IGDCC4

Summary

IGDCC4 (immunoglobulin superfamily DCC subclass member 4, HGNC:13770) is a protein-coding gene on chromosome 15q22.31, encoding Immunoglobulin superfamily DCC subclass member 4 (Q8TDY8).

Predicted to be involved in cell-cell adhesion. Predicted to be located in plasma membrane.

Source: NCBI Gene 57722 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 245 total
• MANE Select transcript: NM_020962

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13770
Approved symbol	IGDCC4
Name	immunoglobulin superfamily DCC subclass member 4
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	NOPE, LOC57722
Ensembl gene	ENSG00000103742
Ensembl biotype	protein_coding
OMIM	616810
Entrez	57722

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000352385, ENST00000558048, ENST00000558819, ENST00000559327, ENST00000560319, ENST00000561309, ENST00000860245, ENST00000961838, ENST00000961839

RefSeq mRNA: 1 — MANE Select: NM_020962 NM_020962

CCDS: CCDS10206

Canonical transcript exons

ENST00000352385 — 20 exons

Exon	Start	End
ENSE00001035277	65411020	65411370
ENSE00001035285	65410178	65410319
ENSE00001135093	65396834	65396989
ENSE00001135101	65400806	65400946
ENSE00001135111	65402351	65402487
ENSE00001284974	65395750	65396163
ENSE00001394268	65422793	65422947
ENSE00001956610	65381484	65384419
ENSE00003462377	65389284	65389411
ENSE00003468989	65395094	65395258
ENSE00003473594	65385831	65386059
ENSE00003521696	65388449	65388586
ENSE00003572963	65394411	65394548
ENSE00003574999	65384954	65385115
ENSE00003577835	65386551	65386656
ENSE00003593289	65388808	65388978
ENSE00003597632	65392134	65392370
ENSE00003632708	65391880	65391981
ENSE00003678726	65393361	65393531
ENSE00003688195	65390155	65390338

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 93.59.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7010 / max 54.2742, expressed in 573 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150550	0.8530	401
150551	0.6500	321
150549	0.1980	120

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	93.59	gold quality
tibia	UBERON:0000979	92.29	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.91	gold quality
tibialis anterior	UBERON:0001385	91.52	gold quality
quadriceps femoris	UBERON:0001377	90.67	gold quality
vastus lateralis	UBERON:0001379	90.50	gold quality
deltoid	UBERON:0001476	90.19	gold quality
biceps brachii	UBERON:0001507	89.47	gold quality
placenta	UBERON:0001987	87.81	gold quality
skeletal muscle tissue	UBERON:0001134	87.37	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.22	gold quality
pigmented layer of retina	UBERON:0001782	87.03	gold quality
adrenal tissue	UBERON:0018303	87.02	gold quality
muscle tissue	UBERON:0002385	84.58	gold quality
body of tongue	UBERON:0011876	84.56	gold quality
ventricular zone	UBERON:0003053	83.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.82	gold quality
cauda epididymis	UBERON:0004360	83.79	gold quality
right ovary	UBERON:0002118	83.44	gold quality
ovary	UBERON:0000992	83.11	gold quality
right adrenal gland cortex	UBERON:0035827	82.96	gold quality
left ovary	UBERON:0002119	82.58	gold quality
right adrenal gland	UBERON:0001233	82.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.33	gold quality
parietal pleura	UBERON:0002400	81.64	gold quality
caput epididymis	UBERON:0004358	80.82	gold quality
medial globus pallidus	UBERON:0002477	80.68	gold quality
muscle of leg	UBERON:0001383	80.56	gold quality
gastrocnemius	UBERON:0001388	80.48	gold quality
adrenal cortex	UBERON:0001235	80.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.16
E-CURD-11	no	147.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

147 targeting IGDCC4, 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-6876-5P	100.00	67.68	2126
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3148	99.97	75.06	6478
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6825-5P	99.96	69.81	3431

Literature-anchored findings (GeneRIF, showing 3)

