role in protecting cells against TNF-induced apoptosis by preventing the recruitment of FADD and caspase 8 to the apoptotic complex I, composed of TRADD, TRAF2 and RIPK1/RIP.

Subunit / interactions. Homohexamer. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with LRPPRC. Interacts with androgen receptor AR (via N-terminus). Interacts with estrogen receptor ESR1; the interaction relocalizes ESR1 from the nucleus to the cytoplasm. In the nucleus, interacts specifically with RELA (via RHD domain) and forms a dynamic complex with NF-kappa-B and is recruited to the NF-kappa-B enhanceosome upon stimulation. Interacts with MECOM. Interacts with URI1. Part of complex I composed of TNF receptor TNFRSF1A, TRADD, TRAF2 and RIPK1 formed in response to TNF stimulation. Within the complex, interacts (via TPQE motif) with TRAF2; the interaction prevents the recruitment of FADD and CASP8/caspase 8 to complex I.

Subcellular location. Cytoplasm Nucleus Cytoplasm. Nucleus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole.

Tissue specificity. Ubiquitous. Expressed in prostate epithelial cells. Expressed in mammary epithelial cells. Highest levels in the heart, skeletal muscle, pancreas, kidney, liver, adrenal gland, peripheral blood leukocytes, lymph node, prostate, and thyroid and the lowest levels in bladder and uterus. Overexpressed in a number of tumor tissues.

Post-translational modifications. Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO7; leading to proteasomal degradation.

Similarity. Belongs to the UXT family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UBK9-1	2, UXT-V2	yes
Q9UBK9-2	1, UXT-V1

RefSeq proteins (2): NP_004173, NP_705582 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003994	UXT	Family
IPR004127	Prefoldin_subunit_alpha	Family
IPR009053	Prefoldin	Homologous_superfamily

Pfam: PF02996

UniProt features (4 total): mutagenesis site 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBK9-F1	88.06	0.71

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
50	causes dislocation from the centrosome; when associated with l-59.
59	causes dislocation from the centrosome; when associated with l-50.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8953750	Transcriptional Regulation by E2F6

MSigDB gene sets: 905 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, E2F_Q4, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, REACTOME_DNA_REPLICATION, E2F_Q4_01, GOBP_REGULATION_OF_DNA_RECOMBINATION, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, WALLACE_PROSTATE_CANCER_RACE_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, HNF3ALPHA_Q6, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), microtubule cytoskeleton organization (GO:0000226), apoptotic process (GO:0006915), centrosome cycle (GO:0007098), mitochondrion transport along microtubule (GO:0047497), protein stabilization (GO:0050821), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224)

GO Molecular Function (5): chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), microtubule binding (GO:0008017), beta-tubulin binding (GO:0048487), protein binding (GO:0005515)

GO Cellular Component (11): chromatin (GO:0000785), spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytoskeleton (GO:0005856), mediator complex (GO:0016592), protein folding chaperone complex (GO:0101031), RPAP3/R2TP/prefoldin-like complex (GO:1990062), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
negative regulation of DNA-templated transcription	2
binding	2
tubulin binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
cytoskeleton organization	1
microtubule-based process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell cycle process	1
microtubule organizing center organization	1
establishment of mitochondrion localization, microtubule-mediated	1
organelle transport along microtubule	1
regulation of protein stability	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
transcription coregulator activity	1
chromosome	1
spindle	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
intracellular membraneless organelle	1
core mediator complex	1
nuclear protein-containing complex	1
intracellular protein-containing complex	1
protein-containing complex	1
cellular_component	1

Protein interactions and networks

STRING

1241 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UXT	PDRG1	Q9NUG6	995
UXT	PFDN2	Q9UHV9	995
UXT	PFDN6	O15212	994
UXT	DNAAF10	Q96MX6	983
UXT	POLR2E	P19388	930
UXT	URI1	O94763	889
UXT	HEBP2	Q9Y5Z4	864
UXT	RPAP3	Q9H6T3	855
UXT	CECR2	Q9BXF3	845
UXT	RFFL	Q8WZ73	764
UXT	MAP1S	Q66K74	761
UXT	PFDN5	Q99471	753
UXT	RPS9	P46781	741
UXT	ASDURF	L0R819	735
UXT	RUVBL1	P82276	729

