NFYC

Summary

NFYC (nuclear transcription factor Y subunit gamma, HGNC:7806) is a protein-coding gene on chromosome 1p34.2, encoding Nuclear transcription factor Y subunit gamma (Q13952). 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 common-essential gene (DepMap: required in 94.3% of cancer cell lines).

This gene encodes one subunit of a trimeric complex forming a highly conserved transcription factor that binds with high specificity to CCAAT motifs in the promoters of a variety of genes. The encoded protein, subunit C, forms a tight dimer with the B subunit, a prerequisite for subunit A association. The resulting trimer binds to DNA with high specificity and affinity. Subunits B and C each contain a histone-like motif. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4802 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 38 total
• Cancer dependency (DepMap): dependent in 94.3% of screened cell lines (common-essential)
• Transcription factor: yes — 24 downstream targets (CollecTRI)
• MANE Select transcript: NM_014223

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7806
Approved symbol	NFYC
Name	nuclear transcription factor Y subunit gamma
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	CBF-C, NF-YC
Ensembl gene	ENSG00000066136
Ensembl biotype	protein_coding
OMIM	605344
Entrez	4802

Gene structure

Transcript identifiers

Ensembl transcripts: 158 — 152 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000308733, ENST00000372651, ENST00000372652, ENST00000372653, ENST00000372654, ENST00000372669, ENST00000414185, ENST00000416859, ENST00000424419, ENST00000425457, ENST00000427410, ENST00000440226, ENST00000447388, ENST00000453631, ENST00000456393, ENST00000467203, ENST00000483091, ENST00000488635, ENST00000496608, ENST00000525290, ENST00000525349, ENST00000530965, ENST00000531464, ENST00000534399, ENST00000900117, ENST00000900118, ENST00000900119, ENST00000900120, ENST00000900121, ENST00000900122, ENST00000900123, ENST00000900124, ENST00000900125, ENST00000900126, ENST00000900127, ENST00000900128, ENST00000900129, ENST00000900130, ENST00000900131, ENST00000900132, ENST00000900133, ENST00000900134, ENST00000900135, ENST00000900136, ENST00000900137, ENST00000900138, ENST00000900139, ENST00000900140, ENST00000900141, ENST00000900142, ENST00000900143, ENST00000900144, ENST00000900145, ENST00000900146, ENST00000900147, ENST00000900148, ENST00000900149, ENST00000900150, ENST00000900151, ENST00000900152, ENST00000900153, ENST00000900154, ENST00000900155, ENST00000900156, ENST00000900157, ENST00000900158, ENST00000900159, ENST00000900160, ENST00000900161, ENST00000900162, ENST00000900163, ENST00000900164, ENST00000900165, ENST00000900166, ENST00000900167, ENST00000900168, ENST00000900169, ENST00000900170, ENST00000900171, ENST00000900172, ENST00000900173, ENST00000900174, ENST00000900175, ENST00000900176, ENST00000900177, ENST00000900178, ENST00000900179, ENST00000914703, ENST00000914704, ENST00000914705, ENST00000914706, ENST00000914707, ENST00000914708, ENST00000914709, ENST00000914710, ENST00000914711, ENST00000914712, ENST00000914713, ENST00000914714, ENST00000914715, ENST00000914716, ENST00000914717, ENST00000914718, ENST00000914719, ENST00000914720, ENST00000914721, ENST00000914722, ENST00000914723, ENST00000914724, ENST00000914725, ENST00000914726, ENST00000947153, ENST00000947154, ENST00000947155, ENST00000947156, ENST00000947157, ENST00000947158, ENST00000947159, ENST00000947160, ENST00000947161, ENST00000947162, ENST00000947163, ENST00000947164, ENST00000947165, ENST00000947166, ENST00000947167, ENST00000947168, ENST00000947169, ENST00000947170, ENST00000947171, ENST00000947172, ENST00000947173, ENST00000947174, ENST00000947175, ENST00000947176, ENST00000947177, ENST00000947178, ENST00000947179, ENST00000947180, ENST00000947181, ENST00000947182, ENST00000947183, ENST00000947184, ENST00000947185, ENST00000947186, ENST00000947187, ENST00000947188, ENST00000947189, ENST00000947190, ENST00000947191, ENST00000947192, ENST00000947193, ENST00000947194, ENST00000947195, ENST00000947196, ENST00000947197, ENST00000947198, ENST00000947199

