ANKFN1

Summary

ANKFN1 (ankyrin repeat and fibronectin type III domain containing 1, HGNC:26766) is a protein-coding gene on chromosome 17q22, encoding Ankyrin repeat and fibronectin type-III domain-containing protein 1 (Q8N957). May play a role in neuronal function.

Predicted to be involved in establishment of mitotic spindle orientation and regulation of establishment of bipolar cell polarity. Predicted to act upstream of or within behavioral fear response; equilibrioception; and locomotor rhythm. Predicted to be active in spindle.

Source: NCBI Gene 162282 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 110 total — 1 pathogenic
• MANE Select transcript: NM_001370326

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26766
Approved symbol	ANKFN1
Name	ankyrin repeat and fibronectin type III domain containing 1
Location	17q22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38335
Ensembl gene	ENSG00000153930
Ensembl biotype	protein_coding
OMIM	620853
Entrez	162282

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000318698, ENST00000566473, ENST00000572312, ENST00000572321, ENST00000572945, ENST00000573365, ENST00000574292, ENST00000575594, ENST00000635860, ENST00000653862, ENST00000682825

RefSeq mRNA: 3 — MANE Select: NM_001370326 NM_001365758, NM_001370326, NM_153228

CCDS: CCDS32686, CCDS92363

Canonical transcript exons

ENST00000682825 — 21 exons

Exon	Start	End
ENSE00001239021	56449079	56449186
ENSE00001239051	56353836	56354046
ENSE00001239110	56442843	56442933
ENSE00001239115	56440327	56440424
ENSE00001239122	56374601	56374714
ENSE00001239129	56372646	56372840
ENSE00001239143	56350766	56350967
ENSE00001239182	56326221	56326355
ENSE00003638415	56227917	56227957
ENSE00003916646	56510473	56517016
ENSE00003917688	56212598	56212679
ENSE00003918473	56153475	56153530
ENSE00003979639	56492187	56492353
ENSE00003979640	56456861	56456960
ENSE00003979641	56480668	56480818
ENSE00003979642	56457257	56457389
ENSE00003979643	56498882	56499098
ENSE00003979645	56482356	56482524
ENSE00003979646	56457863	56457979
ENSE00003979647	56477488	56477654
ENSE00003979648	56466356	56466571

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 93.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6379 / max 39.9588, expressed in 141 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161797	0.5852	119
161796	0.0266	10
161795	0.0262	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.52	gold quality
bronchial epithelial cell	CL:0002328	86.94	gold quality
bronchus	UBERON:0002185	85.91	gold quality
oviduct epithelium	UBERON:0004804	84.52	gold quality
right uterine tube	UBERON:0001302	83.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.36	gold quality
ventricular zone	UBERON:0003053	78.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	75.06	gold quality
myocardium	UBERON:0002349	74.35	gold quality
nasal cavity epithelium	UBERON:0005384	74.25	gold quality
fallopian tube	UBERON:0003889	73.86	gold quality
parotid gland	UBERON:0001831	73.66	gold quality
vena cava	UBERON:0004087	72.50	gold quality
ganglionic eminence	UBERON:0004023	72.10	gold quality
cartilage tissue	UBERON:0002418	71.93	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	71.51	gold quality
vastus lateralis	UBERON:0001379	71.39	gold quality
quadriceps femoris	UBERON:0001377	71.29	gold quality
corpus callosum	UBERON:0002336	69.88	gold quality
biceps brachii	UBERON:0001507	69.63	gold quality
medial globus pallidus	UBERON:0002477	68.32	gold quality
trabecular bone tissue	UBERON:0002483	68.21	gold quality
globus pallidus	UBERON:0001875	67.60	silver quality
gingiva	UBERON:0001828	67.58	gold quality
skin of leg	UBERON:0001511	67.51	gold quality
pharyngeal mucosa	UBERON:0000355	67.28	gold quality
heart right ventricle	UBERON:0002080	67.13	gold quality
deltoid	UBERON:0001476	67.09	gold quality
decidua	UBERON:0002450	67.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.63

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• ANKFN1 expression is significantly downregulated in human masticatory mucosa during wound healing (PMID:28005267)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankfn1a	ENSDARG00000060941
mus_musculus	Ankfn1	ENSMUSG00000047773
rattus_norvegicus		ENSRNOG00000081540

Protein

Protein identifiers

Ankyrin repeat and fibronectin type-III domain-containing protein 1 — Q8N957 (reviewed: Q8N957)

All UniProt accessions (5): Q8N957, A0A1B0GTR8, A0A590UK59, H3BM45, I3L0N6

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in neuronal function.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N957-1	1	yes
Q8N957-2	2

