NFYA

Summary

NFYA (nuclear transcription factor Y subunit alpha, HGNC:7804) is a protein-coding gene on chromosome 6p21.1, encoding Nuclear transcription factor Y subunit alpha (P23511). Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5’-CCAAT-3’ box motif found in the promoters of its target genes. It is a selective cancer dependency (DepMap: 12.3% of cell lines).

The protein encoded by this gene is one subunit of a trimeric complex, forming a highly conserved transcription factor that binds to CCAAT motifs in the promoter regions in a variety of genes. Subunit A associates with a tight dimer composed of the B and C subunits, resulting in a trimer that binds to DNA with high specificity and affinity. The sequence specific interactions of the complex are made by the A subunit, suggesting a role as the regulatory subunit. In addition, there is evidence of post-transcriptional regulation in this gene product, either by protein degradation or control of translation. Further regulation is represented by alternative splicing in the glutamine-rich activation domain, with clear tissue-specific preferences for the two isoforms.

Source: NCBI Gene 4800 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 31 total
• Cancer dependency (DepMap): dependent in 12.3% of screened cell lines
• Transcription factor: yes — 98 downstream targets (CollecTRI)
• MANE Select transcript: NM_002505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7804
Approved symbol	NFYA
Name	nuclear transcription factor Y subunit alpha
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	HAP2, CBF-B, NF-YA
Ensembl gene	ENSG00000001167
Ensembl biotype	protein_coding
OMIM	189903
Entrez	4800

Gene structure

Transcript identifiers

Ensembl transcripts: 52 — 52 protein_coding

ENST00000341376, ENST00000353205, ENST00000902856, ENST00000902857, ENST00000902858, ENST00000902859, ENST00000902860, ENST00000902861, ENST00000902862, ENST00000902863, ENST00000902864, ENST00000902865, ENST00000902866, ENST00000902867, ENST00000902868, ENST00000902869, ENST00000902870, ENST00000902871, ENST00000902872, ENST00000902873, ENST00000902874, ENST00000902875, ENST00000902876, ENST00000902877, ENST00000914455, ENST00000914456, ENST00000914457, ENST00000914458, ENST00000914459, ENST00000914460, ENST00000914461, ENST00000914462, ENST00000914463, ENST00000914464, ENST00000914465, ENST00000914466, ENST00000914467, ENST00000955092, ENST00000955093, ENST00000955094, ENST00000955095, ENST00000955096, ENST00000955097, ENST00000955098, ENST00000955099, ENST00000955100, ENST00000955101, ENST00000955102, ENST00000955103, ENST00000955104, ENST00000955105, ENST00000955106

RefSeq mRNA: 2 — MANE Select: NM_002505 NM_002505, NM_021705

CCDS: CCDS4849, CCDS4850

Canonical transcript exons

ENST00000341376 — 10 exons

Exon	Start	End
ENSE00000750570	41094396	41094497
ENSE00000750577	41091528	41091694
ENSE00000750637	41084046	41084192
ENSE00000849858	41079029	41079164
ENSE00000849861	41089579	41089710
ENSE00000849862	41090204	41090309
ENSE00000849864	41092912	41093085
ENSE00001299015	41097357	41102403
ENSE00001382968	41080811	41080897
ENSE00001924448	41072974	41073084

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 94.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.1390 / max 305.7493, expressed in 1817 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67732	22.9147	1813
67735	3.4430	1239
67733	0.4093	212
67734	0.3081	164
203988	0.0638	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.13	gold quality
buccal mucosa cell	CL:0002336	90.86	gold quality
ganglionic eminence	UBERON:0004023	90.56	gold quality
right testis	UBERON:0004534	90.41	gold quality
left testis	UBERON:0004533	90.32	gold quality
sperm	CL:0000019	90.09	gold quality
testis	UBERON:0000473	89.67	gold quality
embryo	UBERON:0000922	89.52	gold quality
male germ cell	CL:0000015	89.29	gold quality
secondary oocyte	CL:0000655	87.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.49	gold quality
bone marrow cell	CL:0002092	87.31	gold quality
islet of Langerhans	UBERON:0000006	87.09	gold quality
monocyte	CL:0000576	87.01	gold quality
leukocyte	CL:0000738	86.81	gold quality
stromal cell of endometrium	CL:0002255	86.79	gold quality
mononuclear cell	CL:0000842	86.77	gold quality
ventricular zone	UBERON:0003053	86.32	gold quality
bone marrow	UBERON:0002371	86.10	gold quality
middle temporal gyrus	UBERON:0002771	85.89	gold quality
rectum	UBERON:0001052	84.94	gold quality
blood	UBERON:0000178	84.60	gold quality
right lobe of thyroid gland	UBERON:0001119	84.41	gold quality
lymph node	UBERON:0000029	84.32	gold quality
tendon of biceps brachii	UBERON:0008188	84.12	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.06	gold quality
granulocyte	CL:0000094	83.99	gold quality
medial globus pallidus	UBERON:0002477	83.87	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.81	silver quality
left ovary	UBERON:0002119	83.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.56