RefSeq mRNA: 7 — MANE Select: NM_014223 NM_001142587, NM_001142588, NM_001142589, NM_001142590, NM_001308114, NM_001308115, NM_014223

CCDS: CCDS44120, CCDS44121, CCDS44122, CCDS44123, CCDS455, CCDS81305, CCDS81306

Canonical transcript exons

ENST00000447388 — 10 exons

Exon	Start	End
ENSE00001683645	40769356	40769415
ENSE00001851333	40770709	40771603
ENSE00002160391	40691704	40691867
ENSE00003539001	40762888	40763046
ENSE00003548961	40747534	40747605
ENSE00003565298	40749573	40749686
ENSE00003611795	40738836	40738948
ENSE00003616963	40758121	40758294
ENSE00003637497	40766596	40766703
ENSE00003785577	40753151	40753246

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 96.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.0487 / max 1247.0957, expressed in 1823 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2398	18.9115	1812
2399	12.5404	1790
2396	7.9036	1726
2403	3.1995	989
2397	0.7052	436
2401	0.6812	336
2400	0.5845	302
2405	0.4692	199
2404	0.0535	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.49	gold quality
apex of heart	UBERON:0002098	95.97	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.47	gold quality
monocyte	CL:0000576	95.36	gold quality
tendon of biceps brachii	UBERON:0008188	95.18	gold quality
right lobe of thyroid gland	UBERON:0001119	94.99	gold quality
right atrium auricular region	UBERON:0006631	94.97	gold quality
mononuclear cell	CL:0000842	94.94	gold quality
leukocyte	CL:0000738	94.91	gold quality
gastrocnemius	UBERON:0001388	94.87	gold quality
ganglionic eminence	UBERON:0004023	94.82	gold quality
muscle of leg	UBERON:0001383	94.79	gold quality
skin of abdomen	UBERON:0001416	94.78	gold quality
skin of leg	UBERON:0001511	94.64	gold quality
minor salivary gland	UBERON:0001830	94.57	gold quality
left lobe of thyroid gland	UBERON:0001120	94.41	gold quality
granulocyte	CL:0000094	94.34	gold quality
left ovary	UBERON:0002119	94.31	gold quality
thyroid gland	UBERON:0002046	94.29	gold quality
body of uterus	UBERON:0009853	94.25	gold quality
endocervix	UBERON:0000458	94.24	gold quality
cardiac atrium	UBERON:0002081	94.20	gold quality
right ovary	UBERON:0002118	94.18	gold quality
ectocervix	UBERON:0012249	94.14	gold quality
left uterine tube	UBERON:0001303	94.07	gold quality
vagina	UBERON:0000996	94.01	gold quality
ventricular zone	UBERON:0003053	93.95	gold quality
heart left ventricle	UBERON:0002084	93.94	gold quality
colonic epithelium	UBERON:0000397	93.89	gold quality
spleen	UBERON:0002106	93.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.44

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

24 targets.

Target	Regulation
ABCB1	Unknown
CCND2	Activation
CDKN1B	Activation
COL1A2	Activation
FAS	Unknown
FDPS	Unknown
FOS	Unknown
FXR2	Activation
GCH1	Activation
GFI1B	Unknown
HBB	Unknown
HOXB7	Unknown
HSPA1A	Activation
HSPA1B	Activation
IL10	Activation
LPIN1	Unknown
NFYA
NOTCH1
NR3C2	Repression
PHGDH	Activation
SCNN1A
SOX18	Activation
SOX3	Unknown
TNFSF11	Repression

JASPAR motifs

Motif	Name	Family
MA1644.1	NFYC	Heteromeric CCAAT-binding
MA1644.2	NFYC	Heteromeric CCAAT-binding

JASPAR matrix evidence (PMIDs): PMID:11895773

Upstream regulators (CollecTRI, top): CEBPA

miRNA regulators (miRDB)

71 targeting NFYC, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-5700	99.64	69.88	2280

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 94.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 17)

