ELFN2

Summary

ELFN2 (extracellular leucine rich repeat and fibronectin type III domain containing 2, HGNC:29396) is a protein-coding gene on chromosome 22q13.1, encoding Protein phosphatase 1 regulatory subunit 29 (Q5R3F8). Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes.

Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in synaptic membrane adhesion. Predicted to act upstream of or within chemical synaptic transmission; establishment of protein localization; and gene expression. Located in extracellular space.

Source: NCBI Gene 114794 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 128 total
• MANE Select transcript: NM_052906

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29396
Approved symbol	ELFN2
Name	extracellular leucine rich repeat and fibronectin type III domain containing 2
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ63G5.3, KIAA1904
Ensembl gene	ENSG00000166897
Ensembl biotype	protein_coding
OMIM	620223
Entrez	114794

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000402918, ENST00000414347, ENST00000415408, ENST00000424973, ENST00000435824, ENST00000451509, ENST00000939364, ENST00000939365

RefSeq mRNA: 1 — MANE Select: NM_052906 NM_052906

CCDS: CCDS33642

Canonical transcript exons

ENST00000402918 — 3 exons

Exon	Start	End
ENSE00001552144	37367960	37375996
ENSE00003703019	37417769	37417919
ENSE00003849946	37427298	37427479

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 91.47.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6599 / max 108.6833, expressed in 446 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194058	1.8911	340
194057	0.3993	162
194060	0.1830	75
194059	0.0947	52
194056	0.0920	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	91.47	gold quality
entorhinal cortex	UBERON:0002728	86.76	gold quality
amygdala	UBERON:0001876	86.44	gold quality
temporal lobe	UBERON:0001871	86.42	gold quality
anterior cingulate cortex	UBERON:0009835	86.27	gold quality
prefrontal cortex	UBERON:0000451	84.93	gold quality
neocortex	UBERON:0001950	84.41	gold quality
cerebral cortex	UBERON:0000956	84.39	gold quality
frontal cortex	UBERON:0001870	84.25	gold quality
endothelial cell	CL:0000115	84.16	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	84.08	gold quality
Ammon’s horn	UBERON:0001954	83.99	gold quality
superior frontal gyrus	UBERON:0002661	83.45	gold quality
right frontal lobe	UBERON:0002810	83.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.16	gold quality
parietal lobe	UBERON:0001872	81.70	gold quality
middle temporal gyrus	UBERON:0002771	81.30	gold quality
primary visual cortex	UBERON:0002436	81.03	gold quality
postcentral gyrus	UBERON:0002581	80.97	gold quality
Brodmann (1909) area 46	UBERON:0006483	80.87	gold quality
nucleus accumbens	UBERON:0001882	80.82	gold quality
occipital lobe	UBERON:0002021	80.74	gold quality
hypothalamus	UBERON:0001898	80.31	gold quality
ganglionic eminence	UBERON:0004023	79.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	79.31	gold quality
superior vestibular nucleus	UBERON:0007227	78.77	gold quality
caudate nucleus	UBERON:0001873	78.48	gold quality
forebrain	UBERON:0001890	78.00	gold quality
putamen	UBERON:0001874	76.99	gold quality
medulla oblongata	UBERON:0001896	76.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

256 targeting ELFN2, 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-4533	100.00	69.48	2758
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034

Literature-anchored findings (GeneRIF, showing 2)

• Authors conclude that extracellular transsynaptic scaffolding by ELFN2 in the brain is a cardinal organizational feature of group III mGluRs essential for their signaling properties and brain function. (PMID:31485013)
• Identification of Key Prognostic-Related miRNA-mRNA Pairs in the Progression of Endometrial Carcinoma. (PMID:35081534)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	elfn2a	ENSDARG00000077609
danio_rerio	ELFN2	ENSDARG00000110874
mus_musculus	Elfn2	ENSMUSG00000043460
rattus_norvegicus	Elfn2	ENSRNOG00000007934
drosophila_melanogaster	Con	FBGN0005775
drosophila_melanogaster	kek3	FBGN0028370
caenorhabditis_elegans	lron-9	WBGENE00011971
caenorhabditis_elegans		WBGENE00020649

Paralogs (22): CHADL (ENSG00000100399), LGI1 (ENSG00000108231), LGR6 (ENSG00000133067), CHAD (ENSG00000136457), LRIG3 (ENSG00000139263), LGR5 (ENSG00000139292), LRIG1 (ENSG00000144749), LRRTM2 (ENSG00000146006), LRIT1 (ENSG00000148602), LGI2 (ENSG00000153012), LGI4 (ENSG00000153902), LRRC52 (ENSG00000162763), LGI3 (ENSG00000168481), LRG1 (ENSG00000171236), CPN2 (ENSG00000178772), LRIT3 (ENSG00000183423), LRRC26 (ENSG00000184709), LRIG2 (ENSG00000198799), LGR4 (ENSG00000205213), ELFN1 (ENSG00000225968), LRRC24 (ENSG00000254402), TRIL (ENSG00000255690)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 29 — Q5R3F8 (reviewed: Q5R3F8)

Alternative names: Extracellular leucine-rich repeat and fibronectin type III domain-containing protein 2, Leucine-rich repeat and fibronectin type-III domain-containing protein 6, Leucine-rich repeat-containing protein 62

All UniProt accessions (1): Q5R3F8

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes.

