NIF3L1

Summary

NIF3L1 (NGG1 interacting factor 3 like 1, HGNC:13390) is a protein-coding gene on chromosome 2q33.1, encoding NIF3-like protein 1 (Q9GZT8). May function as a transcriptional corepressor through its interaction with COPS2, negatively regulating the expression of genes involved in neuronal differentiation.

Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and identical protein binding activity. Involved in positive regulation of DNA-templated transcription. Located in cytoplasm.

Source: NCBI Gene 60491 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 72 total
• MANE Select transcript: NM_001369441

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13390
Approved symbol	NIF3L1
Name	NGG1 interacting factor 3 like 1
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	CALS-7, MDS015
Ensembl gene	ENSG00000196290
Ensembl biotype	protein_coding
OMIM	605778
Entrez	60491

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 28 protein_coding

ENST00000359683, ENST00000409020, ENST00000409129, ENST00000409357, ENST00000409588, ENST00000426253, ENST00000436412, ENST00000454952, ENST00000651500, ENST00000900050, ENST00000900051, ENST00000900052, ENST00000900053, ENST00000900054, ENST00000900055, ENST00000900056, ENST00000917598, ENST00000917599, ENST00000917600, ENST00000917601, ENST00000917602, ENST00000917603, ENST00000917604, ENST00000917605, ENST00000917606, ENST00000917607, ENST00000951015, ENST00000951016

RefSeq mRNA: 9 — MANE Select: NM_001369441 NM_001136039, NM_001142355, NM_001142356, NM_001369441, NM_001369442, NM_001369443, NM_001369444, NM_001369445, NM_021824

CCDS: CCDS42797, CCDS46485, CCDS46486

Canonical transcript exons

ENST00000409020 — 7 exons

Exon	Start	End
ENSE00000784486	200893246	200893408
ENSE00000784487	200895264	200895390
ENSE00000784489	200897076	200897214
ENSE00001420060	200891918	200892379
ENSE00001576620	200889371	200889652
ENSE00003675698	200899385	200899468
ENSE00003901549	200903494	200903925

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 94.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3453 / max 178.9283, expressed in 1771 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24591	6.5000	1679
24592	5.9657	1612
24593	0.6729	371
24594	0.2067	96

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.49	gold quality
oocyte	CL:0000023	93.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.43	gold quality
rectum	UBERON:0001052	91.02	gold quality
islet of Langerhans	UBERON:0000006	90.50	gold quality
calcaneal tendon	UBERON:0003701	90.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.97	gold quality
biceps brachii	UBERON:0001507	89.49	gold quality
palpebral conjunctiva	UBERON:0001812	89.26	gold quality
middle temporal gyrus	UBERON:0002771	88.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.94	gold quality
prefrontal cortex	UBERON:0000451	88.62	gold quality
right adrenal gland	UBERON:0001233	88.59	gold quality
vastus lateralis	UBERON:0001379	88.53	silver quality
embryo	UBERON:0000922	88.41	gold quality
bronchial epithelial cell	CL:0002328	88.30	gold quality
tendon	UBERON:0000043	88.13	gold quality
quadriceps femoris	UBERON:0001377	88.10	gold quality
right adrenal gland cortex	UBERON:0035827	88.10	gold quality
left adrenal gland	UBERON:0001234	87.97	gold quality
muscle of leg	UBERON:0001383	87.94	gold quality
muscle organ	UBERON:0001630	87.87	gold quality
gastrocnemius	UBERON:0001388	87.72	gold quality
mucosa of transverse colon	UBERON:0004991	87.51	gold quality
pons	UBERON:0000988	87.34	gold quality
left adrenal gland cortex	UBERON:0035825	87.32	gold quality
granulocyte	CL:0000094	87.18	gold quality
deltoid	UBERON:0001476	87.12	gold quality
triceps brachii	UBERON:0001509	87.08	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	1606.68
E-GEOD-100618	yes	193.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting NIF3L1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-384	98.71	67.34	1229
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-345-5P	96.40	66.43	663

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nif3l1	ENSDARG00000045249
mus_musculus	Nif3l1	ENSMUSG00000026036
rattus_norvegicus	Nif3l1	ENSRNOG00000013446
drosophila_melanogaster	CG4278	FBGN0014092

Protein

Protein identifiers

NIF3-like protein 1 — Q9GZT8 (reviewed: Q9GZT8)

Alternative names: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 1 protein

All UniProt accessions (5): B8ZZI0, C9JN42, E7EXA3, Q9GZT8, H7C1A8

UniProt curated annotations — full annotation on UniProt →

Function. May function as a transcriptional corepressor through its interaction with COPS2, negatively regulating the expression of genes involved in neuronal differentiation.

Subunit / interactions. Homodimer. Interacts with COPS2. Interacts with THOC7.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the GTP cyclohydrolase I type 2/NIF3 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9GZT8-1	1	yes
Q9GZT8-2	2
Q9GZT8-3	3, beta

RefSeq proteins (9): NP_001129511, NP_001135827, NP_001135828, NP_001356370, NP_001356371, NP_001356372, NP_001356373, NP_001356374, NP_068596 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002678	DUF34/NIF3	Family
IPR017222	DUF34/NIF3_animal	Family
IPR036069	DUF34/NIF3_sf	Homologous_superfamily

Pfam: PF01784

UniProt features (9 total): modified residue 3, splice variant 2, chain 1, region of interest 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZT8-F1	91.79	0.82

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 (3): 109, 255, 259

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 126 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_NEUROGENESIS, FISCHER_G2_M_CELL_CYCLE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, FISCHER_DREAM_TARGETS, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, BLALOCK_ALZHEIMERS_DISEASE_DN, JEPSEN_SMRT_TARGETS, SCGGAAGY_ELK1_02, KIM_WT1_TARGETS_DN, MGGAAGTG_GABP_B, MANALO_HYPOXIA_DN, GOMF_TRANSCRIPTION_FACTOR_BINDING, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_TURQUOISE_DN, MIKKELSEN_NPC_ICP_WITH_H3K4ME3

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), neuron differentiation (GO:0030182), positive regulation of DNA-templated transcription (GO:0045893), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (4): identical protein binding (GO:0042802), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
intracellular membrane-bounded organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cell differentiation	1
generation of neurons	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein binding	1
DNA-binding transcription factor binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NIF3L1	THOC7	Q6I9Y2	939
NIF3L1	CTDSP1	Q9GZU7	768
NIF3L1	MLX	Q9UH92	765
NIF3L1	MXD4	Q14582	765
NIF3L1	TADA3	O75528	738
NIF3L1	PPIL3	Q9H2H8	705
NIF3L1	PKLR	P11973	693
NIF3L1	MLXIPL	Q9NP71	683
NIF3L1	ALS2	Q96Q42	669
NIF3L1	MNT	Q99583	666
NIF3L1	COPS2	P61201	656
NIF3L1	HYCC2	Q8IXS8	649
NIF3L1	BZW1	Q7L1Q6	554
NIF3L1	KLHL30	Q0D2K2	536
NIF3L1	NDUFB3	O43676	527

IntAct

297 interactions, top by confidence:

A	B	Type	Score
DMC1	NIF3L1	psi-mi:“MI:0915”(physical association)	0.810
NIF3L1	DMC1	psi-mi:“MI:0915”(physical association)	0.810
TRIM27	NIF3L1	psi-mi:“MI:0915”(physical association)	0.740
CCDC102B	NIF3L1	psi-mi:“MI:0915”(physical association)	0.720
NIF3L1	NUDT14	psi-mi:“MI:0915”(physical association)	0.720
NIF3L1	CDKN2C	psi-mi:“MI:0915”(physical association)	0.720
NATD1	NIF3L1	psi-mi:“MI:0915”(physical association)	0.720
NIF3L1	CCDC102B	psi-mi:“MI:0915”(physical association)	0.720
CDKN2C	NIF3L1	psi-mi:“MI:0915”(physical association)	0.720
NUDT14	NIF3L1	psi-mi:“MI:0915”(physical association)	0.720
SAT1	NIF3L1	psi-mi:“MI:0915”(physical association)	0.700

BioGRID (213): NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid), NIF3L1 (Two-hybrid)

ESM2 similar proteins: A2AV36, A2VD33, A4QN59, A4QP75, A6QQV6, B0WSX1, B3MZN7, B4PYH5, B8A5G9, D3ZG52, D9IVE5, E1BMP7, F1QCV2, O95470, P51530, Q14CH1, Q16GH0, Q16P90, Q28CZ7, Q2VPA6, Q32PX9, Q3T0H0, Q3TZM9, Q4KLT3, Q4V7D6, Q502I6, Q58E95, Q5U4E8, Q5U534, Q5ZIB9, Q5ZKG3, Q655R6, Q6NTR1, Q6P4Z6, Q6PCI6, Q6ZQJ5, Q8AWD2, Q8BIP0, Q8GWT4, Q8LGM7

Diamond homologs: O25613, P67272, P67273, Q5HFK1, Q5HNY9, Q5XCH0, Q6G907, Q6GGE0, Q8CSD9, Q8NWB9, Q97JI0, Q9CGM3, Q9GZT8, Q9PPK2, Q9ZKP2, O94404, P53081, P54472, Q05B89, Q4V7D6, Q55E83, Q9EQ80, Q9KD39, Q9NK57, Q8XIV9, Q8YS75, Q97PK0, Q9L012, Q9PQE0, O69481, P0A657, P0DG84, P0DG85, P67274, P67276, P9WFM0, P9WFM1, Q58337, Q98QB0, O27214

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1476 predictions. Top by Δscore:

Variant	Effect	Δscore
2:200893372:G:GT	donor_gain	1.0000
2:200893373:A:T	donor_gain	1.0000
2:200895259:CCTA:C	acceptor_loss	1.0000
2:200895261:TAG:T	acceptor_loss	1.0000
2:200895262:A:AG	acceptor_gain	1.0000
2:200895262:AG:A	acceptor_gain	1.0000
2:200895263:G:GA	acceptor_gain	1.0000
2:200895263:GG:G	acceptor_gain	1.0000
2:200895263:GGA:G	acceptor_gain	1.0000
2:200895263:GGAC:G	acceptor_gain	1.0000
2:200895263:GGACT:G	acceptor_gain	1.0000
2:200895387:GAAG:G	donor_gain	1.0000
2:200895390:GGT:G	donor_loss	1.0000
2:200895390:GGTAA:G	donor_gain	1.0000
2:200895391:G:GG	donor_gain	1.0000
2:200895391:GTAAT:G	donor_loss	1.0000
2:200895392:T:G	donor_loss	1.0000
2:200891909:T:TA	acceptor_gain	0.9900
2:200891958:C:CA	acceptor_gain	0.9900
2:200891962:C:G	acceptor_gain	0.9900
2:200891967:A:AG	acceptor_gain	0.9900
2:200891968:G:GG	acceptor_gain	0.9900
2:200892026:T:TA	acceptor_gain	0.9900
2:200892027:G:A	acceptor_gain	0.9900
2:200892081:T:A	acceptor_gain	0.9900
2:200892374:GGC:G	donor_gain	0.9900
2:200892375:GCTTG:G	donor_gain	0.9900
2:200893232:A:AG	acceptor_gain	0.9900
2:200893242:CTA:C	acceptor_loss	0.9900
2:200893244:A:AG	acceptor_gain	0.9900

AlphaMissense

2451 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:200897104:G:C	R252P	0.991
2:200892206:T:C	L88P	0.990
2:200892220:C:G	H93D	0.990
2:200903575:G:C	R344P	0.989
2:200899406:C:A	A296D	0.988
2:200899457:T:C	L313P	0.985
2:200892322:C:G	H127D	0.983
2:200899415:C:A	A299D	0.983
2:200892091:G:C	D50H	0.982
2:200892313:T:G	Y124D	0.982
2:200899463:T:C	L315P	0.982
2:200903580:T:C	F346L	0.982
2:200903582:T:A	F346L	0.982
2:200903582:T:G	F346L	0.982
2:200892232:T:C	F97L	0.981
2:200892234:C:A	F97L	0.981
2:200892234:C:G	F97L	0.981
2:200903573:A:C	E343D	0.980
2:200903573:A:T	E343D	0.980
2:200892110:T:A	V56E	0.979
2:200892365:T:C	L141S	0.978
2:200903572:A:T	E343V	0.978
2:200892092:A:C	D50A	0.977
2:200892222:T:A	H93Q	0.977
2:200892222:T:G	H93Q	0.977
2:200903562:A:C	S340R	0.977
2:200903564:C:A	S340R	0.977
2:200903564:C:G	S340R	0.977
2:200892092:A:T	D50V	0.976
2:200892289:G:C	A116P	0.976

dbSNP variants (sampled 300 via entrez): RS1000033092 (2:200892373 G>A), RS1000160673 (2:200899061 T>C), RS1000494812 (2:200900641 A>T), RS1000550407 (2:200901099 C>G), RS1000653203 (2:200900337 C>T), RS1001772453 (2:200899645 T>C), RS1002339176 (2:200900162 A>G), RS1002507148 (2:200904039 C>G,T), RS1002598742 (2:200890567 C>T), RS1002630060 (2:200890921 G>T), RS1002664372 (2:200903715 G>A,C,T), RS1003042283 (2:200896945 G>A,T), RS1003157427 (2:200891778 T>C), RS1003270867 (2:200891317 C>A), RS1003282542 (2:200903728 T>C)

Disease associations

OMIM: gene MIM:605778 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003008_2	Triptolide cytotoxicity	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
Acetaminophen	decreases expression	2
Phenobarbital	affects expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Gallic Acid	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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