MLF1

Summary

MLF1 (myeloid leukemia factor 1, HGNC:7125) is a protein-coding gene on chromosome 3q25.32, encoding Myeloid leukemia factor 1 (P58340). Involved in lineage commitment of primary hemopoietic progenitors by restricting erythroid formation and enhancing myeloid formation.

This gene encodes an oncoprotein which is thought to play a role in the phenotypic determination of hemopoetic cells. Translocations between this gene and nucleophosmin have been associated with myelodysplastic syndrome and acute myeloid leukemia. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4291 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_001369783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7125
Approved symbol	MLF1
Name	myeloid leukemia factor 1
Location	3q25.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178053
Ensembl biotype	protein_coding
OMIM	601402
Entrez	4291

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 16 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000355893, ENST00000359117, ENST00000466246, ENST00000469452, ENST00000471745, ENST00000477042, ENST00000478894, ENST00000482628, ENST00000484955, ENST00000487838, ENST00000491767, ENST00000495452, ENST00000497004, ENST00000498592, ENST00000618075, ENST00000619577, ENST00000650750, ENST00000650753, ENST00000651874, ENST00000651984, ENST00000652045

RefSeq mRNA: 20 — MANE Select: NM_001369783 NM_001130156, NM_001130157, NM_001195432, NM_001195433, NM_001195434, NM_001369781, NM_001369782, NM_001369783, NM_001369784, NM_001369785, NM_001378845, NM_001378846, NM_001378847, NM_001378848, NM_001378850, NM_001378851, NM_001378852, NM_001378853, NM_001378855, NM_022443

CCDS: CCDS3182, CCDS46945, CCDS56287, CCDS56288, CCDS93413, CCDS93414, CCDS93415, CCDS93416, CCDS93417

Canonical transcript exons

ENST00000466246 — 8 exons

Exon	Start	End
ENSE00001871810	158571194	158571347
ENSE00001878627	158605097	158606456
ENSE00001894439	158593382	158593426
ENSE00003471769	158596862	158596945
ENSE00003535581	158598080	158598208
ENSE00003665785	158592434	158592581
ENSE00003790968	158602807	158602939
ENSE00003791652	158600014	158600173

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7355 / max 502.0576, expressed in 1617 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39503	11.6577	1568
39504	2.6706	1073
39502	1.4073	685

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.60	gold quality
sperm	CL:0000019	99.57	gold quality
right testis	UBERON:0004534	99.52	gold quality
male germ cell	CL:0000015	99.41	gold quality
bronchial epithelial cell	CL:0002328	99.13	gold quality
adult organism	UBERON:0007023	98.84	gold quality
epithelium of bronchus	UBERON:0002031	98.46	gold quality
bronchus	UBERON:0002185	98.17	gold quality
myocardium	UBERON:0002349	98.15	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.13	gold quality
testis	UBERON:0000473	98.10	gold quality
heart right ventricle	UBERON:0002080	98.09	gold quality
cardiac atrium	UBERON:0002081	97.92	gold quality
right atrium auricular region	UBERON:0006631	97.87	gold quality
biceps brachii	UBERON:0001507	97.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.99	gold quality
right uterine tube	UBERON:0001302	96.69	gold quality
cardiac ventricle	UBERON:0002082	96.57	gold quality
heart left ventricle	UBERON:0002084	96.54	gold quality
triceps brachii	UBERON:0001509	96.41	gold quality
left ventricle myocardium	UBERON:0006566	96.41	gold quality
apex of heart	UBERON:0002098	96.23	gold quality
vastus lateralis	UBERON:0001379	96.03	gold quality
body of tongue	UBERON:0011876	95.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.43	gold quality
quadriceps femoris	UBERON:0001377	95.36	gold quality
heart	UBERON:0000948	95.07	gold quality
oocyte	CL:0000023	95.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.03	gold quality
choroid plexus epithelium	UBERON:0003911	94.90	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	3136.67
E-MTAB-9388	yes	1385.43
E-HCAD-10	yes	18.55
E-CURD-114	yes	11.58
E-MTAB-7249	yes	11.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting MLF1, 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-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-7978	99.86	66.90	856

Literature-anchored findings (GeneRIF, showing 16)