Subunit / interactions. Interacts with PPP1CA.

Subcellular location. Membrane.

RefSeq proteins (1): NP_443138* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050541	LRR_TM_domain-containing	Family
IPR055106	ELFN_Fn3	Domain

Pfam: PF13855, PF22986

UniProt features (27 total): glycosylation site 6, repeat 5, region of interest 4, modified residue 3, domain 2, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5R3F8-F1	61.79	0.25

Functional residue map

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

Post-translational modifications (3): 619, 668, 672

Glycosylation sites (6): 54, 80, 85, 117, 205, 247

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): CACCAGC_MIR138, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION, CCTGTGA_MIR513, GOBP_SYNAPTIC_SIGNALING, SENESE_HDAC3_TARGETS_DN, GOCC_POSTSYNAPSE, GOCC_SYNAPSE, GOCC_POSTSYNAPTIC_MEMBRANE, chr22q13, GOCC_PLASMA_MEMBRANE_REGION, GOCC_SYNAPTIC_MEMBRANE, GOMF_PHOSPHATASE_INHIBITOR_ACTIVITY, AAGCACA_MIR218

GO Biological Process (4): chemical synaptic transmission (GO:0007268), gene expression (GO:0010467), establishment of protein localization (GO:0045184), synaptic membrane adhesion (GO:0099560)

GO Molecular Function (3): protein phosphatase inhibitor activity (GO:0004864), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), postsynaptic density membrane (GO:0098839), membrane (GO:0016020), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anterograde trans-synaptic signaling	1
macromolecule biosynthetic process	1
establishment of localization	1
synapse organization	1
cell-cell adhesion	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELFN2	KRTAP13-4	Q3LI77	452
ELFN2	C3orf70	A6NLC5	415
ELFN2	GRM6	O15303	415
ELFN2	NOM1	Q5C9Z4	399
ELFN2	ZFP69B	Q9UJL9	391
ELFN2	SLC67A2	Q8NBP5	383
ELFN2	SVOP	Q8N4V2	370
ELFN2	MINAR1	Q9UPX6	353
ELFN2	SLC6A18	Q96N87	350
ELFN2	LRRC10B	A6NIK2	350
ELFN2	AAGAB	Q6PD74	340
ELFN2	DPYS	Q14117	320
ELFN2	JPH3	Q8WXH2	318
ELFN2	LRRC61	Q9BV99	306
ELFN2	CDH7	Q9ULB5	306

IntAct

11 interactions, top by confidence:

A	B	Type	Score
EVA1B	NRP1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SLC31A1	PRORP	psi-mi:“MI:0914”(association)	0.530
ELFN2	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.440
ELFN2	TBC1D4	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
DLK1	PLPP3	psi-mi:“MI:0914”(association)	0.350
SIGLECL1	IPO5	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (24): ELFN2 (Proximity Label-MS), ELFN2 (Affinity Capture-RNA), ELFN2 (Affinity Capture-RNA), ELFN2 (Affinity Capture-MS), ELFN2 (Affinity Capture-RNA), TBC1D1 (Affinity Capture-MS), CALM3 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), KCMF1 (Affinity Capture-MS), CTDSPL2 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), TBC1D4 (Affinity Capture-MS), ACAD11 (Affinity Capture-MS), ELFN1 (Affinity Capture-MS), PDF (Affinity Capture-MS)

ESM2 similar proteins: A1XQX3, A1XQY0, A1XQY3, A2ALI5, A6QLD2, B5X216, D0PRN4, E9PUN2, O35181, O75151, O94933, O94991, P0C7U0, P15379, P23470, P49415, P56975, P58401, P80560, Q05909, Q3SXY7, Q3UH99, Q3V1G4, Q4W8E7, Q58EG3, Q5EGE1, Q5R3F8, Q5R5B8, Q63376, Q63475, Q68BL8, Q68FM6, Q6QD51, Q6ZSJ9, Q76KF0, Q80Z10, Q810B7, Q810B9, Q8AXP2, Q8C8T7

