IGFL4

Summary

IGFL4 (IGF like family member 4, HGNC:32931) is a protein-coding gene on chromosome 19q13.32, encoding Insulin growth factor-like family member 4 (Q6B9Z1).

Predicted to enable signaling receptor binding activity. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 444882 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_001002923

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32931
Approved symbol	IGFL4
Name	IGF like family member 4
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204869
Ensembl biotype	protein_coding
OMIM	610547
Entrez	444882

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000377697, ENST00000595006, ENST00000596694, ENST00000601672

RefSeq mRNA: 1 — MANE Select: NM_001002923 NM_001002923

CCDS: CCDS33057

Canonical transcript exons

ENST00000377697 — 4 exons

Exon	Start	End
ENSE00001474878	46039182	46039936
ENSE00001474881	46040944	46041002
ENSE00003464338	46040518	46040568
ENSE00003534999	46040157	46040416

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 86.90.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9072 / max 139.3816, expressed in 189 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181609	0.5949	160
181605	0.1354	54
181610	0.0724	36
181608	0.0658	41
181607	0.0154	3
181604	0.0130	5
181606	0.0103	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primary visual cortex	UBERON:0002436	86.90	gold quality
right frontal lobe	UBERON:0002810	84.59	gold quality
superior frontal gyrus	UBERON:0002661	83.30	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.89	gold quality
cerebellar hemisphere	UBERON:0002245	80.88	gold quality
cerebellar cortex	UBERON:0002129	80.82	gold quality
cerebellum	UBERON:0002037	80.66	gold quality
nucleus accumbens	UBERON:0001882	80.14	gold quality
pituitary gland	UBERON:0000007	79.93	gold quality
anterior cingulate cortex	UBERON:0009835	79.58	gold quality
cerebral cortex	UBERON:0000956	77.82	gold quality
brain	UBERON:0000955	77.66	gold quality
putamen	UBERON:0001874	77.26	gold quality
adenohypophysis	UBERON:0002196	77.25	gold quality
caudate nucleus	UBERON:0001873	76.66	gold quality
hypothalamus	UBERON:0001898	76.38	gold quality
frontal cortex	UBERON:0001870	76.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.92	gold quality
amygdala	UBERON:0001876	75.62	gold quality
Ammon’s horn	UBERON:0001954	75.62	gold quality
temporal lobe	UBERON:0001871	75.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.49	gold quality
cortical plate	UBERON:0005343	73.00	gold quality
skin of abdomen	UBERON:0001416	72.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	71.21	gold quality
zone of skin	UBERON:0000014	71.14	gold quality
substantia nigra	UBERON:0002038	70.42	gold quality
skin of leg	UBERON:0001511	70.28	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.74
E-ENAD-20	no	68.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting IGFL4, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-376A-5P	97.70	65.61	863
HSA-MIR-8079	96.33	66.11	484
HSA-MIR-4522	95.76	66.23	742
HSA-MIR-5586-3P	95.51	67.00	805

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Igfl3	ENSMUSG00000066756
rattus_norvegicus	AC093995.2	ENSRNOG00000032940

Paralogs (3): IGFL1 (ENSG00000188293), IGFL3 (ENSG00000188624), IGFL2 (ENSG00000204866)

Protein

Protein identifiers

Insulin growth factor-like family member 4 — Q6B9Z1 (reviewed: Q6B9Z1)

All UniProt accessions (2): M0QYY9, Q6B9Z1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Detected in the cerebellum.

Similarity. Belongs to the IGFL family.

RefSeq proteins (1): NP_001002923* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032744	IGFL	Family

Pfam: PF14653

UniProt features (6 total): glycosylation site 2, sequence variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6B9Z1-F1	70.03	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 57, 84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): GOMF_SIGNALING_RECEPTOR_BINDING, ATF5_TARGET_GENES, FOXD2_TARGET_GENES, MIER1_TARGET_GENES, SIX1_TARGET_GENES, TOP2B_TARGET_GENES, ZNF10_TARGET_GENES, ZNF350_TARGET_GENES, ZNF528_TARGET_GENES, ZNF561_TARGET_GENES, ZNF596_TARGET_GENES, ZNF664_TARGET_GENES, ZNF711_TARGET_GENES, ZSCAN30_TARGET_GENES, MIR3529_3P

GO Biological Process (0):

GO Molecular Function (1): signaling receptor binding (GO:0005102)

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
cellular anatomical structure	1

Protein interactions and networks

STRING

138 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGFL4	MAB21L4	Q08AI8	478
IGFL4	XKRX	Q6PP77	472
IGFL4	FAM171B	Q6P995	432
IGFL4	EVA1C	P58658	397
IGFL4	KRTAP3-1	Q9BYR8	391
IGFL4	TMEM64	Q6YI46	365
IGFL4	ZNF341	Q9BYN7	350
IGFL4	DDIT4L	Q96D03	307
IGFL4	SNTB1	Q13884	290
IGFL4	B3GNT2	Q9NY97	277
IGFL4	PPFIBP1	Q86W92	272
IGFL4	AIRIM	Q9NX04	255
IGFL4	CCDC80	Q76M96	249
IGFL4	ZNF703	Q9H7S9	244
IGFL4	SLC39A10	Q9ULF5	244

IntAct

0 interactions, top by confidence:

BioGRID (1): IGFL4 (Negative Genetic)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

455 predictions. Top by Δscore:

Variant	Effect	Δscore
19:46040151:CCTTA:C	donor_loss	0.9700
19:46040152:CTTAC:C	donor_loss	0.9700
19:46040153:TTA:T	donor_loss	0.9700
19:46040154:TACCT:T	donor_loss	0.9700
19:46040156:C:CA	donor_loss	0.9700
19:46040414:GATC:G	acceptor_loss	0.9500
19:46040415:AT:A	acceptor_gain	0.9500
19:46040415:ATC:A	acceptor_loss	0.9500
19:46040417:C:CG	acceptor_loss	0.9500
19:46040418:T:A	acceptor_loss	0.9500
19:46039934:TTC:T	acceptor_gain	0.9200
19:46040414:GAT:G	acceptor_gain	0.9200
19:46039937:C:CA	acceptor_loss	0.9100
19:46040417:C:CC	acceptor_gain	0.9100
19:46040512:TCTCA:T	donor_loss	0.9100
19:46040513:CTCAC:C	donor_loss	0.9100
19:46040514:TCA:T	donor_loss	0.9100
19:46040515:CAC:C	donor_loss	0.9100
19:46040516:A:C	donor_loss	0.9100
19:46040517:C:CG	donor_loss	0.9100
19:46040414:GATCT:G	acceptor_gain	0.9000
19:46040415:ATCTG:A	acceptor_gain	0.9000
19:46040417:C:A	acceptor_gain	0.8900
19:46040419:GGAA:G	acceptor_loss	0.8900
19:46040420:GAAG:G	acceptor_loss	0.8900
19:46040421:AAGA:A	acceptor_loss	0.8900
19:46039935:TC:T	acceptor_gain	0.8800
19:46039936:CC:C	acceptor_gain	0.8800
19:46040155:A:AC	donor_gain	0.8800
19:46040156:C:CC	donor_gain	0.8800

AlphaMissense

808 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:46040280:C:A	W69C	0.950
19:46040280:C:G	W69C	0.950
19:46040283:G:C	F68L	0.949
19:46040283:G:T	F68L	0.949
19:46040285:A:G	F68L	0.949
19:46040272:A:C	F72C	0.947
19:46040347:C:G	C47S	0.931
19:46040348:A:T	C47S	0.931
19:46040344:C:G	C48S	0.922
19:46040345:A:T	C48S	0.922
19:46040262:G:C	C75W	0.919
19:46040348:A:G	C47R	0.915
19:46040263:C:G	C75S	0.913
19:46040264:A:T	C75S	0.913
19:46040302:C:G	C62S	0.912
19:46040303:A:T	C62S	0.912
19:46040271:G:C	F72L	0.902
19:46040271:G:T	F72L	0.902
19:46040273:A:G	F72L	0.902
19:46040284:A:C	F68C	0.902
19:46040346:G:C	C47W	0.902
19:46040264:A:G	C75R	0.899
19:46040274:G:C	C71W	0.899
19:46040263:C:T	C75Y	0.897
19:46040380:C:G	C36S	0.888
19:46040381:A:T	C36S	0.888
19:46040344:C:T	C48Y	0.886
19:46040366:A:C	Y41D	0.876
19:46040191:C:G	C99S	0.874
19:46040192:A:T	C99S	0.874

dbSNP variants (sampled 300 via entrez): RS1000139917 (19:46078374 C>A,G), RS1000197114 (19:46053385 T>C), RS1000215602 (19:46042645 TACAC>T), RS1000233477 (19:46063765 A>T), RS1000293705 (19:46049647 A>G), RS1000336965 (19:46045968 T>G), RS1000390075 (19:46056868 G>A,C), RS1000463434 (19:46056664 G>A,C), RS1000610053 (19:46052969 A>AG), RS1000665497 (19:46049969 A>G), RS1000689230 (19:46059933 G>A), RS1000796980 (19:46058010 A>G), RS1001055565 (19:46074165 AG>A,AGG), RS1001234485 (19:46063548 T>C), RS1001249401 (19:46070196 T>C)

Disease associations

OMIM: gene MIM:610547 | 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

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
licochalcone B	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Copper	affects cotreatment, decreases expression	1
Asbestos, Serpentine	decreases methylation	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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