NAIF1

Summary

NAIF1 (nuclear apoptosis inducing factor 1, HGNC:25446) is a protein-coding gene on chromosome 9q34.11, encoding Nuclear apoptosis-inducing factor 1 (Q69YI7). Induces apoptosis.

Involved in negative regulation of cell growth and regulation of mitochondrial membrane permeability involved in apoptotic process. Located in cytosol; nucleoplasm; and plasma membrane.

Source: NCBI Gene 203245 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_197956

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25446
Approved symbol	NAIF1
Name	nuclear apoptosis inducing factor 1
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp762G199, bA379C10.2
Ensembl gene	ENSG00000171169
Ensembl biotype	protein_coding
OMIM	610673
Entrez	203245

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000373078, ENST00000466139, ENST00000470245, ENST00000488519

RefSeq mRNA: 1 — MANE Select: NM_197956 NM_197956

CCDS: CCDS6889

Canonical transcript exons

ENST00000373078 — 2 exons

Exon	Start	End
ENSE00001459466	128061233	128063900
ENSE00001459468	128066591	128067320

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 84.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6228 / max 66.4794, expressed in 1561 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102647	3.6228	1561

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	84.33	silver quality
granulocyte	CL:0000094	83.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.61	gold quality
mucosa of transverse colon	UBERON:0004991	81.41	gold quality
lower esophagus mucosa	UBERON:0035834	79.78	gold quality
tibialis anterior	UBERON:0001385	79.71	silver quality
left testis	UBERON:0004533	79.56	gold quality
right testis	UBERON:0004534	79.49	gold quality
stromal cell of endometrium	CL:0002255	78.59	gold quality
testis	UBERON:0000473	78.59	gold quality
leukocyte	CL:0000738	78.34	gold quality
right adrenal gland	UBERON:0001233	78.32	gold quality
right adrenal gland cortex	UBERON:0035827	78.24	gold quality
ileal mucosa	UBERON:0000331	78.17	silver quality
calcaneal tendon	UBERON:0003701	77.94	gold quality
monocyte	CL:0000576	77.89	gold quality
left adrenal gland	UBERON:0001234	77.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.84	gold quality
right lobe of liver	UBERON:0001114	77.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.47	gold quality
prefrontal cortex	UBERON:0000451	77.39	gold quality
left adrenal gland cortex	UBERON:0035825	77.30	gold quality
muscle of leg	UBERON:0001383	77.28	gold quality
islet of Langerhans	UBERON:0000006	77.12	gold quality
gastrocnemius	UBERON:0001388	77.03	gold quality
spleen	UBERON:0002106	76.64	gold quality
ganglionic eminence	UBERON:0004023	76.42	gold quality
ventricular zone	UBERON:0003053	76.22	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	75.97	gold quality
skin of abdomen	UBERON:0001416	75.93	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-81608	no	23.62
E-ANND-3	no	3.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting NAIF1, 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-12118	100.00	65.88	1270
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4649-3P	99.56	66.90	1783

Literature-anchored findings (GeneRIF, showing 7)

• NAIF1 (C9orf90)is a nuclear protein that induces apoptosis when overexpressed (PMID:16378748)
• The functions of two transposon-derived human proteins: HARBI1, a domesticated transposase-derived protein, and NAIF1, which contains a trihelix motif similar to that described in the Myb-like protein, was investigated. (PMID:18339812)
• NAIF1 is down-regulated in gastric cancer. (PMID:21286669)
• NAIF1 plays a role in regulating cellular migration and invasion through the MAPK pathways and may function as a tumor suppressor in the progression of gastric carcinoma. (PMID:25432142)
• MiR-24 acted as an oncomir, at least partially through regulation of its functional target NAIF1 in non-small cell lung cancer. (PMID:25725584)
• MicroRNA-351 Promotes the Proliferation and Invasion of Glioma Cells through Downregulation of NAIF1. (PMID:32506303)
• Long noncoding RNA SRY-box transcription factor 2 overlapping transcript participates in Parkinson’s disease by regulating the microRNA-942-5p/nuclear apoptosis-inducing factor 1 axis. (PMID:34607512)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	naif1	ENSDARG00000062753
mus_musculus	Naif1	ENSMUSG00000039164
rattus_norvegicus	Naif1	ENSRNOG00000050204
drosophila_melanogaster	CG10209	FBGN0033971

Protein

Protein identifiers

Nuclear apoptosis-inducing factor 1 — Q69YI7 (reviewed: Q69YI7)

All UniProt accessions (1): Q69YI7

UniProt curated annotations — full annotation on UniProt →

Function. Induces apoptosis.

Subunit / interactions. Interacts with HARBI1.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed.

Similarity. Belongs to the NAIF1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q69YI7-1	1	yes
Q69YI7-2	2

RefSeq proteins (1): NP_931045* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028002	Myb_DNA-bind_5	Domain

Pfam: PF13873

UniProt features (9 total): region of interest 3, compositionally biased region 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q69YI7-F1	71.92	0.43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_MEMBRANE_ORGANIZATION, GOBP_REGULATION_OF_MEMBRANE_PERMEABILITY, GOBP_CELL_GROWTH, GOBP_REGULATION_OF_GROWTH, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOBP_INTRACELLULAR_TRANSPORT, chr9q34, ASH1L_TARGET_GENES, ATF6_TARGET_GENES, CEBPZ_TARGET_GENES, DLX4_TARGET_GENES, GREB1_TARGET_GENES

GO Biological Process (3): negative regulation of cell growth (GO:0030308), regulation of mitochondrial membrane permeability involved in apoptotic process (GO:1902108), apoptotic process (GO:0006915)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
apoptotic process	1
apoptotic mitochondrial changes	1
regulation of mitochondrial membrane permeability	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
binding	1
nuclear lumen	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAIF1	HARBI1	Q96MB7	801
NAIF1	KRT36	O76013	612
NAIF1	POGK	Q9P215	537
NAIF1	SMIM12	Q96EX1	536
NAIF1	CASP3	P42574	524
NAIF1	TIGD5	Q53EQ6	511
NAIF1	ZNF276	Q8N554	508
NAIF1	TIGD3	Q6B0B8	491
NAIF1	LRRC40	Q9H9A6	487
NAIF1	TIGD4	Q8IY51	485
NAIF1	MNMIP1	A4FU49	485
NAIF1	SHISA4	Q96DD7	484
NAIF1	PGBD5	Q8N414	476
NAIF1	KSR2	Q6VAB6	473
NAIF1	RIT1	Q92963	471
NAIF1	ZBTB48	P10074	471

IntAct

14 interactions, top by confidence:

A	B	Type	Score
SOX14	NAIF1	psi-mi:“MI:0915”(physical association)	0.670
NAIF1	SOX14	psi-mi:“MI:0915”(physical association)	0.670
HARBI1	NAIF1	psi-mi:“MI:0915”(physical association)	0.590
CCNDBP1	NAIF1	psi-mi:“MI:0915”(physical association)	0.560
NAIF1	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.560
TERF2	NAIF1	psi-mi:“MI:0915”(physical association)	0.510
NAIF1	TERF2IP	psi-mi:“MI:0915”(physical association)	0.370
ING5	CCDC85C	psi-mi:“MI:0914”(association)	0.350
TERF2	NAIF1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): NAIF1 (Two-hybrid), NAIF1 (Two-hybrid), NAIF1 (Affinity Capture-MS), NAIF1 (Affinity Capture-MS), NAIF1 (Two-hybrid), NAIF1 (Affinity Capture-MS), NAIF1 (Affinity Capture-MS), NAIF1 (Affinity Capture-MS), NAIF1 (Affinity Capture-MS), DDX18 (Cross-Linking-MS (XL-MS)), NAIF1 (Affinity Capture-RNA), NAIF1 (Affinity Capture-MS), NAIF1 (Affinity Capture-MS), NAIF1 (Affinity Capture-MS), NAIF1 (Two-hybrid)

ESM2 similar proteins: A0A1W2PQ72, A4IFD2, A7MBH3, D3ZXW3, O35260, O35750, O57337, P14003, P15257, P20823, P22361, P35428, P39880, P42128, P53564, P53565, P56524, P81069, P83038, P85037, Q01167, Q01664, Q04666, Q0V8G2, Q14469, Q3UCQ1, Q3ZBG4, Q5R902, Q5ZI27, Q69YI7, Q6NSM8, Q6NZM9, Q6PFD7, Q6ZTZ1, Q7TSZ8, Q7ZX03, Q80ZH1, Q8BIL2, Q8TAK5, Q8UW00

Diamond homologs: A7MBH3, Q5ZI27, Q69YI7, Q6PFD7, Q96NA8, Q9BE21, G3V7P1, O15400, O70257, Q2KJB9, Q3ZBT5, Q501L3, Q5R602, Q5RBW6, Q6GLA1, Q86Y82, Q8NCY6, Q91YU3, Q9ER00

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

447 predictions. Top by Δscore:

Variant	Effect	Δscore
9:128063627:T:TA	donor_gain	1.0000
9:128063901:C:CC	acceptor_gain	1.0000
9:128063901:C:T	acceptor_loss	1.0000
9:128063904:C:CT	acceptor_gain	1.0000
9:128066589:A:AC	donor_gain	1.0000
9:128066590:C:CC	donor_gain	1.0000
9:128066590:CT:C	donor_gain	1.0000
9:128063896:GGGGA:G	acceptor_gain	0.9900
9:128063897:GGGA:G	acceptor_gain	0.9900
9:128063898:GGA:G	acceptor_gain	0.9900
9:128063899:GA:G	acceptor_gain	0.9900
9:128063906:C:CT	acceptor_gain	0.9900
9:128063907:A:T	acceptor_gain	0.9900
9:128063908:G:C	acceptor_gain	0.9900
9:128063908:G:GC	acceptor_gain	0.9900
9:128066584:CACT:C	donor_loss	0.9900
9:128066587:TCACT:T	donor_loss	0.9900
9:128066588:CAC:C	donor_loss	0.9900
9:128066589:ACT:A	donor_gain	0.9900
9:128066589:ACTCT:A	donor_loss	0.9900
9:128066590:C:CT	donor_loss	0.9900
9:128066590:CTC:C	donor_gain	0.9900
9:128066590:CTCT:C	donor_gain	0.9900
9:128066590:CTCTG:C	donor_gain	0.9900
9:128063898:GGACT:G	acceptor_gain	0.9800
9:128063899:GACTG:G	acceptor_gain	0.9800
9:128063900:ACTG:A	acceptor_gain	0.9800
9:128063901:C:A	acceptor_gain	0.9800
9:128063902:T:A	acceptor_gain	0.9800
9:128066583:TCAC:T	donor_loss	0.9800

AlphaMissense

2112 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128063726:A:G	L229P	1.000
9:128066698:A:G	L135P	1.000
9:128066874:C:A	K76N	1.000
9:128066874:C:G	K76N	1.000
9:128066876:T:C	K76E	1.000
9:128066878:A:G	L75P	1.000
9:128066881:T:A	D74V	1.000
9:128066881:T:C	D74G	1.000
9:128066881:T:G	D74A	1.000
9:128066882:C:G	D74H	1.000
9:128066886:C:A	W72C	1.000
9:128066886:C:G	W72C	1.000
9:128066887:C:G	W72S	1.000
9:128066888:A:G	W72R	1.000
9:128066888:A:T	W72R	1.000
9:128066889:C:A	K71N	1.000
9:128066889:C:G	K71N	1.000
9:128066891:T:C	K71E	1.000
9:128066892:C:A	K70N	1.000
9:128066892:C:G	K70N	1.000
9:128066895:C:A	K69N	1.000
9:128066895:C:G	K69N	1.000
9:128066899:A:T	V68D	1.000
9:128066913:T:A	R63S	1.000
9:128066913:T:G	R63S	1.000
9:128066914:C:A	R63I	1.000
9:128066914:C:G	R63T	1.000
9:128066934:G:C	N56K	1.000
9:128066934:G:T	N56K	1.000
9:128066938:A:T	V55D	1.000

dbSNP variants (sampled 300 via entrez): RS1000191648 (9:128068882 C>A), RS1000257794 (9:128063332 G>A), RS1000690611 (9:128064496 T>C,G), RS1001619776 (9:128066120 A>T), RS1001766678 (9:128062929 G>A), RS1002503742 (9:128064149 C>T), RS1002650261 (9:128067355 C>A,T), RS1002693067 (9:128064532 C>T), RS1002828032 (9:128065606 A>C,T), RS1003547347 (9:128069119 C>T), RS1003698187 (9:128063047 G>A), RS1004139493 (9:128066209 T>C), RS1004268382 (9:128061276 C>G,T), RS1004342110 (9:128061012 T>A,C), RS1004519387 (9:128067888 G>A)

Disease associations

OMIM: gene MIM:610673 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005951_65	Body mass index	5.000000e-09
GCST005977_23	Monocyte count	2.000000e-10
GCST005987_46	Albumin-globulin ratio	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005091	monocyte count
EFO:0005128	albumin:globulin ratio measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression	2
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
Benzo(a)pyrene	increases methylation	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Lactic Acid	increases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SZ85	HAP1 NAIF1 (-) 1	Cancer cell line	Male
CVCL_SZ86	HAP1 NAIF1 (-) 2	Cancer cell line	Male
CVCL_SZ87	HAP1 NAIF1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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