IntAct

179 interactions, top by confidence:

A	B	Type	Score
NPHP1	NPHP4	psi-mi:“MI:2364”(proximity)	0.930
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
POLR2E	POLR1C	psi-mi:“MI:0914”(association)	0.770
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
UXT	PFDN2	psi-mi:“MI:0915”(physical association)	0.740
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
POLR2A	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2J	POLR2D	psi-mi:“MI:0914”(association)	0.730
RPRD1B	POLR2D	psi-mi:“MI:0914”(association)	0.730
KRTAP10-8	UXT	psi-mi:“MI:0915”(physical association)	0.720
KRT31	UXT	psi-mi:“MI:0915”(physical association)	0.720
NOTCH2NLA	UXT	psi-mi:“MI:0915”(physical association)	0.670
UXT	PAK5	psi-mi:“MI:0915”(physical association)	0.670
UXT	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
PAK5	UXT	psi-mi:“MI:0915”(physical association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670

BioGRID (249): UXT (Two-hybrid), UXT (Two-hybrid), UXT (Two-hybrid), UXT (Two-hybrid), PAK7 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-8 (Two-hybrid), NOTCH2NL (Two-hybrid), UXT (Affinity Capture-MS), UXT (Affinity Capture-MS), UXT (Affinity Capture-MS), UXT (Affinity Capture-MS), UXT (Affinity Capture-MS), URI1 (Affinity Capture-MS)

ESM2 similar proteins: A2AQW0, A7T0W1, F1LVW7, F1RCP1, O35099, O75558, P56962, P57741, P57742, Q2TBQ7, Q32P97, Q3B8I4, Q3EBL9, Q3KPR1, Q3SYS9, Q498D5, Q4A1L3, Q4G074, Q4SPU8, Q5BJ48, Q5E9Y2, Q5R558, Q5RGJ6, Q63ZY7, Q6DGZ3, Q6GP52, Q6GPR9, Q6ID77, Q6PBN5, Q6ZN16, Q6ZPU9, Q76N33, Q80V94, Q8BSE0, Q8CG73, Q95JP6, Q96EK5, Q96FJ0, Q96LZ7, Q99683

Diamond homologs: A7T0W1, Q32P97, Q54ND3, Q63ZY7, Q9UBK9, Q9WTZ0, Q8HYI9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CREB1	“up-regulates quantity by expression”	UXT	“transcriptional regulation”
UXT	“form complex”	“URI1 prefoldin co-chaperone”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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
RNA Polymerase III Chain Elongation	10	75.5×	4e-15
FGFR2 mutant receptor activation	7	63.4×	1e-10
RNA Polymerase III Transcription Termination	10	59.1×	3e-14
Signaling by FGFR2 IIIa TM	8	57.2×	1e-11
RNA Polymerase III Transcription Initiation From Type 2 Promoter	11	55.4×	4e-15
RNA Polymerase III Transcription Initiation From Type 1 Promoter	11	53.4×	4e-15
RNA Polymerase III Transcription Initiation From Type 3 Promoter	11	53.4×	4e-15
Abortive elongation of HIV-1 transcript in the absence of Tat	9	53.2×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	7	6.8×	8e-03
transcription by RNA polymerase II	10	6.7×	8e-04
protein stabilization	10	6.3×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2043 predictions. Top by Δscore:

Variant	Effect	Δscore
4:67558859:A:T	donor_gain	1.0000
4:67571083:GGA:G	acceptor_gain	1.0000
4:67571156:G:GG	donor_gain	1.0000
4:67574696:C:G	donor_gain	1.0000
4:67575381:GCAGT:G	acceptor_loss	1.0000
4:67575383:A:AG	acceptor_gain	1.0000
4:67575383:AGTAT:A	acceptor_gain	1.0000
4:67575384:G:GT	acceptor_gain	1.0000
4:67575384:GT:G	acceptor_gain	1.0000
4:67575384:GTA:G	acceptor_gain	1.0000
4:67575384:GTAT:G	acceptor_gain	1.0000
4:67575384:GTATG:G	acceptor_gain	1.0000
4:67575484:G:GT	donor_gain	1.0000
4:67575494:TGAAG:T	donor_loss	1.0000
4:67575495:GAAGG:G	donor_loss	1.0000
4:67575496:AAG:A	donor_loss	1.0000
4:67575497:AGG:A	donor_loss	1.0000
4:67575498:GGT:G	donor_loss	1.0000
4:67575499:G:GA	donor_loss	1.0000
4:67575500:T:A	donor_loss	1.0000
4:67581293:AATT:A	acceptor_gain	1.0000
4:67581470:GC:G	donor_gain	1.0000
4:67583701:GA:G	donor_gain	1.0000
4:67583703:G:GG	donor_gain	1.0000
4:67590882:A:AG	acceptor_gain	1.0000
4:67590883:G:GG	acceptor_gain	1.0000
4:67590883:GC:G	acceptor_gain	1.0000
4:67590949:AACCT:A	donor_gain	1.0000
4:67590954:G:GG	donor_gain	1.0000
X:47657181:A:AC	donor_gain	1.0000

