THOC5

Summary

THOC5 (THO complex subunit 5, HGNC:19074) is a protein-coding gene on chromosome 22q12.2, encoding THO complex subunit 5 (Q13769). Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. It is a common-essential gene (DepMap: required in 98.1% of cancer cell lines).

Predicted to enable mRNA binding activity. Involved in mRNA export from nucleus and monocyte differentiation. Located in chromosome, telomeric region and nucleoplasm. Part of THO complex part of transcription export complex. Implicated in breast carcinoma.

Source: NCBI Gene 8563 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 85 total
• Cancer dependency (DepMap): dependent in 98.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_003678

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19074
Approved symbol	THOC5
Name	THO complex subunit 5
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	PK1.3, KIAA0983, Fmip, fSAP79
Ensembl gene	ENSG00000100296
Ensembl biotype	protein_coding
OMIM	612733
Entrez	8563

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 24 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000358079, ENST00000397871, ENST00000397872, ENST00000397873, ENST00000414902, ENST00000418021, ENST00000428374, ENST00000440771, ENST00000442555, ENST00000443089, ENST00000455450, ENST00000472164, ENST00000475187, ENST00000484924, ENST00000488052, ENST00000490103, ENST00000492707, ENST00000853415, ENST00000853416, ENST00000853417, ENST00000853418, ENST00000853419, ENST00000853420, ENST00000853421, ENST00000928651, ENST00000928652, ENST00000928654, ENST00000928656, ENST00000928658, ENST00000957724, ENST00000957725, ENST00000957726

RefSeq mRNA: 4 — MANE Select: NM_003678 NM_001002877, NM_001002878, NM_001002879, NM_003678

CCDS: CCDS13859

Canonical transcript exons

ENST00000490103 — 20 exons

Exon	Start	End
ENSE00001255472	29549052	29549158
ENSE00001835034	29553671	29553757
ENSE00001925326	29505879	29508520
ENSE00003459918	29517263	29517366
ENSE00003462264	29520008	29520104
ENSE00003481349	29543429	29543542
ENSE00003509799	29536624	29536738
ENSE00003520207	29511106	29511296
ENSE00003522628	29528078	29528177
ENSE00003523836	29542859	29542956
ENSE00003537607	29520998	29521099
ENSE00003541111	29539330	29539476
ENSE00003588871	29512021	29512136
ENSE00003590007	29519006	29519120
ENSE00003635316	29528426	29528466
ENSE00003648280	29544460	29544603
ENSE00003651178	29529162	29529239
ENSE00003654330	29531831	29531963
ENSE00003673289	29517029	29517116
ENSE00003785255	29525838	29525946

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 95.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.4522 / max 258.3651, expressed in 1808 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193536	21.1651	1808
193533	0.5736	293
193535	0.2943	132
193534	0.2724	127
193538	0.0794	30
193537	0.0674	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	95.30	gold quality
stromal cell of endometrium	CL:0002255	94.69	gold quality
calcaneal tendon	UBERON:0003701	94.31	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.20	gold quality
lower esophagus	UBERON:0013473	93.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.92	gold quality
popliteal artery	UBERON:0002250	93.87	gold quality
tibial artery	UBERON:0007610	93.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.65	gold quality
aorta	UBERON:0000947	93.61	gold quality
ascending aorta	UBERON:0001496	93.56	gold quality
body of uterus	UBERON:0009853	93.56	gold quality
right coronary artery	UBERON:0001625	93.53	gold quality
thoracic aorta	UBERON:0001515	93.46	gold quality
apex of heart	UBERON:0002098	93.45	gold quality
descending thoracic aorta	UBERON:0002345	93.31	gold quality
smooth muscle tissue	UBERON:0001135	93.01	gold quality
left coronary artery	UBERON:0001626	93.00	gold quality
left uterine tube	UBERON:0001303	92.79	gold quality
coronary artery	UBERON:0001621	92.53	gold quality
gastrocnemius	UBERON:0001388	92.48	gold quality
muscle of leg	UBERON:0001383	92.45	gold quality
sural nerve	UBERON:0015488	92.35	gold quality
endocervix	UBERON:0000458	92.21	gold quality
blood	UBERON:0000178	92.05	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.59	gold quality
heart left ventricle	UBERON:0002084	91.22	gold quality
cardiac ventricle	UBERON:0002082	90.85	gold quality
tendon	UBERON:0000043	90.79	gold quality
right ovary	UBERON:0002118	90.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

22 targeting THOC5, 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-9-5P	100.00	72.28	2361
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-647	97.73	67.79	927
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-4296	96.35	63.55	1233

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 13)