• phosphorylation of 14-3-3 binding site by MADM (PMID:12176995)
• These findings suggest that an NPM/MLF1 fusion is the primary molecular abnormality in t(3;5) MDS and AML with multilineage dysplasia, and that cases with NPM/MLF1 may be clinically distinct from other MDS-associated disease (PMID:14506644)
• Over-expression of MLF1 has little impact on skeletal muscle function in mice; progressive formation of protein aggregates in muscle are not necessarily pathogenic; MLF1 and MRJ may function together to ameliorate the toxic effects of mutant proteins. (PMID:17854834)
• shuttling of MLF1 is critical for the regulation of cell proliferation and a disturbance in the shuttling balance increases the cell’s susceptibility to oncogenic transformation (PMID:17967869)
• MLF1 gene rearrangement is associated with acute myeloid leukemia. (PMID:20471513)
• Data present the high-resolution crystal structure of this binding motif [MLF1(29-42)pSer34] in complex with 14-3-3epsilon and analyse the interaction with isothermal titration calorimetry. (PMID:22151054)
• changes in the subcellular localization of NPM, due to alterations in the relative abundance of NPM and NPM-MLF1 proteins, may contribute to the enhanced myeloid progenitor activity of Npm +/- cells (PMID:22193965)
• The subcellular localization of full-length human MLF1 is 14-3-3epsilon-independent. (PMID:23271436)
• Data indicte that acute myeloid leukemia (AML) with NPM1-MLF1 and AML with NPM1 mutations showed similar immunophenotypical and molecular features, including gene mutation patterns and gene expression profiling (GEP). (PMID:23403313)
• Mutation in HTT causes Huntington’s disease (HD); aggregates of mutated HTT cause apoptosis in neurons of HD patients. Data suggest that both MLF1 and MLF2 preferentially interact with mutated N-terminal HTT; MLF1/MLF2 reduce number of neurons (Neuro2A cell line) containing mutant HTT aggregates and subsequent apoptosis. (HTT = Huntingtin protein; MLF = myeloid leukemia factor) (PMID:27840155)
• These findings suggest that MLF and the associated co-chaperones play a direct role in modulating gene transcription. (PMID:27984043)
• The data indicate that MLF1 serves as a proapoptotic antagonist that interacts with the HAX1/HtrA2-OMI/PARL (HOP) mitochondrial complex to modulate cell survival. (PMID:28137643)
• SNP associated with neuroblastoma resides upstream of the MLF1. Gene silencing of MLF1 in neuroblastoma cells results in significant growth inhibition. (PMID:28545128)
• the abnormal gene regulation imposed by NPM-MLF1 can be characterized by the enhanced recruitment of NuRD to gene regulatory regions. Thus, different mechanisms would orchestrate the dysregulation of NPM function in NPMc+- versus NPM1-MLF1-associated leukemia. (PMID:31675375)
• CRL4(DCAF8) and USP11 oppositely regulate the stability of myeloid leukemia factors (MLFs). (PMID:32703400)
• Epigenetic deregulation of MLF1 drives intrahepatic cholangiocarcinoma progression through EGFR/AKT and Wnt/beta-catenin signaling. (PMID:37486965)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mlf1	ENSDARG00000077301
mus_musculus	Mlf1	ENSMUSG00000048416
rattus_norvegicus	Mlf1	ENSRNOG00000012827
drosophila_melanogaster	Mlf	FBGN0034051
caenorhabditis_elegans		WBGENE00012468

Paralogs (1): MLF2 (ENSG00000089693)

Protein

Protein identifiers

Myeloid leukemia factor 1 — P58340 (reviewed: P58340)

Alternative names: Myelodysplasia-myeloid leukemia factor 1

All UniProt accessions (13): A0A0S2Z4A4, A0A0S2Z4U8, A0A140VKD2, A0A494C127, A0A494C175, A0A494C1P6, A0A494C1S3, A0A499FJ64, C9JNE5, C9K0D4, P58340, F8VXT4, F8WEY0

UniProt curated annotations — full annotation on UniProt →

Function. Involved in lineage commitment of primary hemopoietic progenitors by restricting erythroid formation and enhancing myeloid formation. Interferes with erythropoietin-induced erythroid terminal differentiation by preventing cells from exiting the cell cycle through suppression of CDKN1B/p27Kip1 levels. Suppresses COP1 activity via CSN3 which activates p53 and induces cell cycle arrest. Binds DNA and affects the expression of a number of genes so may function as a transcription factor in the nucleus.