AlphaMissense

1020 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:47657223:C:G	A106P	0.997
X:47657846:C:G	R39P	0.993
X:47658859:G:C	F23L	0.992
X:47658859:G:T	F23L	0.992
X:47658861:A:G	F23L	0.992
X:47657807:A:G	L52P	0.990
X:47657212:G:C	F109L	0.985
X:47657212:G:T	F109L	0.985
X:47657214:A:G	F109L	0.985
X:47657584:A:T	V79D	0.985
X:47652130:A:G	L124P	0.984
X:47657222:G:T	A106D	0.984
X:47657600:C:G	G74R	0.984
X:47657258:C:T	G94E	0.983
X:47657599:C:A	G74V	0.983
X:47651891:A:G	L142P	0.982
X:47652104:C:G	A133P	0.982
X:47657267:A:T	V91E	0.980
X:47658860:A:G	F23S	0.980
X:47652119:A:G	S128P	0.979
X:47657200:C:A	K113N	0.979
X:47657200:C:G	K113N	0.979
X:47657248:A:C	F97L	0.978
X:47657248:A:T	F97L	0.978
X:47657250:A:G	F97L	0.978
X:47657259:C:G	G94R	0.977
X:47657259:C:T	G94R	0.977
X:47658845:A:G	L28P	0.977
X:47657602:A:G	L73S	0.976
X:47657189:A:G	L117P	0.975

dbSNP variants (sampled 300 via entrez): RS1000508259 (X:47657019 A>G,T), RS1000944829 (X:47656362 T>A), RS1001210462 (X:47655802 A>G), RS1001545882 (X:47658915 G>A), RS1001766142 (X:47656155 AC>A), RS1001914470 (X:47659204 A>G), RS1002767447 (X:47653285 A>C), RS1002955508 (X:47660528 A>G), RS1003634336 (X:47654014 A>G), RS1004106888 (X:47657363 C>A,T), RS1004558393 (X:47658149 G>A), RS1004711758 (X:47656011 C>T), RS1005516907 (X:47654942 T>G), RS1005639860 (X:47658839 C>T), RS1007140596 (X:47660057 T>C)

Disease associations

OMIM: gene MIM:300234 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004621_83	Red cell distribution width	3.000000e-09
GCST008362_104	Birth weight	2.000000e-08
GCST009391_1752	Metabolite levels	8.000000e-06
GCST90000025_27	Appendicular lean mass	3.000000e-18
GCST90002390_127	Mean corpuscular hemoglobin	1.000000e-10
GCST90002392_625	Mean corpuscular volume	8.000000e-13
GCST90002396_299	Mean reticulocyte volume	6.000000e-14
GCST90002397_33	Mean spheric corpuscular volume	2.000000e-15
GCST90002404_223	Red cell distribution width	2.000000e-19

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004344	birth weight
EFO:0010369	lysophosphatidylethanolamine 18:2 measurement
EFO:0004980	appendicular lean mass
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	3
sodium arsenite	decreases expression, increases abundance	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Fluorouracil	increases expression	2
Smoke	increases expression, decreases expression, increases abundance	2
Cyclosporine	increases expression	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
bleomycetin	decreases expression	1
bicalutamide	affects response to substance	1
CD 437	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Tobacco Smoke Pollution	decreases expression	1
Metribolone	increases reaction, affects reaction, increases expression, affects response to substance, affects binding	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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