• role in repressing Smad2 and Smad3 transactivating activity (PMID:12023901)
• The NF-YB/NF-YC structure gives insight into DNA binding and transcription regulation by CCAAT factor NF-Y. (PMID:12401788)
• p300 binds to multiple NF-Y trimers to regulate cyclin B2 promoter function (PMID:12482752)
• 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)
• C/EBPbeta contributes to the induction of hepatocyte replication in response to HGF in rodents, which is likely due to post-translational modifications. (PMID:15922473)
• Expression levels of NF-Y target genes changed by CDKN1B correlate with clinical prognosis in multiple neoplasms. (PMID:19559782)
• NF-YC complexity is generated by dual promoters and alternative splicing (PMID:19690168)
• NF-YC functions as a new corepressor of agonist-bound mineralocorticoid receptor via alteration of aldosterone-induced MR conformation (PMID:20054001)
• NFY-C expression was elevated in colorectal adenocarcinomas; moreover, NFY-C mRNA levels correlated with time to disease progression, while NFY-C protein expression was significantly higher in metastatic disease (PMID:22104449)
• Sp1, NF-Y and FOXO transcription factors are involved in the regulation of LKB1 transcription. (PMID:22412893)
• 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)
• the expression of the adipogenic differentiation genes fatty acid binding protein-4, adiponectin, and leptin and the formation of fat droplets were impaired. (PMID:23657974)
• TAF12 and NFYC are transcription factors that regulate the epigenome, whereas RAD54L plays a central role in DNA repair (PMID:25965574)
• Presence of NF-Y transcription factor plays a pivotal role in transcriptional regulation of ID genes in development. (PMID:26509926)
• NF-YC was significantly increased in gliomas. Knockdown of NF-YC reduced brain tumor size in vivo. NF-YC played as an independent predictor of patient survival. (PMID:27495011)
• p53 negatively regulates the expression of the PRR11-SKA2 bidirectional transcription unit through NF-Y, suggesting that the inability to repress the PRR11-SKA2 bidirectional transcription unit after loss of p53 might contribute to tumorigenesis. (PMID:28257042)
• The genes FABP7 and NFYC(-AS1) could play a role in airflow obstruction in never-smokers specifically. (PMID:30845926)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfyc	ENSDARG00000070151
mus_musculus	Nfyc	ENSMUSG00000032897
rattus_norvegicus	Nfyc	ENSRNOG00000010735
drosophila_melanogaster	Nf-YC	FBGN0029905
caenorhabditis_elegans		WBGENE00017742

Paralogs (2): POLE4 (ENSG00000115350), DRAP1 (ENSG00000175550)

Protein

Protein identifiers

Nuclear transcription factor Y subunit gamma — Q13952 (reviewed: Q13952)

Alternative names: CAAT box DNA-binding protein subunit C, Nuclear transcription factor Y subunit C, Transactivator HSM-1/2

All UniProt accessions (9): Q13952, A0A0A0MT00, E9PI99, E9PJA8, E9PL11, E9PQR2, H0Y803, Q5T6K5, Q5T6K7

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.

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.

Subcellular location. Nucleus.

Similarity. Belongs to the NFYC/HAP5 subunit family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q13952-1	3, DS2.8	yes
Q13952-2	1, Gamma
Q13952-3	2
Q13952-4	4
Q13952-5	5
Q13952-6	6
Q13952-7	7

RefSeq proteins (7): NP_001136059, NP_001136060, NP_001136061, NP_001136062, NP_001295043, NP_001295044, NP_055038* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007125	H2A/H2B/H3	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR050568	Transcr_DNA_Rep_Reg	Family

Pfam: PF00125

UniProt features (32 total): sequence conflict 13, helix 5, splice variant 5, strand 3, compositionally biased region 2, chain 1, region of interest 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
8QU4	X-RAY DIFFRACTION	1.38
8QU3	X-RAY DIFFRACTION	1.41
8QU2	X-RAY DIFFRACTION	1.45
4CSR	X-RAY DIFFRACTION	1.5
1N1J	X-RAY DIFFRACTION	1.67
9R4D	X-RAY DIFFRACTION	1.7
6QMS	X-RAY DIFFRACTION	1.8
6QMP	X-RAY DIFFRACTION	2
6QMQ	X-RAY DIFFRACTION	2.5
7AH8	X-RAY DIFFRACTION	2.7
4AWL	X-RAY DIFFRACTION	3.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13952-F1	50.55	0.22

