SUPT6H

Summary

SUPT6H (SPT6 homolog, histone chaperone and transcription elongation factor, HGNC:11470) is a protein-coding gene on chromosome 17q11.2, encoding Transcription elongation factor SPT6 (Q7KZ85). Histone H3-H4 chaperone that plays a key role in the regulation of transcription elongation and mRNA processing. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Enables histone binding activity. Involved in positive regulation of transcription elongation by RNA polymerase II and transcription elongation-coupled chromatin remodeling. Predicted to be located in nucleoplasm. Predicted to be part of transcription elongation factor complex.

Source: NCBI Gene 6830 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 188 total
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_003170

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11470
Approved symbol	SUPT6H
Name	SPT6 homolog, histone chaperone and transcription elongation factor
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0162, SPT6H
Ensembl gene	ENSG00000109111
Ensembl biotype	protein_coding
OMIM	601333
Entrez	6830

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 8 retained_intron, 1 nonsense_mediated_decay

ENST00000314616, ENST00000347486, ENST00000577713, ENST00000577939, ENST00000580471, ENST00000581510, ENST00000581908, ENST00000583340, ENST00000583972, ENST00000584285, ENST00000584312, ENST00000585230, ENST00000868880, ENST00000868881, ENST00000868882, ENST00000868883, ENST00000868884, ENST00000868885, ENST00000937412, ENST00000937413, ENST00000937414, ENST00000954877, ENST00000954878

RefSeq mRNA: 2 — MANE Select: NM_003170 NM_001320755, NM_003170

CCDS: CCDS32596

Canonical transcript exons

ENST00000314616 — 37 exons

Exon	Start	End
ENSE00000706989	28677715	28677816
ENSE00000706990	28678076	28678192
ENSE00000706991	28678545	28678634
ENSE00000706993	28678821	28678963
ENSE00000706995	28681256	28681404
ENSE00000706997	28681882	28681980
ENSE00000707000	28682727	28682856
ENSE00000707003	28683268	28683422
ENSE00000707005	28683621	28683816
ENSE00000707007	28684586	28684725
ENSE00000707153	28700941	28701128
ENSE00001113891	28674970	28675162
ENSE00001113893	28675401	28675485
ENSE00001113894	28676157	28676430
ENSE00001198328	28687088	28687225
ENSE00001198336	28686654	28686789
ENSE00001214176	28682942	28683092
ENSE00001292212	28690921	28691063
ENSE00001309163	28697906	28698030
ENSE00001311232	28697620	28697733
ENSE00001318887	28700346	28700512
ENSE00001320686	28695352	28695547
ENSE00001353653	28696844	28697082
ENSE00001353657	28693696	28693836
ENSE00001353661	28689354	28689561
ENSE00001408762	28673371	28673510
ENSE00001423211	28686339	28686415
ENSE00001428273	28701439	28702679
ENSE00001504437	28684844	28684961
ENSE00002731622	28662205	28662342
ENSE00003497636	28700173	28700250
ENSE00003501754	28674537	28674613
ENSE00003552105	28688091	28688218
ENSE00003569593	28690082	28690229
ENSE00003586424	28674283	28674441
ENSE00003644802	28687304	28687471
ENSE00003671057	28699781	28699893

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.8224 / max 889.9241, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160049	32.5542	1821
160051	4.5327	1597
160052	0.7355	405

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.22	gold quality
colonic epithelium	UBERON:0000397	97.15	gold quality
stromal cell of endometrium	CL:0002255	95.13	gold quality
mucosa of stomach	UBERON:0001199	94.83	gold quality
adrenal tissue	UBERON:0018303	94.72	gold quality
adenohypophysis	UBERON:0002196	94.69	gold quality
skin of leg	UBERON:0001511	94.42	gold quality
granulocyte	CL:0000094	94.31	gold quality
pituitary gland	UBERON:0000007	94.15	gold quality
gastrocnemius	UBERON:0001388	93.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.85	gold quality
lower esophagus	UBERON:0013473	93.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.81	gold quality
popliteal artery	UBERON:0002250	93.74	gold quality
tibial artery	UBERON:0007610	93.74	gold quality
left adrenal gland cortex	UBERON:0035825	93.74	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.73	gold quality
right adrenal gland cortex	UBERON:0035827	93.72	gold quality
muscle of leg	UBERON:0001383	93.65	gold quality
skin of abdomen	UBERON:0001416	93.62	gold quality
adrenal gland	UBERON:0002369	93.60	gold quality
left adrenal gland	UBERON:0001234	93.59	gold quality
right adrenal gland	UBERON:0001233	93.38	gold quality
body of stomach	UBERON:0001161	93.35	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.34	gold quality
adrenal cortex	UBERON:0001235	93.32	gold quality
left lobe of thyroid gland	UBERON:0001120	93.18	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.15	gold quality
left ovary	UBERON:0002119	93.14	gold quality
tibial nerve	UBERON:0001323	93.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting SUPT6H, 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-6748-5P	100.00	65.81	1057
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-4758-3P	99.12	63.96	869