• THOC5 protein expression can potentiate receptor signalling to transcription factor expression and monocyte differentiation. (PMID:19015024)
• THOC7 (50-137, amino acid numbers) binds to the N-terminal portion (1-199) of FMIP directly. (PMID:19059247)
• Thoc5 exhibits in vitro RNA-binding activity and is associated with HSP70 mRNPs in vivo as a component of the stable THO complex (PMID:19165146)
• show here that DNA damage drastically decreased the cytoplasmic pool of a set of THOC5-dependent mRNAs and impaired the THOC5/mRNA complex formation (PMID:21937706)
• show that THOC5 Y225 phosphorylation governs mRNA binding. In addition, CXCL12 is shown to induce THOC5 Y225 phosphorylation, and site-directed mutagenesis demonstrates that this modulates motile response (PMID:23032722)
• Authors suggest a model in which human Thoc5 controls polyadenylation site choice through the co-transcriptional loading of CFIm68 onto target genes. (PMID:23685434)
• THOC5 to be a novel gene involved in the regulation of serum HDL-C levels (PMID:24023261)
• Data suggest that the suppression of the multiple THOC5 target genes may represent a novel strategy for hepatocellular carcinoma (HCC) therapy. (PMID:26549021)
• THOC5 regulates transcription termination and subsequent transcript release from the HSPA1A locus. (PMID:30721563)
• Polymorphism of the THOC5 of the transcription/export multiprotein complex and its correlation with the lipid and metabolic profile in middle-aged women. (PMID:31402763)
• Human THO maintains the stability of repetitive DNA. (PMID:32065701)
• RNA editing enzyme APOBEC3A promotes pro-inflammatory M1 macrophage polarization. (PMID:33483601)
• THOC5 regulates human osteoclastogenesis. (PMID:35688054)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	thoc5	ENSDARG00000038290
mus_musculus	Thoc5	ENSMUSG00000034274
rattus_norvegicus	Thoc5	ENSRNOG00000008456
drosophila_melanogaster	thoc5	FBGN0034939
caenorhabditis_elegans		WBGENE00021311

Protein

Protein identifiers

THO complex subunit 5 — Q13769 (reviewed: Q13769)

Alternative names: Functional spliceosome-associated protein 79, NF2/meningioma region protein pK1.3, Placental protein 39.2, hTREX90

All UniProt accessions (9): Q13769, C9JCL9, C9JXG5, C9JXU6, F5GZF3, F8WCP5, F8WES8, H7C072, H7C441

UniProt curated annotations — full annotation on UniProt →

Function. Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. Plays a key structural role in the oligomerization of the THO-DDX39B complex. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5’ end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway. THOC5 in conjunction with ALYREF/THOC4 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim. Involved in transcription elongation and genome stability. Involved in alternative polyadenylation site choice by recruiting CPSF6 to 5’ region of target genes; probably mediates association of the TREX and CFIm complexes. Regulates the expression of myeloid transcription factors CEBPA, CEBPB and GAB2 by enhancing the levels of phosphatidylinositol 3,4,5-trisphosphate. May be involved in the differentiation of granulocytes and adipocytes. Essential for hematopoietic primitive cell survival and plays an integral role in monocytic development. (Microbial infection) The TREX complex is essential for the export of Kaposi’s sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production.

Subunit / interactions. Component of the THO subcomplex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7. The THO subcomplex interacts with DDX39B to form the THO-DDX39B complex which multimerizes into a 28-subunit tetrameric assembly. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; in the complex interacts with THOC1, THOC2, THOC5, THOC6 and THOC7; forms a coiled-coil dimer with THOC7; together with THOC6 and THOC7, plays a key structural role in oligomerization of the THO-DDX39B complex. TREX seems to have a dynamic structure involving ATP-dependent remodeling. Interacts with phosphorylated CSF1R. Interacts (via N-terminus) with the NTF2 domain of NXF1. Forms a complex with CEBPB. Interacts with CPSF6; indicative for an association with the cleavage factor Im (CFIm) complex. Interacts with LUZP4. Interacts with NCBP3.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated on tyrosine upon binding to activated CSF1R; which causes a dissociation of the two proteins. Phosphorylation on Ser-5 and/or Ser-6 is required for nuclear export. Phosphorylated on Thr-328 in insulin-stimulated adipocytes. Phosphorylation at Tyr-225 modulates mRNA binding.

Similarity. Belongs to the THOC5 family.