RefSeq proteins (3): NP_001352687, NP_001357255, NP_694960 (=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
IPR039269	ANKFN1	Family

Pfam: PF00041

UniProt features (13 total): region of interest 4, splice variant 3, repeat 2, chain 1, sequence variant 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N957-F1	66.55	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 67 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_BEHAVIOR, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_SPINDLE_LOCALIZATION, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_BALANCE, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_FEAR_RESPONSE, GOBP_MITOTIC_CELL_CYCLE, GOBP_RHYTHMIC_BEHAVIOR, GOBP_SENSORY_PERCEPTION, GOBP_REGULATION_OF_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, RFX1_02, GOBP_NEUROMUSCULAR_PROCESS

GO Biological Process (5): establishment of mitotic spindle orientation (GO:0000132), behavioral fear response (GO:0001662), locomotor rhythm (GO:0045475), equilibrioception (GO:0050957), regulation of establishment of bipolar cell polarity (GO:0061172)

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

GO Cellular Component (1): spindle (GO:0005819)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
behavioral defense response	1
fear response	1
locomotory behavior	1
circadian behavior	1
sensory perception	1
neuromuscular process controlling balance	1
establishment of bipolar cell polarity	1
regulation of establishment of cell polarity	1
binding	1
microtubule cytoskeleton	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

600 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKFN1	C17orf67	Q0P5P2	560
ANKFN1	CDRT15L2	A8MXV6	477
ANKFN1	SLC35G1	Q2M3R5	475
ANKFN1	SYNGR2	O43760	471
ANKFN1	PCTP	Q9UKL6	464
ANKFN1	C17orf58	Q2M2W7	447
ANKFN1	MRM1	Q6IN84	434
ANKFN1	FNDC9	Q8TBE3	430
ANKFN1	SCPEP1	Q9HB40	411
ANKFN1	STXBP4	Q6ZWJ1	402
ANKFN1	TBC1D28	Q2M2D7	400
ANKFN1	CSMD1	Q96PZ7	393
ANKFN1	MMD	Q15546	390
ANKFN1	OR8K3	Q8NH51	389
ANKFN1	AATF	Q9NY61	384

IntAct

0 interactions, top by confidence:

BioGRID (1): ANKFN1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2KIZ8, A0A1L8GXY4, A0A571BF63, A0A8M9QN10, A2CEI4, A2RRP1, A4D1P6, A6H8T2, A9X1C6, B0FXQ5, B1WC10, B2KIQ4, B2RY71, B2RYI0, B7FF09, B7FF12, E9PYY5, F1QHZ6, Q1LXZ7, Q2HJE1, Q3UMY5, Q402B2, Q4V8G4, Q5R6T6, Q5RE88, Q5U1Z0, Q5VTH9, Q5XIZ9, Q5ZLL7, Q6DFC6, Q6DTM3, Q6GPB9, Q6P2C0, Q6TEN6, Q7TMQ7, Q7ZVR1, Q8BMG7, Q8BX17, Q8C147, Q8IWG1

Diamond homologs: A0A571BF63, A0A8M9QN10, Q8N957

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	98
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
987739	Single allele	Pathogenic

SpliceAI

3783 predictions. Top by Δscore:

Variant	Effect	Δscore
17:56227916:GA:G	acceptor_gain	1.0000
17:56227958:G:GG	donor_gain	1.0000
17:56350944:C:G	donor_gain	1.0000
17:56350955:G:GT	donor_gain	1.0000
17:56350965:GTG:G	donor_gain	1.0000
17:56353834:A:AG	acceptor_gain	1.0000
17:56353835:G:GT	acceptor_gain	1.0000
17:56353835:GA:G	acceptor_gain	1.0000
17:56353835:GAA:G	acceptor_gain	1.0000
17:56353835:GAAT:G	acceptor_gain	1.0000
17:56353835:GAATT:G	acceptor_gain	1.0000
17:56354042:ACACT:A	donor_gain	1.0000
17:56354043:CACT:C	donor_gain	1.0000
17:56354043:CACTG:C	donor_loss	1.0000
17:56354044:ACT:A	donor_gain	1.0000
17:56354045:CT:C	donor_gain	1.0000
17:56354045:CTGT:C	donor_loss	1.0000
17:56354046:TG:T	donor_loss	1.0000
17:56354047:G:A	donor_loss	1.0000
17:56354047:G:GG	donor_gain	1.0000
17:56354048:TAA:T	donor_loss	1.0000
17:56372644:A:AG	acceptor_gain	1.0000
17:56372645:G:GG	acceptor_gain	1.0000
17:56372645:GTT:G	acceptor_gain	1.0000
17:56372837:GCCA:G	donor_gain	1.0000
17:56372841:G:GG	donor_gain	1.0000
17:56440307:T:A	acceptor_gain	1.0000
17:56440316:A:AG	acceptor_gain	1.0000
17:56440317:C:G	acceptor_gain	1.0000
17:56440322:TCCAG:T	acceptor_loss	1.0000

