SUPT4H1

Summary

SUPT4H1 (SPT4 homolog, DSIF elongation factor subunit, HGNC:11467) is a protein-coding gene on chromosome 17q22, encoding Transcription elongation factor SPT4 (P63272). Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. It is a selective cancer dependency (DepMap: 74.3% of cell lines).

This gene encodes the small subunit of DRB (5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole) sensitivity-inducing factor (DSIF) complex, which regulates mRNA processing and transcription elongation by RNA polymerase II. The encoded protein is localized to the nucleus and interacts with the large subunit (SUPT5H) to form the DSIF complex. Related pseudogenes have been identified on chromosomes 2 and 12. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 6827 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 21 total
• Cancer dependency (DepMap): dependent in 74.3% of screened cell lines
• MANE Select transcript: NM_003168

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11467
Approved symbol	SUPT4H1
Name	SPT4 homolog, DSIF elongation factor subunit
Location	17q22
Locus type	gene with protein product
Status	Approved
Aliases	SPT4H, Spt4, Supt4a
Ensembl gene	ENSG00000213246
Ensembl biotype	protein_coding
OMIM	603555
Entrez	6827

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000225504, ENST00000577396, ENST00000579289, ENST00000580947, ENST00000581166, ENST00000581204, ENST00000581540

RefSeq mRNA: 1 — MANE Select: NM_003168 NM_003168

CCDS: CCDS11606

Canonical transcript exons

ENST00000225504 — 5 exons

Exon	Start	End
ENSE00000820278	58352067	58352201
ENSE00003498022	58347188	58347241
ENSE00003595534	58351402	58351508
ENSE00003648974	58345178	58346313
ENSE00003664209	58347529	58347584

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 98.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 91.1724 / max 1141.8882, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167250	90.9577	1825
167251	0.2146	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.48	gold quality
leukocyte	CL:0000738	98.46	gold quality
granulocyte	CL:0000094	97.79	gold quality
blood	UBERON:0000178	97.26	gold quality
calcaneal tendon	UBERON:0003701	96.92	gold quality
bone marrow	UBERON:0002371	96.90	gold quality
stromal cell of endometrium	CL:0002255	96.84	gold quality
lymph node	UBERON:0000029	96.79	gold quality
islet of Langerhans	UBERON:0000006	96.63	gold quality
embryo	UBERON:0000922	96.59	gold quality
ganglionic eminence	UBERON:0004023	96.59	gold quality
bone marrow cell	CL:0002092	96.57	gold quality
right adrenal gland	UBERON:0001233	96.56	gold quality
right adrenal gland cortex	UBERON:0035827	96.53	gold quality
vermiform appendix	UBERON:0001154	96.52	gold quality
left adrenal gland	UBERON:0001234	96.30	gold quality
left adrenal gland cortex	UBERON:0035825	96.22	gold quality
prefrontal cortex	UBERON:0000451	96.14	gold quality
mucosa of transverse colon	UBERON:0004991	96.14	gold quality
placenta	UBERON:0001987	96.04	gold quality
spleen	UBERON:0002106	96.03	gold quality
right coronary artery	UBERON:0001625	95.99	gold quality
adrenal gland	UBERON:0002369	95.92	gold quality
descending thoracic aorta	UBERON:0002345	95.88	gold quality
cortex of kidney	UBERON:0001225	95.87	gold quality
adrenal tissue	UBERON:0018303	95.85	gold quality
right lung	UBERON:0002167	95.80	gold quality
adult mammalian kidney	UBERON:0000082	95.74	gold quality
thoracic aorta	UBERON:0001515	95.67	gold quality
ascending aorta	UBERON:0001496	95.63	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	23.06
E-ANND-3	yes	4.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting SUPT4H1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6853-3P	99.36	70.79	1558

