IGSF9

Summary

IGSF9 (immunoglobulin superfamily member 9, HGNC:18132) is a protein-coding gene on chromosome 1q23.2, encoding Protein turtle homolog A (Q9P2J2). Functions in dendrite outgrowth and synapse maturation.

Predicted to enable cell-cell adhesion mediator activity. Predicted to be involved in axon guidance; dendrite self-avoidance; and homophilic cell adhesion via plasma membrane adhesion molecules. Predicted to act upstream of or within dendrite development and regulation of synapse organization. Predicted to be located in dendrite and inhibitory synapse. Predicted to be active in axon; glutamatergic synapse; and postsynaptic density membrane.

Source: NCBI Gene 57549 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 254 total
• MANE Select transcript: NM_001135050

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18132
Approved symbol	IGSF9
Name	immunoglobulin superfamily member 9
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1355, Nrt1, IGSF9A
Ensembl gene	ENSG00000085552
Ensembl biotype	protein_coding
OMIM	609738
Entrez	57549

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000361509, ENST00000368094, ENST00000476102, ENST00000493195, ENST00000496645, ENST00000874210, ENST00000874211, ENST00000874212, ENST00000912646, ENST00000912647, ENST00000912648, ENST00000912649, ENST00000950265, ENST00000950266

RefSeq mRNA: 2 — MANE Select: NM_001135050 NM_001135050, NM_020789

CCDS: CCDS1190, CCDS44254

Canonical transcript exons

ENST00000368094 — 21 exons

Exon	Start	End
ENSE00003461150	159943397	159943628
ENSE00003464485	159934425	159934570
ENSE00003473514	159929351	159929393
ENSE00003487331	159931812	159931928
ENSE00003496128	159942963	159943151
ENSE00003507900	159936399	159936516
ENSE00003573410	159928158	159929018
ENSE00003576507	159936754	159936908
ENSE00003581896	159934681	159934822
ENSE00003588314	159931138	159931261
ENSE00003624009	159931453	159931603
ENSE00003631925	159930692	159930867
ENSE00003641434	159930189	159930439
ENSE00003641778	159927760	159927887
ENSE00003666412	159929891	159929975
ENSE00003668831	159937686	159937838
ENSE00003677242	159934190	159934332
ENSE00003689608	159932512	159932652
ENSE00003694527	159929638	159929814
ENSE00003846841	159945573	159945613
ENSE00003849110	159927041	159927526

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 92.40.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0795 / max 123.8938, expressed in 516 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15450	2.0755	469
15451	0.9765	342
15449	0.0275	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	92.40	gold quality
ventricular zone	UBERON:0003053	92.19	gold quality
ganglionic eminence	UBERON:0004023	89.56	gold quality
oocyte	CL:0000023	88.80	gold quality
right lobe of liver	UBERON:0001114	87.09	gold quality
right uterine tube	UBERON:0001302	86.98	gold quality
skin of abdomen	UBERON:0001416	85.64	gold quality
ileal mucosa	UBERON:0000331	84.15	gold quality
upper arm skin	UBERON:0004263	83.47	gold quality
lower esophagus mucosa	UBERON:0035834	83.31	gold quality
skin of leg	UBERON:0001511	83.30	gold quality
jejunal mucosa	UBERON:0000399	82.65	gold quality
zone of skin	UBERON:0000014	82.57	gold quality
cortical plate	UBERON:0005343	82.09	gold quality
esophagus mucosa	UBERON:0002469	80.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.63	gold quality
epithelial cell of pancreas	CL:0000083	79.24	gold quality
liver	UBERON:0002107	78.64	gold quality
secondary oocyte	CL:0000655	78.56	gold quality
gingival epithelium	UBERON:0001949	78.52	silver quality
germinal epithelium of ovary	UBERON:0001304	78.37	gold quality
pancreatic ductal cell	CL:0002079	77.95	silver quality
nasal cavity epithelium	UBERON:0005384	77.70	silver quality
transverse colon	UBERON:0001157	77.48	gold quality
gingiva	UBERON:0001828	75.90	gold quality
duodenum	UBERON:0002114	75.89	gold quality
minor salivary gland	UBERON:0001830	75.80	gold quality
mouth mucosa	UBERON:0003729	75.40	gold quality
sperm	CL:0000019	75.22	gold quality
pigmented layer of retina	UBERON:0001782	75.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting IGSF9, 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-8485	100.00	77.57	4731
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-3622B-3P	96.82	66.36	988
HSA-MIR-5707	96.34	66.10	89