Subunit / interactions. Interacts with CENPU. Also interacts with NRBP1/MADM, YWHAZ/14-3-3-zeta and HNRPUL2/MANP. NRBP1 recruits a serine kinase which phosphorylates both itself and MLF1. Phosphorylated MLF1 then binds to YWHAZ and is retained in the cytoplasm. Retained in the nucleus by binding to HNRPUL2. Binds to COPS3/CSN3 which is required for suppression of COP1 and activation of p53.

Subcellular location. Cytoplasm. Nucleus. Cell projection. Cilium. Cytoskeleton. Cilium basal body.

Tissue specificity. Most abundant in testis, ovary, skeletal muscle, heart, kidney and colon. Low expression in spleen, thymus and peripheral blood leukocytes.

Post-translational modifications. Phosphorylation is required for binding to YWHAZ.

Disease relevance. A chromosomal aberration involving MLF1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with NPM1/NPM.

Similarity. Belongs to the MLF family.

Isoforms (5)

UniProt ID	Names	Canonical?
P58340-1	1	yes
P58340-2	2
P58340-3	3
P58340-5	5
P58340-4	4

RefSeq proteins (20): NP_001123628, NP_001123629, NP_001182361, NP_001182362, NP_001182363, NP_001356710, NP_001356711, NP_001356712, NP_001356713, NP_001356714, NP_001365774, NP_001365775, NP_001365776, NP_001365777, NP_001365779, NP_001365780, NP_001365781, NP_001365782, NP_001365784, NP_071888 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019376	Myeloid_leukemia_factor	Family

Pfam: PF10248

UniProt features (15 total): splice variant 4, region of interest 3, modified residue 3, compositionally biased region 2, chain 1, sequence variant 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6Y8E	X-RAY DIFFRACTION	1.42
3UAL	X-RAY DIFFRACTION	1.8
3UBW	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P58340-F1	67.28	0.24

Functional residue map

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

Catalytic / active sites (1): 16–17 (breakpoint for translocation to form npm-mlf1)

Post-translational modifications (3): 8, 32, 34

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 169 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_DN, BROWNE_HCMV_INFECTION_16HR_UP, MODULE_503, GOCC_MICROTUBULE_ORGANIZING_CENTER, ACCAATC_MIR509, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GNF2_CCNA1, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR

GO Biological Process (6): myeloid progenitor cell differentiation (GO:0002318), DNA-templated transcription (GO:0006351), regulation of DNA-templated transcription (GO:0006355), regulation of signal transduction by p53 class mediator (GO:1901796), regulation of cell cycle G1/S phase transition (GO:1902806), cell differentiation (GO:0030154)

GO Molecular Function (3): DNA binding (GO:0003677), protein domain specific binding (GO:0019904), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), cilium (GO:0005929), ciliary basal body (GO:0036064), perinuclear region of cytoplasm (GO:0048471), cytoskeleton (GO:0005856), motile cilium (GO:0031514), cell projection (GO:0042995), ciliary base (GO:0097546), non-motile cilium (GO:0097730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cilium	4
hematopoietic progenitor cell differentiation	1
gene expression	1
RNA biosynthetic process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
cell cycle G1/S phase transition	1
regulation of cell cycle phase transition	1
cellular developmental process	1
nucleic acid binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
microtubule organizing center	1
cytoplasm	1
intracellular membraneless organelle	1
ciliary transition zone	1
ciliary transition fiber	1

Protein interactions and networks

STRING

1054 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MLF1	CENPU	Q71F23	918
MLF1	NPM1	P06748	838
MLF1	YWHAE	P29360	709
MLF1	CENPQ	Q7L2Z9	685
MLF1	NRBP1	Q9UHY1	661
MLF1	CENPP	Q6IPU0	649
MLF1	CENPO	Q9BU64	649
MLF1	CENPN	Q96H22	631
MLF1	CENPT	Q96BT3	593
MLF1	CENPM	Q9NSP4	584
MLF1	DRC12	Q494R4	572
MLF1	DNAJB6	O75190	552
MLF1	ADAM23	O75077	542
MLF1	CENPI	Q92674	540
MLF1	PRDM5	Q9NQX1	519