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 74.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• Upon induction of NF-kappaB, a subset of target genes is regulated differentially by either P-TEFb or DSIF.[P-TEFb, DSIF] (PMID:17502349)
• These findings reveal a dynamic regulation of DSIF involving either E-box or NF-kappaB depending on the physiological circumstances. (PMID:17962196)
• Spt4 was purified and characterized. (PMID:18373978)
• These results suggest that one of the functions of Spt5 is to suppress senescence and apoptosis, and that this function is exerted through its association with Spt4 and Pol II. (PMID:19210550)
• crystal structure of hSpt4 in complex with the dimerization region of hSpt5 (PMID:19860741)
• he Paf1 complex (Paf1C) and Tat-SF1, two factors implicated previously in elongation control, collaborate with DSIF to facilitate efficient elongation (PMID:19952111)
• Chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. (PMID:27461012)
• Knockdown of SUPT4H1, the human Spt4 ortholog, similarly decreased production of sense and antisense RNA foci, as well as dipeptide repeat proteins, in patient cells. (PMID:27516603)
• Authors depleted SUPT4H1 by RNA interference to inhibit the function of the SUPT4H1/SUPT5H transcription elongation complex. Depletion of SUPT4H1 leads to a global reduction in all cellular RNA. (PMID:30605685)
• CRISPRi-mediated depletion of Spt4 and Spt5 reveals a role for DSIF in the control of HIV latency. (PMID:33333262)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	supt4h1	ENSDARG00000113969
mus_musculus	Supt4a	ENSMUSG00000020485
rattus_norvegicus	Supt4h1	ENSRNOG00000007845
rattus_norvegicus		ENSRNOG00000068353
drosophila_melanogaster	spt4	FBGN0028683
caenorhabditis_elegans		WBGENE00005014

Protein

Protein identifiers

Transcription elongation factor SPT4 — P63272 (reviewed: P63272)

Alternative names: DRB sensitivity-inducing factor 14 kDa subunit, DRB sensitivity-inducing factor small subunit

All UniProt accessions (4): D3DTZ5, P63272, J3KSQ6, J3QSB9

UniProt curated annotations — full annotation on UniProt →

Function. Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3’ terminus and may allow repeated attempts at transcription through natural pause sites. DSIF can also positively regulate transcriptional elongation and is required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences.

Subunit / interactions. Interacts with SUPT5H to form DSIF. DSIF interacts with the positive transcription elongation factor b complex (P-TEFb complex), which is composed of CDK9 and cyclin-T (CCNT1 or CCNT2). DSIF interacts with RNA polymerase II (Pol II); forms DNA and RNA clamps that stabilize Pol II elongation complex while maintaining the nontemplate DNA strand in the transcription bubble and nascent RNA in the exit channel. This interaction is reduced by phosphorylation of the C-terminal domain (CTD) of POLR2A by P-TEFb. DSIF also interacts with the NELF complex, which is composed of NELFA, NELFB, NELFD and NELFE, and this interaction occurs following prior binding of DSIF to RNA polymerase II. DSIF also interacts with PRMT1/HRMT1L2, HTATSF1/TATSF1, RNGTT/CAP1A, PRMT5/SKB1, SUPT6H, and can interact with PIN1.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed.

Post-translational modifications. Ubiquitinated by UBR5 when not assembled in the DSIF complex, leading to its degradation: UBR5 recognizes and binds a degron that is not accessible when SUPT4H1 is part of the DSIF complex.

Similarity. Belongs to the SPT4 family.

RefSeq proteins (1): NP_003159* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009287	Spt4	Family
IPR022800	Spt4/RpoE2_Znf	Domain
IPR029040	RPABC4/Spt4	Homologous_superfamily
IPR038510	Spt4_sf	Homologous_superfamily

