PTMA

Summary

PTMA (prothymosin alpha, HGNC:9623) is a protein-coding gene on chromosome 2q37.1, encoding Prothymosin alpha (P06454). Prothymosin alpha may mediate immune function by conferring resistance to certain opportunistic infections. It is a selective cancer dependency (DepMap: 54.9% of cell lines).

Enables DNA-binding transcription factor binding activity and histone binding activity. Involved in negative regulation of apoptotic process. Located in cytosol and nucleoplasm.

Source: NCBI Gene 5757 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 21 total
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 54.9% of screened cell lines
• MANE Select transcript: NM_002823

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9623
Approved symbol	PTMA
Name	prothymosin alpha
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187514
Ensembl biotype	protein_coding
OMIM	188390
Entrez	5757

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 37 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000341369, ENST00000409115, ENST00000409321, ENST00000409683, ENST00000410064, ENST00000412128, ENST00000440384, ENST00000448874, ENST00000466801, ENST00000467816, ENST00000468027, ENST00000481928, ENST00000858026, ENST00000858027, ENST00000928473, ENST00000928474, ENST00000928475, ENST00000928476, ENST00000928477, ENST00000928478, ENST00000928479, ENST00000928480, ENST00000928481, ENST00000928482, ENST00000928483, ENST00000928484, ENST00000928485, ENST00000928486, ENST00000928487, ENST00000928488, ENST00000928489, ENST00000928490, ENST00000928491, ENST00000928492, ENST00000928493, ENST00000928494, ENST00000928495, ENST00000928496, ENST00000941372, ENST00000941373, ENST00000941374, ENST00000941375

RefSeq mRNA: 2 — MANE Select: NM_002823 NM_001099285, NM_002823

CCDS: CCDS42833, CCDS46541

Canonical transcript exons

ENST00000409115 — 5 exons

Exon	Start	End
ENSE00001873409	231708525	231708751
ENSE00001879102	231712804	231713551
ENSE00003475971	231711348	231711419
ENSE00003520861	231711890	231711983
ENSE00003550625	231712443	231712516

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.3152 / max 292.7918, expressed in 1815 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25929	15.0057	1785
25930	13.9353	1780
25933	3.1071	817
25928	1.6353	1066
25924	0.8259	379
25926	0.7069	324
25931	0.6490	240
25925	0.1874	87
25932	0.1672	57
25927	0.0716	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.88	gold quality
monocyte	CL:0000576	99.87	gold quality
leukocyte	CL:0000738	99.86	gold quality
corpus callosum	UBERON:0002336	99.84	gold quality
ganglionic eminence	UBERON:0004023	99.83	gold quality
endometrium	UBERON:0001295	99.82	gold quality
popliteal artery	UBERON:0002250	99.81	gold quality
tibial artery	UBERON:0007610	99.81	gold quality
thyroid gland	UBERON:0002046	99.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.80	gold quality
endocervix	UBERON:0000458	99.79	gold quality
left lobe of thyroid gland	UBERON:0001120	99.79	gold quality
metanephros cortex	UBERON:0010533	99.79	gold quality
left uterine tube	UBERON:0001303	99.78	gold quality
skin of abdomen	UBERON:0001416	99.78	gold quality
ascending aorta	UBERON:0001496	99.78	gold quality
thoracic aorta	UBERON:0001515	99.78	gold quality
right lung	UBERON:0002167	99.78	gold quality
ventricular zone	UBERON:0003053	99.78	gold quality
colonic epithelium	UBERON:0000397	99.77	gold quality
vermiform appendix	UBERON:0001154	99.77	gold quality
right uterine tube	UBERON:0001302	99.77	gold quality
descending thoracic aorta	UBERON:0002345	99.77	gold quality
cortical plate	UBERON:0005343	99.77	gold quality
omental fat pad	UBERON:0010414	99.77	gold quality
uterine cervix	UBERON:0000002	99.76	gold quality
zone of skin	UBERON:0000014	99.76	gold quality
adipose tissue	UBERON:0001013	99.76	gold quality
right lobe of thyroid gland	UBERON:0001119	99.76	gold quality
tibial nerve	UBERON:0001323	99.76	gold quality

Single-cell (SCXA)

