IGFL2

Summary

IGFL2 (IGF like family member 2, HGNC:32929) is a protein-coding gene on chromosome 19q13.32, encoding Insulin growth factor-like family member 2 (Q6UWQ7). Potential ligand of the IGFLR1 cell membrane receptor.

IGFL2 belongs to the insulin-like growth factor (IGF; see MIM 147440) family of signaling molecules that play critical roles in cellular energy metabolism and in growth and development, especially prenatal growth (Emtage et al., 2006 [PubMed 16890402]).

Source: NCBI Gene 147920 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_001135113

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32929
Approved symbol	IGFL2
Name	IGF like family member 2
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	UNQ645
Ensembl gene	ENSG00000204866
Ensembl biotype	protein_coding
OMIM	610545
Entrez	147920

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000377693, ENST00000434646, ENST00000593592, ENST00000600243, ENST00000601052

RefSeq mRNA: 2 — MANE Select: NM_001135113 NM_001002915, NM_001135113

CCDS: CCDS46121, CCDS46122

Canonical transcript exons

ENST00000377693 — 4 exons

Exon	Start	End
ENSE00001739643	46148238	46148297
ENSE00002992017	46161070	46161289
ENSE00003552499	46160614	46160881
ENSE00003663839	46160415	46160468

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 93.68.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9277 / max 484.9021, expressed in 91 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176528	0.9064	90
176529	0.0213	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	93.68	gold quality
skin of leg	UBERON:0001511	92.99	gold quality
skin of abdomen	UBERON:0001416	92.01	gold quality
zone of skin	UBERON:0000014	91.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.67	gold quality
mammalian vulva	UBERON:0000997	76.25	gold quality
upper leg skin	UBERON:0004262	75.43	gold quality
left testis	UBERON:0004533	75.42	gold quality
right testis	UBERON:0004534	75.17	gold quality
testis	UBERON:0000473	73.63	gold quality
amniotic fluid	UBERON:0000173	70.82	silver quality
germinal epithelium of ovary	UBERON:0001304	70.78	gold quality
gingival epithelium	UBERON:0001949	69.41	gold quality
nipple	UBERON:0002030	67.90	gold quality
skin of hip	UBERON:0001554	67.76	silver quality
epithelial cell of pancreas	CL:0000083	66.15	gold quality
mucosa of transverse colon	UBERON:0004991	62.24	gold quality
superficial temporal artery	UBERON:0001614	60.67	gold quality
parietal pleura	UBERON:0002400	60.58	silver quality
sperm	CL:0000019	59.05	gold quality
rectum	UBERON:0001052	58.41	gold quality
calcaneal tendon	UBERON:0003701	58.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	57.62	gold quality
epithelium of nasopharynx	UBERON:0001951	56.71	gold quality
omental fat pad	UBERON:0010414	56.65	gold quality
peritoneum	UBERON:0002358	56.60	gold quality
nasal cavity epithelium	UBERON:0005384	56.58	gold quality
spinal cord	UBERON:0002240	56.03	gold quality
adipose tissue of abdominal region	UBERON:0007808	55.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting IGFL2, 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-4789-3P	99.99	70.75	2484
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-6508-3P	96.73	65.48	576

Cross-species orthologs

0 orthologs

Paralogs (3): IGFL1 (ENSG00000188293), IGFL3 (ENSG00000188624), IGFL4 (ENSG00000204869)

Protein

Protein identifiers

Insulin growth factor-like family member 2 — Q6UWQ7 (reviewed: Q6UWQ7)

All UniProt accessions (2): M0R089, Q6UWQ7

UniProt curated annotations — full annotation on UniProt →

Function. Potential ligand of the IGFLR1 cell membrane receptor.

Subcellular location. Secreted.

Tissue specificity. Detected in cerebellum, heart, placenta, spleen, stomach, testis and thymus.

Similarity. Belongs to the IGFL family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UWQ7-1	1	yes
Q6UWQ7-2	2

RefSeq proteins (2): NP_001002915, NP_001128585* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032744	IGFL	Family

Pfam: PF14653

UniProt features (3 total): signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWQ7-F1	73.77	0.31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 18 (showing top): RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOMF_SIGNALING_RECEPTOR_BINDING, ANDERSEN_CHOLANGIOCARCINOMA_CLASS2, ATF6_TARGET_GENES, FEV_TARGET_GENES, NFKBIA_TARGET_GENES, PAX7_TARGET_GENES, MIR3177_5P, MIR3606_5P, CUI_DEVELOPING_HEART_VALVAR_ENDOTHELIAL_CELL, DESCARTES_MAIN_FETAL_THYMIC_EPITHELIAL_CELLS, ZNF677_TARGET_GENES, TRAVAGLINI_LUNG_MESOTHELIAL_CELL, chr19q13, GSE4748_CYANOBACTERIUM_LPSLIKE_VS_LPS_AND_CYANOBACTERIUM_LPSLIKE_STIM_DC_3H_DN

GO Biological Process (0):

GO Molecular Function (2): signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGFL2	PTGDR	Q13258	479
IGFL2	ARPP19	P56211	396
IGFL2	WDR88	Q6ZMY6	377
IGFL2	WDSUB1	Q8N9V3	353
IGFL2	PRR27	Q6MZM9	323
IGFL2	HES2	Q9Y543	302
IGFL2	IGKV2-28	A0A075B6P5	289
IGFL2	PDIK1L	Q8N165	286
IGFL2	C5orf46	Q6UWT4	274
IGFL2	ASB12	Q8WXK4	269
IGFL2	SLC39A12	Q504Y0	264
IGFL2	IGFLR1	Q9H665	253
IGFL2	LCE2D	Q5TA82	247
IGFL2	LCE6A	A0A183	247
IGFL2	IGFBP6	P24592	244

IntAct

2 interactions, top by confidence:

A	B	Type	Score
IGFLR1	IGFL2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (3): IGFL2 (Two-hybrid), IGFL2 (Two-hybrid), IGFL2 (Two-hybrid)

ESM2 similar proteins: A2BDC9, A4IFM1, A4IHZ3, B1AL88, B4DS77, E7F5F0, E7FAP8, F8W2C9, O35181, O62647, P12272, P13085, P13385, P17251, P22858, P25308, P43145, P51864, P52211, P56975, P58073, P97297, P97766, Q02816, Q13361, Q28022, Q2YDG7, Q4RU86, Q4V9H3, Q5PQX1, Q60485, Q62923, Q640B5, Q64387, Q6B9Z1, Q6INW9, Q6P1H6, Q6UWQ7, Q6UXB1, Q6UXQ4

Diamond homologs: Q6B9Z0, Q6B9Z1, Q6UW32, Q6UWQ7, Q6UXB1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

478 predictions. Top by Δscore:

Variant	Effect	Δscore
19:46160413:A:AG	acceptor_gain	1.0000
19:46160414:G:GG	acceptor_gain	1.0000
19:46160411:CCA:C	acceptor_loss	0.9900
19:46160412:CAGC:C	acceptor_loss	0.9900
19:46160413:AGC:A	acceptor_loss	0.9900
19:46160607:T:TA	acceptor_gain	0.9900
19:46160609:TCCA:T	acceptor_loss	0.9900
19:46160612:A:AG	acceptor_gain	0.9900
19:46160613:G:GA	acceptor_gain	0.9900
19:46160613:GCT:G	acceptor_gain	0.9900
19:46160613:GCTC:G	acceptor_gain	0.9900
19:46160613:GCTCC:G	acceptor_gain	0.9900
19:46160739:G:GA	donor_gain	0.9900
19:46160878:AAAG:A	donor_gain	0.9900
19:46161068:A:AG	acceptor_gain	0.9900
19:46161069:G:GG	acceptor_gain	0.9900
19:46147907:GTTTG:G	donor_gain	0.9800
19:46160414:GCTC:G	acceptor_gain	0.9800
19:46160466:TCGGT:T	donor_loss	0.9800
19:46160469:G:C	donor_loss	0.9800
19:46160469:G:GG	donor_gain	0.9800
19:46160470:T:C	donor_loss	0.9800
19:46160471:GAGTA:G	donor_loss	0.9800
19:46160472:A:AA	donor_loss	0.9800
19:46160473:G:C	donor_loss	0.9800
19:46160604:A:AG	acceptor_gain	0.9800
19:46160605:T:G	acceptor_gain	0.9800
19:46160609:TCCAG:T	acceptor_gain	0.9800
19:46160610:CCAGC:C	acceptor_gain	0.9800
19:46160611:CAGCT:C	acceptor_gain	0.9800

AlphaMissense

771 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:46160754:T:C	F72L	0.941
19:46160756:C:A	F72L	0.941
19:46160756:C:G	F72L	0.941
19:46160759:G:C	W73C	0.928
19:46160759:G:T	W73C	0.928
19:46160691:T:A	C51S	0.908
19:46160692:G:C	C51S	0.908
19:46160658:T:A	C40S	0.903
19:46160659:G:C	C40S	0.903
19:46160767:T:G	F76C	0.902
19:46160755:T:G	F72C	0.893
19:46160694:T:A	C52S	0.892
19:46160695:G:C	C52S	0.892
19:46160673:T:G	Y45D	0.881
19:46160775:T:A	C79S	0.880
19:46160776:G:C	C79S	0.880
19:46160691:T:C	C51R	0.878
19:46160832:G:T	G98C	0.876
19:46160847:T:A	C103S	0.869
19:46160848:G:C	C103S	0.869
19:46160765:C:G	C75W	0.867
19:46160658:T:C	C40R	0.863
19:46160640:T:A	C34S	0.859
19:46160641:G:C	C34S	0.859
19:46160825:G:C	K95N	0.859
19:46160825:G:T	K95N	0.859
19:46160693:C:G	C51W	0.857
19:46160736:T:A	C66S	0.856
19:46160737:G:C	C66S	0.856
19:46160847:T:C	C103R	0.853

dbSNP variants (sampled 300 via entrez): RS1000022887 (19:46110670 A>G), RS1000033429 (19:46117316 C>T), RS1000056862 (19:46211173 C>T), RS1000060789 (19:46156635 T>C), RS1000078441 (19:46181601 C>T), RS1000086680 (19:46116907 T>G), RS1000093882 (19:46197213 C>A,T), RS1000097552 (19:46098854 T>A), RS1000097963 (19:46102316 G>C), RS1000115686 (19:46091488 G>A,T), RS1000139917 (19:46078374 C>A,G), RS1000206166 (19:46174082 G>A), RS1000254686 (19:46208566 C>A,G), RS1000259991 (19:46122517 C>T), RS1000268878 (19:46093618 T>C)

Disease associations

OMIM: gene MIM:610545 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
Valproic Acid	increases expression	2
abemaciclib	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
jinfukang	increases expression, affects cotreatment	1
Aldehydes	increases expression	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Dronabinol	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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