Pfam: PF06093

UniProt features (26 total): helix 7, strand 7, binding site 4, turn 2, initiator methionine 1, chain 1, zinc finger region 1, region of interest 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3H7H	X-RAY DIFFRACTION	1.55
9HVQ	ELECTRON MICROSCOPY	2
9MLC	ELECTRON MICROSCOPY	2.4
8UHD	ELECTRON MICROSCOPY	2.8
9EGX	ELECTRON MICROSCOPY	2.9
9EGY	ELECTRON MICROSCOPY	2.9
9EGZ	ELECTRON MICROSCOPY	2.9
7UND	ELECTRON MICROSCOPY	3
6GMH	ELECTRON MICROSCOPY	3.1
6TED	ELECTRON MICROSCOPY	3.1
9EH1	ELECTRON MICROSCOPY	3.1
9EH2	ELECTRON MICROSCOPY	3.1
9G0A	ELECTRON MICROSCOPY	3.1
8XRM	ELECTRON MICROSCOPY	3.13
6GML	ELECTRON MICROSCOPY	3.2
9FYX	ELECTRON MICROSCOPY	3.3
9J0O	ELECTRON MICROSCOPY	3.3
9J0P	ELECTRON MICROSCOPY	3.3
8A3Y	ELECTRON MICROSCOPY	3.3
9J0N	ELECTRON MICROSCOPY	3.4
8UHA	ELECTRON MICROSCOPY	3.5
8P4D	ELECTRON MICROSCOPY	3.6
9EH0	ELECTRON MICROSCOPY	3.6
5OIK	ELECTRON MICROSCOPY	3.7
8P4C	ELECTRON MICROSCOPY	3.8
8W8E	ELECTRON MICROSCOPY	3.9
8P4F	ELECTRON MICROSCOPY	4
8W8F	ELECTRON MICROSCOPY	4
9RTT	ELECTRON MICROSCOPY	4.01
7OKY	ELECTRON MICROSCOPY	4.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63272-F1	96.58	0.95

Functional residue map

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

Ligand- & substrate-binding residues (4): 16; 19; 33; 36

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

27 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-113418	Formation of the Early Elongation Complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158	Formation of the HIV-1 Early Elongation Complex
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167242	Abortive elongation of HIV-1 transcript in the absence of Tat
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-162587	HIV Life Cycle
R-HSA-162599	Late Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
R-HSA-167169	HIV Transcription Elongation
R-HSA-167172	Transcription of the HIV genome
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 219 (showing top): ENK_UV_RESPONSE_KERATINOCYTE_UP, GOZGIT_ESR1_TARGETS_DN, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, IVANOVA_HEMATOPOIESIS_MATURE_CELL, RACCACAR_AML_Q6, MEF2_02, GCM_RING1, REACTOME_HIV_INFECTION, GCM_FCGR2B, GCM_DPF2, HFH8_01, HSIAO_LIVER_SPECIFIC_GENES, FOXJ2_01, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6, MORF_PPP6C

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), transcription elongation by RNA polymerase II (GO:0006368), negative regulation of DNA-templated transcription, elongation (GO:0032785), positive regulation of DNA-templated transcription, elongation (GO:0032786), regulation of transcription elongation by RNA polymerase II (GO:0034243), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), positive regulation of transcription by RNA polymerase II (GO:0045944), transcription elongation-coupled chromatin remodeling (GO:0140673)

GO Molecular Function (5): RNA polymerase II complex binding (GO:0000993), zinc ion binding (GO:0008270), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), DSIF complex (GO:0032044)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Transcription of the HIV genome	6
HIV Transcription Elongation	3
RNA Polymerase II Transcription	3
RNA Polymerase II Transcription Elongation	2
Tat-mediated elongation of the HIV-1 transcript	1
Transcriptional Regulation by TP53	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
DNA-templated transcription elongation	3
regulation of DNA-templated transcription elongation	3
transcription elongation by RNA polymerase II	3
regulation of transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
chromatin remodeling	1
RNA polymerase core enzyme binding	1
transition metal ion binding	1
protein dimerization activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
transcription elongation factor complex	1

Protein interactions and networks

STRING

2082 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUPT4H1	SUPT5H	O00267	999
SUPT4H1	SUPT6H	Q7KZ85	988
SUPT4H1	NELFE	P18615	957
SUPT4H1	NELFCD	Q8IXH7	926
SUPT4H1	NELFB	Q8WX92	926
SUPT4H1	TCEA3	O75764	872
SUPT4H1	TCEA1	P23193	872
SUPT4H1	TCEA2	Q15560	872
SUPT4H1	NELFA	Q9H3P2	866
SUPT4H1	POLR2A	P24928	832
SUPT4H1	POLR2D	O15514	822
SUPT4H1	POLR2B	P30876	814
SUPT4H1	CDK9	P50750	808
SUPT4H1	SETX	Q7Z333	731
SUPT4H1	SUPT16H	Q9Y5B9	718