Detected in 53 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	18802.26
E-HCAD-4	yes	18605.61
E-MTAB-10042	yes	11069.70
E-HCAD-31	yes	8422.62
E-CURD-88	yes	7917.69
E-CURD-122	yes	7888.03
E-MTAB-10553	yes	7246.89
E-HCAD-9	yes	6089.41
E-MTAB-9067	yes	4737.23
E-MTAB-9801	yes	4093.45
E-HCAD-25	yes	3475.61
E-HCAD-35	yes	2184.31
E-MTAB-5061	yes	1756.87
E-GEOD-134144	yes	52.19
E-GEOD-137537	yes	30.79

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
CDKN1A	Unknown
IDO1	Activation
IDO2	Activation
TLR9	Repression

Upstream regulators (CollecTRI, top): ESR1, MAX, MYC, RBPJ, SP1, TP53

miRNA regulators (miRDB)

46 targeting PTMA, 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-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-3940-5P	99.14	65.26	493

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 54.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• induces unravelling of metaphase chromosomes in vitro (PMID:11528108)
• we demonstrate the existence of three binding partners (31, 29, and 19 kDa) for ProTalpha in the membrane of PHA-activated lymphoblasts. These surface molecules possess the expected affinity and specificity for a ProTalpha receptor (PMID:11727831)
• prothymosin alpha is capable of forming regular elongated fibrils (PMID:12062405)
• regulatory roles of oncoprotein ProT and tumor suppressor PHAP in apoptosis (PMID:12522243)
• study suggests involvement of prothymosin a, in the formation, maintenance, or functioning of the mitotic spindle (PMID:15325071)
• PTMA associates with SET and is involved in chromatin decondensation. (PMID:15556635)
• Prothymosin alpha functions as intranuclear dissociator of the Nrf2-Keap1 complex. (PMID:15657435)
• PTMA expression is intimately involved in the differentiation and progression of human prostate cancers, and could be a target for therapy and diagnostic purposes. (PMID:16353248)
• Antiapoptotic response of cells requires expression of both p8 and ProTalpha. (PMID:16478804)
• the anti-apoptotic effect previously attributed separately to p8 and prothymosin alpha is in fact borne by the p8/ProTalpha complex, the two proteins being individually inactive (PMID:16628001)
• Marked differences in the expression of PTMA and Tim10 were observed during the differentiation of human primary skeletal muscle cells. (PMID:16669873)
• suppression of viral replication by ProTalpha is not HIV LTR specific (PMID:16940531)
• interaction of ProTalpha with core histones in the nucleus may be related to structural modification of histones H3 & H4, & hence to chromatin activity, raising the possibility that other proteins in the nuclear complex may play a role in this process. (PMID:17012289)
• Decreased ERbeta and increased ProTalpha expression in advanced gastric adenocarcinoma indicated that ERbeta may play an anti-proliferation role which is opposed to the role of ProTalpha in gastric epithelium. (PMID:17046193)
• although prothymosin-alpha is overexpressed in gastric adenocarcinoma, it is not associated with alterations in survival (PMID:17188166)
• PTMA may be a novel marker for predicting the effectiveness of radiotherapy in clinical cases. (PMID:17876542)
• Basis on site-specific information obtained here, as well as results from previous studies, we propose that the conformational and dynamic changes upon zinc binding may act as an entropic switch that greatly facilitates the binding to other proteins (PMID:17929838)
• ProTalpha and Nrf2 compete for interaction with Keap1, therefore ProTalpha is able to liberate Nrf2 from complex with Keap1 and hence contribute to Nrf2-dependent transcription. (PMID:18240569)
• Influence of prothymosin alpha and its mutants on activity of the p53 tumor suppressor (PMID:18856068)
• immune response stimulation by ProTalpha is in principle exerted via its bioactive C-terminal decapaptide, which can acquire a sequence-specific beta-sheet conformation and induce DC maturation. (PMID:18976813)
• Prothymosin alpha amino acid residues 4-14, 31-43, 84-87, and 106-110 strongly and specifically bind to apoptotic protease activating factor 1 (Apaf-1) in the regulation of the mitochondrial cell death pathway. (PMID:20121050)
• Data suggest that prothymosin alpha immunostaining may be helpful in predicting pituitary tumor recurrence. (PMID:20430720)
• A study on the relationship between prothymosin alpha kinase(ProTalphaK) activity and pyruvate kinase isoforms confirmed that the M2 isoform is the enzyme responsible for ProTalphaK activity in proliferating cells. (PMID:20977946)
• Nuclear PTMA may serve as prognostic marker in head and neck squamous cell carcinoma to determine the subset of patients that are likely to show recurrence of the disease. (PMID:21573209)
• These results are consistent with the model that ProTa may enhance p53 transcription activity by displacement of histone H1 from p53-H1 repressive complex. (PMID:21954601)
• The PTMA is one of miR-1 target genes which involve in miR-1 inducing apoptosis. (PMID:22059741)
• The prothymosin alpha is one of miR-1 target genes which involve in miR-1 inducing apoptosis (PMID:22059741)
• when added to cultured cells expressing mHtt, the purified recombinant ProTalpha protein not only entered the cells but it also significantly suppressed the mHtt-caused cytotoxicity. (PMID:22110140)
• Findings suggest that the binding of prothymosin alpha (ProTalpha) and Neh2 to Keap1 occurs synergistically via preformed structural elements. (PMID:22125611)
• The decrease of ProTalpha mRNA during differentiation was not accompanied by changes in the methylation status (PMID:22463375)
• Data suggest that plasma thymosin-alpha1 (TA1) and prothymosin-alpha (PTMA) level may be a biomarker for differentiating between renal cell carcinoma (RCC) and urothelial carcinoma. (PMID:22609059)
• ProTalpha is crucial for the interaction with the Kelch domain, while the flanking residues play relatively minor roles in the affinity of binding. (PMID:23318954)
• Western blot analysis of protein extracts from sperm head fractions confirms that the peptide is specifically associated with the inner acrosomal membrane fraction. (PMID:23359453)
• These results demonstrate the clinical relevance of prothymosin alpha in regulating acetylation events during the pathogenesis of emphysema. (PMID:23695700)
• PTalpha offers cardioprotection against ischemic injury by an Akt-dependent mechanism. (PMID:23857453)
• phosphorylation of ProTalpha is required for its antiapoptotic activity, but it does not affect its nuclear import (PMID:23859021)
• prothymosin-alpha expression is a determinant of disease progression in superficial bladder cancer (PMID:24733561)
• disease-free survival and overall survival rates were significantly lower among colorectal cancer patients with PTMA- and TP53-positive tumors (PMID:25197357)
• Data suggest that KEAP1 (kelch-like ECH-associated protein 1) mutations (as those observed in lung cancer patients) affect conformation/folding/stability of KEAP1 and binding affinity for ligands PTMA and NRF2 (nuclear factor erythroid 2-like 2). (PMID:25582950)
• PTMA is a potential novel therapeutic target for type 2 diabetes (PMID:26348351)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-222l21.1	ENSDARG00000076532
mus_musculus	Ptma	ENSMUSG00000026238
rattus_norvegicus		ENSRNOG00000072334

Protein

Protein identifiers

Prothymosin alpha — P06454 (reviewed: P06454)

All UniProt accessions (8): B8ZZA1, B8ZZQ6, B8ZZW7, P06454, F8WCE8, H7C031, H7C2N1, Q53S24

UniProt curated annotations — full annotation on UniProt →

Function. Prothymosin alpha may mediate immune function by conferring resistance to certain opportunistic infections.

Subunit / interactions. Interacts with NUPR1; regulates apoptotic process.

Subcellular location. Nucleus.

Post-translational modifications. Covalently linked to a small RNA of about 20 nucleotides.

Similarity. Belongs to the pro/parathymosin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P06454-1	1	yes
P06454-2	2

RefSeq proteins (2): NP_001092755, NP_002814* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004931	Pro/parathymosin	Family

Pfam: PF03247

UniProt features (25 total): modified residue 13, compositionally biased region 3, chain 2, helix 2, initiator methionine 1, cross-link 1, splice variant 1, peptide 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2L9I	SOLUTION NMR
2MNQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06454-F1	58.32	0.00

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 (14): 2, 8, 9, 10, 13, 14, 15, 15, 102, 103, 107, 103, 1, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 313 (showing top): RNGTGGGC_UNKNOWN, E2F_Q4_01, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, MODULE_151, GCM_NPM1, MORF_UBE2I, CAIRO_PML_TARGETS_BOUND_BY_MYC_UP, HSIAO_HOUSEKEEPING_GENES, USF_C, YY1_Q6, MODULE_503, SREBP1_02, PUJANA_CHEK2_PCC_NETWORK, CDP_01

