NFIC

Summary

NFIC (nuclear factor I C, HGNC:7786) is a protein-coding gene on chromosome 19p13.3, encoding Nuclear factor 1 C-type (P08651). Recognizes and binds the palindromic sequence 5’-TTGGCNNNNNGCCAA-3’ present in viral and cellular promoters and in the origin of replication of adenovirus type 2.

The protein encoded by this gene belongs to the CTF/NF-I family. These are dimeric DNA-binding proteins, and function as cellular transcription factors and as replication factors for adenovirus DNA replication. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 4782 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 78 total
• Transcription factor: yes — 93 downstream targets (CollecTRI)
• MANE Select transcript: NM_001245002

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7786
Approved symbol	NFIC
Name	nuclear factor I C
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CTF, NF-I, CTF5
Ensembl gene	ENSG00000141905
Ensembl biotype	protein_coding
OMIM	600729
Entrez	4782

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000341919, ENST00000395111, ENST00000443272, ENST00000586919, ENST00000588839, ENST00000589123, ENST00000589164, ENST00000589537, ENST00000589969, ENST00000590282, ENST00000641145, ENST00000904729, ENST00000904730, ENST00000904731, ENST00000904732, ENST00000959766, ENST00000959767

RefSeq mRNA: 5 — MANE Select: NM_001245002 NM_001245002, NM_001245004, NM_001245005, NM_005597, NM_205843

CCDS: CCDS12107, CCDS45914, CCDS58640, CCDS59330, CCDS59331

Canonical transcript exons

ENST00000443272 — 11 exons

Exon	Start	End
ENSE00000951224	3435083	3435207
ENSE00000951229	3433518	3433592
ENSE00000951230	3434277	3434400
ENSE00001148792	3366583	3366666
ENSE00001148821	3425106	3425177
ENSE00001389269	3381712	3382243
ENSE00002752767	3462752	3469217
ENSE00003492747	3453763	3453916
ENSE00003594123	3452482	3452666
ENSE00003631673	3456550	3456635
ENSE00003681589	3449014	3449139

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.8952 / max 528.5159, expressed in 1814 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173177	30.9690	1629
173175	11.0254	1640
173174	2.7613	1174
173186	1.2854	786
173183	1.1521	730
173181	0.9487	515
173185	0.6806	436
173178	0.6298	421
173182	0.6228	345
173173	0.2576	95

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	99.49	gold quality
parotid gland	UBERON:0001831	99.40	gold quality
cardia of stomach	UBERON:0001162	99.36	gold quality
pylorus	UBERON:0001166	99.13	gold quality
seminal vesicle	UBERON:0000998	99.12	gold quality
renal medulla	UBERON:0000362	98.87	gold quality
pericardium	UBERON:0002407	98.56	gold quality
urethra	UBERON:0000057	98.55	gold quality
trigeminal ganglion	UBERON:0001675	98.49	gold quality
body of tongue	UBERON:0011876	98.41	gold quality
gastrocnemius	UBERON:0001388	98.38	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.36	gold quality
vena cava	UBERON:0004087	98.35	gold quality
ventral tegmental area	UBERON:0002691	98.30	gold quality
inferior vagus X ganglion	UBERON:0005363	98.27	gold quality
saphenous vein	UBERON:0007318	98.24	gold quality
muscle of leg	UBERON:0001383	97.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.91	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.89	gold quality
lower lobe of lung	UBERON:0008949	97.82	gold quality
mammalian vulva	UBERON:0000997	97.81	gold quality
parietal lobe	UBERON:0001872	97.80	gold quality
heart right ventricle	UBERON:0002080	97.73	gold quality
postcentral gyrus	UBERON:0002581	97.72	gold quality
pharyngeal mucosa	UBERON:0000355	97.54	gold quality
dorsal root ganglion	UBERON:0000044	97.53	gold quality
synovial joint	UBERON:0002217	97.47	gold quality
biceps brachii	UBERON:0001507	97.39	gold quality
lateral globus pallidus	UBERON:0002476	97.34	gold quality
type B pancreatic cell	CL:0000169	97.25	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	57.28
E-GEOD-134144	yes	30.90
E-HCAD-11	yes	6.55
E-GEOD-111727	no	241.36
E-MTAB-4850	no	109.58
E-CURD-112	no	2.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

93 targets.