• identified Nope as a novel oncofetal surface marker for murine and human HCC. Nope is specifically expressed by epithelial tumor cells but not in preneoplastic stages and is a promising marker (PMID:20658536)
• First evaluation of Neighbor of Punc E11 (NOPE) as a novel marker in human hepatocellular carcinoma. (PMID:32986656)
• Expression of Neighbor of Punc E11 (NOPE) in early stage esophageal adenocarcinoma is associated with reduced survival. (PMID:35246597)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	igdcc4	ENSDARG00000076919
mus_musculus	Igdcc4	ENSMUSG00000032816
rattus_norvegicus	Igdcc4	ENSRNOG00000033496

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), NEO1 (ENSG00000067141), SDK2 (ENSG00000069188), IGSF9B (ENSG00000080854), IGSF9 (ENSG00000085552), NRCAM (ENSG00000091129), MXRA5 (ENSG00000101825), CNTN3 (ENSG00000113805), IGSF21 (ENSG00000117154), CNTN6 (ENSG00000134115), CHL1 (ENSG00000134121), PTPRQ (ENSG00000139304), CNTN4 (ENSG00000144619), BOC (ENSG00000144857), SDK1 (ENSG00000146555), HMCN2 (ENSG00000148357), NCAM1 (ENSG00000149294), CNTN5 (ENSG00000149972), IGSF10 (ENSG00000152580), ROBO4 (ENSG00000154133), ROBO3 (ENSG00000154134), NCAM2 (ENSG00000154654), VCAM1 (ENSG00000162692), NFASC (ENSG00000163531), PRTG (ENSG00000166450), ROBO1 (ENSG00000169855), DSCAM (ENSG00000171587), IGDCC3 (ENSG00000174498), VSIG10 (ENSG00000176834), DSCAML1 (ENSG00000177103), CNTN2 (ENSG00000184144), ROBO2 (ENSG00000185008), VSIG10L (ENSG00000186806), DCC (ENSG00000187323), L1CAM (ENSG00000198910)

Protein

Protein identifiers

Immunoglobulin superfamily DCC subclass member 4 — Q8TDY8 (reviewed: Q8TDY8)

Alternative names: Neighbor of punc e11, Protein DDM36

All UniProt accessions (1): Q8TDY8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Similarity. Belongs to the immunoglobulin superfamily. DCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TDY8-1	1	yes
Q8TDY8-2	2

RefSeq proteins (1): NP_066013* (*=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

Pfam: PF00041, PF07679, PF13927

UniProt features (32 total): domain 9, glycosylation site 5, sequence variant 5, disulfide bond 4, region of interest 2, topological domain 2, signal peptide 1, chain 1, modified residue 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDY8-F1	71.07	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 (1): 995

Disulfide bonds (4): 57–121, 164–212, 265–312, 356–405

Glycosylation sites (5): 90, 102, 157, 252, 582

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): ACTACCT_MIR196A_MIR196B, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, TTTGTAG_MIR520D, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, MARTINEZ_RB1_TARGETS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, DOUGLAS_BMI1_TARGETS_UP

GO Biological Process (2): negative regulation of neurogenesis (GO:0050768), cell-cell adhesion (GO:0098609)

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

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
negative regulation of nervous system development	1
cell adhesion	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

848 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGDCC4	INTS14	Q96SY0	479
IGDCC4	DPP8	Q6V1X1	471
IGDCC4	TIMM17B	O60830	459
IGDCC4	ATPSCKMT	Q6P4H8	458
IGDCC4	SLC41A3	Q96GZ6	457
IGDCC4	TULP4	Q9NRJ4	456
IGDCC4	PGAP6	Q9HCN3	454
IGDCC4	USP38	Q8NB14	442
IGDCC4	CDHR2	Q9BYE9	433
IGDCC4	TTLL4	Q14679	418
IGDCC4	HACD3	Q9P035	377
IGDCC4	SLC24A1	O60721	376
IGDCC4	DENND4A	Q7Z401	368
IGDCC4	KLHL36	Q8N4N3	345
IGDCC4	MAPK6	Q16659	342

IntAct

25 interactions, top by confidence:

A	B	Type	Score
IGDCC4	ICAM5	psi-mi:“MI:0915”(physical association)	0.540
WFIKKN2	IGDCC4	psi-mi:“MI:0915”(physical association)	0.540
LTF	IGDCC4	psi-mi:“MI:0915”(physical association)	0.540
ICAM5	IGDCC4	psi-mi:“MI:0407”(direct interaction)	0.540
IGDCC4	WFIKKN2	psi-mi:“MI:0407”(direct interaction)	0.540
IGDCC4	LTF	psi-mi:“MI:0407”(direct interaction)	0.540
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
FLVCR1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
IGFBPL1	IGDCC4	psi-mi:“MI:0407”(direct interaction)	0.440
IGDCC4	IGFBP7	psi-mi:“MI:0407”(direct interaction)	0.440
IGDCC4	HAPLN1	psi-mi:“MI:0915”(physical association)	0.400
LRRTM2	IGDCC4	psi-mi:“MI:0915”(physical association)	0.400
ALB	SH3BP5	psi-mi:“MI:0914”(association)	0.350
RAET1E	GOLIM4	psi-mi:“MI:0914”(association)	0.350
GDF11	TSPY2	psi-mi:“MI:0914”(association)	0.350
IGDCC4	SGCE	psi-mi:“MI:0914”(association)	0.350
HCRTR2	FADS1	psi-mi:“MI:0914”(association)	0.350
IGDCC4	PLPP2	psi-mi:“MI:0914”(association)	0.350
SLC15A3	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SLC39A10	CASK	psi-mi:“MI:0914”(association)	0.350

BioGRID (41): IGDCC4 (Affinity Capture-MS), IGDCC4 (Affinity Capture-MS), IGDCC4 (Negative Genetic), USP12 (Affinity Capture-MS), IGDCC4 (Affinity Capture-MS), RYK (Affinity Capture-MS), ST7 (Affinity Capture-MS), IGDCC4 (Affinity Capture-MS), USP46 (Affinity Capture-MS), PTGFRN (Affinity Capture-MS), IGDCC4 (Affinity Capture-MS), DPY19L1 (Affinity Capture-MS), DMWD (Affinity Capture-MS), IGDCC4 (Affinity Capture-MS), IGDCC4 (Affinity Capture-MS)

ESM2 similar proteins: A2A8L5, A4IFW2, A7MBJ4, B0V2N1, F1NWE3, O00533, O42414, O55005, O89026, O94856, O97394, P10586, P11627, P16621, P22063, P23468, P28685, P32004, P70232, P97685, P97686, Q02246, Q05695, Q13332, Q28902, Q2EY14, Q2EY15, Q2VWP7, Q2VWP9, Q3UH53, Q589G5, Q58EX2, Q61330, Q64487, Q64604, Q64605, Q6V4S5, Q7Z5N4, Q810U3, Q810U4

Diamond homologs: A0A1Y9G8H0, A0A452E9Y6, A1KZ92, A2A8L5, A2AJ76, A4IGL7, A5JUY8, A7MBJ4, A8WQH2, B3A0Q8, B3MH43, B3NS99, B4HNW4, B4P5Q9, B4QC63, D3YXG0, G5EBF1, G5EG78, H2A0M7, O01761, O15146, O35158, O55005, O89026, O94779, P05164, P05548, P07202, P09933, P0C5H6, P10586, P11247, P11678, P14650, P16621, P20241, P22079, P28685, P35419, P43146

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	219
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3866 predictions. Top by Δscore:

Variant	Effect	Δscore
15:65386056:TTCC:T	acceptor_gain	1.0000
15:65386057:TCC:T	acceptor_gain	1.0000
15:65386058:CC:C	acceptor_gain	1.0000
15:65386058:CCC:C	acceptor_gain	1.0000
15:65386059:CC:C	acceptor_gain	1.0000
15:65386060:C:CA	acceptor_loss	1.0000
15:65386546:CTCA:C	donor_loss	1.0000
15:65386547:TCA:T	donor_loss	1.0000
15:65386548:CA:C	donor_loss	1.0000
15:65386550:C:CT	donor_loss	1.0000
15:65386652:CGAGT:C	acceptor_gain	1.0000
15:65386653:GAGT:G	acceptor_gain	1.0000
15:65386654:AGT:A	acceptor_gain	1.0000
15:65386655:GT:G	acceptor_gain	1.0000
15:65386657:C:CC	acceptor_gain	1.0000
15:65386658:T:C	acceptor_loss	1.0000
15:65386660:G:GC	acceptor_gain	1.0000
15:65388806:AC:A	donor_gain	1.0000
15:65388807:CC:C	donor_gain	1.0000
15:65388807:CCCTG:C	donor_gain	1.0000
15:65388976:GCC:G	acceptor_gain	1.0000
15:65388976:GCCCT:G	acceptor_loss	1.0000
15:65388977:CC:C	acceptor_gain	1.0000
15:65388977:CCC:C	acceptor_gain	1.0000
15:65388978:CC:C	acceptor_gain	1.0000
15:65388979:C:CA	acceptor_loss	1.0000
15:65388979:C:CC	acceptor_gain	1.0000
15:65388980:T:A	acceptor_loss	1.0000
15:65388984:G:C	acceptor_gain	1.0000
15:65388984:G:GC	acceptor_gain	1.0000

AlphaMissense

8016 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:65389358:A:G	F821S	1.000
15:65390253:C:A	W770C	1.000
15:65390253:C:G	W770C	1.000
15:65390255:A:G	W770R	1.000
15:65390255:A:T	W770R	1.000
15:65390260:A:G	L768P	1.000
15:65395168:A:G	F501S	1.000
15:65395814:C:A	W449C	1.000
15:65395814:C:G	W449C	1.000
15:65395816:A:G	W449R	1.000
15:65395816:A:T	W449R	1.000
15:65395866:G:T	P432H	1.000
15:65396057:C:A	W368C	1.000
15:65396057:C:G	W368C	1.000
15:65396100:A:G	F354S	1.000
15:65400816:C:A	W277C	1.000
15:65400816:C:G	W277C	1.000
15:65400818:A:G	W277R	1.000
15:65400818:A:T	W277R	1.000
15:65410213:C:A	W176C	1.000
15:65410213:C:G	W176C	1.000
15:65390254:C:G	W770S	0.999
15:65390260:A:T	L768H	0.999
15:65392311:A:G	W649R	0.999
15:65392311:A:T	W649R	0.999
15:65393447:C:G	R600P	0.999
15:65394486:A:G	W547R	0.999
15:65394486:A:T	W547R	0.999
15:65395134:G:C	S512R	0.999
15:65395134:G:T	S512R	0.999

dbSNP variants (sampled 300 via entrez): RS1000065496 (15:65386091 G>A,C,T), RS1000074587 (15:65416105 C>T), RS1000130719 (15:65388237 T>C), RS1000214909 (15:65383092 G>A), RS1000257743 (15:65421922 C>T), RS1000265856 (15:65402863 A>G), RS1000418513 (15:65385755 C>T), RS1000423055 (15:65388542 G>A,C,T), RS1000450584 (15:65395202 C>G), RS1000491301 (15:65409441 G>T), RS1000552312 (15:65404115 A>C), RS1000719280 (15:65403169 G>A), RS1000761762 (15:65404987 G>A), RS1001000880 (15:65398706 A>G), RS1001018295 (15:65384549 T>C)

Disease associations

OMIM: gene MIM:616810 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000587_7	Mean corpuscular hemoglobin	3.000000e-09
GCST005996_1	Red blood cell count	3.000000e-08
GCST006585_1387	Blood protein levels	4.000000e-16
GCST006979_927	Heel bone mineral density	3.000000e-25
GCST90002391_148	Mean corpuscular hemoglobin concentration	4.000000e-16

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0009270	heel bone mineral density
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
Aflatoxin B1	increases expression, affects expression	4
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
beta-Naphthoflavone	decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	decreases methylation	1
pentanal	increases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	increases expression, affects cotreatment	1
Dactinomycin	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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