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 17)

• Reults establish that human Spt6 (hSpt6) is a classic transcription elongation factor that enhances the rate of RNA polymerase II elongation. (PMID:15060154)
• Knockdown of Spt6 resulted in severe reduction of class switch recombination in the endogenous Ig locus in B cells. (PMID:21518874)
• Abolishing UL69’s ability to interact with the SPT6 protein inhibited human cytomegalovirus replication. (PMID:22171252)
• These results show that intracellular levels of Spt6 are fine-tuned by PAAF1 and proteasome, which is required for HIV-1 transcription and extends to cellular genes implicated in cancer. (PMID:22316138)
• Spt6 is a unique histone chaperone capable of regulating the histone epigenetic state of both AID targets and the AID locus. (PMID:22843687)
• identified fibronectin, a component of the extracellular matrix and a mesenchymal marker, as a transcriptional target of Pak1 signaling (PMID:24441044)
• Altogether, these results indicate that a complex containing LEDGF/p75, Iws1, and Spt6 participates in regulating postintegration steps of HIV latency. (PMID:25590759)
• cryo-EM structure of an activated elongation complex of Sus scrofa Pol II and Homo sapiens DSIF, PAF and SPT6 was determined at 3.1 A resolution and compared to the structure of the paused elongation complex formed by Pol II, DSIF and NELF (PMID:30135578)
• SPT6 acts as a master regulator of Pol II elongation, favoring productive protein coding over non-productive and potentially deleterious lncRNA transcription. (PMID:30449723)
• Spt6 is a maintenance factor for centromeric CENP-A. (PMID:32522980)
• SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells. (PMID:32948765)
• SPT6 recruits SND1 to co-activate human telomerase reverse transcriptase to promote colon cancer progression. (PMID:33305480)
• SPT6 promotes epidermal differentiation and blockade of an intestinal-like phenotype through control of transcriptional elongation. (PMID:33542242)
• Two distinct mechanisms of RNA polymerase II elongation stimulation in vivo. (PMID:34146481)
• Targeted protein degradation reveals a direct role of SPT6 in RNAPII elongation and termination. (PMID:34233157)
• Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6. (PMID:36852700)
• Insights into Spt6: a histone chaperone that functions in transcription, DNA replication, and genome stability. (PMID:37481442)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	supt6h	ENSDARG00000006524
mus_musculus	Supt6	ENSMUSG00000002052
rattus_norvegicus	Supt6h	ENSRNOG00000012240
drosophila_melanogaster	Spt6	FBGN0028982
caenorhabditis_elegans		WBGENE00001259

Protein

Protein identifiers

Transcription elongation factor SPT6 — Q7KZ85 (reviewed: Q7KZ85)

Alternative names: Histone chaperone suppressor of Ty6, Tat-cotransactivator 2 protein

All UniProt accessions (3): Q7KZ85, J3QS64, K7EK85

UniProt curated annotations — full annotation on UniProt →

Function. Histone H3-H4 chaperone that plays a key role in the regulation of transcription elongation and mRNA processing. Enhances the transcription elongation by RNA polymerase II (RNAPII) and is also required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. Besides chaperoning histones in transcription, acts to transport and splice mRNA by forming a complex with IWS1 and the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2), to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription. SUPT6H via its association with SETD1A, regulates both class-switch recombination and somatic hypermutation through formation of H3K4me3 epigenetic marks on activation-induced cytidine deaminase (AICDA) target loci. Promotes the activation of the myogenic gene program by entailing erasure of the repressive H3K27me3 epigenetic mark through stabilization of the chromatin interaction of the H3K27 demethylase KDM6A.

Subunit / interactions. Interacts with RNA polymerase II and the DRB sensitivity-inducing factor complex (DSIF complex), which is composed of SUPT5H and SUPT4H1. Interacts with KDM6A. Interacts (via SH2 domain) with SETD1A. Interacts (via SH2 domain) with POLR2A phosphorylated at ‘Ser-2’. Interacts with IWS1, AICDA and PAAF1. Interacts with histone H2B and H3. Interacts with WDR43. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL69.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Dephosphorylated at Ser-1530 by the PNUTS-PP1 complex during RNA polymerase II transcription pause-release.