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: 224 (showing top): REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, PAL_PRMT5_TARGETS_UP, MODULE_45, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, NIKOLSKY_OVERCONNECTED_IN_BREAST_CANCER, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, YY1_Q6, GGCNKCCATNK_UNKNOWN, MODULE_66, GOBP_PROTEIN_MATURATION, MCAATNNNNNGCG_UNKNOWN, YY1_02

GO Biological Process (5): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), protein folding (GO:0006457), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein heterodimerization activity (GO:0046982), transcription cis-regulatory region binding (GO:0000976), protein binding (GO:0005515)

GO Cellular Component (7): 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), transcription regulator complex (GO:0005667)

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
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
protein-containing complex	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular process	1
protein maturation	1
positive regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
protein dimerization 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
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFYC	NFYB	P25208	999
NFYC	NFYA	P23511	999
NFYC	HAP1	P54257	943
NFYC	REPIN1	Q9BWE0	924
NFYC	RFXANK	O14593	841
NFYC	CEBPZ	Q03701	827
NFYC	POLE3	Q9NRF9	728
NFYC	RFXAP	O00287	725
NFYC	RFX5	P48382	725
NFYC	ZHX1	Q9UKY1	713
NFYC	TP53	P04637	706
NFYC	TBP	P20226	681
NFYC	RFX1	P22670	636
NFYC	CIITA	P33076	625
NFYC	H2AC19	P20670	564
NFYC	H2AC20	Q16777	564

IntAct

54 interactions, top by confidence:

A	B	Type	Score
NFYB	NFYC	psi-mi:“MI:0407”(direct interaction)	0.870
NFYB	NFYC	psi-mi:“MI:0915”(physical association)	0.870
NFYC	NFYA	psi-mi:“MI:0914”(association)	0.850
NFYA	NFYB	psi-mi:“MI:0915”(physical association)	0.840
NFYA	NFYB	psi-mi:“MI:0914”(association)	0.840
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
NFYB	NFYA	psi-mi:“MI:0914”(association)	0.670
MILR1	INPPL1	psi-mi:“MI:0914”(association)	0.640
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
PRR20E	SIAH2	psi-mi:“MI:0914”(association)	0.530
DDX60	NFYC	psi-mi:“MI:0915”(physical association)	0.400
CXCL9	NFYC	psi-mi:“MI:0915”(physical association)	0.370
NFYC	SNX2	psi-mi:“MI:0915”(physical association)	0.370
NFYC	GAPDH	psi-mi:“MI:0915”(physical association)	0.370
Nfya	NFYB	psi-mi:“MI:0914”(association)	0.350
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
FOXK2	PHF20L1	psi-mi:“MI:0914”(association)	0.350
SRF	GPC4	psi-mi:“MI:0914”(association)	0.350
LIN28A	AGPS	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
NXT1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
BAG1	PSMD11	psi-mi:“MI:0914”(association)	0.350
TGM7	HGS	psi-mi:“MI:0914”(association)	0.350
NFYA	NME2P1	psi-mi:“MI:0914”(association)	0.350
CR1L	ACTL6B	psi-mi:“MI:0914”(association)	0.350

BioGRID (230): NFYC (Affinity Capture-MS), NFYC (Affinity Capture-MS), CORO1B (Co-fractionation), CORO1C (Co-fractionation), DR1 (Co-fractionation), NFYB (Co-fractionation), NFYC (Co-fractionation), NFYC (Affinity Capture-MS), NFYC (Affinity Capture-MS), NFYC (Affinity Capture-MS), NFYC (Affinity Capture-MS), NFYC (Affinity Capture-MS), NFYB (Affinity Capture-MS), PON1 (Affinity Capture-MS), NFYC (Affinity Capture-MS)

ESM2 similar proteins: A4QNP0, O70477, O70494, O89090, O94842, P08047, P11831, P14859, P15143, P15257, P16143, P18576, P18846, P20823, P22361, P23511, P23708, P23790, P25425, P27699, P52655, P79145, Q01714, Q02086, Q02446, Q02447, Q03060, Q03061, Q05041, Q07243, Q08DA8, Q0P5K4, Q13952, Q1LZH5, Q28BL7, Q29076, Q2HJ84, Q5E9S2, Q5E9U0, Q5R6A9