Diamond homologs: P0C7U0, Q5R3F8, Q68FM6, Q8C8T7, Q8BGX3, A2ARI4, A6H793, C3YZ59, F1MLX5, G5EFX6, O15335, O46542, O75093, O75094, O75325, O88279, O88280, O94813, O94933, O94991, P07585, P21793, P28654, P28675, P35859, P59034, P59035, P70193, P70389, P83503, Q01129, Q1ENI8, Q27972, Q28888, Q29393, Q2I0M4, Q3ZBN5, Q5R1V9, Q6P7C4, Q80TR4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	120
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1541 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37427296:AC:A	donor_gain	1.0000
22:37427297:CC:C	donor_gain	1.0000
22:37427292:ACTT:A	donor_loss	0.9900
22:37427293:CTTA:C	donor_loss	0.9900
22:37427294:TTA:T	donor_loss	0.9900
22:37427296:A:AC	donor_gain	0.9900
22:37427296:A:C	donor_loss	0.9900
22:37427296:ACC:A	donor_gain	0.9900
22:37427297:C:CC	donor_gain	0.9900
22:37427297:CCC:C	donor_gain	0.9900
22:37389826:AAGG:A	donor_gain	0.9800
22:37419944:T:A	donor_gain	0.9700
22:37373097:C:CA	donor_gain	0.9600
22:37427241:C:CA	donor_gain	0.9600
22:37427240:TCC:T	donor_gain	0.9500
22:37427241:CCC:C	donor_gain	0.9500
22:37427296:ACCC:A	donor_gain	0.9500
22:37427297:CCCC:C	donor_gain	0.9500
22:37427297:CCCCA:C	donor_gain	0.9400
22:37373101:T:TA	donor_gain	0.9000
22:37390756:C:CA	donor_gain	0.8900
22:37400737:T:A	donor_gain	0.8700
22:37418875:TCC:T	donor_gain	0.8700
22:37402727:G:C	donor_gain	0.8500
22:37417920:C:CC	acceptor_gain	0.8500
22:37419714:C:CA	donor_gain	0.8500
22:37419860:G:A	donor_gain	0.8500
22:37420342:T:TA	donor_gain	0.8500
22:37426871:CCAG:C	donor_gain	0.8500
22:37418871:G:T	donor_gain	0.8400

AlphaMissense

5345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37373098:C:A	G813W	1.000
22:37373098:C:G	G813R	1.000
22:37373098:C:T	G813R	1.000
22:37373099:C:A	K812N	1.000
22:37373099:C:G	K812N	1.000
22:37373102:C:A	W811C	1.000
22:37373102:C:G	W811C	1.000
22:37373103:C:G	W811S	1.000
22:37373104:A:G	W811R	1.000
22:37373104:A:T	W811R	1.000
22:37373109:T:A	D809V	1.000
22:37373112:A:G	L808P	1.000
22:37373112:A:T	L808H	1.000
22:37373115:A:C	I807S	1.000
22:37373115:A:G	I807T	1.000
22:37373115:A:T	I807N	1.000
22:37373124:A:G	L804P	1.000
22:37373124:A:T	L804Q	1.000
22:37373139:G:T	A799D	1.000
22:37373157:C:G	R793P	1.000
22:37373158:G:T	R793S	1.000
22:37373160:A:G	L792P	1.000
22:37373160:A:T	L792Q	1.000
22:37373169:C:T	G789D	1.000
22:37373871:A:G	L555P	1.000
22:37373871:A:T	L555H	1.000
22:37373882:G:C	C551W	1.000
22:37373884:A:G	C551R	1.000
22:37373892:A:C	I548S	1.000
22:37373892:A:T	I548N	1.000

dbSNP variants (sampled 300 via entrez): RS1000007446 (22:37343501 G>T), RS1000008404 (22:37378173 G>A), RS1000010647 (22:37356820 G>A), RS1000134549 (22:37351826 T>G), RS1000138849 (22:37368294 G>C), RS1000237295 (22:37429010 G>A,C), RS1000242199 (22:37383352 A>G), RS1000263257 (22:37407209 C>T), RS1000269187 (22:37396543 C>G), RS1000318448 (22:37418530 G>A), RS1000365649 (22:37405907 C>T), RS1000466281 (22:37423940 T>G), RS1000489861 (22:37424067 G>A), RS1000523722 (22:37377944 G>A), RS1000544347 (22:37386542 T>A,C,G)

Disease associations

OMIM: gene MIM:620223 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002408_16	Response to methotrexate in juvenile idiopathic arthritis	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	4
(+)-JQ1 compound	decreases expression	3
Benzo(a)pyrene	affects methylation, increases methylation	2
Diethylhexyl Phthalate	decreases expression, decreases methylation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Rotenone	increases expression	2
1-Methyl-4-phenylpyridinium	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sulforaphane	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
entinostat	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
dimethylarsinous acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Glucose	decreases expression	1
Lead	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methapyrilene	affects methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SL89	HAP1 ELFN2 (-) 1	Cancer cell line	Male
CVCL_SL90	HAP1 ELFN2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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