AlphaMissense

7562 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:56350860:C:A	R98S	0.999
17:56350870:G:C	R101T	0.999
17:56350870:G:T	R101M	0.999
17:56350871:G:C	R101S	0.999
17:56350871:G:T	R101S	0.999
17:56350876:T:C	L103P	0.999
17:56353870:T:A	V145D	0.999
17:56353977:G:C	A181P	0.999
17:56353978:C:A	A181D	0.999
17:56456923:T:C	F427L	0.999
17:56456924:T:C	F427S	0.999
17:56456925:C:A	F427L	0.999
17:56456925:C:G	F427L	0.999
17:56457325:C:A	P462Q	0.999
17:56457325:C:G	P462R	0.999
17:56457378:T:A	W480R	0.999
17:56457378:T:C	W480R	0.999
17:56457975:T:C	L521P	0.999
17:56466380:G:A	G531R	0.999
17:56466380:G:C	G531R	0.999
17:56466407:G:C	D540H	0.999
17:56466479:T:A	W564R	0.999
17:56466479:T:C	W564R	0.999
17:56350855:C:A	A96D	0.998
17:56350876:T:A	L103H	0.998
17:56353866:G:C	A144P	0.998
17:56354014:T:C	L193P	0.998
17:56372676:T:C	L214P	0.998
17:56374655:T:C	L287P	0.998
17:56374661:T:A	V289D	0.998

dbSNP variants (sampled 300 via entrez): RS1000001995 (17:56481510 A>G), RS1000012961 (17:56397892 A>G), RS1000013511 (17:56468959 C>G,T), RS1000033684 (17:56383133 C>G), RS1000039632 (17:56417615 T>G), RS1000041462 (17:56254861 G>A), RS1000054478 (17:56481743 C>T), RS1000061915 (17:56104324 C>A,T), RS1000062301 (17:56119721 T>C), RS1000066294 (17:56125462 G>A), RS1000068248 (17:56410703 C>G,T), RS1000074126 (17:56254464 A>G), RS1000077961 (17:56125721 G>A), RS1000083278 (17:56362256 C>A), RS1000088298 (17:56211062 C>T)

Disease associations

OMIM: gene MIM:620853 | disease phenotypes: MIM:189800, MIM:184460

GenCC curated gene-disease

Mondo (2): preeclampsia (MONDO:0005081), stapes ankylosis with broad thumbs and toes (MONDO:0008484)

Orphanet (2): Preeclampsia (Orphanet:275555), Stapes ankylosis with broad thumbs and toes (Orphanet:140917)

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000176_1	Height	2.000000e-06
GCST000861_6	Cannabis dependence	6.000000e-07
GCST002112_6	Celiac disease	4.000000e-06
GCST003783_15	Multiple system atrophy (pathologically confirmed)	1.000000e-07
GCST005174_46	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	4.000000e-06
GCST006288_292	Heel bone mineral density	1.000000e-24
GCST006288_361	Heel bone mineral density	2.000000e-13
GCST006288_59	Heel bone mineral density	1.000000e-10
GCST006979_506	Heel bone mineral density	2.000000e-56
GCST006979_507	Heel bone mineral density	5.000000e-16
GCST007429_132	Lung function (FVC)	1.000000e-18
GCST007432_91	FEV1	4.000000e-18
GCST007576_289	Chronotype	1.000000e-10
GCST008839_263	Height	5.000000e-11
GCST008839_534	Height	1.000000e-08
GCST009847_6	Hallux valgus	1.000000e-06
GCST90000025_599	Appendicular lean mass	2.000000e-19
GCST90007006_3	Gut microbiota relative abundance (unclassified genus belonging to family Erysipelotrichaceae)	4.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0009270	heel bone mineral density
EFO:0004312	vital capacity
EFO:0004314	forced expiratory volume
EFO:0008328	chronotype measurement
EFO:0004980	appendicular lean mass
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011225	Pre-Eclampsia	C12.050.703.395.249

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9915451	Efficacy	3	hydrochlorothiazide	Essential hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9915451	ANKFN1	3	0.00	1	hydrochlorothiazide

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
sodium arsenite	increases expression	1
zinc chromate	increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
Ethyl Methanesulfonate	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Lead	affects expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	PHASE4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	PHASE4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	PHASE4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	PHASE4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665	PHASE4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial