HIVEP1

Summary

HIVEP1 (HIVEP zinc finger 1, HGNC:4920) is a protein-coding gene on chromosome 6p24.1, encoding Zinc finger protein 40 (P15822). This protein specifically binds to the DNA sequence 5’-GGGACTTTCC-3’ which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV-1.

This gene encodes a transcription factor belonging to the ZAS family, members of which are large proteins that contain a ZAS domain - a modular protein structure consisting of a pair of C2H2 zinc fingers with an acidic-rich region and a serine/threonine-rich sequence. These proteins bind specifically to the DNA sequence motif, GGGACTTTCC, found in the enhancer elements of several viral promoters, including human immunodeficiency virus (HIV), and to related sequences found in the enhancer elements of a number of cellular promoters. This protein binds to this sequence motif, suggesting a role in the transcriptional regulation of both viral and cellular genes.

Source: NCBI Gene 3096 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 483 total
• Druggable target: yes
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_002114

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4920
Approved symbol	HIVEP1
Name	HIVEP zinc finger 1
Location	6p24.1
Locus type	gene with protein product
Status	Approved
Aliases	CIRIP, MBP-1, CRYBP1, PRDII-BF1, ZAS1, Schnurri-1, ZNF40A
Ensembl gene	ENSG00000095951
Ensembl biotype	protein_coding
OMIM	194540
Entrez	3096

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 nonsense_mediated_decay

ENST00000379388, ENST00000399469, ENST00000442081, ENST00000478545, ENST00000484210, ENST00000487103, ENST00000491710, ENST00000627968, ENST00000714231, ENST00000714232, ENST00000925922

RefSeq mRNA: 1 — MANE Select: NM_002114 NM_002114

CCDS: CCDS43426

Canonical transcript exons

ENST00000379388 — 9 exons

Exon	Start	End
ENSE00001817961	12119890	12125870
ENSE00001961408	12089184	12089237
ENSE00003663871	12015526	12015668
ENSE00003849970	12012312	12012566
ENSE00004023254	12130767	12130942
ENSE00004023255	12163283	12164999
ENSE00004023257	12135791	12135892
ENSE00004023259	12161439	12161929
ENSE00004023261	12129759	12129892

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 93.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6676 / max 1137.0313, expressed in 1792 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65836	6.9795	1606
65835	5.1073	1397
65832	3.6158	1188
65840	2.3071	1113
65837	1.6395	688
65833	1.1281	327
65839	0.4069	190
65838	0.2768	98
65834	0.2066	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.16	gold quality
cartilage tissue	UBERON:0002418	92.31	gold quality
sural nerve	UBERON:0015488	89.06	gold quality
colonic epithelium	UBERON:0000397	86.99	gold quality
superficial temporal artery	UBERON:0001614	85.56	gold quality
cortical plate	UBERON:0005343	85.30	gold quality
jejunal mucosa	UBERON:0000399	84.98	gold quality
seminal vesicle	UBERON:0000998	84.90	gold quality
oral cavity	UBERON:0000167	83.99	gold quality
right lobe of liver	UBERON:0001114	83.77	gold quality
caput epididymis	UBERON:0004358	83.63	gold quality
liver	UBERON:0002107	83.62	gold quality
ventricular zone	UBERON:0003053	83.18	gold quality
lower esophagus mucosa	UBERON:0035834	82.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.53	gold quality
corpus epididymis	UBERON:0004359	81.92	gold quality
bone marrow cell	CL:0002092	81.84	gold quality
skin of leg	UBERON:0001511	81.71	gold quality
colonic mucosa	UBERON:0000317	81.69	gold quality
right coronary artery	UBERON:0001625	81.67	gold quality
mucosa of sigmoid colon	UBERON:0004993	81.65	gold quality
skin of abdomen	UBERON:0001416	81.60	gold quality
tendon	UBERON:0000043	81.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.51	gold quality
zone of skin	UBERON:0000014	81.48	gold quality
ganglionic eminence	UBERON:0004023	81.41	gold quality
subcutaneous adipose tissue	UBERON:0002190	81.34	gold quality
mucosa of transverse colon	UBERON:0004991	81.31	gold quality
descending thoracic aorta	UBERON:0002345	81.29	gold quality
pigmented layer of retina	UBERON:0001782	81.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.14

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets.