Similarity. Belongs to the SPT6 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7KZ85-1	1	yes
Q7KZ85-2	2
Q7KZ85-3	3

RefSeq proteins (2): NP_001307684, NP_003161* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR003029	S1_domain	Domain
IPR006641	YqgF/RNaseH-like_dom	Domain
IPR010994	RuvA_2-like	Homologous_superfamily
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR017072	TF_Spt6	Family
IPR023319	Tex-like_HTH_dom_sf	Homologous_superfamily
IPR023323	Tex-like_dom_sf	Homologous_superfamily
IPR028083	Spt6_acidic_N_dom	Domain
IPR028088	Spt6_HTH_DNA-bd_dom	Domain
IPR028231	Spt6_YqgF	Domain
IPR032706	Spt6_HHH	Domain
IPR035018	Spt6_SH2_C	Domain
IPR035019	Spt6_SH2_N	Domain
IPR035420	Spt6_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR037027	YqgF/RNaseH-like_dom_sf	Homologous_superfamily
IPR041692	HHH_9	Domain
IPR042066	Spt6_death-like	Homologous_superfamily
IPR055179	Tex-like_central_region	Domain

Pfam: PF00575, PF14632, PF14633, PF14635, PF14639, PF14641, PF17674, PF22706

UniProt features (163 total): helix 56, strand 45, modified residue 23, compositionally biased region 11, turn 9, region of interest 7, sequence conflict 5, splice variant 3, domain 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
6GME	X-RAY DIFFRACTION	1.8
9HVQ	ELECTRON MICROSCOPY	2
8OEV	ELECTRON MICROSCOPY	2.86
7OOP	ELECTRON MICROSCOPY	2.9
9EGX	ELECTRON MICROSCOPY	2.9
9EGY	ELECTRON MICROSCOPY	2.9
9EGZ	ELECTRON MICROSCOPY	2.9
7OPC	ELECTRON MICROSCOPY	3
7OPD	ELECTRON MICROSCOPY	3
7UNC	ELECTRON MICROSCOPY	3
7UND	ELECTRON MICROSCOPY	3
8OEU	ELECTRON MICROSCOPY	3.04
8OF0	ELECTRON MICROSCOPY	3.05
6GMH	ELECTRON MICROSCOPY	3.1
6TED	ELECTRON MICROSCOPY	3.1
9EH2	ELECTRON MICROSCOPY	3.1
8XRM	ELECTRON MICROSCOPY	3.13
8A3Y	ELECTRON MICROSCOPY	3.3
9QEQ	ELECTRON MICROSCOPY	3.5
9EH0	ELECTRON MICROSCOPY	3.6
9RZD	ELECTRON MICROSCOPY	3.69
9RTN	ELECTRON MICROSCOPY	3.82
9RTT	ELECTRON MICROSCOPY	4.01
9S3G	ELECTRON MICROSCOPY	6.4
9S0U	ELECTRON MICROSCOPY	6.72
9RZE	ELECTRON MICROSCOPY	8.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7KZ85-F1	73.66	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.

Post-translational modifications (23): 2, 7, 12, 73, 78, 91, 125, 267, 743, 1515, 1523, 1526, 1528, 1530, 1532, 1535, 1539, 1676, 1697, 1701 …

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 170 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_DNA_RECOMBINATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_B_CELL_ACTIVATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, LHX3_01, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, chr17q11, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_IMMUNOGLOBULIN_PRODUCTION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY

GO Biological Process (11): blastocyst formation (GO:0001825), transcription elongation by RNA polymerase II (GO:0006368), mRNA processing (GO:0006397), RNA splicing (GO:0008380), nucleosome organization (GO:0034728), regulation of isotype switching (GO:0045191), mRNA transport (GO:0051028), regulation of muscle cell differentiation (GO:0051147), transcription elongation-coupled chromatin remodeling (GO:0140673), nucleobase-containing compound metabolic process (GO:0006139), positive regulation of transcription elongation by RNA polymerase II (GO:0032968)

GO Molecular Function (6): DNA binding (GO:0003677), RNA binding (GO:0003723), nucleosome binding (GO:0031491), histone binding (GO:0042393), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), transcription elongation factor complex (GO:0008023), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RNA Polymerase II Transcription	2
RNA Polymerase II Transcription Elongation	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
chromatin remodeling	2
transcription elongation by RNA polymerase II	2
nucleic acid binding	2
binding	2
blastocyst development	1
anatomical structure formation involved in morphogenesis	1
DNA-templated transcription elongation	1
transcription by RNA polymerase II	1
mRNA metabolic process	1
protein-DNA complex organization	1
regulation of DNA recombination	1
regulation of immunoglobulin production	1
regulation of immunoglobulin mediated immune response	1
isotype switching	1
regulation of B cell activation	1
RNA transport	1
muscle cell differentiation	1
regulation of cell differentiation	1
primary metabolic process	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
chromatin binding	1
protein-containing complex binding	1
protein binding	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2914 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUPT6H	IWS1	Q96ST2	997
SUPT6H	SUPT5H	O00267	996
SUPT6H	SUPT4H1	P63272	988
SUPT6H	SUPT16H	Q9Y5B9	944
SUPT6H	POLR2A	P24928	919
SUPT6H	H3C1	P02295	903
SUPT6H	H3-3A	P06351	901
SUPT6H	H3-4	Q16695	899
SUPT6H	H3C14	Q71DI3	899
SUPT6H	H3-7	Q5TEC6	898
SUPT6H	H3-5	Q6NXT2	898
SUPT6H	JAG2	Q9Y219	895
SUPT6H	SSRP1	Q08945	891
SUPT6H	H2BC21	Q16778	849
SUPT6H	SETD2	Q9BYW2	829

IntAct

139 interactions, top by confidence:

A	B	Type	Score
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
POLR2J	POLR1C	psi-mi:“MI:0914”(association)	0.830
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
RPRD1B	RECQL5	psi-mi:“MI:0914”(association)	0.730
DDB2	CCT2	psi-mi:“MI:0914”(association)	0.730
POLR2D	MED19	psi-mi:“MI:0914”(association)	0.730
POLR2E	MED19	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
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
VBP1	PFDN6	psi-mi:“MI:0914”(association)	0.640
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640
PIN1	POLR2D	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2L	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
RPAP3	POLR3A	psi-mi:“MI:0914”(association)	0.560
STRAP	CDK2AP1	psi-mi:“MI:0914”(association)	0.530
FBXW4	TXNDC9	psi-mi:“MI:0914”(association)	0.530
PIH1D1	POLR3A	psi-mi:“MI:0914”(association)	0.530

BioGRID (292): SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), SUPT6H (Affinity Capture-MS)

ESM2 similar proteins: A0A098DRQ4, A0A1D3PCM3, A1CAN8, A1CT57, A1DF15, A2QCJ2, A5PJG7, A6RJQ7, A6S8P6, A7E559, A7F172, A7KAL4, C8V9Y5, C8VDI2, F7VSU2, G2XNY3, I1RKA1, I1RX50, M7UQV4, P0CM34, P0CM35, P53702, Q0U388, Q0WWQ1, Q1DPD9, Q2H427, Q2U002, Q2U7R4, Q2UM19, Q4IPN9, Q4IR87, Q4WUE5, Q4X0Z7, Q51LD2, Q5AT15, Q5AZC9, Q5AZT7, Q5EAV6, Q5I0S6, Q62383

Diamond homologs: P34703, Q497V5, Q5RDI0, Q62383, Q7KZ85, Q8N5C6, Q8UVK2, Q93148, Q9W420, A1ST53, A4XYD6, A5F913, A5W983, A7ZS61, A8A4Y0, A8J637, B0KHX3, B1IQV7, B1J2B3, B1XGX6, B2U211, B2VGN7, B5YS54, B6I1N9, B7LH99, B7M072, B7NKN3, C3K255, C3LSQ2, C4ZSQ5, O06000, O31489, O87792, P05055, P38494, P39694, P46837, P57072, P71353, Q057K3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SUPT6H	“form complex”	“Iws1:Spt6:CTD complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 162 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
FGFR2 mutant receptor activation	8	50.3×	2e-11
Signaling by FGFR2 IIIa TM	9	44.7×	5e-12
Abortive elongation of HIV-1 transcript in the absence of Tat	10	41.0×	1e-12
RNA Polymerase III Chain Elongation	7	36.7×	5e-09
Pausing and recovery of Tat-mediated HIV elongation	12	36.5×	4e-14
Tat-mediated HIV elongation arrest and recovery	12	36.5×	4e-14
HIV elongation arrest and recovery	12	34.3×	6e-14
Pausing and recovery of HIV elongation	12	34.3×	6e-14

