PIF1

Summary

PIF1 (PIF1 5’-to-3’ DNA helicase, HGNC:26220) is a protein-coding gene on chromosome 15q22.31, encoding ATP-dependent DNA helicase PIF1 (Q9H611). DNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of both mitochondrial and nuclear genome stability.

This gene encodes a DNA-dependent adenosine triphosphate (ATP)-metabolizing enzyme that functions as a 5’ to 3’ DNA helicase. The encoded protein can resolve G-quadruplex structures and RNA-DNA hybrids at the ends of chromosomes. It also prevents telomere elongation by inhibiting the actions of telomerase. Alternative splicing and the use of alternative start codons results in multiple isoforms that are differentially localized to either the mitochondria or the nucleus.

Source: NCBI Gene 80119 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 162 total
• MANE Select transcript: NM_001286496

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26220
Approved symbol	PIF1
Name	PIF1 5’-to-3’ DNA helicase
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22692
Ensembl gene	ENSG00000140451
Ensembl biotype	protein_coding
OMIM	610953
Entrez	80119

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 25 protein_coding, 6 retained_intron

ENST00000268043, ENST00000333425, ENST00000558380, ENST00000558547, ENST00000559239, ENST00000559522, ENST00000559872, ENST00000560444, ENST00000560504, ENST00000880617, ENST00000880618, ENST00000923742, ENST00000923743, ENST00000923744, ENST00000923745, ENST00000923746, ENST00000923747, ENST00000923748, ENST00000923749, ENST00000923750, ENST00000923751, ENST00000923752, ENST00000923753, ENST00000923754, ENST00000923755, ENST00000923756, ENST00000923757, ENST00000923758, ENST00000923759, ENST00000923760, ENST00000923761

RefSeq mRNA: 4 — MANE Select: NM_001286496 NM_001286496, NM_001286497, NM_001286499, NM_025049

CCDS: CCDS10195, CCDS66797

Canonical transcript exons

ENST00000559239 — 13 exons

Exon	Start	End
ENSE00000943118	64821367	64821520
ENSE00000943121	64819847	64819986
ENSE00000943124	64817946	64818091
ENSE00000943125	64816574	64816765
ENSE00001297084	64815632	64816357
ENSE00001484274	64822266	64822391
ENSE00001484280	64822478	64822610
ENSE00002546536	64825569	64825647
ENSE00003522445	64818257	64818344
ENSE00003547762	64820982	64821088
ENSE00003599977	64821167	64821281
ENSE00003620845	64823778	64824354
ENSE00003622394	64819117	64819223

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 92.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.3668 / max 62.0633, expressed in 1236 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150494	3.7242	896
150493	0.6426	437

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	92.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.19	gold quality
ganglionic eminence	UBERON:0004023	82.94	gold quality
lower esophagus mucosa	UBERON:0035834	82.51	gold quality
stromal cell of endometrium	CL:0002255	81.87	gold quality
mucosa of transverse colon	UBERON:0004991	81.13	gold quality
vermiform appendix	UBERON:0001154	79.45	gold quality
granulocyte	CL:0000094	77.87	gold quality
bone marrow cell	CL:0002092	77.06	gold quality
spleen	UBERON:0002106	76.94	gold quality
esophagus mucosa	UBERON:0002469	76.02	gold quality
lymph node	UBERON:0000029	75.65	gold quality
transverse colon	UBERON:0001157	75.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.23	gold quality
esophagus	UBERON:0001043	74.79	gold quality
pancreatic ductal cell	CL:0002079	74.75	silver quality
lower esophagus	UBERON:0013473	74.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	74.14	gold quality
ileal mucosa	UBERON:0000331	74.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	73.95	gold quality
muscle layer of sigmoid colon	UBERON:0035805	73.86	gold quality
small intestine	UBERON:0002108	73.27	gold quality
smooth muscle tissue	UBERON:0001135	73.23	gold quality
rectum	UBERON:0001052	71.37	gold quality
apex of heart	UBERON:0002098	71.32	gold quality
intestine	UBERON:0000160	71.24	gold quality
colon	UBERON:0001155	71.23	gold quality
gall bladder	UBERON:0002110	71.22	gold quality
caecum	UBERON:0001153	71.05	gold quality
body of stomach	UBERON:0001161	70.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-99795	yes	56.23
E-MTAB-6524	no	189.99
E-ANND-3	no	3.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting PIF1, 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-1184	99.99	68.19	1458
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-6732-3P	98.17	67.52	802