Target	Regulation
CCND1	Activation
CD74
COL2A1	Unknown
CRYAA
HP
IRF1
MYC	Repression
PTGS2	Unknown
SOX9	Repression
SPEN
TP53
TPM1

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

108 targeting HIVEP1, 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-3120-5P	100.00	65.56	965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-433-3P	99.98	69.37	1203
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 2)

• HIVEP1 rs169713C allele was associated with venous thrombosis. (PMID:20226436)
• Downregulation of tumor suppressor MBP-1 by microRNA-363 in gastric carcinogenesis. (PMID:23975832)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hivep1	ENSDARG00000103658
mus_musculus	Hivep1	ENSMUSG00000021366
rattus_norvegicus	Hivep1	ENSRNOG00000014460

Paralogs (14): HIVEP2 (ENSG00000010818), SALL4 (ENSG00000101115), ZNF516 (ENSG00000101493), SALL1 (ENSG00000103449), BCL11A (ENSG00000119866), ZNF831 (ENSG00000124203), RREB1 (ENSG00000124782), HIVEP3 (ENSG00000127124), BCL11B (ENSG00000127152), ZNF219 (ENSG00000165804), SALL2 (ENSG00000165821), ZNF217 (ENSG00000171940), ZNF536 (ENSG00000198597), SALL3 (ENSG00000256463)

Protein

Protein identifiers

Zinc finger protein 40 — P15822 (reviewed: P15822)

Alternative names: Cirhin interaction protein, Gate keeper of apoptosis-activating protein, Human immunodeficiency virus type I enhancer-binding protein 1, Major histocompatibility complex-binding protein 1, Positive regulatory domain II-binding factor 1

All UniProt accessions (9): P15822, A0A0D9SFF3, A0AAQ5BHS1, C9J2N3, C9JAW2, C9JLG1, C9JZF8, C9JZV1, H7BYU7

UniProt curated annotations — full annotation on UniProt →

Function. This protein specifically binds to the DNA sequence 5’-GGGACTTTCC-3’ which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV-1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, and interferon-beta genes. It may act in T-cell activation. Involved in activating HIV-1 gene expression. Isoform 2 and isoform 3 also bind to the IPCS (IRF1 and p53 common sequence) DNA sequence in the promoter region of interferon regulatory factor 1 and p53 genes and are involved in transcription regulation of these genes. Isoform 2 does not activate HIV-1 gene expression. Isoform 2 and isoform 3 may be involved in apoptosis.

Subunit / interactions. Interacts with UTP4.

Subcellular location. Nucleus Cytoplasm. Nucleus.

Domain organisation. Contains two sets of 2 zinc-fingers, which are widely separated and recognize the same DNA sequence. There is a fifth zinc-finger in-between.

Induction. By mitogens and phorbol ester.

Isoforms (3)

UniProt ID	Names	Canonical?
P15822-1	1	yes
P15822-2	2, Delta 2, GAAP-1
P15822-3	3, GAAP-2

RefSeq proteins (1): NP_002105* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR034729	Znf_CCHC_HIVEP	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051969

Pfam: PF00096

UniProt features (102 total): modified residue 27, compositionally biased region 23, region of interest 15, sequence variant 12, sequence conflict 9, zinc finger region 5, splice variant 4, strand 3, helix 2, chain 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1BBO	SOLUTION NMR
3ZNF	SOLUTION NMR
4ZNF	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for P15822 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (27): 141, 429, 476, 479, 492, 495, 571, 577, 670, 681, 1036, 1051, 1091, 1158, 1161, 1180, 1268, 1735, 1740, 1749 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 252 (showing top): CREL_01, YAATNRNNNYNATT_UNKNOWN, chr6p24, MEF2_02, GCM_PRKCG, GTGCCTT_MIR506, PAX8_B, IRF7_01, LINDSTEDT_DENDRITIC_CELL_MATURATION_B, BRN2_01, MODULE_206, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GGGNNTTTCC_NFKB_Q6_01, MODULE_123, ARGGGTTAA_UNKNOWN

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), BMP signaling pathway (GO:0030509), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), nuclear body (GO:0016604), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
DNA-templated transcription	2
intracellular membrane-bounded organelle	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
positive regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
nuclear lumen	1
nucleoplasm	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIVEP1	UTP4	Q969X6	629
HIVEP1	SMAD4	Q13485	612
HIVEP1	CLIC4	Q9Y696	588
HIVEP1	PPM1A	P35813	510
HIVEP1	PTCHD4	Q6ZW05	457
HIVEP1	SPEN	Q96T58	456
HIVEP1	FGG	P02679	444
HIVEP1	SSTR2	P30874	439
HIVEP1	BMP2	P12643	439
HIVEP1	GFOD1	Q9NXC2	438
HIVEP1	GNAS	Q5JWF2	435
HIVEP1	TBL1XR1	Q9BZK7	432
HIVEP1	TCF4	P15884	428
HIVEP1	RFX3	P48380	406
HIVEP1	CCDC17	Q96LX7	400

IntAct

192 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
ATXN1	HIVEP1	psi-mi:“MI:0915”(physical association)	0.630
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
SMAD3	HIVEP1	psi-mi:“MI:0915”(physical association)	0.550
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
FBXW11	AHCYL1	psi-mi:“MI:0914”(association)	0.530
HIVEP1	NHLH1	psi-mi:“MI:0915”(physical association)	0.520
CACNA1A	HIVEP1	psi-mi:“MI:0915”(physical association)	0.510
HIVEP1	UTP4	psi-mi:“MI:0915”(physical association)	0.510
UTP4	HIVEP1	psi-mi:“MI:0915”(physical association)	0.510
FOS	MYO1C	psi-mi:“MI:2364”(proximity)	0.480
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
ETV7	NFIB	psi-mi:“MI:2364”(proximity)	0.470
EN1	NFIB	psi-mi:“MI:2364”(proximity)	0.470
HIVEP1	NPM1	psi-mi:“MI:0915”(physical association)	0.400
HIVEP1	MYH9	psi-mi:“MI:0915”(physical association)	0.400
HIVEP1	PARP1	psi-mi:“MI:0915”(physical association)	0.400
HIVEP1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
HIVEP1	NS	psi-mi:“MI:0915”(physical association)	0.370
HIVEP1	NS1	psi-mi:“MI:0915”(physical association)	0.370
NS1	HIVEP1	psi-mi:“MI:0915”(physical association)	0.370
NS	HIVEP1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (225): HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), HIVEP1 (Biochemical Activity), HIVEP1 (Biochemical Activity), HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GSA2, A0A1L8H0H2, A0JP82, A0MS83, A2AWL7, A2RRX6, A2X0Q0, A6NCI8, A9ZPC9, F8VPJ6, K9JHZ4, O13186, O46567, O60284, O75362, P15822, P35547, P37275, P48552, P52551, P79269, Q03172, Q14207, Q28DZ0, Q2KHR2, Q3V0A6, Q3Y4E1, Q4JK59, Q4V7J0, Q5DTW7, Q5R782, Q5W1J6, Q5ZJK5, Q61624, Q62806, Q6N021, Q6YXZ4, Q7SZL5, Q80TY4, Q8BMA5