Diamond homologs: A0JPP1, A6BLW4, A6QQ14, B0XTT5, C6Y4D0, P40096, P70353, Q02516, Q10315, Q13952, Q14919, Q2YDP3, Q4PSE2, Q4X095, Q54DA1, Q58CM8, Q5E9X1, Q5RA23, Q62725, Q655V5, Q6C6M5, Q8L4B2, Q8LCG7, Q9CQ36, Q9D6N5, Q9FGP6, Q9FMV5, Q9NR33, Q9SMP0, Q9XE33, Q9ZVL3, O17072, P79007, Q557I1, Q6BX14, Q6CLM5, Q9FGP7, Q9FGP8, Q9JKP8, Q9NRG0

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
RNF4	“up-regulates activity”	NFYC	binding
NFYC	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
NFYC	“up-regulates quantity by expression”	GFI1B	“transcriptional regulation”
NFYC	“up-regulates quantity by expression”	SOX18	“transcriptional regulation”
NFYC	“up-regulates quantity by expression”	PHGDH	“transcriptional regulation”
NFYC	“form complex”	NFY	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2361 predictions. Top by Δscore:

Variant	Effect	Δscore
1:40691868:GTGT:G	donor_gain	1.0000
1:40722761:C:G	donor_gain	1.0000
1:40738834:A:AG	acceptor_gain	1.0000
1:40738835:G:GA	acceptor_gain	1.0000
1:40738835:GTT:G	acceptor_gain	1.0000
1:40738945:AGTGG:A	donor_loss	1.0000
1:40738946:GTG:G	donor_gain	1.0000
1:40738947:TGGTG:T	donor_loss	1.0000
1:40738949:G:GA	donor_loss	1.0000
1:40738950:T:A	donor_loss	1.0000
1:40738954:G:GT	donor_gain	1.0000
1:40747528:TTTCA:T	acceptor_loss	1.0000
1:40747529:TTCA:T	acceptor_loss	1.0000
1:40747530:TCA:T	acceptor_loss	1.0000
1:40747532:A:AG	acceptor_gain	1.0000
1:40747532:A:G	acceptor_loss	1.0000
1:40747533:G:GA	acceptor_gain	1.0000
1:40747533:G:T	acceptor_loss	1.0000
1:40747533:GA:G	acceptor_gain	1.0000
1:40747533:GAA:G	acceptor_gain	1.0000
1:40747533:GAAA:G	acceptor_gain	1.0000
1:40747601:TGAAG:T	donor_loss	1.0000
1:40747602:GAAGG:G	donor_loss	1.0000
1:40747603:AAGGT:A	donor_loss	1.0000
1:40747604:AGGTG:A	donor_loss	1.0000
1:40747605:GGTGA:G	donor_loss	1.0000
1:40747606:G:T	donor_loss	1.0000
1:40753144:GTTAC:G	acceptor_loss	1.0000
1:40753145:TTACA:T	acceptor_loss	1.0000
1:40753146:TACA:T	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000013139 (1:40716985 T>A,C), RS1000025325 (1:40761170 A>C,G), RS1000043897 (1:40769491 T>A), RS1000059839 (1:40747009 T>C), RS1000092254 (1:40710288 G>C), RS1000121240 (1:40760376 G>A), RS1000168945 (1:40735317 A>T), RS1000187547 (1:40717468 C>T), RS1000190320 (1:40710381 G>A), RS1000207240 (1:40741823 C>A,G), RS1000215626 (1:40692598 A>G,T), RS1000217957 (1:40760144 A>T), RS1000263376 (1:40735560 A>T), RS1000275866 (1:40693406 G>A), RS1000473025 (1:40704307 G>A,C)

Disease associations

OMIM: gene MIM:605344 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001061_5	Platelet count	4.000000e-06
GCST003090_4	Depressive and manic episodes in bipolar disorder	6.000000e-07
GCST008246_1	Airway obstruction (FEV1/FVC<lower limit of normal) in never smokers	2.000000e-06
GCST008247_1	Airway obstruction (FEV1/FVC<70%) in never smokers	1.000000e-06
GCST010002_380	Refractive error	4.000000e-10
GCST010988_529	Adult body size	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007704	depressive episode measurement
EFO:0007705	manic episode measurement
EFO:0003892	pulmonary function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression	3
Valproic Acid	affects expression, decreases expression	3
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	decreases 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
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Methylnitronitrosoguanidine	increases reaction, increases expression, affects binding	1
Plant Extracts	decreases expression, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
Vitamin E	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Lactic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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