Target	Regulation
ACOT7	Activation
ACTB
ADAM2
ADCYAP1
ADRA1D
AFP
AHR
ALAS1	Unknown
AP1	Unknown
AR
C4BPB	Activation
CAT
CCL2	Activation
CCND1	Unknown
CDKN1A	Unknown
CEL	Unknown
CLU	Activation
CNTF
CNTN2	Activation
COL18A1	Unknown
COL1A1	Unknown
COL1A2
COL2A1	Unknown
CREBBP
CSF1
CSH1	Unknown
CSN1S2AP
CYP17A1	Activation
CYP1A1	Repression
CYP2A13

JASPAR motifs

Motif	Name	Family
MA0119.1	NFIC::TLX1	Nuclear factor 1::NK
MA0161.1	NFIC	Nuclear factor 1
MA0161.2	NFIC	Nuclear factor 1
MA0161.3	NFIC	Nuclear factor 1
MA1527.1	NFIC	Nuclear factor 1
MA1527.2	NFIC	Nuclear factor 1

JASPAR matrix evidence (PMIDs): PMID:10327073, PMID:12101405, PMID:22456058

Upstream regulators (CollecTRI, top): AHR, AP1, MTF1, NFATC1, NFATC4, NFIC, NR1I2, SP1, SP3

miRNA regulators (miRDB)

265 targeting NFIC, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-4778-3P	99.93	70.40	1818

Literature-anchored findings (GeneRIF, showing 33)

• diminished NF-1C-dependent repression may be one mechanism underlying increased basal CYP17 promoter activity and altered gene expression in PCOS (polycystic ovary syndrome) theca cells. (PMID:14684846)
• The BAF complex & NF1/CTF might act as components of the RNAP II holoenzyme to participate in formation of transcriptional pre-initiation complex. (PMID:15999204)
• Data demonstrate that nuclear Jak2 regulates the amount of active NF1-C2 through tyrosine phosphorylation and proteasomal degradation. (PMID:16847321)
• the chromatin architecture of the promoters does not permit strong association of GR in the absence of NF1 (PMID:17186943)
• we suggest that bHLH factors recruit NFI to enhance skeletal muscle Na(+) channel expression. (PMID:17936922)
• All NFI isoforms were found to be expressed in human corneal epithelial cells grown on laminin. (PMID:18421093)
• These are the first studies to analyze the expression of NFI-C isoforms in dental versus nondental cells/tissues. (PMID:18765927)
• These results suggest that alpha5 gene expression is likely dictated by subtle alterations in the nuclear ratio of TFs that either repress (NFI) or activate (Sp1 and AP-1) alpha5 transcription in corneal epithelial cells. (PMID:18775869)
• Knockdown of NFIB and NFIC expression using siRNA decreased and increased IGFBP5 expression, respectively. (PMID:18809517)
• These results imply a central role of NFI-C in the interplay of the two signaling pathways and in regulation of the progression of tissue regeneration. (PMID:19752192)
• A specific region (-688 to -611 bp) was discovered in the IRS2 promoter essential for basal promoter activity and oxidative stress induced transcription depending on ERK activation and SP1 and NFI binding in human hepatocytes. (PMID:19755487)
• novel role of NF1-C2 in tumor development and epithelial-to-mesenchymal transition in breast cancer; NF1-C2 is lost during tumor progression and virtully absent from lymph node metastases; FoxF1 was was found to be a direct repressed target of NF1-C2 (PMID:20145151)
• the influence of i3T3 on the expression and DNA binding of NFI, another TF important for cell proliferation and cell cycle progression (PMID:22420942)
• transcription factor Nuclear Factor 1-C (NF1C) as a candidate to regulate AHR transcription in a polymorphism-dependent manner (PMID:23208493)
• These data suggest a critical role for calcineurin in NFI transcriptional regulation and in the determination of malignant glioma infiltrative properties. (PMID:23839947)
• Results suggest that NFI-C acts as a transcriptional switch in cell fate determination between osteoblast and adipocyte differentiation in BMSCs. (PMID:24801901)
• TGF-beta-mediated suppression of ANT2 through NF1/Smad4 complexes contributes to oxidative stress and DNA damage during induction of cellular senescence. (PMID:25220407)
• Over-expression of NFIC increased cell proliferation, mineralization nodule formation and alkaline phosphatase activity in stem cells from the apical papilla. (PMID:25668322)
• Nuclear factor I-C regulates E-cadherin via control of KLF4 in breast cancer (PMID:25879941)
• Studies indicate the role of nuclear factor one (NFIs) as epigenetic regulators in cancer. (PMID:28076901)
• Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 x 10(-8)) were identified for the interaction of the (apolipoprotein E) APOE epsilon4 allele with NFIC SNP. (PMID:28183528)
• miR-550a-3/NFIC plays a driving role in esophageal squamous cell cancer cells proliferation and metastasis partly through EMT process. (PMID:32567032)
• NFI-C Is Required for Epiphyseal Chondrocyte Proliferation during Postnatal Cartilage Development. (PMID:32759468)
• Hsa-miRNA-143-3p regulates the odontogenic differentiation of human stem cells from the apical papilla by targeting NFIC. (PMID:34807471)
• Transcription factor NFIC functions as a tumor suppressor in lung squamous cell carcinoma progression by modulating lncRNA CASC2. (PMID:34985387)
• Insulin-like growth factor 2 mRNA-binding protein 2-regulated alternative splicing of nuclear factor 1 C-type causes excessive granulosa cell proliferation in polycystic ovary syndrome. (PMID:35293050)
• Bioinformatics and Experimental Analyses Reveal NFIC as an Upstream Transcriptional Regulator for Ischemic Cardiomyopathy. (PMID:35741813)
• Nuclear factor I-C overexpression promotes monocytic development and cell survival in acute myeloid leukemia. (PMID:36572750)
• NFIC1 inhibits the migration and invasion of MDA-MB-231 cells through S100A2-mediated inactivation of MEK/ERK pathway. (PMID:36574914)
• NFIC regulates ribosomal biology and ER stress in pancreatic acinar cells and restrains PDAC initiation. (PMID:37353485)
• Adipose-derived stem cell exosome NFIC improves diabetic foot ulcers by regulating miR-204-3p/HIPK2. (PMID:37710299)
• Activation of CHPF by transcription factor NFIC promotes NLRP3 activation during the progression of colorectal cancer. (PMID:38267731)
• rs822336 binding to C/EBPbeta and NFIC modulates induction of PD-L1 expression and predicts anti-PD-1/PD-L1 therapy in advanced NSCLC. (PMID:38528526)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfic	ENSDARG00000043210
mus_musculus	Nfic	ENSMUSG00000055053
rattus_norvegicus	Nfic	ENSRNOG00000004505
drosophila_melanogaster	NfI	FBGN0042696
caenorhabditis_elegans		WBGENE00003592

Paralogs (3): NFIX (ENSG00000008441), NFIB (ENSG00000147862), NFIA (ENSG00000162599)

Protein

Protein identifiers

Nuclear factor 1 C-type — P08651 (reviewed: P08651)

Alternative names: CCAAT-box-binding transcription factor, Nuclear factor I/C, TGGCA-binding protein

All UniProt accessions (2): A0A286YEX4, P08651

UniProt curated annotations — full annotation on UniProt →

Function. Recognizes and binds the palindromic sequence 5’-TTGGCNNNNNGCCAA-3’ present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.

Subunit / interactions. Binds DNA as a homodimer.

Subcellular location. Nucleus.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Similarity. Belongs to the CTF/NF-I family.