Diamond homologs: A1L2U9, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, O35615, O62836, O77459, P08048, P10925, P15822, P17010, P17012, P20662, P31505, P31629, P60319, P78871, P80944, Q00900, Q01611, Q02031, Q03172, Q0IH98, Q0VCJ6, Q292R5, Q29419, Q3UHF7, Q52V16, Q5JPB2, Q5T1R4, Q6B4Z5, Q7JM44, Q811F1, Q86UZ6, Q8BID6, Q8CII0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 197 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
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	35.4×	9e-08
Activation of BAD and translocation to mitochondria	6	34.4×	1e-06
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	30.3×	2e-06
Activation of BH3-only proteins	7	26.1×	7e-07
RHO GTPases activate PKNs	8	19.1×	8e-07
Intrinsic Pathway for Apoptosis	8	17.6×	1e-06
FOXO-mediated transcription	6	15.2×	9e-05
Apoptosis	9	11.4×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	13	21.8×	6e-12
positive regulation of erythrocyte differentiation	7	20.7×	9e-06
negative regulation of miRNA transcription	5	18.0×	7e-04
placenta development	6	15.4×	3e-04
somatic stem cell population maintenance	8	11.5×	9e-05
protein targeting	5	10.6×	5e-03
regulation of circadian rhythm	7	10.5×	5e-04
thymus development	5	9.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	380
Likely benign	53
Benign	23

Top pathogenic / likely-pathogenic (0)

SpliceAI

2851 predictions. Top by Δscore:

Variant	Effect	Δscore
6:12015520:TTTCA:T	acceptor_loss	1.0000
6:12015522:TCA:T	acceptor_loss	1.0000
6:12015523:CAGCA:C	acceptor_loss	1.0000
6:12015524:A:AG	acceptor_gain	1.0000
6:12015524:AGC:A	acceptor_loss	1.0000
6:12015525:G:GC	acceptor_gain	1.0000
6:12015525:GC:G	acceptor_gain	1.0000
6:12015525:GCA:G	acceptor_gain	1.0000
6:12015525:GCAC:G	acceptor_gain	1.0000
6:12015525:GCACA:G	acceptor_gain	1.0000
6:12015666:GAG:G	donor_gain	1.0000
6:12015667:AG:A	donor_loss	1.0000
6:12015668:GG:G	donor_loss	1.0000
6:12015669:GT:G	donor_loss	1.0000
6:12015670:T:G	donor_loss	1.0000
6:12089179:CTTAG:C	acceptor_loss	1.0000
6:12089180:TTAGA:T	acceptor_loss	1.0000
6:12089181:TAG:T	acceptor_loss	1.0000
6:12089182:A:AG	acceptor_gain	1.0000
6:12089183:G:GG	acceptor_gain	1.0000
6:12089183:GA:G	acceptor_gain	1.0000
6:12089183:GAC:G	acceptor_gain	1.0000
6:12089183:GACA:G	acceptor_gain	1.0000
6:12089183:GACAA:G	acceptor_gain	1.0000
6:12089235:AAGG:A	donor_loss	1.0000
6:12089237:GGTAA:G	donor_loss	1.0000
6:12089238:G:GC	donor_loss	1.0000
6:12089239:T:A	donor_loss	1.0000
6:12089687:T:TA	donor_gain	1.0000
6:12089688:A:AA	donor_gain	1.0000

AlphaMissense

17770 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:12121017:T:A	C408S	1.000
6:12121017:T:C	C408R	1.000
6:12121018:G:A	C408Y	1.000
6:12121018:G:C	C408S	1.000
6:12121019:T:G	C408W	1.000
6:12121026:T:C	C411R	1.000
6:12121027:G:A	C411Y	1.000
6:12121027:G:T	C411F	1.000
6:12121028:C:G	C411W	1.000
6:12121038:T:C	C415R	1.000
6:12121040:T:G	C415W	1.000
6:12121044:A:G	K417E	1.000
6:12121057:T:C	L421P	1.000
6:12121062:A:G	K423E	1.000
6:12121064:G:C	K423N	1.000
6:12121064:G:T	K423N	1.000
6:12121065:C:A	H424N	1.000
6:12121065:C:G	H424D	1.000
6:12121066:A:C	H424P	1.000
6:12121066:A:G	H424R	1.000
6:12121066:A:T	H424L	1.000
6:12121067:T:A	H424Q	1.000
6:12121067:T:G	H424Q	1.000
6:12121071:C:A	R426S	1.000
6:12121072:G:C	R426P	1.000
6:12121077:C:A	H428N	1.000
6:12121077:C:G	H428D	1.000
6:12121079:C:A	H428Q	1.000
6:12121079:C:G	H428Q	1.000
6:12121101:T:C	C436R	1.000