GO Biological Process (4): chromatin organization (GO:0006325), DNA-templated transcription (GO:0006351), negative regulation of apoptotic process (GO:0043066), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (5): calcium ion binding (GO:0005509), histone binding (GO:0042393), DNA-binding transcription factor binding (GO:0140297), histone chaperone activity (GO:0140713), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cellular component organization	1
gene expression	1
RNA biosynthetic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
metal ion binding	1
protein binding	1
transcription factor binding	1
histone binding	1
protein carrier activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

1692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTMA	H1-0	P07305	991
PTMA	F5GXR3	F5GXR3	977
PTMA	KEAP1	Q14145	936
PTMA	ANP32A	P39687	845
PTMA	SLC6A7	Q99884	771
PTMA	NUPR1	O60356	713
PTMA	TMSB4X	P01253	620
PTMA	CASP9	P55211	614
PTMA	TLR4	O00206	600
PTMA	TMPO	P08918	581
PTMA	CASP3	P42574	573
PTMA	EP300	Q09472	560
PTMA	TAAR1	Q96RJ0	543
PTMA	H1-2	P16403	527
PTMA	ACTB	P02570	506

IntAct

70 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PTMA	NUPR1	psi-mi:“MI:0915”(physical association)	0.670
PTMA	NUPR1	psi-mi:“MI:0407”(direct interaction)	0.670
P/V	HSPA4L	psi-mi:“MI:0914”(association)	0.530
PTMA	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
SET	PTMA	psi-mi:“MI:0915”(physical association)	0.510
PTMA	SET	psi-mi:“MI:0915”(physical association)	0.510
M	PTMA	psi-mi:“MI:0915”(physical association)	0.400
PTMA	TERF1	psi-mi:“MI:0915”(physical association)	0.370
PTMA	TERF2	psi-mi:“MI:0915”(physical association)	0.370
GSK3A	PTMA	psi-mi:“MI:0915”(physical association)	0.370
	PTMA	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
RPGRIP1L	KIF2A	psi-mi:“MI:0914”(association)	0.350
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
ARHGEF15	CALU	psi-mi:“MI:0914”(association)	0.350
ARHGAP11A	LTF	psi-mi:“MI:0914”(association)	0.350

BioGRID (251): KEAP1 (Two-hybrid), HIST1H1A (Affinity Capture-Western), EP300 (Affinity Capture-Western), EP300 (Reconstituted Complex), PTMA (Two-hybrid), PTMA (Two-hybrid), PTMA (Co-fractionation), PTMA (Co-fractionation), PTMA (Co-fractionation), PTMA (Co-fractionation), PTMA (Affinity Capture-MS), PTMA (Affinity Capture-MS), PTMA (Affinity Capture-MS), PTMA (Reconstituted Complex), PTMA (Affinity Capture-MS)

ESM2 similar proteins: A1CQS5, A1D3N8, A2QPM6, A3LXX5, A4QYF9, A5DLG8, A5E145, A5PLC8, A6SMQ7, A6ZQX9, A7ER98, A7TR90, A8N7N4, B0D1Q8, O45181, P01252, P04550, P06302, P06454, P08814, P20962, P26350, P34618, P40019, P91753, Q0C807, Q0V3E0, Q10020, Q10239, Q1E4L8, Q2GNS7, Q2UBH8, Q4WJ31, Q56WH4, Q59RN6, Q59VR3, Q5B2V2, Q5R790, Q5U274, Q68F55

Diamond homologs: A5PLC8, P01252, P06302, P06454, P26350, Q5R790, Q5U274, Q6NV32, Q68F55, Q90ZK2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PTMA	down-regulates	CASP9	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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
Cellular Senescence	6	15.6×	7e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — MGCT.

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	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

990 predictions. Top by Δscore:

Variant	Effect	Δscore
2:231711343:T:TA	acceptor_gain	1.0000
2:231711347:G:A	acceptor_loss	1.0000
2:231711416:TGCT:T	donor_gain	1.0000
2:231711417:GCT:G	donor_gain	1.0000
2:231711417:GCTG:G	donor_gain	1.0000
2:231711417:GCTGT:G	donor_loss	1.0000
2:231711418:CT:C	donor_gain	1.0000
2:231711418:CTGT:C	donor_loss	1.0000
2:231711419:TG:T	donor_loss	1.0000
2:231711420:G:GG	donor_gain	1.0000
2:231711420:GTGA:G	donor_loss	1.0000
2:231711421:TGAG:T	donor_loss	1.0000
2:231711880:T:TA	acceptor_gain	1.0000
2:231711980:GATG:G	donor_gain	1.0000
2:231711983:GGTG:G	donor_loss	1.0000
2:231711984:G:GA	donor_loss	1.0000
2:231711984:G:GG	donor_gain	1.0000
2:231711985:T:G	donor_loss	1.0000
2:231712439:CCAG:C	acceptor_loss	1.0000
2:231712441:A:AG	acceptor_gain	1.0000
2:231712441:AG:A	acceptor_gain	1.0000
2:231712442:G:GC	acceptor_gain	1.0000
2:231712442:GG:G	acceptor_gain	1.0000
2:231712442:GGT:G	acceptor_gain	1.0000
2:231712442:GGTGA:G	acceptor_gain	1.0000
2:231712513:TGAGG:T	donor_loss	1.0000
2:231712514:GAG:G	donor_gain	1.0000
2:231712517:GTG:G	donor_loss	1.0000
2:231712802:A:AG	acceptor_gain	1.0000
2:231712803:G:GG	acceptor_gain	1.0000

AlphaMissense

743 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:231711411:G:T	G37W	0.936
2:231712827:G:C	K104N	0.921
2:231712827:G:T	K104N	0.921
2:231712833:G:C	K106N	0.921
2:231712833:G:T	K106N	0.921
2:231711412:G:A	G37E	0.906
2:231712824:G:C	K103N	0.905
2:231712824:G:T	K103N	0.905
2:231711411:G:A	G37R	0.894
2:231711411:G:C	G37R	0.894
2:231711902:G:T	G45W	0.882
2:231711390:G:A	G30R	0.871
2:231711390:G:C	G30R	0.871
2:231712495:G:C	K89N	0.867
2:231712495:G:T	K89N	0.867
2:231711412:G:T	G37V	0.864
2:231712503:C:A	A92D	0.860
2:231712502:G:C	A92P	0.859
2:231711356:G:C	K18N	0.857
2:231711356:G:T	K18N	0.857
2:231711901:T:A	N44K	0.852
2:231711901:T:G	N44K	0.852
2:231711352:T:C	L17S	0.842
2:231711391:G:A	G30E	0.839
2:231712490:G:C	G88R	0.830
2:231712832:A:T	K106M	0.824
2:231712830:G:C	Q105H	0.823
2:231712830:G:T	Q105H	0.823
2:231712831:A:G	K106E	0.818
2:231712832:A:C	K106T	0.815

dbSNP variants (sampled 300 via entrez): RS1000544796 (2:231711495 C>A,G,T), RS1000848774 (2:231713827 T>G), RS1000990007 (2:231709737 G>A,C), RS1001024214 (2:231709858 C>A,T), RS1001218985 (2:231713642 G>C), RS1001350611 (2:231711063 GCTC>G), RS1001720763 (2:231713197 C>A,G), RS1001783688 (2:231710907 C>T), RS1001914040 (2:231709074 C>G,T), RS1001971458 (2:231714007 G>A,T), RS1002087988 (2:231712961 C>T), RS1002196896 (2:231710072 C>A,G,T), RS1002253647 (2:231706865 G>C), RS1002567514 (2:231709928 G>A), RS1002586016 (2:231708039 G>A)

Disease associations

OMIM: gene MIM:188390 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000175_5	Height	1.000000e-06
GCST001959_2	Eating disorders (purging via substances)	7.000000e-07
GCST004610_54	White blood cell count	3.000000e-09
GCST004627_90	Lymphocyte count	6.000000e-13
GCST90002388_182	Lymphocyte count	6.000000e-19
GCST90002394_225	Monocyte percentage of white cells	7.000000e-12
GCST90002398_117	Neutrophil count	8.000000e-12
GCST90002407_39	White blood cell count	2.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066338 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, increases expression, affects expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol F	increases expression, affects cotreatment	2
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Copper	affects binding, decreases expression	2
Cadmium Chloride	decreases expression, decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
testosterone enanthate	affects expression	1
uranyl acetate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression, increases response to substance	1
zinc chromate	decreases expression, increases abundance	1
nickel sulfate	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
vandetanib	decreases 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
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652193	Binding	Binding affinity to human PTMA incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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