RefSeq proteins (4): NP_001002877, NP_001002878, NP_001002879, NP_003669* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019163	THO_Thoc5	Family

Pfam: PF09766

UniProt features (71 total): helix 24, strand 13, modified residue 8, turn 8, region of interest 5, sequence variant 5, compositionally biased region 2, initiator methionine 1, chain 1, cross-link 1, mutagenesis site 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7APK	ELECTRON MICROSCOPY	3.3
7ZNL	ELECTRON MICROSCOPY	3.45
7ZNK	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13769-F1	83.19	0.46

Functional residue map

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

Post-translational modifications (9): 2, 5, 6, 225, 307, 312, 314, 328, 153

Mutagenesis-validated functional residues (1):

Position	Phenotype
225	impairs mrna binding, enhances cxcl12-dependent cell migration.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72187	mRNA 3’-end processing
R-HSA-9680350	Signaling by CSF1 (M-CSF) in myeloid cells
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 127 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_EMBRYONIC_HEMOPOIESIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, FOXD3_01, MODULE_59, PATIL_LIVER_CANCER, GOBP_NUCLEAR_TRANSPORT, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, AAAGACA_MIR511, GOBP_RNA_SPLICING

GO Biological Process (7): mRNA processing (GO:0006397), mRNA export from nucleus (GO:0006406), RNA splicing (GO:0008380), monocyte differentiation (GO:0030224), primitive hemopoiesis (GO:0060215), cell differentiation (GO:0030154), mRNA transport (GO:0051028)

GO Molecular Function (3): mRNA binding (GO:0003729), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): transcription export complex (GO:0000346), THO complex (GO:0000347), THO complex part of transcription export complex (GO:0000445), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), chromosome, telomeric region (GO:0000781)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	2
Transport of Mature Transcript to Cytoplasm	1
Cytokine Signaling in Immune system	1
RNA Polymerase II Transcription	1
Immune System	1
Metabolism of RNA	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
nuclear protein-containing complex	2
cellular anatomical structure	2
mRNA metabolic process	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
embryonic hemopoiesis	1
cellular developmental process	1
RNA transport	1
RNA binding	1
nucleic acid binding	1
binding	1
transcription export complex	1
THO complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
chromosomal region	1

Protein interactions and networks

STRING

1660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THOC5	THOC7	Q6I9Y2	998
THOC5	THOC6	Q86W42	998
THOC5	THOC2	Q8NI27	997
THOC5	THOC3	Q96J01	997
THOC5	THOC1	Q96FV9	996
THOC5	DDX39B	Q13838	927
THOC5	CPSF2	Q9P2I0	920
THOC5	ALYREF	Q86V81	869
THOC5	NXF1	Q9UBU9	841
THOC5	NXT1	Q9UKK6	792
THOC5	FYTTD1	Q96QD9	789
THOC5	NIPSNAP1	Q9BPW8	781
THOC5	CHTOP	Q9Y3Y2	773
THOC5	SARNP	P82979	758
THOC5	ETV6	P41212	714

IntAct

109 interactions, top by confidence:

A	B	Type	Score
THOC1	THOC5	psi-mi:“MI:0914”(association)	0.930
THOC1	THOC5	psi-mi:“MI:0915”(physical association)	0.930
THOC5	THOC1	psi-mi:“MI:0915”(physical association)	0.930
THOC1	THOC5	psi-mi:“MI:0403”(colocalization)	0.930
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
DDX39B	THOC5	psi-mi:“MI:0915”(physical association)	0.800
THOC2	THOC5	psi-mi:“MI:0914”(association)	0.730
ALYREF	THOC5	psi-mi:“MI:0914”(association)	0.710
THOC5	ALYREF	psi-mi:“MI:0914”(association)	0.710
THOC1	EIF4A3	psi-mi:“MI:0914”(association)	0.660
CHTOP	THOC5	psi-mi:“MI:0914”(association)	0.660
THOC7	THOC5	psi-mi:“MI:0915”(physical association)	0.650
THOC5	THOC7	psi-mi:“MI:0915”(physical association)	0.650
THOC5	THOC7	psi-mi:“MI:0914”(association)	0.650
THOC7	THOC5	psi-mi:“MI:0914”(association)	0.650
THOC7	THOC5	psi-mi:“MI:0403”(colocalization)	0.650
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640

BioGRID (212): THOC5 (Affinity Capture-MS), THOC5 (Affinity Capture-MS), THOC5 (Affinity Capture-Western), THOC5 (Two-hybrid), THOC2 (Co-fractionation), THOC3 (Co-fractionation), THOC5 (Co-fractionation), THOC6 (Co-fractionation), THOC7 (Co-fractionation), TJP1 (Co-fractionation), FMNL1 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), PDGFRA (Affinity Capture-MS), RPL6 (Affinity Capture-MS), RPL22 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A2AAE1, A2RV80, A4IFQ0, A6QQW8, F1Q8X5, O35382, P48553, P70398, Q08BT5, Q13769, Q2LD37, Q5F361, Q5R903, Q5RAQ5, Q5REX9, Q62824, Q68FX7, Q6DFZ1, Q6IC98, Q6NRC7, Q6P6Y1, Q6SP92, Q6ZWH5, Q7SXV1, Q7TSG1, Q7Z7G8, Q80TY5, Q8BHY8, Q8BKT7, Q8BQZ4, Q8CB44, Q8CIB5, Q8K3W0, Q8N960, Q8WN69, Q8WN70, Q91W96, Q92538