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

98 targets.

Target	Regulation
ABCB1	Unknown
ACLY
ACSBG1
ACTB	Activation
ADAM2
ADIPOQ
AKR1C1
AMELX	Activation
ASF1A
ASF1B	Activation
AURKA	Activation
BMAL1
CASP1
CBS	Activation
CCNB2	Unknown
CCND2	Activation
CDC25A	Activation
CDC25C	Activation
CDK1	Repression
CDKN1B	Activation
CDKN2A
CGA	Unknown
CHEK2	Repression
CLDN11	Activation
COL1A2	Activation
CYC1	Unknown
CYP2A6	Activation
DDIT3	Unknown
DLST
E2F1	Activation

JASPAR motifs

Motif	Name	Family
MA0060.1	NFYA	Heteromeric CCAAT-binding
MA0060.2	NFYA	Heteromeric CCAAT-binding
MA0060.3	NFYA	Heteromeric CCAAT-binding
MA0060.4	NFYA	Heteromeric CCAAT-binding

JASPAR matrix evidence (PMIDs): PMID:9469818

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CREB1, DDIT3, E2F1, ESR1, ETV4, FOXA2, FOXC1, GATA4, HOXB4, IRF6, JUN, KAT7, MEIS1, MYBL2, NFKB, NFYA, NFYB, NFYC, NR1H3, POU2F1, SP1, SP3, SREBF1, TCF3, TP53, TP63, TP73, USF1, ZHX2, ZNF148, ZNF160

miRNA regulators (miRDB)

177 targeting NFYA, 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-7110-3P	100.00	73.18	2486
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-545-3P	99.95	70.74	2783

