FIGNL2

Summary

FIGNL2 (fidgetin like 2, HGNC:13287) is a protein-coding gene on chromosome 12q13.13, encoding Fidgetin-like protein 2 (A6NMB9). Microtubule-severing enzyme that negatively regulates cell migration and wound healing.

Predicted to enable ATP hydrolysis activity and microtubule severing ATPase activity. Involved in microtubule severing and negative regulation of cell migration. Located in cell leading edge.

Source: NCBI Gene 401720 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_001384995

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13287
Approved symbol	FIGNL2
Name	fidgetin like 2
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000261308
Ensembl biotype	protein_coding
OMIM	620503
Entrez	401720

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000618634, ENST00000938505, ENST00000948593

RefSeq mRNA: 3 — MANE Select: NM_001384995 NM_001013690, NM_001384995, NM_001384996

CCDS: CCDS86302

Canonical transcript exons

ENST00000618634 — 2 exons

Exon	Start	End
ENSE00003743520	51817899	51822424
ENSE00003806739	51848540	51848718

Expression profiles

Bgee: expression breadth broad, 97 present calls, max score 70.17.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2606 / max 60.9365, expressed in 330 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130972	2.2606	330

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	70.17	gold quality
adult mammalian kidney	UBERON:0000082	66.49	gold quality
kidney	UBERON:0002113	63.58	gold quality
cortex of kidney	UBERON:0001225	61.66	gold quality
ventricular zone	UBERON:0003053	61.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	59.64	gold quality
cerebellar hemisphere	UBERON:0002245	59.11	gold quality
cerebellar cortex	UBERON:0002129	59.09	gold quality
cerebellum	UBERON:0002037	59.07	gold quality
pituitary gland	UBERON:0000007	58.50	gold quality
sural nerve	UBERON:0015488	58.50	silver quality
right lobe of liver	UBERON:0001114	57.86	gold quality
adenohypophysis	UBERON:0002196	57.23	gold quality
stromal cell of endometrium	CL:0002255	56.55	gold quality
liver	UBERON:0002107	56.50	gold quality
granulocyte	CL:0000094	56.40	gold quality
tibial nerve	UBERON:0001323	56.22	gold quality
placenta	UBERON:0001987	56.14	gold quality
ganglionic eminence	UBERON:0004023	55.91	silver quality
prefrontal cortex	UBERON:0000451	55.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	54.23	gold quality
frontal cortex	UBERON:0001870	54.10	gold quality
colonic epithelium	UBERON:0000397	53.87	gold quality
superior frontal gyrus	UBERON:0002661	53.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	53.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	52.91	gold quality
bone marrow cell	CL:0002092	52.89	gold quality
cerebral cortex	UBERON:0000956	52.72	gold quality
brain	UBERON:0000955	52.59	gold quality
anterior cingulate cortex	UBERON:0009835	52.07	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

146 targeting FIGNL2, 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-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7D-5P	99.96	71.76	1632

Literature-anchored findings (GeneRIF, showing 1)

• Fidgetin-like 2 depletion enhances cell migration by regulating GEF-H1, RhoA, and FAK. (PMID:36523161)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	fignl2	ENSDARG00000057062
mus_musculus	Fignl2	ENSMUSG00000095440
rattus_norvegicus	Fignl2	ENSRNOG00000032026
drosophila_melanogaster	Fign	FBGN0031519
drosophila_melanogaster	kat-60L1	FBGN0037375
drosophila_melanogaster	Kat60	FBGN0040208
caenorhabditis_elegans	mei-1	WBGENE00003183
caenorhabditis_elegans		WBGENE00017981

Paralogs (9): SPAST (ENSG00000021574), KATNAL1 (ENSG00000102781), VPS4B (ENSG00000119541), FIGNL1 (ENSG00000132436), VPS4A (ENSG00000132612), ATAD1 (ENSG00000138138), KATNAL2 (ENSG00000167216), FIGN (ENSG00000182263), KATNA1 (ENSG00000186625)

Protein

Protein identifiers

Fidgetin-like protein 2 — A6NMB9 (reviewed: A6NMB9)

All UniProt accessions (1): A6NMB9

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-severing enzyme that negatively regulates cell migration and wound healing. In migrating cells, targets dynamic microtubules (MTs) at the leading edge and severs them, thereby suppressing motility. Microtubule severing releases ARHGEF2 which activates RHOA, which in turn regulates focal ahesion turnover via focal adhesion kinase, as opposed to F-actin polymerization, to suppress cell motility. Negative regulator of axon regeneration that suppresses axonal growth by selectively severing dynamic MTs in the distal axon shaft and growth cone. Contributes to proper cell branching during endothelial and neuronal development.

Subcellular location. Cytoplasm. Cell cortex.

Similarity. Belongs to the AAA ATPase family.

RefSeq proteins (3): NP_001013712, NP_001371924, NP_001371925 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR047828	Fidgetin_ATPase	Domain
IPR050304	MT-severing_AAA_ATPase	Family

Pfam: PF00004

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (11 total): compositionally biased region 4, region of interest 3, binding site 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NMB9-F1	60.73	0.27

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 395; 435–440

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_RESPONSE_TO_AXON_INJURY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_WOUND_HEALING, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIAL_SHEET, GOBP_REGULATION_OF_RESPONSE_TO_WOUNDING, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_EPIBOLY, GOBP_REGULATION_OF_NEURON_PROJECTION_REGENERATION, GOBP_NEGATIVE_REGULATION_OF_CELL_PROJECTION_ORGANIZATION

GO Biological Process (5): morphogenesis of a branching structure (GO:0001763), negative regulation of cell migration (GO:0030336), negative regulation of axon regeneration (GO:0048681), microtubule severing (GO:0051013), negative regulation of wound healing, spreading of epidermal cells (GO:1903690)

GO Molecular Function (5): ATP binding (GO:0005524), microtubule severing ATPase activity (GO:0008568), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cell cortex (GO:0005938), cell leading edge (GO:0031252)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule cytoskeleton organization	2
ATP-dependent activity	2
cellular anatomical structure	2
anatomical structure morphogenesis	1
multicellular organismal process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
axon regeneration	1
negative regulation of response to external stimulus	1
regulation of axon regeneration	1
negative regulation of neuron projection regeneration	1
negative regulation of response to wounding	1
negative regulation of cell migration	1
wound healing, spreading of epidermal cells	1
negative regulation of wound healing	1
regulation of wound healing, spreading of epidermal cells	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
polypeptide conformation or assembly isomerase activity	1
catalytic activity, acting on a protein	1
microtubule destabilizing activity	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cell periphery	1

Protein interactions and networks

STRING

1190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FIGNL2	ANKRD33	Q7Z3H0	477
FIGNL2	RGL3	Q3MIN7	445
FIGNL2	DORIP1	Q4W4Y0	402
FIGNL2	MKLN1	Q9UL63	401
FIGNL2	SPEF1	Q9Y4P9	378
FIGNL2	KCTD15	Q96SI1	359
FIGNL2	LSM14A	Q8ND56	356
FIGNL2	ELAVL3	Q14576	337
FIGNL2	TASOR	Q9UK61	327
FIGNL2	SPIDR	Q14159	305
FIGNL2	TRIP12	Q14669	304
FIGNL2	LDAH	Q9H6V9	292
FIGNL2	NME7	Q9Y5B8	278
FIGNL2	STC2	O76061	270
FIGNL2	CSPG5	O95196	270

IntAct

2 interactions, top by confidence:

A	B	Type	Score
FIGNL2	EOLA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): FIGNL2 (Affinity Capture-MS), EFHD1 (Affinity Capture-MS), CXorf40A (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6AGW3, A2A9A2, A6NMB9, A8MYZ6, E9PZZ1, J3QK54, O02755, O02756, O35392, O35767, O60548, O70220, P05554, P17676, P21272, P28033, P35713, P42582, P49715, P49716, P52952, P53566, P58012, Q12952, Q13461, Q14526, Q60843, Q61345, Q63244, Q63250, Q6BEB4, Q6VFT5, Q6VFT6, Q6ZQN5, Q70KY4, Q8IU81, Q8MIP2, Q8NDY6, Q8R2I0, Q98937

Diamond homologs: A0A8I6AGW3, A0LR74, A2VDN5, A4IHT0, A6NMB9, B2RYN7, B3M301, B3P8A3, B4F6J6, B4G437, B4HGG6, B4JII0, B4K799, B4M0H8, B4NBP4, B4PL32, B4QSF0, B7PXE3, D0FH76, D2VS83, E9QEA3, F4JEX5, F6QV99, J3QK54, O05209, O14114, O14325, O15381, O16299, O28972, O57940, O60058, P03974, P23787, P25694, P32794, P36966, P40340, P46462, P54609

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4055 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:51822238:A:G	L59P	1.000
12:51822231:C:A	K61N	0.999
12:51822231:C:G	K61N	0.999
12:51822235:A:G	L60P	0.999
12:51822247:G:T	A56D	0.999
12:51822262:A:G	I51T	0.999
12:51822262:A:T	I51N	0.999
12:51822215:A:C	Y67D	0.998
12:51822224:C:G	A64P	0.998
12:51822227:A:C	Y63D	0.998
12:51822262:A:C	I51S	0.998
12:51822276:C:A	W46C	0.998
12:51822276:C:G	W46C	0.998
12:51822233:T:C	K61E	0.997
12:51822235:A:T	L60Q	0.997
12:51822244:G:A	S57F	0.997
12:51822245:A:G	S57P	0.997
12:51822268:T:A	D49V	0.997
12:51822278:A:G	W46R	0.997
12:51822278:A:T	W46R	0.997
12:51822229:C:G	R62P	0.996
12:51822238:A:T	L59H	0.996
12:51822248:C:G	A56P	0.996
12:51822250:G:A	T55I	0.996
12:51821119:C:T	G432E	0.995
12:51822232:T:G	K61T	0.995
12:51822253:A:G	L54P	0.995
12:51821211:C:A	K401N	0.994
12:51821211:C:G	K401N	0.994
12:51822227:A:G	Y63H	0.994

dbSNP variants (sampled 300 via entrez): RS1000008144 (12:51846857 G>A), RS1000081908 (12:51828966 C>T), RS1000233378 (12:51834407 C>A,T), RS1000237075 (12:51824259 C>T), RS1000338889 (12:51829582 G>A), RS1000359570 (12:51846614 C>A,T), RS1000365533 (12:51840724 A>G,T), RS1000475273 (12:51847232 C>A,T), RS1000479367 (12:51834581 T>G), RS1000606913 (12:51835792 C>T), RS1000893033 (12:51845621 G>A,C,T), RS1001012641 (12:51818193 G>A,T), RS1001027572 (12:51820211 G>A,C), RS1001059483 (12:51836060 C>T), RS1001146569 (12:51818050 G>A)

Disease associations

OMIM: gene MIM:620503 | 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
GCST006402_3	Energy intake	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009374	energy intake measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation	1
butyraldehyde	decreases expression	1
jinfukang	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Estradiol	affects expression, increases reaction	1
Lead	affects expression	1
Silver	increases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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