Diamond homologs: A4IFQ0, F4K4J0, Q13769, Q28DG8, Q5ZJK1, Q68FX7, Q6DFL5, Q6NY52, Q7ZXA8, Q8BKT7, Q9USR5, F4HRC1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKCA	up-regulates	THOC5	phosphorylation
THOC5	“form complex”	“TREX complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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
mRNA 3’-end processing	15	46.9×	3e-19
Transport of Mature Transcript to Cytoplasm	7	42.3×	1e-08
RNA Polymerase II Transcription Termination	10	34.9×	2e-11
Transport of Mature mRNA derived from an Intron-Containing Transcript	14	33.8×	5e-16
Processing of Capped Intron-Containing Pre-mRNA	15	19.6×	8e-14
mRNA Splicing	9	15.7×	3e-07
mRNA Splicing - Major Pathway	18	15.6×	5e-15
mRNA Polyadenylation	10	13.9×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
mRNA export from nucleus	13	49.3×	2e-16
poly(A)+ mRNA export from nucleus	5	43.2×	1e-05
mRNA splicing, via spliceosome	15	17.6×	1e-12
RNA splicing	14	15.8×	4e-11
mRNA processing	14	14.1×	1e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3054 predictions. Top by Δscore:

Variant	Effect	Δscore
22:29511100:CCTCA:C	donor_loss	1.0000
22:29511101:CTCAC:C	donor_loss	1.0000
22:29511102:TCACC:T	donor_loss	1.0000
22:29511104:A:AC	donor_gain	1.0000
22:29511104:ACCTG:A	donor_loss	1.0000
22:29511105:C:CC	donor_gain	1.0000
22:29511292:ATGGC:A	acceptor_gain	1.0000
22:29511293:TGGC:T	acceptor_gain	1.0000
22:29511295:GC:G	acceptor_gain	1.0000
22:29511295:GCCTG:G	acceptor_loss	1.0000
22:29511296:CC:C	acceptor_gain	1.0000
22:29511297:C:CC	acceptor_gain	1.0000
22:29511298:T:C	acceptor_loss	1.0000
22:29517363:TGTT:T	acceptor_gain	1.0000
22:29517366:TC:T	acceptor_loss	1.0000
22:29517367:C:CC	acceptor_gain	1.0000
22:29517367:CTA:C	acceptor_loss	1.0000
22:29517368:T:A	acceptor_loss	1.0000
22:29520997:CCCAA:C	donor_gain	1.0000
22:29521001:A:C	donor_gain	1.0000
22:29525833:AATAC:A	donor_gain	1.0000
22:29525836:AC:A	donor_gain	1.0000
22:29525837:CC:C	donor_gain	1.0000
22:29528074:AGAC:A	donor_loss	1.0000
22:29528075:GACC:G	donor_loss	1.0000
22:29528076:ACCT:A	donor_loss	1.0000
22:29528077:CCTT:C	donor_loss	1.0000
22:29528087:T:TA	donor_gain	1.0000
22:29528173:CGCTT:C	acceptor_gain	1.0000
22:29528175:CTT:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005684 (22:29547935 A>G), RS1000159417 (22:29522593 T>C), RS1000169030 (22:29514571 T>C), RS1000173221 (22:29517073 C>A,T), RS1000199585 (22:29514166 G>C), RS1000341199 (22:29528563 C>A), RS1000370068 (22:29534966 A>G), RS1000381493 (22:29534994 T>C,G), RS1000399966 (22:29520782 C>T), RS1000461028 (22:29552470 G>A,C), RS1000501458 (22:29546676 G>C,T), RS1000596640 (22:29552309 T>C), RS1000650477 (22:29553008 G>A,C), RS1000651855 (22:29538754 G>A), RS1000664997 (22:29552780 C>T)

Disease associations

OMIM: gene MIM:612733 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000555_7	Carotid atherosclerosis in HIV infection	2.000000e-06
GCST002173_4	Lipid traits	2.000000e-07
GCST010241_368	Apolipoprotein A1 levels	3.000000e-10
GCST010242_450	HDL cholesterol levels	5.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment, decreases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
beta-methylcholine	affects expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Coumestrol	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Quercetin	increases phosphorylation	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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