Isoforms (6)

UniProt ID	Names	Canonical?
P08651-1	4	yes
P08651-2	1
P08651-3	2
P08651-4	3
P08651-5	5
P08651-6	6

RefSeq proteins (5): NP_001231931, NP_001231933, NP_001231934, NP_005588, NP_995315 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000647	CTF/NFI	Family
IPR003619	MAD_homology1_Dwarfin-type	Domain
IPR019548	CTF/NFI_DNA-bd_N	Domain
IPR019739	CTF/NFI_DNA-bd_CS	Conserved_site
IPR020604	CTF/NFI_DNA-bd-dom	Domain

Pfam: PF00859, PF03165, PF10524

UniProt features (38 total): modified residue 19, splice variant 6, sequence conflict 4, region of interest 3, compositionally biased region 2, chain 1, DNA-binding region 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9XVO	X-RAY DIFFRACTION	2.5
9XVD	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08651-F1	62.05	0.32

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 (19): 294, 300, 302, 304, 305, 323, 333, 337, 339, 343, 365, 365, 395, 451, 475, 477, 487, 1, 194

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-73980	RNA Polymerase III Transcription Termination
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation

MSigDB gene sets: 0 (showing top):

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA replication (GO:0006260), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), odontogenesis of dentin-containing tooth (GO:0042475), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (9): 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 transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase III Transcription	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	4
DNA-templated transcription	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
DNA metabolic process	1
DNA biosynthetic process	1
odontogenesis	1
positive regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	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
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
DNA binding	1
binding	1
chromosome	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

1068 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFIC	NF1	P21359	765
NFIC	JUND	P17535	665
NFIC	SLC20A2	Q08357	636
NFIC	FOXA1	P55317	596
NFIC	RUNX2	Q13950	576
NFIC	TP53	P04637	573
NFIC	EGR1	P18146	564
NFIC	TLX1	P31314	563
NFIC	KLF4	P78338	553
NFIC	RFX1	P22670	540
NFIC	H3-3A	P06351	529
NFIC	USF2	Q15853	528
NFIC	H3C1	P02295	527
NFIC	H3-4	Q16695	526
NFIC	H3C14	Q71DI3	525
NFIC	FOXM1	Q08050	525

IntAct

115 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:0915”(physical association)	0.690
NFIB	NFIC	psi-mi:“MI:0914”(association)	0.690
NFIC	NFIB	psi-mi:“MI:0914”(association)	0.690
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
BIRC2	HTRA2	psi-mi:“MI:0914”(association)	0.650
NFIC	GATA2	psi-mi:“MI:0915”(physical association)	0.600
NFIA	NFIB	psi-mi:“MI:0914”(association)	0.570
NFIX	NFIB	psi-mi:“MI:0914”(association)	0.570
NFIC	PARP1	psi-mi:“MI:0915”(physical association)	0.560
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
NFIC	GATA3	psi-mi:“MI:0915”(physical association)	0.470
NFIC	SOX2	psi-mi:“MI:0915”(physical association)	0.470
NFIC	TLX3	psi-mi:“MI:0915”(physical association)	0.470
NFIC	SOX5	psi-mi:“MI:0915”(physical association)	0.470
NFIC	PAX7	psi-mi:“MI:0915”(physical association)	0.470
NFIC	SOX6	psi-mi:“MI:0915”(physical association)	0.470
NFIC	SP7	psi-mi:“MI:0915”(physical association)	0.470
NFIC	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
NFIC	NFIC	psi-mi:“MI:0915”(physical association)	0.400
SF3B1	NFIC	psi-mi:“MI:0915”(physical association)	0.400
NFIC	TBXT	psi-mi:“MI:0915”(physical association)	0.400
NFIC	ETV7	psi-mi:“MI:0915”(physical association)	0.400
NFIC	FOS	psi-mi:“MI:0915”(physical association)	0.400
NFIC	KLF16	psi-mi:“MI:0915”(physical association)	0.400
NFIC	FOXI1	psi-mi:“MI:0915”(physical association)	0.400
NFIC	EN1	psi-mi:“MI:0915”(physical association)	0.400
NFIC	LHX2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (970): LLPH (Two-hybrid), TPD52L3 (Two-hybrid), ZCCHC14 (Two-hybrid), ZKSCAN7 (Two-hybrid), TKTL2 (Two-hybrid), NFIC (Affinity Capture-MS), NFIC (Affinity Capture-MS), NFIC (Affinity Capture-MS), NFIC (Affinity Capture-MS), NFIC (Affinity Capture-MS), NFIC (Affinity Capture-MS), NFIC (Affinity Capture-MS), NFIC (Affinity Capture-MS), NFIC (Affinity Capture-MS), NFIC (Affinity Capture-RNA)

ESM2 similar proteins: A1A4R9, A9CB91, O54835, O70436, P05549, P06435, P08651, P09286, P09414, P0C734, P11823, P11824, P13623, P17923, P19893, P21999, P30119, P34056, P42003, P58197, P70257, Q02780, Q09585, Q0ZME3, Q12857, Q14938, Q14EA6, Q15796, Q1HVD3, Q1W668, Q2T9K2, Q3KPS4, Q5R7C0, Q5RJ20, Q61312, Q61313, Q62432, Q6SW29, Q6SWP7, Q76HI7

Diamond homologs: O00712, P08651, P09414, P13622, P13623, P14057, P17923, P17924, P17926, P21999, P70255, P70257, P97863, Q02780, Q0VCL6, Q12857, Q14938, Q5H9N3, Q90932

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NFIB	“down-regulates activity”	NFIC	binding
SMURF1	“down-regulates quantity”	NFIC	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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
Gastrulation	6	20.5×	7e-05
Deactivation of the beta-catenin transactivating complex	5	15.3×	1e-03
TP53 Regulates Transcription of DNA Repair Genes	6	14.3×	3e-04
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	7	13.5×	1e-04
MITF-M-dependent gene expression	5	11.9×	3e-03
Signaling by WNT	7	10.3×	4e-04
TCF dependent signaling in response to WNT	6	9.3×	2e-03
MITF-M-regulated melanocyte development	6	9.0×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
neuron fate specification	7	50.1×	9e-09
positive regulation of miRNA transcription	11	32.6×	7e-12
branching involved in ureteric bud morphogenesis	5	18.7×	3e-04
somatic stem cell population maintenance	7	17.7×	1e-05
anatomical structure morphogenesis	12	17.1×	1e-09
positive regulation of cell differentiation	6	16.4×	1e-04
cartilage development	6	15.4×	2e-04
inner ear morphogenesis	5	15.3×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2098 predictions. Top by Δscore:

Variant	Effect	Δscore
19:3425101:TGCA:T	acceptor_loss	1.0000
19:3425102:GCAG:G	acceptor_loss	1.0000
19:3425103:CAG:C	acceptor_loss	1.0000
19:3425104:A:AC	acceptor_loss	1.0000
19:3425104:A:AG	acceptor_gain	1.0000
19:3425105:G:A	acceptor_loss	1.0000
19:3425105:G:GA	acceptor_gain	1.0000
19:3425173:GCTGG:G	donor_gain	1.0000
19:3425176:GG:G	donor_gain	1.0000
19:3425176:GGGTG:G	donor_loss	1.0000
19:3425177:GG:G	donor_gain	1.0000
19:3425178:G:GC	donor_loss	1.0000
19:3425178:G:GG	donor_gain	1.0000
19:3425179:T:A	donor_loss	1.0000
19:3425180:GAG:G	donor_loss	1.0000
19:3433510:T:TA	acceptor_gain	1.0000
19:3433513:TCCA:T	acceptor_loss	1.0000
19:3433514:CCA:C	acceptor_loss	1.0000
19:3433516:A:AG	acceptor_gain	1.0000
19:3433516:A:C	acceptor_loss	1.0000
19:3433517:G:A	acceptor_loss	1.0000
19:3433517:G:GA	acceptor_gain	1.0000
19:3433517:GAC:G	acceptor_gain	1.0000
19:3433517:GACA:G	acceptor_gain	1.0000
19:3433517:GACAC:G	acceptor_gain	1.0000
19:3433589:CGGA:C	donor_gain	1.0000
19:3433590:GGA:G	donor_gain	1.0000
19:3433590:GGAG:G	donor_gain	1.0000
19:3433591:GA:G	donor_gain	1.0000
19:3433591:GAG:G	donor_gain	1.0000