dbSNP variants (sampled 300 via entrez): RS1000001951 (6:12033868 A>C), RS1000013027 (6:12181342 AGAGT>A), RS1000028970 (6:12140410 G>C), RS1000068408 (6:12190288 G>A), RS1000087102 (6:12198817 A>G), RS1000090095 (6:12014332 C>T), RS1000092534 (6:12134139 T>C), RS1000098266 (6:12113912 A>G), RS1000116129 (6:12055917 G>T), RS1000133957 (6:12014067 G>A,C,T), RS1000145164 (6:12108002 T>C), RS1000185912 (6:12018016 C>A,T), RS1000213059 (6:12090708 T>A,C), RS1000231690 (6:12179240 G>C), RS1000237400 (6:12055395 C>A,G)

Disease associations

OMIM: gene MIM:194540 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): myoepithelial tumor (MONDO:0002380), hearing loss disorder (MONDO:0005365), attention deficit-hyperactivity disorder (MONDO:0007743)

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001471_4	Alcohol and nicotine co-dependence	2.000000e-06
GCST002783_271	Body mass index	3.000000e-07
GCST002783_39	Body mass index	4.000000e-06
GCST002783_626	Body mass index	1.000000e-06
GCST004904_73	Body mass index	1.000000e-10
GCST006575_8	Takayasu arteritis	5.000000e-06
GCST006923_10	Loneliness	3.000000e-09
GCST006924_12	Loneliness (MTAG)	9.000000e-09
GCST006950_11	Feeling worry	3.000000e-09
GCST007325_163	General risk tolerance (MTAG)	2.000000e-11
GCST007576_313	Chronotype	1.000000e-08
GCST008129_46	Body mass index	3.000000e-13
GCST009323_1	Figural/spatial cognitive ability	1.000000e-06
GCST009391_797	Metabolite levels	8.000000e-06
GCST010043_135	Asthma	5.000000e-09
GCST010988_349	Adult body size	2.000000e-10
GCST90002389_278	Lymphocyte percentage of white cells	4.000000e-16
GCST90002393_9	Monocyte count	2.000000e-11
GCST90002398_17	Neutrophil count	8.000000e-10
GCST90002399_312	Neutrophil percentage of white cells	8.000000e-15
GCST90002403_373	Red blood cell count	3.000000e-09

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007865	loneliness measurement
EFO:0009589	worry measurement
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0008354	cognitive function measurement
EFO:0010395	sphingomyelin 22:0 measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004305	erythrocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2909 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	6
bisphenol A	affects cotreatment, affects methylation, increases expression	2
sodium arsenite	decreases expression, increases abundance, affects cotreatment	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
nickel sulfate	increases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance	2
Estradiol	increases expression	2
Cyclosporine	decreases methylation, increases expression	2
Asbestos, Crocidolite	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Palmitic Acid	affects expression, increases phosphorylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
Glupearl 19S	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
geraniol	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
coumarin	increases phosphorylation	1
mercuric bromide	affects cotreatment, decreases expression	1
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1

ChEMBL screening assays

26 unique, capped per target: 26 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL689305	Binding	Inhibition of human DNA binding to HIV-EP1 (enhancer binding protein) at 0.01 mM concentration	Novel zinc chelators which inhibit the binding of HIV-EP1 (HIV enhancer binding protein) to NF-kappa B recognition sequence. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity