FEZ2

Summary

FEZ2 (fasciculation and elongation protein zeta 2, HGNC:3660) is a protein-coding gene on chromosome 2p22.2, encoding Fasciculation and elongation protein zeta-2 (Q9UHY8). Involved in axonal outgrowth and fasciculation.

This gene is an ortholog of the C. elegans unc-76 gene, which is necessary for normal axonal bundling and elongation within axon bundles. Other orthologs include the rat gene that encodes zygin II, which can bind to synaptotagmin.

Source: NCBI Gene 9637 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 114 total
• MANE Select transcript: NM_005102

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3660
Approved symbol	FEZ2
Name	fasciculation and elongation protein zeta 2
Location	2p22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171055
Ensembl biotype	protein_coding
OMIM	604826
Entrez	9637

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000305852, ENST00000357996, ENST00000379245, ENST00000405912, ENST00000406220, ENST00000413938, ENST00000414288, ENST00000432869, ENST00000441005, ENST00000451623, ENST00000464964, ENST00000475815, ENST00000484205, ENST00000487282, ENST00000487919, ENST00000535666, ENST00000861470, ENST00000957251

RefSeq mRNA: 2 — MANE Select: NM_005102 NM_001042548, NM_005102

CCDS: CCDS46257, CCDS46258

Canonical transcript exons

ENST00000405912 — 8 exons

Exon	Start	End
ENSE00001825826	36597877	36598168
ENSE00003489785	36552258	36553179
ENSE00003491901	36583353	36583469
ENSE00003603733	36581290	36581431
ENSE00003629621	36590903	36591011
ENSE00003636828	36558438	36558513
ENSE00003647649	36578597	36578865
ENSE00003678670	36555683	36555748

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.1204 / max 237.9970, expressed in 1810 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27743	24.6226	1810
27741	0.5915	263
27740	0.2448	119
27742	0.1689	76
27733	0.1382	29
27730	0.1199	41
27729	0.0623	28
27736	0.0463	12
202157	0.0391	17
27735	0.0357	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.68	gold quality
secondary oocyte	CL:0000655	99.59	gold quality
oocyte	CL:0000023	99.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.49	gold quality
biceps brachii	UBERON:0001507	99.36	gold quality
diaphragm	UBERON:0001103	99.23	gold quality
deltoid	UBERON:0001476	99.07	gold quality
parietal pleura	UBERON:0002400	99.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.97	gold quality
pleura	UBERON:0000977	98.83	gold quality
visceral pleura	UBERON:0002401	98.65	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.60	gold quality
germinal epithelium of ovary	UBERON:0001304	98.54	gold quality
palpebral conjunctiva	UBERON:0001812	98.42	gold quality
inferior vagus X ganglion	UBERON:0005363	98.42	gold quality
skeletal muscle tissue	UBERON:0001134	98.40	gold quality
corpus callosum	UBERON:0002336	98.38	gold quality
dorsal root ganglion	UBERON:0000044	98.34	gold quality
tibialis anterior	UBERON:0001385	98.31	gold quality
middle temporal gyrus	UBERON:0002771	98.22	gold quality
vastus lateralis	UBERON:0001379	98.21	gold quality
quadriceps femoris	UBERON:0001377	98.16	gold quality
trigeminal ganglion	UBERON:0001675	98.10	gold quality
eye	UBERON:0000970	98.06	gold quality
muscle tissue	UBERON:0002385	97.96	gold quality
muscle organ	UBERON:0001630	97.79	gold quality
skeletal muscle organ	UBERON:0014892	97.79	gold quality
metanephric glomerulus	UBERON:0004736	97.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting FEZ2, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699

Literature-anchored findings (GeneRIF, showing 2)

• the C-terminal regions of FEZ1, and especially its coiled-coil region, are involved in its dimerization, its heterodimerization with FEZ2, and in the interaction with 10 of the identified interacting proteins (PMID:16484223)
• FEZ2 interacted with 59 proteins and that of these only 40 interacted with FEZ1. (PMID:21408165)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fez2	ENSMUSG00000056121
rattus_norvegicus	Fez2	ENSRNOG00000004577
drosophila_melanogaster	Unc-76	FBGN0040395
caenorhabditis_elegans		WBGENE00006808

Paralogs (1): FEZ1 (ENSG00000149557)

Protein

Protein identifiers

Fasciculation and elongation protein zeta-2 — Q9UHY8 (reviewed: Q9UHY8)

Alternative names: Zygin II, Zygin-2

All UniProt accessions (8): Q9UHY8, F8W6C0, F8WB37, G3V0F5, H7C0L4, H7C0W1, H7C434, Q7Z674

UniProt curated annotations — full annotation on UniProt →

Function. Involved in axonal outgrowth and fasciculation.

Subunit / interactions. Homodimer; disulfide-linked. May form heterodimers with FEZ1. Interacts with synaptotagmin.

Tissue specificity. Expressed in nonneural tissues, such as heart, lung, spleen, muscle, testis, placenta and melanocytes.

Similarity. Belongs to the zygin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UHY8-1	1	yes
Q9UHY8-2	2

RefSeq proteins (2): NP_001036013, NP_005093* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011680	FEZ	Family

Pfam: PF07763

UniProt features (15 total): sequence conflict 3, modified residue 3, region of interest 2, sequence variant 2, chain 1, coiled-coil region 1, compositionally biased region 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHY8-F1	71.78	0.23

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): 135, 176, 195

Disulfide bonds (1): 153

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 231 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_VACUOLE_ORGANIZATION, SWEET_KRAS_ONCOGENIC_SIGNATURE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_MACROAUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, WANG_LMO4_TARGETS_DN, FOSTER_TOLERANT_MACROPHAGE_UP

GO Biological Process (4): signal transduction (GO:0007165), nervous system development (GO:0007399), axon guidance (GO:0007411), negative regulation of autophagosome assembly (GO:1902902)

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

GO Cellular Component (2): cytoplasm (GO:0005737), axon (GO:0030424)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
axonogenesis	1
neuron projection guidance	1
autophagosome assembly	1
negative regulation of macroautophagy	1
negative regulation of organelle assembly	1
regulation of autophagosome assembly	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
neuron projection	1

Protein interactions and networks

STRING

690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FEZ2	CRIM1	Q9NZV1	892
FEZ2	LZTS1	Q9Y250	794
FEZ2	ATF5	Q9Y2D1	668
FEZ2	DNAAF9	Q5TEA3	580
FEZ2	SCOC	Q9UIL1	566
FEZ2	TBC1D19	Q8N5T2	564
FEZ2	PRKCZ	Q05513	528
FEZ2	UXT	Q9UBK9	466
FEZ2	SENP7	Q9BQF6	465
FEZ2	SRBD1	Q8N5C6	462
FEZ2	TTBK2	Q6IQ55	460
FEZ2	NEK1	Q96PY6	460
FEZ2	SAP30	O75446	446
FEZ2	RAB11FIP2	Q7L804	443
FEZ2	FEZF2	Q8TBJ5	434

IntAct

94 interactions, top by confidence:

A	B	Type	Score
FEZ2	SCOC	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	APP	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	DCTN1	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	DNM2	psi-mi:“MI:0915”(physical association)	0.560
FEZ2		psi-mi:“MI:0915”(physical association)	0.560
PRKN	FEZ2	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	PRPS1	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	PSEN1	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	SMN1	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	TTR	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	WFS1	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	PINK1	psi-mi:“MI:0915”(physical association)	0.560
SNCA	FEZ2	psi-mi:“MI:0915”(physical association)	0.560
HTT	FEZ2	psi-mi:“MI:0915”(physical association)	0.560
ATXN3	FEZ2	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	FEZ2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (48): FEZ2 (Two-hybrid), FEZ2 (Affinity Capture-Western), FEZ2 (Affinity Capture-MS), FEZ2 (Affinity Capture-MS), FEZ2 (Synthetic Lethality), FEZ2 (Affinity Capture-MS), FEZ2 (Affinity Capture-MS), FEZ2 (Affinity Capture-MS), FEZ2 (Affinity Capture-MS), FEZ2 (Affinity Capture-MS), FEZ2 (Affinity Capture-MS), FEZ2 (Affinity Capture-RNA), FEZ2 (Affinity Capture-MS), FEZ2 (Affinity Capture-Western), PRKCZ (Affinity Capture-Western)

ESM2 similar proteins: A0JNJ3, A0M8T5, A0PJT0, A2BIJ3, D3ZTQ1, O35867, O94876, P42566, P42567, P97578, Q00PJ1, Q02225, Q09YI1, Q09YK4, Q09YM8, Q16643, Q2IBF8, Q2QL82, Q2QLA2, Q2QLG9, Q2T9N1, Q3SX22, Q3UQU0, Q3USH5, Q5BJ78, Q5RDH2, Q5T1M5, Q5U3K5, Q5ZIK6, Q68EF0, Q69ZZ6, Q6INU2, Q6NTW1, Q6P9Q6, Q6TYB5, Q6ZPJ0, Q80Y55, Q8IWB9, Q8IWE2, Q8N0X7

Diamond homologs: P97577, P97578, Q6TYB5, Q8K0X8, Q99689, Q9UHY8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of neuron apoptotic process	5	15.8×	1e-03
positive regulation of apoptotic process	5	8.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3016 predictions. Top by Δscore:

Variant	Effect	Δscore
2:36537523:G:GT	donor_gain	1.0000
2:36544375:GAAAT:G	acceptor_gain	1.0000
2:36553175:CAGAA:C	acceptor_gain	1.0000
2:36553180:C:CC	acceptor_gain	1.0000
2:36555678:CTCA:C	donor_loss	1.0000
2:36555679:TCA:T	donor_loss	1.0000
2:36555680:CA:C	donor_loss	1.0000
2:36555682:CCTTT:C	donor_gain	1.0000
2:36555744:AAGAA:A	acceptor_gain	1.0000
2:36555745:AGAA:A	acceptor_gain	1.0000
2:36555746:GAA:G	acceptor_gain	1.0000
2:36555747:AA:A	acceptor_gain	1.0000
2:36555747:AACT:A	acceptor_loss	1.0000
2:36555748:ACT:A	acceptor_loss	1.0000
2:36555749:C:CC	acceptor_gain	1.0000
2:36555749:C:CG	acceptor_loss	1.0000
2:36555750:T:C	acceptor_loss	1.0000
2:36555752:C:CT	acceptor_gain	1.0000
2:36555756:A:AC	acceptor_gain	1.0000
2:36555756:A:C	acceptor_gain	1.0000
2:36556566:T:TA	donor_gain	1.0000
2:36558436:A:AC	donor_gain	1.0000
2:36558437:C:CC	donor_gain	1.0000
2:36578739:T:TA	donor_gain	1.0000
2:36578740:C:A	donor_gain	1.0000
2:36581283:C:CA	donor_gain	1.0000
2:36581288:A:AC	donor_gain	1.0000
2:36581289:C:CC	donor_gain	1.0000
2:36581289:CT:C	donor_gain	1.0000
2:36581289:CTCT:C	donor_gain	1.0000

AlphaMissense

2335 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:36555688:A:G	L347P	1.000
2:36555688:A:T	L347Q	1.000
2:36555691:A:C	I346S	1.000
2:36555691:A:G	I346T	1.000
2:36555691:A:T	I346N	1.000
2:36555703:A:G	L342S	1.000
2:36555745:A:G	L328P	1.000
2:36558497:A:T	I307N	1.000
2:36578712:A:G	L263P	1.000
2:36578723:A:C	F259L	1.000
2:36578723:A:T	F259L	1.000
2:36578724:A:G	F259S	1.000
2:36578725:A:G	F259L	1.000
2:36578754:A:G	L249P	1.000
2:36578784:A:G	L239P	1.000
2:36553172:A:C	C351W	0.999
2:36553174:A:G	C351R	0.999
2:36555695:A:C	Y345D	0.999
2:36555700:G:A	T343I	0.999
2:36555715:A:T	V338D	0.999
2:36555740:C:G	A330P	0.999
2:36555745:A:T	L328H	0.999
2:36558455:A:G	L321P	0.999
2:36558494:G:T	P308H	0.999
2:36558495:G:A	P308S	0.999
2:36558495:G:T	P308T	0.999
2:36558497:A:C	I307S	0.999
2:36558497:A:G	I307T	0.999
2:36578721:A:T	I260N	0.999
2:36578763:C:G	R246P	0.999

dbSNP variants (sampled 300 via entrez): RS1000030893 (2:36555302 A>C,G), RS1000055876 (2:36572834 G>A,C), RS1000105948 (2:36566045 T>C), RS1000185615 (2:36577901 C>G,T), RS1000242401 (2:36558742 A>G), RS1000284185 (2:36590031 C>A,G), RS1000366172 (2:36598470 C>G,T), RS1000384792 (2:36577660 T>C), RS1000399593 (2:36594463 C>T), RS1000423012 (2:36564216 C>G), RS1000437313 (2:36594573 G>A,C), RS1000468273 (2:36558169 G>A,C), RS1000497616 (2:36598855 G>A), RS1000531578 (2:36573001 T>C), RS1000546424 (2:36590935 G>A,C,T)

Disease associations

OMIM: gene MIM:604826 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005580_296	Intraocular pressure	3.000000e-09
GCST008363_25	Offspring birth weight	9.000000e-10
GCST009391_1598	Metabolite levels	9.000000e-06
GCST010241_349	Apolipoprotein A1 levels	4.000000e-08
GCST012226_158	Waist circumference adjusted for body mass index	3.000000e-08
GCST012227_1182	Hip circumference adjusted for BMI	2.000000e-12
GCST012227_1183	Hip circumference adjusted for BMI	1.000000e-08
GCST90014033_8	Haemorrhoidal disease	1.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0010376	phosphatidylcholine 34:2 measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases methylation	2
cobaltous chloride	decreases expression, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
ethylbenzene	affects cotreatment, decreases expression, increases methylation	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
nickel sulfate	increases expression	1
coumarin	decreases phosphorylation	1
K 7174	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	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
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants, Occupational	decreases expression, increases methylation	1
Antimycin A	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Coal	increases abundance, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Dimethylnitrosamine	increases expression	1
Doxorubicin	increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Quercetin	increases expression	1
Rotenone	increases expression	1
Smoke	decreases expression, increases abundance	1
Testosterone	increases expression	1

Clinical trials (associated diseases)

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