AlphaMissense

3290 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:3381718:T:C	F13L	1.000
19:3381720:C:A	F13L	1.000
19:3381720:C:G	F13L	1.000
19:3381727:T:C	F16L	1.000
19:3381728:T:C	F16S	1.000
19:3381729:C:A	F16L	1.000
19:3381729:C:G	F16L	1.000
19:3381731:T:A	I17N	1.000
19:3381740:T:C	L20P	1.000
19:3381743:T:C	L21P	1.000
19:3381752:T:A	V24D	1.000
19:3381764:C:A	A28D	1.000
19:3381766:T:G	Y29D	1.000
19:3381772:T:A	W31R	1.000
19:3381772:T:C	W31R	1.000
19:3381774:G:C	W31C	1.000
19:3381774:G:T	W31C	1.000
19:3381775:T:A	F32I	1.000
19:3381775:T:C	F32L	1.000
19:3381776:T:C	F32S	1.000
19:3381776:T:G	F32C	1.000
19:3381777:C:A	F32L	1.000
19:3381777:C:G	F32L	1.000
19:3381780:C:A	N33K	1.000
19:3381780:C:G	N33K	1.000
19:3381782:T:C	L34P	1.000
19:3381786:G:C	Q35H	1.000
19:3381786:G:T	Q35H	1.000
19:3381791:G:C	R37P	1.000
19:3381793:A:G	K38E	1.000

dbSNP variants (sampled 300 via entrez): RS1000065890 (19:3364784 G>A), RS1000090492 (19:3465985 A>G), RS1000094901 (19:3401500 C>T), RS1000120621 (19:3388949 G>A,C), RS1000127923 (19:3396756 G>A), RS1000132424 (19:3387047 C>T), RS1000133053 (19:3405150 C>A,T), RS1000143319 (19:3370405 G>A,T), RS1000161462 (19:3431978 C>A,G), RS1000172940 (19:3457132 C>G), RS1000177787 (19:3416189 G>A), RS1000212744 (19:3425343 C>A,T), RS1000265005 (19:3425558 C>G), RS1000284107 (19:3392147 C>G,T), RS1000316397 (19:3425711 C>A,T)

Disease associations

OMIM: gene MIM:600729 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000817_188	Height	4.000000e-16
GCST002647_159	Height	2.000000e-20
GCST004247_1	Alzheimer’s disease (APOE e4 interaction)	2.000000e-08
GCST006426_5	Serum urate levels in chronic kidney disease	5.000000e-08
GCST006611_6	HDL cholesterol	1.000000e-09
GCST006979_739	Heel bone mineral density	3.000000e-12
GCST007329_13	Automobile speeding propensity	4.000000e-09
GCST007505_17	Nevus count or cutaneous melanoma	3.000000e-08
GCST008152_66	Weight	2.000000e-06
GCST008156_96	Hip circumference adjusted for BMI	7.000000e-06
GCST008162_8	Hip circumference	2.000000e-06
GCST008163_226	Height	5.000000e-07
GCST008839_286	Height	2.000000e-19
GCST010241_372	Apolipoprotein A1 levels	4.000000e-10
GCST010242_456	HDL cholesterol levels	7.000000e-11
GCST011011_79	Youthful appearance (self-reported)	1.000000e-10
GCST90000025_666	Appendicular lean mass	1.000000e-13
GCST90002385_305	High light scatter reticulocyte count	5.000000e-10
GCST90002393_634	Monocyte count	3.000000e-12
GCST90002400_262	Plateletcrit	7.000000e-25
GCST90002402_610	Platelet count	5.000000e-14

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0004632	nevus count
EFO:0004338	body weight
EFO:0008039	BMI-adjusted hip circumference
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004980	appendicular lean mass
EFO:0007986	reticulocyte count
EFO:0005091	monocyte count
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation	5
sodium arsenite	decreases expression, increases expression	4
(+)-JQ1 compound	affects expression, increases reaction, decreases expression	3
Estradiol	increases expression, decreases reaction	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Cisplatin	decreases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
pyrimidin-2-one beta-ribofuranoside	increases expression	1
2-butenal	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	increases phosphorylation	1
1-hydroxypyrene	decreases methylation, affects cotreatment	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
JP8 aviation fuel	decreases expression	1
entinostat	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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4N3	SEES3-1V human NFIC, clone1	Embryonic stem cell	Male
CVCL_A4N4	SEES3-1V human NFIC, clone2	Embryonic stem cell	Male
CVCL_D6CU	HyCyte U2OS KO-hNFIC	Cancer cell line	Female

Clinical trials (associated diseases)

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