IntAct

59 interactions, top by confidence:

A	B	Type	Score
SUPT5H	SUPT4H1	psi-mi:“MI:0915”(physical association)	0.960
SUPT4H1	SUPT5H	psi-mi:“MI:0915”(physical association)	0.960
SUPT5H	SUPT4H1	psi-mi:“MI:0407”(direct interaction)	0.960
SUPT4H1	SUPT5H	psi-mi:“MI:0407”(direct interaction)	0.960
POLR2D	POLR2K	psi-mi:“MI:0915”(physical association)	0.730
POLR2E	POLR2B	psi-mi:“MI:0915”(physical association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
SUPT4H1	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
SUPT4H1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
SUPT4H1	SMARCA2	psi-mi:“MI:0915”(physical association)	0.370
EWSR1	SUPT4H1	psi-mi:“MI:0915”(physical association)	0.370
SUPT4H1	LRIF1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (86): SUPT4H1 (Affinity Capture-RNA), SUPT4H1 (Affinity Capture-RNA), SUPT4H1 (Co-fractionation), SUPT4H1 (Co-fractionation), SUPT4H1 (Co-fractionation), SUPT4H1 (Co-fractionation), SUPT4H1 (Co-fractionation), SUPT4H1 (Co-fractionation), SUPT4H1 (Co-fractionation), SUPT4H1 (Co-fractionation), SUPT4H1 (Co-fractionation), SUPT4H1 (Co-fractionation), SUPT4H1 (Co-fractionation), SUPT4H1 (Affinity Capture-MS), SUPT4H1 (Affinity Capture-MS)

ESM2 similar proteins: A0A4X1TB62, A4VCH4, F1LNJ2, O43513, O75643, P47757, P48603, P63271, P63272, P79136, P93431, Q28C34, Q2F7Z4, Q2HJ41, Q3SYX6, Q3T123, Q42450, Q4R8N2, Q4R941, Q5EAV6, Q5HZ97, Q5R7U7, Q5RCP7, Q5RE03, Q5RFH5, Q5RJU0, Q5RK19, Q5TKA1, Q5U3V9, Q5XI83, Q658Y4, Q6DGQ0, Q6GMH0, Q6NRD0, Q6P4T2, Q7ZUV0, Q7ZYD9, Q8BM39, Q8C735, Q8C8N2

Diamond homologs: P0CR68, P0CR69, P32914, P63271, P63272, P81205, Q3SYX6, Q4I5W5, Q4R941, Q4WU00, Q5AK73, Q5HZ97, Q5RFH5, Q628A6, Q6BHA5, Q6DGQ0, Q6FMX1, Q752J8, Q7S743, Q8LCQ3, Q94C60, Q9P7K8, Q9TVQ5, Q9TZ93, Q9Z199

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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	5	100.2×	2e-08
Signaling by FGFR2 IIIa TM	5	79.1×	5e-08
Abortive elongation of HIV-1 transcript in the absence of Tat	6	78.4×	3e-09
Pausing and recovery of Tat-mediated HIV elongation	7	67.9×	4e-10
Tat-mediated HIV elongation arrest and recovery	7	67.9×	4e-10
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	6	64.4×	9e-09
RNA Pol II CTD phosphorylation and interaction with CE	6	64.4×	9e-09
HIV elongation arrest and recovery	7	63.8×	5e-10

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	5	11.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

676 predictions. Top by Δscore:

Variant	Effect	Δscore
17:58346313:CCTGA:C	acceptor_loss	1.0000
17:58346320:C:CT	acceptor_gain	1.0000
17:58346321:A:T	acceptor_gain	1.0000
17:58347182:TATTA:T	donor_loss	1.0000
17:58347184:TTACC:T	donor_loss	1.0000
17:58347185:TACCT:T	donor_loss	1.0000
17:58347186:A:C	donor_loss	1.0000
17:58347187:C:CT	donor_loss	1.0000
17:58347237:GTTAC:G	acceptor_gain	1.0000
17:58347238:TTAC:T	acceptor_gain	1.0000
17:58347239:TAC:T	acceptor_gain	1.0000
17:58347242:C:CC	acceptor_gain	1.0000
17:58347242:CTG:C	acceptor_loss	1.0000
17:58347527:A:AC	donor_gain	1.0000
17:58347528:C:CT	donor_gain	1.0000
17:58347528:CTG:C	donor_gain	1.0000
17:58347528:CTGA:C	donor_gain	1.0000
17:58347580:TGATT:T	acceptor_gain	1.0000
17:58347583:TT:T	acceptor_gain	1.0000
17:58347583:TTCTA:T	acceptor_loss	1.0000
17:58347584:TCT:T	acceptor_loss	1.0000
17:58347585:C:CC	acceptor_gain	1.0000
17:58347585:CT:C	acceptor_loss	1.0000
17:58347586:T:A	acceptor_loss	1.0000
17:58351396:GCTTA:G	donor_loss	1.0000
17:58351397:CTTA:C	donor_loss	1.0000
17:58351398:TTACC:T	donor_loss	1.0000
17:58351399:TA:T	donor_loss	1.0000
17:58351400:A:AC	donor_gain	1.0000
17:58351400:AC:A	donor_gain	1.0000

AlphaMissense

756 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:58347202:C:A	G91V	1.000
17:58347202:C:T	G91D	1.000
17:58347203:C:G	G91R	1.000
17:58347208:A:T	V89D	1.000
17:58347217:G:T	A86E	1.000
17:58347226:C:T	G83D	1.000
17:58347227:C:G	G83R	1.000
17:58347539:C:A	W74C	1.000
17:58347539:C:G	W74C	1.000
17:58347541:A:G	W74R	1.000
17:58347541:A:T	W74R	1.000
17:58347551:C:A	W70C	1.000
17:58347551:C:G	W70C	1.000
17:58347553:A:G	W70R	1.000
17:58347553:A:T	W70R	1.000
17:58347576:G:T	A62E	1.000
17:58351402:C:A	G59V	1.000
17:58351402:C:T	G59E	1.000
17:58351403:C:G	G59R	1.000
17:58351403:C:T	G59R	1.000
17:58351407:A:C	F57L	1.000
17:58351407:A:T	F57L	1.000
17:58351409:A:G	F57L	1.000
17:58351416:G:C	S54R	1.000
17:58351416:G:T	S54R	1.000
17:58351418:T:G	S54R	1.000
17:58351471:C:T	C36Y	1.000
17:58351472:A:G	C36R	1.000
17:58351473:A:C	N35K	1.000
17:58351473:A:T	N35K	1.000

dbSNP variants (sampled 300 via entrez): RS1000187834 (17:58348264 A>C,G), RS1000195216 (17:58350298 G>A), RS1000416541 (17:58350809 A>C,G), RS1001197581 (17:58353981 TG>T), RS1001355375 (17:58345131 TG>T), RS1001463885 (17:58351273 A>C), RS1001927069 (17:58346898 G>A), RS1002389827 (17:58352697 TCCACTTGCTTCCCACAGGAATG>T), RS1002456661 (17:58352609 C>T), RS1002464816 (17:58352401 G>A), RS1003086697 (17:58350240 G>A), RS1003256982 (17:58352402 T>C,G), RS1003304543 (17:58352521 G>C), RS1003462850 (17:58346581 G>A), RS1003863984 (17:58345154 T>A,G)

Disease associations

OMIM: gene MIM:603555 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008550_30	Mental health study participation (completed survey)	1.000000e-08
GCST010002_126	Refractive error	7.000000e-42
GCST90002382_478	Eosinophil percentage of white cells	8.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010130	health study participation
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	affects binding, increases reaction	1
cupric oxide	increases expression	1
(+)-JQ1 compound	increases expression	1
Decitabine	affects expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	affects expression	1
Copper	affects binding, decreases expression	1
Cycloheximide	decreases reaction, decreases expression	1
Disulfiram	decreases expression, affects binding	1
Nicotine	decreases expression	1
Rotenone	increases expression	1
Tetrachlorodibenzodioxin	decreases reaction, decreases expression	1
Tretinoin	increases expression	1
Vitamin E	increases expression	1
2-Naphthylamine	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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