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	5	20.0×	9e-04
positive regulation of double-strand break repair via homologous recombination	5	13.2×	4e-03
positive regulation of DNA repair	5	12.4×	4e-03
heterochromatin formation	6	10.6×	4e-03
positive regulation of transcription elongation by RNA polymerase II	5	10.4×	7e-03
transcription by RNA polymerase II	13	6.3×	1e-04
protein stabilization	13	6.0×	1e-04
protein folding	8	5.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	141
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5030 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28671672:G:T	donor_gain	1.0000
17:28672104:G:GT	donor_gain	1.0000
17:28673366:CCTAG:C	acceptor_loss	1.0000
17:28673367:CTA:C	acceptor_loss	1.0000
17:28673368:TAG:T	acceptor_loss	1.0000
17:28673369:A:AG	acceptor_gain	1.0000
17:28673370:G:GG	acceptor_gain	1.0000
17:28673370:GT:G	acceptor_gain	1.0000
17:28673370:GTT:G	acceptor_gain	1.0000
17:28673370:GTTA:G	acceptor_gain	1.0000
17:28673370:GTTAT:G	acceptor_gain	1.0000
17:28673466:T:TA	donor_gain	1.0000
17:28673467:G:GA	donor_gain	1.0000
17:28673495:G:GT	donor_gain	1.0000
17:28673501:G:GT	donor_gain	1.0000
17:28673516:G:GT	donor_gain	1.0000
17:28674282:GATGA:G	acceptor_gain	1.0000
17:28674437:ACGCA:A	donor_gain	1.0000
17:28674438:CGCA:C	donor_gain	1.0000
17:28674439:GCA:G	donor_gain	1.0000
17:28674439:GCAG:G	donor_gain	1.0000
17:28674440:CA:C	donor_gain	1.0000
17:28674441:AG:A	donor_loss	1.0000
17:28674442:G:GG	donor_gain	1.0000
17:28674611:GGA:G	donor_gain	1.0000
17:28674612:GAG:G	donor_gain	1.0000
17:28674614:G:GG	donor_gain	1.0000
17:28674968:A:AG	acceptor_gain	1.0000
17:28674969:G:GA	acceptor_gain	1.0000
17:28674969:GC:G	acceptor_gain	1.0000

AlphaMissense

11519 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28674576:T:A	L103H	1.000
17:28674576:T:C	L103P	1.000
17:28674579:T:A	I104N	1.000
17:28675412:T:C	F184L	1.000
17:28675413:T:G	F184C	1.000
17:28675414:C:A	F184L	1.000
17:28675414:C:G	F184L	1.000
17:28675416:T:A	I185N	1.000
17:28675416:T:G	I185S	1.000
17:28676363:T:C	L277P	1.000
17:28677766:G:C	A317P	1.000
17:28677772:T:A	W319R	1.000
17:28677772:T:C	W319R	1.000
17:28678567:G:C	R380P	1.000
17:28678571:G:C	K381N	1.000
17:28678571:G:T	K381N	1.000
17:28678606:T:C	L393P	1.000
17:28678852:T:C	L413P	1.000
17:28682747:G:A	G540R	1.000
17:28682747:G:C	G540R	1.000
17:28682747:G:T	G540W	1.000
17:28682748:G:A	G540E	1.000
17:28682751:T:C	L541P	1.000
17:28682768:G:A	G547R	1.000
17:28682768:G:C	G547R	1.000
17:28682768:G:T	G547W	1.000
17:28682769:G:A	G547E	1.000
17:28682776:C:A	N549K	1.000
17:28682776:C:G	N549K	1.000
17:28682778:T:C	L550P	1.000

dbSNP variants (sampled 300 via entrez): RS1000122604 (17:28702432 G>A), RS1000171026 (17:28695045 C>A), RS1000560219 (17:28684238 T>C), RS1000612590 (17:28684514 A>G), RS1000623428 (17:28689242 C>T), RS1000690767 (17:28673208 GAAGAGTTGGA>G), RS1000725791 (17:28691265 G>A,T), RS1000776434 (17:28696526 T>TG), RS1000785832 (17:28679475 G>C), RS1000864247 (17:28661006 T>C), RS1000923674 (17:28699997 A>C), RS1000997158 (17:28688874 T>G), RS1001029448 (17:28669915 G>A), RS1001134549 (17:28692009 C>T), RS1001197066 (17:28666916 T>A)

Disease associations

OMIM: gene MIM:601333 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007269_161	Pulse pressure	7.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases abundance	3
cobaltous chloride	increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
coumarin	increases phosphorylation	1
nivalenol	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Theophylline	decreases expression	1
Tretinoin	affects cotreatment, increases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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