IGFN1

Summary

IGFN1 (immunoglobulin like and fibronectin type III domain containing 1, HGNC:24607) is a protein-coding gene on chromosome 1q32.1, encoding Immunoglobulin-like and fibronectin type III domain-containing protein 1 (Q86VF2).

Predicted to act upstream of or within myoblast differentiation and myoblast fusion. Predicted to be located in Z disc and nucleus.

Source: NCBI Gene 91156 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 901 total
• MANE Select transcript: NM_001164586

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24607
Approved symbol	IGFN1
Name	immunoglobulin like and fibronectin type III domain containing 1
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434B1231, EEF1A2BP1
Ensembl gene	ENSG00000163395
Ensembl biotype	protein_coding
OMIM	617309
Entrez	91156

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000295591, ENST00000335211, ENST00000437879, ENST00000444705, ENST00000473483

RefSeq mRNA: 2 — MANE Select: NM_001164586 NM_001164586, NM_001367841

CCDS: CCDS53455, CCDS91141

Canonical transcript exons

ENST00000335211 — 24 exons

Exon	Start	End
ENSE00001074099	201215539	201215838
ENSE00003465531	201215013	201215154
ENSE00003468111	201226882	201227208
ENSE00003490815	201216454	201216753
ENSE00003519041	201218530	201218658
ENSE00003553285	201214177	201214301
ENSE00003564195	201228386	201228952
ENSE00003568533	201206083	201213621
ENSE00003577685	201217287	201217460
ENSE00003595406	201224679	201224874
ENSE00003619443	201221444	201221746
ENSE00003638486	201205082	201205354
ENSE00003645213	201222739	201222827
ENSE00003718291	201200237	201200411
ENSE00003725291	201203738	201203906
ENSE00003727529	201199334	201199378
ENSE00003728565	201197218	201197317
ENSE00003729169	201193247	201193300
ENSE00003735447	201194154	201194273
ENSE00003736930	201199609	201199654
ENSE00003738745	201201719	201201832
ENSE00003746968	201195839	201195978
ENSE00003748595	201225824	201226123
ENSE00003897309	201190824	201190907

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 94.01.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8094 / max 330.2967, expressed in 171 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7679	1.7535	166
7678	0.0559	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	94.01	gold quality
left lobe of thyroid gland	UBERON:0001120	93.88	gold quality
right lobe of thyroid gland	UBERON:0001119	93.50	gold quality
thyroid gland	UBERON:0002046	92.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.48	gold quality
muscle of leg	UBERON:0001383	91.28	gold quality
kidney epithelium	UBERON:0004819	90.40	gold quality
tibialis anterior	UBERON:0001385	88.36	silver quality
quadriceps femoris	UBERON:0001377	86.16	silver quality
vastus lateralis	UBERON:0001379	86.06	silver quality
body of pancreas	UBERON:0001150	85.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.36	silver quality
left ventricle myocardium	UBERON:0006566	83.73	gold quality
cardiac muscle of right atrium	UBERON:0003379	83.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.65	gold quality
epithelial cell of pancreas	CL:0000083	83.11	gold quality
trabecular bone tissue	UBERON:0002483	82.55	gold quality
skeletal muscle tissue	UBERON:0001134	82.46	gold quality
deltoid	UBERON:0001476	82.13	gold quality
muscle tissue	UBERON:0002385	80.81	gold quality
myocardium	UBERON:0002349	80.67	gold quality
superficial temporal artery	UBERON:0001614	79.42	gold quality
nasal cavity epithelium	UBERON:0005384	75.94	gold quality
biceps brachii	UBERON:0001507	75.40	silver quality
upper arm skin	UBERON:0004263	74.06	gold quality
pancreas	UBERON:0001264	73.52	gold quality
tendon of biceps brachii	UBERON:0008188	73.51	silver quality
left testis	UBERON:0004533	72.28	gold quality
sperm	CL:0000019	71.98	gold quality
parotid gland	UBERON:0001831	71.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.05

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• a model in which this increased expression of IGFN1 serves to down-regulate protein synthesis via interaction with eEF1A during denervation. (PMID:18756455)
• A novel variant, c.6196A>G in the IGFN1 gene, was significantly associated with only Polypoidal choroidal vasculopathy (combined p = 7.1 x 10(-11) , odds ratio = 9.44), but not with neovascular age-related macular degeneration(combined p = 0.683, odds ratio = 1.30). (PMID:29323771)
• Study results in UOK146 renal cell carcinoma cell line provide evidence of novel splicing in intron 15 of IGFN1 leading to the formation of two more alternative spliced isoforms. Potential G-quadruplex forming sequence (PQS) in this intron forms a stable G-quadruplex which is involved in the alternative splicing and regulates splicing efficiency. (PMID:30335789)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Igfn1	ENSMUSG00000051985
rattus_norvegicus	Igfn1	ENSRNOG00000026087
drosophila_melanogaster	bt	FBGN0005666
caenorhabditis_elegans		WBGENE00001000
caenorhabditis_elegans		WBGENE00006759
caenorhabditis_elegans	unc-89	WBGENE00006820

Paralogs (9): SPEG (ENSG00000072195), MYOT (ENSG00000120729), PALLD (ENSG00000129116), ALPK3 (ENSG00000136383), MYPN (ENSG00000138347), HMCN1 (ENSG00000143341), OBSCN (ENSG00000154358), CCDC141 (ENSG00000163492), SPEGNB (ENSG00000286095)

Protein

Protein identifiers

Immunoglobulin-like and fibronectin type III domain-containing protein 1 — Q86VF2 (reviewed: Q86VF2)

Alternative names: EEF1A2-binding protein 1, KY-interacting protein 1

All UniProt accessions (1): Q86VF2

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with FLNC. Interacts with KY.

Subcellular location. Nucleus. Cytoplasm. Myofibril. Sarcomere. Z line.

Tissue specificity. Expressed in skeletal muscle.

Isoforms (5)

UniProt ID	Names	Canonical?
Q86VF2-1	1	yes
Q86VF2-2	2
Q86VF2-3	3
Q86VF2-4	4
Q86VF2-5	5

RefSeq proteins (2): NP_001158058, NP_001354770 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR040849	MyBP-C_THB	Domain
IPR050964	Striated_Muscle_Regulatory	Family

Pfam: PF00041, PF07679, PF18362

UniProt features (24 total): domain 9, splice variant 7, region of interest 2, compositionally biased region 2, sequence variant 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VF2-F1	77.48	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): GOCC_I_BAND, FORTSCHEGGER_PHF8_TARGETS_DN, GOCC_SUPRAMOLECULAR_COMPLEX, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_129_MOUSE_UP, GOCC_SUPRAMOLECULAR_POLYMER, MIR6764_5P, MIR665, BLANCO_MELO_RESPIRATORY_SYNCYTIAL_VIRUS_INFECTION_A594_CELLS_UP, MANNO_MIDBRAIN_NEUROTYPES_HGABA, DESCARTES_MAIN_FETAL_CCL19_CCL21_POSITIVE_CELLS, DESCARTES_FETAL_ADRENAL_STROMAL_CELLS, DESCARTES_FETAL_KIDNEY_STROMAL_CELLS, DESCARTES_FETAL_PANCREAS_CCL19_CCL21_POSITIVE_CELLS, ZNF490_TARGET_GENES, NOURUZI_NEPC_ASCL1_TARGETS

GO Biological Process (0):

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

GO Cellular Component (3): nucleus (GO:0005634), Z disc (GO:0030018), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
intracellular membrane-bounded organelle	1
I band	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGFN1	FLNC	Q14315	664
IGFN1	COBL	O75128	528
IGFN1	MSS51	Q4VC12	452
IGFN1	FSIP2	Q5CZC0	420
IGFN1	OSBPL3	Q9H4L5	409
IGFN1	FRAS1	Q86XX4	406
IGFN1	FNDC10	F2Z333	401
IGFN1	FNDC7	Q5VTL7	380
IGFN1	OR2W1	Q9Y3N9	379
IGFN1	PRAMEF13	Q5VWM6	378
IGFN1	MUC12	Q9UKN1	367
IGFN1	NKAIN1	Q4KMZ8	356
IGFN1	OR2T12	Q8NG77	351
IGFN1	KCNG4	Q8TDN1	349
IGFN1	OR5T1	Q8NG75	348

IntAct

11 interactions, top by confidence:

A	B	Type	Score
MEOX2	IGFN1	psi-mi:“MI:0915”(physical association)	0.560
IGFN1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
KLHL25	IGFN1	psi-mi:“MI:0915”(physical association)	0.560
TRPS1	MTA2	psi-mi:“MI:0914”(association)	0.530
GAREM1	IGFN1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	IGFN1	psi-mi:“MI:0915”(physical association)	0.370
IGFN1	HSPD1	psi-mi:“MI:0914”(association)	0.350
ATP6V0A4	ATP6V0C	psi-mi:“MI:0914”(association)	0.350
GPC3	PXDNL	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid), IGFN1 (Two-hybrid)

ESM2 similar proteins: A1A5C7, A6NCF5, A6QLN9, A8MUP2, D3YYU8, D3ZZ80, F1LTR1, O75147, O88843, P08887, Q28D01, Q3SZQ2, Q3UHH2, Q3ZCW2, Q4R539, Q5EA19, Q5R4Q7, Q5R5K6, Q5RCI5, Q5RFN0, Q5SP67, Q5ZHQ2, Q642A6, Q67FW5, Q6AZB0, Q6IA17, Q6PCB0, Q7TPB4, Q86TI4, Q86VF2, Q8BGR6, Q8BZI6, Q8C6G8, Q8N5I2, Q8N653, Q8R2Z5, Q8VE98, Q8VED9, Q969P0, Q96NJ5

Diamond homologs: A2ASS6, A2CG49, A4IFM7, A8C984, A8X6H4, E9PT87, F1M0Z1, O02827, O14936, O43293, O44997, O49717, O54784, O60229, O70589, O75962, O80673, O88764, O94768, P07313, P08414, P0C5E3, P11801, P13234, P20689, P25323, P53355, P53681, P53684, P70402, P93759, P97924, Q05623, Q06850, Q0KL02, Q0V7M1, Q10KY3, Q13203, Q14012, Q16566

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	752
Likely benign	124
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3771 predictions. Top by Δscore:

Variant	Effect	Δscore
1:201190905:CAGGT:C	donor_loss	1.0000
1:201190906:AGGTA:A	donor_loss	1.0000
1:201190908:GTA:G	donor_loss	1.0000
1:201193243:TCA:T	acceptor_loss	1.0000
1:201193244:CAGG:C	acceptor_loss	1.0000
1:201193246:G:GC	acceptor_loss	1.0000
1:201193299:AGG:A	donor_loss	1.0000
1:201193301:GT:G	donor_loss	1.0000
1:201193302:T:A	donor_loss	1.0000
1:201194142:T:TA	acceptor_gain	1.0000
1:201194270:GAGG:G	donor_gain	1.0000
1:201194272:GG:G	donor_gain	1.0000
1:201194273:GG:G	donor_gain	1.0000
1:201195834:TGCA:T	acceptor_loss	1.0000
1:201195836:CAGGG:C	acceptor_loss	1.0000
1:201195837:A:AG	acceptor_gain	1.0000
1:201195837:AG:A	acceptor_gain	1.0000
1:201195837:AGGGA:A	acceptor_loss	1.0000
1:201195838:G:A	acceptor_loss	1.0000
1:201195838:G:GG	acceptor_gain	1.0000
1:201195838:GG:G	acceptor_gain	1.0000
1:201195975:GCAG:G	donor_gain	1.0000
1:201195977:AGGTA:A	donor_loss	1.0000
1:201195978:GGT:G	donor_loss	1.0000
1:201195979:G:GG	donor_gain	1.0000
1:201195980:T:G	donor_loss	1.0000
1:201199289:T:A	acceptor_gain	1.0000
1:201199293:T:A	acceptor_gain	1.0000
1:201199298:A:AG	acceptor_gain	1.0000
1:201199298:ACATC:A	acceptor_gain	1.0000

AlphaMissense

23960 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000053111 (1:201221273 G>T), RS1000104375 (1:201191078 C>T), RS1000138379 (1:201215802 G>T), RS1000205792 (1:201216932 C>T), RS1000313065 (1:201199720 A>G), RS1000536969 (1:201198126 C>T), RS1000606566 (1:201221297 C>A), RS1000606938 (1:201192784 C>T), RS1000653436 (1:201198387 C>A,T), RS1000670373 (1:201194126 C>A,T), RS1000757318 (1:201212302 A>G,T), RS1000805061 (1:201205064 T>C), RS1000901008 (1:201202734 T>A,C), RS1001033863 (1:201203511 C>G,T), RS1001182307 (1:201197123 C>T)

Disease associations

OMIM: gene MIM:617309 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005212_6	Asthma	2.000000e-06
GCST008163_627	Height	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
aristolochic acid I	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
bisphenol S	decreases expression	1
(+)-JQ1 compound	increases expression	1
Arsenic	affects methylation	1
Methapyrilene	decreases methylation	1
Oxygen	increases expression	1
Rotenone	increases expression	1
Valproic Acid	increases methylation	1
Gold Compounds	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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