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• immunodepletion of Oct-1 and NF-YA proteins or mutations in the OCT-1 and CAAT motifs disrupt BRCA1 binding to the GADD45 promoter (PMID:11777930)
• NF-YA increases during CaCo-2 differentiation and that the constitutive expression of NF-YA, obtained in stably transfected CaCo-2 cells, results in the expression of differentiation markers (PMID:12392713)
• confirms the important transactivating role of NF-YA isoforms for the cystathionine beta synthase 1b promoter via its synergism with Sp1 (PMID:12427542)
• p300 binds to multiple NF-Y trimers to regulate cyclin B2 promoter function (PMID:12482752)
• role in inhibiting von Willebrand factor promoter activation through recruitment of histone deacetylases (PMID:12511565)
• NF-Y is a developmentally regulated inducer of the HOXB4 gene in hematopoietic cells. (PMID:12791656)
• NF-YA is phosphorylated in a pathway involving Cdk2 (PMID:12857729)
• Histone deacetylase inhibitors can induce Gadd45 through its promoter without the need for functional p53, and both Oct-1 and NF-Y concertedly participate in trichostatin A-induced activation of the gadd45 promoter. (PMID:14586402)
• NF-YA has a role in regulating the induction of human OGG1 following administration of DNA-alkylating agents (PMID:14688259)
• p53 negatively regulates Chk2 gene transcription through modulation of NF-Y function and that this regulation may be important for reentry of cells into the cell cycle after DNA damage is repaired. (PMID:15044452)
• NF-Y has a role in regulating EPHX1 expression through its interaction with C/EBPalpha (PMID:15150264)
• transforming growth factor beta type II receptor promoter activity and acetylation of Sp1 by recruitment of PCAF/p300 to a Sp1.NF-Y complex are induced by Trichostatin A (PMID:15647279)
• These results indicate that 1,25(OH)2D3 may affect transcription of the human PTH gene both by competitive binding of VDR and NF-Y, and by modulating transcriptional activity of NF-Y. (PMID:15707954)
• NF-Ya is a potent cellular regulator of hematopoietic stem cell self-renewal (PMID:16081537)
• Data suggest that the cell specifity of HIV-1 expression and replication may be regulated, in part, through the control of TRBP1 expression by NF-Y factors. (PMID:16343534)
• cyclin B2 expression in colorectal adenocarcinoma is dependent on NF-Y (PMID:17289878)
• Our data indicate that multiple CCAAT control elements are involved in the regulation of the SOX3 promoter, suggesting that NF-Y functions as a key regulator of SOX3 gene expression. (PMID:17910945)
• NF-Y is an important mediator of EBV stress response in switching from a latent to lytic state (PMID:18281530)
• p53 overexpression strongly downregulates the transcriptional efficiency driven by an H ferritin promoter construct containing only the NF-Y recognition sequence. (PMID:18372207)
• NF-Y is a fundamental switch at the heart of decision between gene activation and repression in CCAAT regulated genes. (PMID:18446193)
• Transcription factors Sp3, ZBP-89 and NF-Y are capable of binding to the SOX18 promoter region. (PMID:18496767)
• The existence of a functional binding site for the tumor suppressor p53 near the proximal CCAAT box and the fact that the basal expression of annexin A1 in human colon adenocarcinoma cells is driven by p53 at the transcriptional level, is shown. (PMID:18541673)
• Genome-wide occupancy of SREBP1 and its partners NFY and SP1 reveals novel functional roles and combinatorial regulation of distinct classes of genes. (PMID:18654640)
• O-GlcNAc of Sp1 serine/threonine-rich region interrupts a physical interaction between Sp1 and NF-YA, thus inhibiting Sp1-NF-Y cooperative activation of gene transcription. (PMID:19302979)
• review: role of the C/EBPbeta isoforms in breast cancer (PMID:19351437)
• the immediate-early ICP0 gene may be among the first genes to be induced during the early events in HSV-1 reactivation, and NF-Y is important for this induction, and other factors induce the ICP22 promoter. (PMID:19828605)
• The phospho-DeltaNp63alpha forms protein-protein complexes with NF-YA transcription factor regulate the transcription of DDIT3 gene implicated in the programmed cell death of head and neck squamous cell carcinoma cells upon cisplatin exposure. (PMID:20023394)
• A novel mechanism involving coordinated regulation of nuclear levels and acetylation of NF-YA and Bcl6 activates RGS4 transcription. (PMID:20630860)
• Findings establish that NF-Y acts upstream of E2F1 in p53-mediated apoptosis. (PMID:20952509)
• This study unveils a new role for NF-Y in the regulation of human proteasome genes. (PMID:22285817)
• Sp1, CREB, HNF-1, and NF-Y, known to be responsive to hormones and diet, regulate NAGS transcription (PMID:22383952)
• NFYA could be a target of mutant TBP in SCA17. (PMID:22530004)
• NF-Y recruits the developmentally regulated, erythroid transcription activator GATA-2 and general repressor BCL11A to modulate transcription of the gamma-globin gene. (PMID:23071749)
• The crystal structure of NF-Y bound to a 25 bp CCAAT oligonucleotide shows that the histone-fold domains dimer binds to the DNA sugar-phosphate backbone, mimicking the nucleosome H2A/H2B-DNA assembly; NF-YA both binds to NF-YB/NF-YC and inserts an alpha helix deeply into the DNA minor groove, providing sequence-specific contacts to the CCAAT box. (PMID:23332751)
• NF-YA binds directly over the CCAAT sequence. (PMID:23595228)
• Association of p21 with NF-YA suppresses the expression of PLK1 and prevents mitotic death in response to DNA damage. (PMID:24407240)
• Stimulation of the lymphocytes with phytohemagglutinin, restores normal OGG1 levels and repair rates. MAP kinase c-Jun N-terminal kinase (JNK) and the recruitment of the transcription factor NFYA to the promoter region of OGG1 are shown to be involved. (PMID:25463392)
• Data show that Zinc-fingers and homeoboxes 2 (ZHX2) represses nuclear transcription factor Y alpha (NF-Y)-mediated activation of multidrug resistance 1 (MDR1) transcription. (PMID:25473899)
• NF-Y inhibits NT2/D1 cell growth in p53-independent manner and decreases SOX2 expression. (PMID:25756534)
• enhanced CDCA8 promoter activities by NF-Y overexpression and reduced CDCA8 transcription by NF-Y knockdown further verified that NF-Y is a positive regulator of CDCA8 transcription. (PMID:26170459)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfyal	ENSDARG00000001621
danio_rerio	nfya	ENSDARG00000042004
mus_musculus	Nfya	ENSMUSG00000023994
rattus_norvegicus	Nfya	ENSRNOG00000012702
drosophila_melanogaster	Nf-YA	FBGN0035993
caenorhabditis_elegans		WBGENE00011614
caenorhabditis_elegans	nfya-2	WBGENE00043056

Protein

Protein identifiers

Nuclear transcription factor Y subunit alpha — P23511 (reviewed: P23511)

Alternative names: CAAT box DNA-binding protein subunit A, Nuclear transcription factor Y subunit A

All UniProt accessions (3): A0A0U4C5A9, P23511, K9JA49

UniProt curated annotations — full annotation on UniProt →

Function. Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5’-CCAAT-3’ box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors. NF-YA positively regulates the transcription of the core clock component BMAL1.

Subunit / interactions. Heterotrimeric transcription factor composed of three components, NF-YA, NF-YB and NF-YC. NF-YB and NF-YC must interact and dimerize for NF-YA association and DNA binding. Interacts with SP1; the interaction is inhibited by glycosylation of SP1. Interacts with ZHX1. Interacts (via N-terminus) with ZHX2 (via homeobox domain). Interacts with ZFX3.

Subcellular location. Nucleus.

Similarity. Belongs to the NFYA/HAP2 subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
P23511-1	Long	yes
P23511-2	Short

RefSeq proteins (2): NP_002496, NP_068351 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001289	NFYA	Family
IPR018362	CCAAT-binding_factor_CS	Conserved_site

Pfam: PF02045

UniProt features (14 total): helix 3, compositionally biased region 2, chain 1, DNA-binding region 1, turn 1, region of interest 1, short sequence motif 1, modified residue 1, splice variant 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8QU4	X-RAY DIFFRACTION	1.38
8QU3	X-RAY DIFFRACTION	1.41
8QU2	X-RAY DIFFRACTION	1.45
9R4D	X-RAY DIFFRACTION	1.7
6QMS	X-RAY DIFFRACTION	1.8
6QMP	X-RAY DIFFRACTION	2
6QMQ	X-RAY DIFFRACTION	2.5
4AWL	X-RAY DIFFRACTION	3.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23511-F1	50.65	0.14

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 (1): 326

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-381183	ATF6 (ATF6-alpha) activates chaperone genes
R-HSA-9614657	FOXO-mediated transcription of cell death genes

MSigDB gene sets: 248 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_NK_CELL_VS_BCELL_UP, MYAATNNNNNNNGGC_UNKNOWN, MODULE_97, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, TGCGCANK_UNKNOWN, GCM_GSPT1, RORA1_01, CMYB_01, GCM_ZNF198, GEORGES_CELL_CYCLE_MIR192_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_182, TGACCTY_ERR1_Q2

GO Biological Process (6): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), rhythmic process (GO:0048511)

GO Molecular Function (6): 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 (GO:0003677), DNA-binding transcription factor activity (GO:0003700), transcription cis-regulatory region binding (GO:0000976), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), CCAAT-binding factor complex (GO:0016602), protein-DNA complex (GO:0032993), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Regulation of lipid metabolism by PPARalpha	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
PERK regulates gene expression	1
ATF6 (ATF6-alpha) activates chaperones	1
FOXO-mediated transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
regulation of DNA-templated transcription	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
biological_process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
RNA polymerase II transcription regulator complex	1
protein-containing complex	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

2202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFYA	NFYB	P25208	999
NFYA	NFYC	Q13952	999
NFYA	ZHX1	Q9UKY1	938
NFYA	ZHX3	Q9H4I2	856
NFYA	RFXANK	O14593	819
NFYA	CEBPZ	Q03701	779
NFYA	RFX5	P48382	749
NFYA	CREB1	P16220	712
NFYA	ATF6	P18850	692
NFYA	RFXAP	O00287	670
NFYA	TP53	P04637	655
NFYA	RFX1	P22670	651
NFYA	CIITA	P33076	623
NFYA	CCNL2	Q96S94	623
NFYA	ATF6B	Q99941	613

IntAct

60 interactions, top by confidence:

A	B	Type	Score
NFYC	NFYA	psi-mi:“MI:0914”(association)	0.850
NFYA	NFYB	psi-mi:“MI:0915”(physical association)	0.840
NFYB	NFYA	psi-mi:“MI:0915”(physical association)	0.840
NFYA	NFYB	psi-mi:“MI:0914”(association)	0.840
CSNK2A1	NFYA	psi-mi:“MI:0915”(physical association)	0.670
LUC7L2	NFYA	psi-mi:“MI:0915”(physical association)	0.670
NFYA	CSNK2A1	psi-mi:“MI:0915”(physical association)	0.670
NFYA	LUC7L2	psi-mi:“MI:0915”(physical association)	0.670
APPBP2	NFYA	psi-mi:“MI:0915”(physical association)	0.620
NFYA	APPBP2	psi-mi:“MI:0915”(physical association)	0.620
NFYA	SRSF1	psi-mi:“MI:0915”(physical association)	0.600
NFYA	SRSF1	psi-mi:“MI:0403”(colocalization)	0.600
GTF2A1	NFYA	psi-mi:“MI:0915”(physical association)	0.560
POGZ	NFYA	psi-mi:“MI:0915”(physical association)	0.560
NFYA	GTF2A1	psi-mi:“MI:0915”(physical association)	0.560
NFYB	TP53	psi-mi:“MI:0914”(association)	0.560
NFYA	POGZ	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (178): NFYA (Two-hybrid), NFYA (Two-hybrid), NFYB (Two-hybrid), POGZ (Two-hybrid), LUC7L2 (Two-hybrid), NFYA (Affinity Capture-RNA), NFYA (Affinity Capture-RNA), NFYA (Affinity Capture-RNA), ME1 (Affinity Capture-MS), NME2P1 (Affinity Capture-MS), UBE2D2 (Affinity Capture-MS), LASP1 (Affinity Capture-MS), HMGCS1 (Affinity Capture-MS), NFYC (Affinity Capture-MS), IRGQ (Affinity Capture-MS)

ESM2 similar proteins: A4IFD2, B0R0I6, E9Q7E2, G5ED89, O08949, O15409, O70494, O94842, P0CF24, P15337, P16220, P18576, P18846, P23511, P23708, P27699, P27925, P39769, P52654, P52655, P58462, P58463, P79145, Q01147, Q03060, Q03061, Q08DA8, Q0P5K4, Q1LZH5, Q498D1, Q4VYS1, Q58NQ4, Q5E9S2, Q5QL03, Q5R6A9, Q5RCU0, Q5W1J5, Q68CP9, Q7ZX03, Q86NP2

Diamond homologs: G5EEG1, P06774, P18576, P23511, P23708, P24488, P53768, Q54S29, Q5E9S2, Q5ZEP9, Q84JP1, Q8LFU0, Q8VY64, Q93ZH2, Q945M9, Q9LNP6, Q9LVJ7, Q9LXV5, Q9M9X4, Q9SYH4

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
RNF4	“up-regulates activity”	NFYA	binding
NFYA	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
NFYA	“up-regulates quantity by expression”	GFI1B	“transcriptional regulation”
NFYA	“up-regulates quantity by expression”	CBS	“transcriptional regulation”
NFYA	“up-regulates activity”	SP1	binding
NFYA	“up-regulates quantity by expression”	OGG1	“transcriptional regulation”
NFYA	“up-regulates quantity by expression”	SOX18	“transcriptional regulation”
NFYA	“up-regulates quantity by expression”	PHGDH	“transcriptional regulation”
NFYA	“form complex”	NFY	binding
CDK2	“up-regulates activity”	NFYA	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1287 predictions. Top by Δscore:

Variant	Effect	Δscore
6:41073082:ACGGT:A	donor_loss	1.0000
6:41073085:G:C	donor_loss	1.0000
6:41079028:GGA:G	acceptor_gain	1.0000
6:41079028:GGAGT:G	acceptor_gain	1.0000
6:41079160:AGCAG:A	donor_loss	1.0000
6:41079161:GCAG:G	donor_gain	1.0000
6:41079162:CAG:C	donor_loss	1.0000
6:41079163:AGG:A	donor_loss	1.0000
6:41079164:GGT:G	donor_loss	1.0000
6:41079166:T:G	donor_loss	1.0000
6:41084039:A:AG	acceptor_gain	1.0000
6:41084157:C:T	donor_gain	1.0000
6:41084189:GCAA:G	donor_gain	1.0000
6:41084190:CAAG:C	donor_loss	1.0000
6:41084193:G:GG	donor_gain	1.0000
6:41084195:G:GT	donor_loss	1.0000
6:41089574:T:TA	acceptor_gain	1.0000
6:41089575:GCA:G	acceptor_loss	1.0000
6:41089576:CA:C	acceptor_loss	1.0000
6:41089577:A:AG	acceptor_gain	1.0000
6:41089578:G:GT	acceptor_gain	1.0000
6:41089578:GA:G	acceptor_gain	1.0000
6:41089578:GAT:G	acceptor_gain	1.0000
6:41089578:GATA:G	acceptor_gain	1.0000
6:41089578:GATAC:G	acceptor_gain	1.0000
6:41089707:TCAGG:T	donor_loss	1.0000
6:41089709:AGG:A	donor_loss	1.0000
6:41089710:GGTA:G	donor_loss	1.0000
6:41089711:G:A	donor_loss	1.0000
6:41089712:T:A	donor_loss	1.0000

AlphaMissense

2244 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:41084119:T:A	V79D	1.000
6:41092987:C:T	P264S	1.000
6:41092988:C:A	P264H	1.000
6:41092988:C:G	P264R	1.000
6:41092991:T:A	L265H	1.000
6:41092991:T:C	L265P	1.000
6:41092993:T:A	Y266N	1.000
6:41092993:T:C	Y266H	1.000
6:41092993:T:G	Y266D	1.000
6:41092994:A:C	Y266S	1.000
6:41092994:A:G	Y266C	1.000
6:41092996:G:A	V267M	1.000
6:41092996:G:C	V267L	1.000
6:41092996:G:T	V267L	1.000
6:41092997:T:A	V267E	1.000
6:41092997:T:C	V267A	1.000
6:41092997:T:G	V267G	1.000
6:41092999:A:G	N268D	1.000
6:41092999:A:T	N268Y	1.000
6:41093000:A:T	N268I	1.000
6:41093001:T:A	N268K	1.000
6:41093001:T:G	N268K	1.000
6:41093003:C:A	A269D	1.000
6:41093003:C:T	A269V	1.000
6:41093005:A:C	K270Q	1.000
6:41093005:A:G	K270E	1.000
6:41093006:A:C	K270T	1.000
6:41093006:A:T	K270I	1.000
6:41093007:A:C	K270N	1.000
6:41093007:A:T	K270N	1.000

dbSNP variants (sampled 300 via entrez): RS1000074411 (6:41089112 T>C), RS1000078279 (6:41102389 C>A,G), RS1000128522 (6:41096700 G>A,T), RS1000201091 (6:41094838 T>C), RS1000225000 (6:41086060 A>C,G), RS1000247557 (6:41093466 CCTTT>C), RS1000353546 (6:41075797 C>T), RS1000511812 (6:41086398 T>A), RS1000686367 (6:41077323 A>C,G), RS1000717191 (6:41077010 G>A,C), RS1000768007 (6:41071007 G>A), RS1000834089 (6:41074450 C>A,T), RS1000962395 (6:41102167 A>G), RS1001003128 (6:41080587 G>GT), RS1001038272 (6:41072411 C>T)

Disease associations

OMIM: gene MIM:189903 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004610_19	White blood cell count	2.000000e-10
GCST90002397_131	Mean spheric corpuscular volume	2.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression	2
Tretinoin	increases expression, affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Mitomycin	increases expression, affects response to substance	2
Cadmium Chloride	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	increases expression	1
glycidyl methacrylate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression, increases abundance	1
nickel chloride	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation	1
coptisine	decreases expression, affects binding, decreases reaction	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Ascorbic Acid	affects cotreatment, decreases expression	1
Benzene	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects binding, increases reaction, increases expression	1
Curcumin	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4P1	SEES3-1V human NFYA, clone1	Embryonic stem cell	Male
CVCL_A4P2	SEES3-1V human NFYA, clone2	Embryonic stem cell	Male
CVCL_A4P3	SEES3-1V human NFYA, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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