Literature-anchored findings (GeneRIF, showing 22)

• hPif1 may regulate telomere elongation by decreasing telomerase processivity, possibly via a mechanism that involves the unwinding of telomerase RNA from telomeric DNA by hPif1. (PMID:16522649)
• Human PIF, like S. cerevisiae Pif1p, plays a role in telomerase regulation. (PMID:17172855)
• hPif1 in the nucleus may be involved in chromosome maintenance in association with DNA replication (PMID:17827721)
• Evidence that the PIF1 N-terminal (PINT) domain as crucial functions in PIF1 helicase. (PMID:18835853)
• hPif1 specifically recognizes and unwinds DNA structures resembling putative stalled replication forks. (PMID:19700773)
• Human Pif1 could have a role in processing G4 structures that arise in the single-stranded nucleic acid intermediates formed during DNA replication and gene expression. (PMID:20524933)
• Findings suggest roles for PIF1 in S-phase entry and progression that are essential to protect human tumor cells from apoptosis. (PMID:21616935)
• PIF1 variant L319P was identified in three breast cancer families (PMID:22347400)
• the yeast ortholog of Pif1 appears to move along DNA in single nucleotide or base pair steps, powered by hydrolysis of 1 molecule of ATP. (PMID:23596008)
• when expressed in yeast, human PIF1 suppressed both G-quadruplex-associated DNA damage and telomere lengthening (PMID:23657261)
• A minimum of 10 oligonucleotide bases are required for PIF1 binding and the hydrolysis of ATP. (PMID:23924759)
• Authors characterised a functional role for human PIF1 in DNA replication that becomes important for cell growth under oncogenic stress. (PMID:25359767)
• Pif1 readily unfolds a parallel quadruplex DNA substrate in a multiturnover reaction and also generates some product under single cycle conditions (PMID:25589786)
• Structural and functional characterization of the unwinding mechanism of Bacteroides and human Pif1 helicases has been reported. (PMID:26904952)
• PIF1 has a role in DNA resection, specifically for defined DNA regions, such as those prone to form G-quadruplexes. (PMID:30232007)
• The functions of human PIF1 (hPIF1) are also critical for survival of certain tumour cell lines during replication stress, making it an important target for cancer therapy. Crystal structures of hPIF1 presented here explore structural events along the chemical reaction coordinate of ATP hydrolysis at an unprecedented level of detail (PMID:30698796)
• Mitochondrial genetic variation is enriched in G-quadruplex regions that stall DNA synthesis in vitro. (PMID:32191790)
• Downregulation of PIF1, a potential new target of MYCN, induces apoptosis and inhibits cell migration in neuroblastoma cells. (PMID:32512012)
• Dynamic regulation of Pif1 acetylation is crucial to the maintenance of genome stability. (PMID:33079209)
• PIF1 helicase promotes break-induced replication in mammalian cells. (PMID:33470420)
• CircNEIL3 mediates pyroptosis to influence lung adenocarcinoma radiotherapy by upregulating PIF1 through miR-1184 inhibition. (PMID:35190532)
• PIF1 Promotes Autophagy to Inhibit Chronic Hypoxia Induced Apoptosis of Pulmonary Artery Endothelial Cells. (PMID:37396201)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pif1	ENSDARG00000020289
mus_musculus	Pif1	ENSMUSG00000041064
rattus_norvegicus	Pif1	ENSRNOG00000015878
drosophila_melanogaster	Pif1	FBGN0031540
caenorhabditis_elegans	pif-1	WBGENE00004028

Protein

Protein identifiers

ATP-dependent DNA helicase PIF1 — Q9H611 (reviewed: Q9H611)

Alternative names: DNA 5’-3’ helicase PIF1, DNA repair and recombination helicase PIF1, PIF1/RRM3 DNA helicase-like protein