IntAct

170 interactions, top by confidence:

A	B	Type	Score
RELL2	OXSR1	psi-mi:“MI:0914”(association)	0.830
MLF1	DNAJB6	psi-mi:“MI:0914”(association)	0.750
DNAJB6	MLF1	psi-mi:“MI:0915”(physical association)	0.750
MLF1	MAGEA11	psi-mi:“MI:0915”(physical association)	0.740
MAGEA11	MLF1	psi-mi:“MI:0915”(physical association)	0.740
MLF1	HAX1	psi-mi:“MI:0914”(association)	0.560
YWHAE	MLF1	psi-mi:“MI:0407”(direct interaction)	0.560
MLF1	HAX1	psi-mi:“MI:0915”(physical association)	0.560
MLF1	BAG2	psi-mi:“MI:0915”(physical association)	0.560
MLF1	DNAJB2	psi-mi:“MI:0915”(physical association)	0.560
AARSD1	MLF1	psi-mi:“MI:0915”(physical association)	0.560
STUB1	MLF1	psi-mi:“MI:0915”(physical association)	0.560
MLF1	NDC80	psi-mi:“MI:0914”(association)	0.530
DNAJB8	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
NRBP1	TBC1D4	psi-mi:“MI:0914”(association)	0.530
KNG1	CTSV	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
DNAJB8	DNAJB6	psi-mi:“MI:0914”(association)	0.530
GPRC5B	STXBP3	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
SLC14A2	MLF1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (184): MLF1 (Affinity Capture-MS), DNAJB6 (Affinity Capture-MS), MAP1B (Affinity Capture-MS), ERCC6L (Affinity Capture-MS), TRO (Affinity Capture-MS), AKAP11 (Affinity Capture-MS), BRCA2 (Affinity Capture-MS), SYNRG (Affinity Capture-MS), FAM83H (Affinity Capture-MS), ZWINT (Affinity Capture-MS), SPC24 (Affinity Capture-MS), PRKACB (Affinity Capture-MS), FAM21A (Affinity Capture-MS), HEATR5B (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A804C8T0, A4ZNR4, A4ZNR5, B2RX88, F7C1E2, O00165, O08623, O35387, O70367, O75829, O77770, P17404, P25686, P58340, Q03157, Q08E24, Q13501, Q15773, Q16626, Q29407, Q2KIE2, Q32KY3, Q3UIL6, Q4R992, Q5R491, Q5R4T3, Q5RBA5, Q5XIA0, Q64337, Q6AYN2, Q6BEG7, Q6IQ23, Q6PAQ9, Q7TNY7, Q7TSE9, Q7Z5B4, Q8BK03, Q8BPM6, Q8K3I4, Q8NFW9

Diamond homologs: P58340, Q15773, Q32KY3, Q5R4T3, Q99KX1, Q9NKV0, Q9QWV4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MLF1	up-regulates	COPS3	binding
MLF1	up-regulates	COP1
MLF1	up-regulates	TP53

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 170 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 response to heat stress	5	18.1×	3e-03
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	5	13.8×	3e-03
Switching of origins to a post-replicative state	5	13.8×	3e-03
Synthesis of DNA	5	13.8×	3e-03
ADORA2B mediated anti-inflammatory cytokines production	5	11.6×	5e-03
GPER1 signaling	5	11.4×	5e-03
DNA Replication	5	10.9×	5e-03
G alpha (z) signalling events	5	10.7×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	9	6.2×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	7
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1360 predictions. Top by Δscore:

Variant	Effect	Δscore
3:158571348:G:GG	donor_gain	1.0000
3:158592578:GACT:G	donor_gain	1.0000
3:158592582:G:GG	donor_gain	1.0000
3:158596860:A:AG	acceptor_gain	1.0000
3:158596861:G:GG	acceptor_gain	1.0000
3:158596861:GC:G	acceptor_gain	1.0000
3:158596941:ACTTC:A	donor_gain	1.0000
3:158596942:CTTC:C	donor_gain	1.0000
3:158596946:G:GG	donor_gain	1.0000
3:158598204:G:GT	donor_gain	1.0000
3:158598204:GAGGA:G	donor_gain	1.0000
3:158598205:AGGA:A	donor_gain	1.0000
3:158598206:GGA:G	donor_gain	1.0000
3:158598206:GGAG:G	donor_gain	1.0000
3:158598206:GGAGT:G	donor_loss	1.0000
3:158598207:GA:G	donor_gain	1.0000
3:158598207:GAG:G	donor_gain	1.0000
3:158598207:GAGTA:G	donor_loss	1.0000
3:158598208:AGTA:A	donor_loss	1.0000
3:158598209:G:GG	donor_gain	1.0000
3:158598209:GTAA:G	donor_loss	1.0000
3:158598210:T:G	donor_loss	1.0000
3:158600004:A:AG	acceptor_gain	1.0000
3:158600008:TTACA:T	acceptor_gain	1.0000
3:158600009:TACAG:T	acceptor_gain	1.0000
3:158600010:A:AG	acceptor_gain	1.0000
3:158600010:ACAG:A	acceptor_gain	1.0000
3:158600011:C:G	acceptor_gain	1.0000
3:158600011:CAGA:C	acceptor_gain	1.0000
3:158600012:A:AG	acceptor_gain	1.0000

AlphaMissense

1907 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:158600068:G:C	A155P	0.997
3:158598176:G:C	A126P	0.995
3:158600095:G:C	A164P	0.995
3:158602833:T:A	W199R	0.994
3:158602833:T:C	W199R	0.994
3:158600093:G:C	R163P	0.993
3:158598179:T:C	S127P	0.992
3:158602821:T:C	F195L	0.992
3:158602823:T:A	F195L	0.992
3:158602823:T:G	F195L	0.992
3:158602835:G:C	W199C	0.992
3:158602835:G:T	W199C	0.992
3:158598125:T:C	S109P	0.990
3:158600077:C:G	H158D	0.990
3:158602834:G:C	W199S	0.990
3:158598122:T:C	S108P	0.987
3:158600032:G:C	A143P	0.987
3:158600098:C:G	H165D	0.987
3:158600156:T:C	F184S	0.986
3:158598192:G:C	R131P	0.985
3:158602822:T:C	F195S	0.985
3:158598140:T:C	S114P	0.984
3:158598186:A:C	Q129P	0.984
3:158602822:T:G	F195C	0.984
3:158598170:T:C	F124L	0.983
3:158598172:T:A	F124L	0.983
3:158598172:T:G	F124L	0.983
3:158600078:A:C	H158P	0.983
3:158600081:A:C	H159P	0.983
3:158598174:A:C	Q125P	0.982

dbSNP variants (sampled 300 via entrez): RS1000158005 (3:158600591 T>A,C), RS1000291678 (3:158578479 T>A), RS1000388153 (3:158581405 C>CT), RS1000440675 (3:158580993 G>A), RS1000486947 (3:158570612 C>T), RS1000569767 (3:158574719 A>G), RS1000622432 (3:158576766 A>G), RS1000668789 (3:158587699 T>C), RS1000719005 (3:158594660 T>C), RS1000837652 (3:158570264 T>C), RS1000975021 (3:158589055 A>G), RS1001010842 (3:158592980 T>C), RS1001133230 (3:158582916 G>A), RS1001179902 (3:158585959 C>T), RS1001389774 (3:158588185 G>C)

Disease associations

OMIM: gene MIM:601402 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004510_8	Sporadic neuroblastoma	1.000000e-11
GCST005839_27	Depression	3.000000e-09
GCST006041_13	Major depressive disorder	1.000000e-08
GCST006624_21	Systolic blood pressure	2.000000e-10
GCST007611_15	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	1.000000e-09
GCST010320_40	PR interval	2.000000e-08
GCST010796_1779	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-13
GCST010796_1780	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-16
GCST010796_1781	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0004462	PR interval
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	7
sodium arsenite	decreases expression, increases abundance, increases expression	3
methylmercuric chloride	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Air Pollutants, Occupational	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression	2
bisphenol A	increases expression	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
zinc chromate	increases expression, increases abundance	1
ferrous chloride	increases expression	1
nickel sulfate	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
seocalcitol	increases 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
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Decitabine	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Leflunomide	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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