FANK1

Summary

FANK1 (fibronectin type III and ankyrin repeat domains 1, HGNC:23527) is a protein-coding gene on chromosome 10q26.2, encoding Fibronectin type 3 and ankyrin repeat domains protein 1 (Q8TC84). Through the activation of JUN and AP-1-mediated transcription, may regulate apoptosis.

Involved in regulation of DNA-templated transcription and regulation of apoptotic process. Located in chromatin; cytosol; and nucleoplasm.

Source: NCBI Gene 92565 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_145235

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23527
Approved symbol	FANK1
Name	fibronectin type III and ankyrin repeat domains 1
Location	10q26.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000203780
Ensembl biotype	protein_coding
OMIM	611640
Entrez	92565

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000368689, ENST00000368691, ENST00000368693, ENST00000417114, ENST00000445510, ENST00000456942, ENST00000464130, ENST00000477963, ENST00000492670, ENST00000494896, ENST00000902356, ENST00000916275, ENST00000916276

RefSeq mRNA: 3 — MANE Select: NM_145235 NM_001350939, NM_001363549, NM_145235

CCDS: CCDS31309

Canonical transcript exons

ENST00000368693 — 11 exons

Exon	Start	End
ENSE00001447770	126009373	126009592
ENSE00001447771	126009222	126009266
ENSE00003479738	126004884	126005049
ENSE00003508912	125997420	125997485
ENSE00003534186	125980161	125980338
ENSE00003537470	125988551	125988675
ENSE00003569531	126008407	126008550
ENSE00003571081	126009054	126009131
ENSE00003631823	125896564	125896655
ENSE00003643358	125996550	125996624
ENSE00003791176	125995417	125995498

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 98.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.3315 / max 96.5322, expressed in 1016 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107572	1.8865	907
107571	0.4201	222
107574	0.0249	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.71	gold quality
bronchial epithelial cell	CL:0002328	97.99	gold quality
bronchus	UBERON:0002185	96.93	gold quality
left testis	UBERON:0004533	96.75	gold quality
right testis	UBERON:0004534	96.34	gold quality
oviduct epithelium	UBERON:0004804	95.19	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.03	gold quality
testis	UBERON:0000473	94.53	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.30	gold quality
sperm	CL:0000019	91.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.80	gold quality
fallopian tube	UBERON:0003889	88.77	gold quality
caput epididymis	UBERON:0004358	87.17	gold quality
epithelium of nasopharynx	UBERON:0001951	86.62	gold quality
nasal cavity epithelium	UBERON:0005384	86.28	silver quality
adrenal tissue	UBERON:0018303	86.22	gold quality
adenohypophysis	UBERON:0002196	85.36	gold quality
left lobe of thyroid gland	UBERON:0001120	85.13	gold quality
thyroid gland	UBERON:0002046	84.85	gold quality
right lobe of thyroid gland	UBERON:0001119	84.32	gold quality
pituitary gland	UBERON:0000007	83.94	gold quality
lower esophagus mucosa	UBERON:0035834	83.82	gold quality
buccal mucosa cell	CL:0002336	83.56	gold quality
endothelial cell	CL:0000115	83.13	silver quality
metanephros cortex	UBERON:0010533	81.62	gold quality
hypothalamus	UBERON:0001898	81.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.64	gold quality
right adrenal gland	UBERON:0001233	80.48	gold quality
corpus epididymis	UBERON:0004359	80.34	gold quality
right adrenal gland cortex	UBERON:0035827	80.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	62.93
E-MTAB-10287	yes	25.55
E-ANND-3	yes	11.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting FANK1, 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-5692A	100.00	74.40	6850
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-769-3P	97.06	64.83	464
HSA-MIR-6854-3P	90.99	65.18	155

Literature-anchored findings (GeneRIF, showing 7)

• FANK1 may have a role in regulating gene expression in the transition from the meiotic phase to the haploid phase during spermatogenesis (PMID:17604233)
• found that Jab1 (Jun activation domain-binding protein 1), a co-activator of AP-1, specifically interacted with Fank1 (PMID:20978819)
• we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males. (PMID:25144706)
• the TNfnIII 1-5 repeats play an important role in PCO pathology. (PMID:25515583)
• RYBP activates FANK1-mediated activator protein 1 (AP-1) signaling pathway which contributes to tumor cell apoptosis. (PMID:27060496)
• [Contact Sites of rDNA Clusters with FANK1 Gene Correspond to Repressed Chromatin]. (PMID:32392195)
• YAF2 exerts anti-apoptotic effect in human tumor cells in a FANK1- and phosphorylation-dependent manner. (PMID:33784512)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fank1	ENSDARG00000039657
mus_musculus	Fank1	ENSMUSG00000053111
rattus_norvegicus	Fank1	ENSRNOG00000018327

Protein

Protein identifiers

Fibronectin type 3 and ankyrin repeat domains protein 1 — Q8TC84 (reviewed: Q8TC84)

All UniProt accessions (6): A0A1B0GX87, A6NKD7, A6NP17, C9JD80, Q8TC84, H7C3M3

UniProt curated annotations — full annotation on UniProt →

Function. Through the activation of JUN and AP-1-mediated transcription, may regulate apoptosis.

Subunit / interactions. Interacts with COPS5; regulates the phosphorylation of JUN and the transcriptional activity of AP-1. Interacts with RYBP; may prevent the ubiquitin-mediated proteasomal degradation of FANK1.

Subcellular location. Nucleus. Cytoplasm. Cytosol. Cytoskeleton. Cilium basal body. Cell projection. Cilium.

Tissue specificity. Mostly restricted to testis.

Post-translational modifications. Polyubiquitinated. Polyubiquitination leads to proteasomal degradation.

Domain organisation. The fibronectin type-III domain mediates interaction with COPS5 and RYBP.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TC84-1	1	yes
Q8TC84-2	2
Q8TC84-3	3

RefSeq proteins (3): NP_001337868, NP_001350478, NP_660278* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF12796

UniProt features (15 total): repeat 6, sequence variant 4, splice variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TC84-F1	92.54	0.82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, SOX9_B1, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_POSITIVE_REGULATION_OF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, TGGAAA_NFAT_Q4_01, GOCC_CILIARY_BASE, GOBP_REGULATION_OF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOCC_CILIUM, GOCC_CILIARY_BASAL_BODY, ROVERSI_GLIOMA_COPY_NUMBER_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3, AKT_UP.V1_DN

GO Biological Process (4): positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of DNA-templated transcription (GO:0045893), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091)

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

GO Cellular Component (10): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cilium (GO:0005929), ciliary basal body (GO:0036064), ciliary base (GO:0097546), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
apoptotic process	2
regulation of apoptotic process	2
cilium	2
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
microtubule organizing center	1
ciliary transition zone	1
ciliary transition fiber	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1222 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FANK1	DHX32	Q7L7V1	673
FANK1	FAM199X	Q6PEV8	591
FANK1	COPS5	Q92905	494
FANK1	ZNF717	Q9BY31	492
FANK1	MALRD1	Q5VYJ5	476
FANK1	SPATA4	Q8NEY3	466
FANK1	FN1	P02751	457
FANK1	FNDC10	F2Z333	456
FANK1	ITPK1	Q13572	428
FANK1	FNDC7	Q5VTL7	423
FANK1	GCNT2	Q8N0V5	418
FANK1	ZNF555	Q8NEP9	417
FANK1	PROSER2	Q86WR7	412
FANK1	ZNF554	Q86TJ5	409
FANK1	FNDC9	Q8TBE3	406

IntAct

24 interactions, top by confidence:

A	B	Type	Score
FANK1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
FANK1	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
FANK1	NEFL	psi-mi:“MI:0915”(physical association)	0.560
FANK1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
FANK1	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
HTT	FANK1	psi-mi:“MI:0915”(physical association)	0.560
MAGEA4	MAGEB16	psi-mi:“MI:0914”(association)	0.530
LZTR1	FANK1	psi-mi:“MI:0915”(physical association)	0.370
FANK1	UBXN2B	psi-mi:“MI:0914”(association)	0.350
TRIM63	FANK1	psi-mi:“MI:0915”(physical association)	0.000
TRIM55	FANK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): ATG4B (Affinity Capture-MS), UBXN2B (Affinity Capture-MS), A4GNT (Affinity Capture-MS), FANK1 (Two-hybrid), FANK1 (Affinity Capture-Western), RYBP (Affinity Capture-Western), FANK1 (Reconstituted Complex), ATG4B (Affinity Capture-MS), A4GNT (Affinity Capture-MS), UBXN2B (Affinity Capture-MS), FANK1 (Affinity Capture-MS), FANK1 (Two-hybrid), FANK1 (Two-hybrid), FANK1 (Negative Genetic), ATG4B (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A0FKG7, A2AGL3, A7MB89, B0LPN4, E9Q401, O60733, P30957, P42694, P49754, P97570, P97819, Q15413, Q29RM5, Q2KIX2, Q2T9K6, Q32PW3, Q3SX45, Q4V890, Q59H18, Q5F361, Q5GIG6, Q5KU39, Q5RF15, Q5U2S6, Q5ZKK2, Q66H07, Q66H63, Q6B858, Q6DFV5, Q6NYU2, Q7T3P8, Q7TQP6, Q8C0T1, Q8CEF1, Q8K0L0, Q8K114, Q8TC84, Q91W86, Q92736

Diamond homologs: A7MB89, Q66H07, Q6B858, Q8CEF1, Q8TC84, Q96JP0, Q9DAM9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3568 predictions. Top by Δscore:

Variant	Effect	Δscore
10:125896654:GA:G	donor_gain	1.0000
10:125896656:G:GG	donor_gain	1.0000
10:125896661:G:GT	donor_gain	1.0000
10:125896662:G:T	donor_gain	1.0000
10:125988638:GT:G	donor_gain	1.0000
10:125996537:T:TA	acceptor_gain	1.0000
10:125996548:A:G	acceptor_gain	1.0000
10:126008402:AACAG:A	acceptor_loss	1.0000
10:126008404:CA:C	acceptor_loss	1.0000
10:126008405:A:AC	acceptor_loss	1.0000
10:126008548:ATGG:A	donor_loss	1.0000
10:126008550:GGTA:G	donor_loss	1.0000
10:126008551:G:T	donor_loss	1.0000
10:126008552:TAGG:T	donor_loss	1.0000
10:125980339:G:GG	donor_gain	0.9900
10:125988549:AGG:A	acceptor_gain	0.9900
10:125988550:GGG:G	acceptor_gain	0.9900
10:125988676:G:GG	donor_gain	0.9900
10:125995494:GGAGG:G	donor_gain	0.9900
10:125995495:GAGGG:G	donor_gain	0.9900
10:125995497:GG:G	donor_gain	0.9900
10:125995498:GG:G	donor_gain	0.9900
10:125996547:A:AG	acceptor_gain	0.9900
10:125996547:AAGCC:A	acceptor_gain	0.9900
10:125996549:G:GG	acceptor_gain	0.9900
10:125996549:GCC:G	acceptor_gain	0.9900
10:125996549:GCCGT:G	acceptor_gain	0.9900
10:126004882:A:AG	acceptor_gain	0.9900
10:126004883:G:GG	acceptor_gain	0.9900
10:126004883:GTCTA:G	acceptor_gain	0.9900

AlphaMissense

2253 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:126004899:C:G	C185W	0.997
10:125988607:T:C	F83S	0.996
10:126004898:G:A	C185Y	0.996
10:125980227:T:C	L27S	0.995
10:125997484:A:C	S180R	0.995
10:126004884:T:A	S180R	0.995
10:126004884:T:G	S180R	0.995
10:126004897:T:C	C185R	0.995
10:125988610:G:C	R84P	0.994
10:125996603:C:A	A151D	0.994
10:126009057:G:C	A285P	0.994
10:125996605:G:C	A152P	0.993
10:125996606:C:A	A152D	0.993
10:126004895:C:A	A184E	0.993
10:126004931:T:C	L196P	0.992
10:125988613:T:C	L85P	0.991
10:125996602:G:C	A151P	0.991
10:126004993:G:C	A217P	0.991
10:126009058:C:A	A285D	0.991
10:126009128:T:A	N308K	0.991
10:126009128:T:G	N308K	0.991
10:125997468:T:A	N174K	0.990
10:125997468:T:G	N174K	0.990
10:126009094:T:C	L297P	0.990
10:125980221:T:A	I25N	0.989
10:126004894:G:C	A184P	0.989
10:125997434:T:C	L163P	0.988
10:125997480:G:C	K178N	0.987
10:125997480:G:T	K178N	0.987
10:126004994:C:A	A217D	0.987

dbSNP variants (sampled 300 via entrez): RS1000018863 (10:125990355 C>T), RS1000037241 (10:125902183 G>A), RS1000087434 (10:125953615 G>C,T), RS1000118253 (10:125897920 G>A), RS1000171849 (10:125968463 T>A), RS1000174271 (10:126006729 G>A), RS1000189611 (10:125952144 T>G), RS1000196484 (10:125981519 A>T), RS1000237999 (10:125897509 C>G), RS1000244863 (10:125987143 C>T), RS1000255318 (10:125949369 C>G,T), RS1000296059 (10:125906602 C>A,G,T), RS1000329475 (10:125972552 T>C), RS1000345543 (10:125992836 T>A), RS1000389630 (10:125938208 G>A)

Disease associations

OMIM: gene MIM:611640 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001525_21	Visceral fat	6.000000e-06
GCST002337_141	Amyotrophic lateral sclerosis (sporadic)	3.000000e-06
GCST011946_15	White matter hyperintensity volume	2.000000e-06
GCST011947_17	White matter hyperintensity volume	1.000000e-06
GCST011949_31	White matter hyperintensity volume (adjusted for hypertension)	3.000000e-06
GCST011950_7	White matter hyperintensity volume (adjusted for hypertension)	2.000000e-06
GCST011953_14	White matter hyperintensity volume x hypertension interaction (2df)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005665	white matter hyperintensity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	decreases expression, affects cotreatment	3
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
pinostrobin	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	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Endosulfan	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases expression, increases methylation	1
Okadaic Acid	decreases expression	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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