All UniProt accessions (1): Q9H611

UniProt curated annotations — full annotation on UniProt →

Function. DNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of both mitochondrial and nuclear genome stability. Efficiently unwinds G-quadruplex (G4) DNA structures and forked RNA-DNA hybrids. Resolves G4 structures, preventing replication pausing and double-strand breaks (DSBs) at G4 motifs. Involved in the maintenance of telomeric DNA. Inhibits telomere elongation, de novo telomere formation and telomere addition to DSBs via catalytic inhibition of telomerase. Reduces the processivity of telomerase by displacing active telomerase from DNA ends. Releases telomerase by unwinding the short telomerase RNA/telomeric DNA hybrid that is the intermediate in the telomerase reaction. Possesses an intrinsic strand annealing activity.

Subunit / interactions. Monomer. Interacts with telomerase.

Subcellular location. Nucleus Mitochondrion.

Tissue specificity. Weak ubiquitous expression.

Domain organisation. The PIF1 N-terminal (PINT) domain enhances the interaction with ssDNA through intrinsic binding activity, it also harbors DNA strand-annealing activity.

Induction. Tightly cell cycle regulated and expressed in late S/G2 phase.

Miscellaneous. Produced by alternative initiation of isoform 1.

Similarity. Belongs to the helicase family. PIF1 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H611-1	1, Isoform alpha	yes
Q9H611-2	2
Q9H611-3	3, Isoform beta
Q9H611-4	4

RefSeq proteins (4): NP_001273425, NP_001273426, NP_001273428, NP_079325 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010285	DNA_helicase_pif1-like_DEAD	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR048293	PIF1_RRM3_pfh1	Family
IPR049163	Pif1-like_2B_dom	Domain
IPR051055	PIF1_helicase	Family
IPR057437	PIF1/LRR1_PH	Domain

Pfam: PF05970, PF21530, PF25344

Enzyme classification (BRENDA):

• EC 3.6.4.12 — DNA helicase (BRENDA: 0 organisms, 0 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (63 total): helix 23, strand 22, splice variant 4, region of interest 4, turn 2, modified residue 2, chain 1, DNA-binding region 1, sequence variant 1, mutagenesis site 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6HPH	X-RAY DIFFRACTION	1.13
6HPQ	X-RAY DIFFRACTION	1.43
6HPT	X-RAY DIFFRACTION	1.44
9FB8	X-RAY DIFFRACTION	1.73
9FI9	X-RAY DIFFRACTION	1.73
5FHH	X-RAY DIFFRACTION	3.6
6HPU	X-RAY DIFFRACTION	3.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H611-F1	78.43	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.

Ligand- & substrate-binding residues (1): 228–235

Post-translational modifications (2): 27, 151

Mutagenesis-validated functional residues (1):

Position	Phenotype
234	loss of atpase activity. lower activity for single-stranded dna.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-171319	Telomere Extension By Telomerase

MSigDB gene sets: 176 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERASE, MODULE_255, MODULE_317, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, GOBP_NEGATIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, MODULE_195, FISCHER_G2_M_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_DNA_DAMAGE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_CHROMOSOME_ORGANIZATION

GO Biological Process (8): protein-DNA-RNA complex disassembly (GO:0001117), DNA repair (GO:0006281), DNA recombination (GO:0006310), telomere maintenance via telomerase (GO:0007004), negative regulation of telomere maintenance via telomerase (GO:0032211), obsolete mitochondrial genome maintenance (GO:0000002), telomere maintenance (GO:0000723), DNA damage response (GO:0006974)

GO Molecular Function (16): magnesium ion binding (GO:0000287), ATP binding (GO:0005524), telomerase inhibitor activity (GO:0010521), ATP hydrolysis activity (GO:0016887), single-stranded DNA helicase activity (GO:0017116), 5’-3’ DNA/RNA helicase activity (GO:0033678), telomeric repeat DNA binding (GO:0042162), 5’-3’ DNA helicase activity (GO:0043139), G-quadruplex DNA binding (GO:0051880), G-quadruplex unwinding activity (GO:0160225), nucleotide binding (GO:0000166), DNA binding (GO:0003677), DNA helicase activity (GO:0003678), helicase activity (GO:0004386), hydrolase activity (GO:0016787), isomerase activity (GO:0016853)

GO Cellular Component (5): chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial nucleoid (GO:0042645)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extension of Telomeres	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
telomerase activity	2
ATP-dependent activity	2
DNA helicase activity	2
catalytic activity, acting on a nucleic acid	2
catalytic activity	2
intracellular membrane-bounded organelle	2
protein-DNA-RNA complex organization	1
protein-containing complex disassembly	1
DNA damage response	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
negative regulation of telomere maintenance via telomere lengthening	1
negative regulation of DNA biosynthetic process	1
telomere organization	1
cellular response to stress	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
enzyme inhibitor activity	1
ribonucleoside triphosphate phosphatase activity	1
DNA/RNA helicase activity	1
sequence-specific DNA binding	1
DNA binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid binding	1
helicase activity	1
ATP-dependent activity, acting on DNA	1
nucleic acid conformation isomerase activity	1
chromosomal region	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
mitochondrion	1
mitochondrial matrix	1
nucleoid	1

Protein interactions and networks

STRING

2644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIF1	A0A087WZY1	A0A087WZY1	885
PIF1	PRH1	P02810	883
PIF1	DNA2	P51530	841
PIF1	ANAPC1	Q9H1A4	827
PIF1	BRIP1	Q9BX63	826
PIF1	WRN	Q14191	806
PIF1	TERT	O14746	793
PIF1	RAD52	P43351	774
PIF1	EXO1	Q9UQ84	728
PIF1	RAD51	Q06609	725
PIF1	BRCA1	P38398	719
PIF1	RTEL1	Q9NZ71	718
PIF1	FEN1	P39748	715
PIF1	ATR	Q13535	702
PIF1	RECQL4	O94761	689

IntAct

11 interactions, top by confidence:

A	B	Type	Score
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
HSF2	PIF1	psi-mi:“MI:0915”(physical association)	0.400
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350
KCTD12	DUSP11	psi-mi:“MI:0914”(association)	0.350
PIF1	GMNN	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
KCTD12	CYTH3	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): PIF1 (Affinity Capture-MS), PIF1 (Affinity Capture-RNA), DICER1 (Affinity Capture-MS), PIF1 (Affinity Capture-MS), PIF1 (Affinity Capture-MS), ANKHD1-EIF4EBP3 (Affinity Capture-MS), DCAF11 (Affinity Capture-MS), PIF1 (Affinity Capture-MS), PCBP3 (Affinity Capture-MS), PIF1 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), GMNN (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), PASK (Affinity Capture-MS), PIF1 (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A0A7N9VSG0, A7YSY2, D3KCC4, D3ZU57, D4A2B7, O08644, O15197, O19179, O43542, O75064, O95382, P0C0K6, P0C0K7, P51840, P52785, P52824, P54777, Q02846, Q05932, Q13470, Q13608, Q1HG60, Q3ZBE0, Q4KM32, Q5JZY3, Q643R3, Q6MG64, Q6NVG1, Q6ZPS2, Q76MJ5, Q7TNJ2, Q80SX8, Q8BYG9, Q8IZY2, Q8NFF5, Q8R5G7, Q8TDZ2, Q8WWN8, Q91V24

Diamond homologs: A5WFR0, A6ZM04, P07271, P38766, Q0R4F1, Q1HG60, Q381V6, Q383A1, Q384Y0, Q580X6, Q59RQ0, Q5AXT5, Q6MHJ5, Q7ZV90, Q80SX8, Q9H611, Q9QSK3, Q9UUA2, Q384Y1, Q196V4, Q57YG0, Q38CE9, P55418, Q0P9V4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	128
Likely benign	10
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

2056 predictions. Top by Δscore:

Variant	Effect	Δscore
15:64816565:C:CA	donor_gain	1.0000
15:64816573:CCAGA:C	donor_gain	1.0000
15:64816762:TGCC:T	acceptor_gain	1.0000
15:64816763:GCC:G	acceptor_gain	1.0000
15:64816764:CC:C	acceptor_gain	1.0000
15:64816764:CCC:C	acceptor_gain	1.0000
15:64816765:CC:C	acceptor_gain	1.0000
15:64816766:C:CC	acceptor_gain	1.0000
15:64816766:C:T	acceptor_gain	1.0000
15:64816773:A:AC	acceptor_gain	1.0000
15:64816773:A:C	acceptor_gain	1.0000
15:64817940:GCTCA:G	donor_loss	1.0000
15:64817942:TCA:T	donor_loss	1.0000
15:64817943:CACTT:C	donor_loss	1.0000
15:64817944:A:AC	donor_gain	1.0000
15:64817945:C:CC	donor_gain	1.0000
15:64817945:CT:C	donor_gain	1.0000
15:64817945:CTTGG:C	donor_gain	1.0000
15:64818087:TAGCC:T	acceptor_gain	1.0000
15:64818088:AGCC:A	acceptor_gain	1.0000
15:64818089:GCC:G	acceptor_gain	1.0000
15:64818090:CC:C	acceptor_gain	1.0000
15:64818090:CCC:C	acceptor_gain	1.0000
15:64818091:CC:C	acceptor_gain	1.0000
15:64818092:C:CC	acceptor_gain	1.0000
15:64818092:C:T	acceptor_gain	1.0000
15:64818093:T:G	acceptor_loss	1.0000
15:64819112:CTCA:C	donor_loss	1.0000
15:64819113:TCA:T	donor_loss	1.0000
15:64819114:CA:C	donor_loss	1.0000

AlphaMissense

4068 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:64821449:A:G	W297R	0.997
15:64821449:A:T	W297R	0.997
15:64822304:G:T	A260D	0.997
15:64822322:G:T	A254D	0.997
15:64821418:T:A	E307V	0.996
15:64821427:A:T	V304D	0.996
15:64822268:G:T	A272E	0.996
15:64822280:A:T	L268H	0.996
15:64822382:T:A	K234M	0.996
15:64816698:G:T	A581D	0.995
15:64816721:A:C	F573L	0.995
15:64816721:A:T	F573L	0.995
15:64816723:A:G	F573L	0.995
15:64817949:G:C	S557R	0.995
15:64817949:G:T	S557R	0.995
15:64817951:T:G	S557R	0.995
15:64821225:T:C	D343G	0.995
15:64821430:A:G	L303S	0.995
15:64821447:C:A	W297C	0.995
15:64821447:C:G	W297C	0.995
15:64822318:G:C	S255R	0.995
15:64822318:G:T	S255R	0.995
15:64822320:T:G	S255R	0.995
15:64822323:C:G	A254P	0.995
15:64817983:A:T	L546H	0.994
15:64821033:C:A	R381M	0.994
15:64821225:T:A	D343V	0.994
15:64821370:G:T	A323D	0.994
15:64821382:A:G	L319P	0.994
15:64821421:T:G	D306A	0.994

dbSNP variants (sampled 300 via entrez): RS1000010407 (15:64822356 C>G,T), RS1000086763 (15:64826301 G>T), RS1000137716 (15:64826729 T>C), RS1000258112 (15:64817033 C>G), RS1000342810 (15:64821198 T>C), RS1000442175 (15:64815775 G>T), RS1001085108 (15:64824999 A>C,T), RS1001137559 (15:64825213 G>A), RS1001271889 (15:64817733 G>T), RS1001293204 (15:64819854 C>G,T), RS1001747714 (15:64820074 T>A,C), RS1001868687 (15:64823365 A>G), RS1002140057 (15:64824007 G>A,C,T), RS1002200118 (15:64823060 GC>G), RS1002347437 (15:64818793 C>T)

Disease associations

OMIM: gene MIM:610953 | 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
GCST009312_11	Antisaccade task score	2.000000e-06
GCST90002401_93	Platelet distribution width	4.000000e-09
GCST90002401_94	Platelet distribution width	3.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007969	cognitive inhibition measurement
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	5
Valproic Acid	affects cotreatment, decreases expression	4
sodium arsenite	increases expression, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
cupric oxide	decreases expression	1
diallyl trisulfide	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
NSC668394	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Gemcitabine	affects reaction, increases activity, increases cleavage, affects response to substance, decreases reaction (+2 more)	1
Azathioprine	decreases expression	1
Calcitriol	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TD47	HAP1 PIF1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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