Literature-anchored findings (GeneRIF, showing 4)

• In the group that combined individuals affected by isolated cleft lip and palate, tooth agenesis, supernumerary teeth, molar incisor hypomineralization, or dental caries, we found an association with rs622260 but not with the rs10798049 marker. We determined that the allele C of rs622260 was overrepresented in all individuals studied compared with a group of unrelated individuals who did not present any of (PMID:29500156)
• Genomic alterations and evolution of cell clusters in metastatic invasive micropapillary carcinoma of the breast. (PMID:35013309)
• Immunoglobulin superfamily 9 (IGSF9) is trans-activated by p53, inhibits breast cancer metastasis via FAK. (PMID:36088502)
• The ALDH2, IGSF9, and PRDM16 Proteins as Predictive Biomarkers for Prognosis in Breast Cancer. (PMID:36639264)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Igsf9	ENSMUSG00000037995
rattus_norvegicus	Igsf9	ENSRNOG00000008054

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), NEO1 (ENSG00000067141), SDK2 (ENSG00000069188), IGSF9B (ENSG00000080854), NRCAM (ENSG00000091129), MXRA5 (ENSG00000101825), IGDCC4 (ENSG00000103742), 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

Protein turtle homolog A — Q9P2J2 (reviewed: Q9P2J2)

Alternative names: Immunoglobulin superfamily member 9A

All UniProt accessions (1): Q9P2J2

UniProt curated annotations — full annotation on UniProt →

Function. Functions in dendrite outgrowth and synapse maturation.

Subunit / interactions. Interacts with MAGI2 and SHANK1.

Subcellular location. Cell membrane. Synapse.

Domain organisation. The PDZ-binding motif mediates interactions with MAGI2 and SHANK1.

Similarity. Belongs to the immunoglobulin superfamily. Turtle family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P2J2-1	1	yes
Q9P2J2-2	2

RefSeq proteins (2): NP_001128522, NP_065840 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051170	Neural/epithelial_adhesion	Family

Pfam: PF00041, PF13927

UniProt features (46 total): domain 7, strand 7, disulfide bond 5, sequence variant 5, region of interest 4, compositionally biased region 4, glycosylation site 4, topological domain 2, modified residue 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1V5J	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2J2-F1	66.46	0.32

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 (2): 809, 972

Disulfide bonds (5): 41–108, 158–206, 248–301, 344–395, 440–486

Glycosylation sites (4): 188, 256, 513, 524

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 120 (showing top): GOBP_DENDRITE_DEVELOPMENT, AP1_01, GOBP_NEURON_RECOGNITION, GOBP_NEUROGENESIS, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION, AP1_Q4_01, FOSTER_TOLERANT_MACROPHAGE_UP, TGANTCA_AP1_C, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GOCC_NEURON_PROJECTION, DOUGLAS_BMI1_TARGETS_UP, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPSE_MATURATION

GO Biological Process (8): homophilic cell-cell adhesion (GO:0007156), axon guidance (GO:0007411), dendrite development (GO:0016358), dendrite self-avoidance (GO:0070593), regulation of synapse maturation (GO:0090128), nervous system development (GO:0007399), cell differentiation (GO:0030154), regulation of synapse organization (GO:0050807)

GO Molecular Function (2): cell-cell adhesion mediator activity (GO:0098632), protein binding (GO:0005515)

GO Cellular Component (8): plasma membrane (GO:0005886), axon (GO:0030424), dendrite (GO:0030425), inhibitory synapse (GO:0060077), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), membrane (GO:0016020), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	2
neuron projection	2
synapse	2
axonogenesis	1
neuron projection guidance	1
neuron projection development	1
anatomical structure development	1
neuron recognition	1
regulation of developmental process	1
regulation of synapse organization	1
synapse maturation	1
system development	1
cellular developmental process	1
regulation of synapse structure or activity	1
synapse organization	1
regulation of cellular component organization	1
cell adhesion mediator activity	1
binding	1
membrane	1
cell periphery	1
dendritic tree	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGSF9	IGSF21	Q96ID5	576
IGSF9	NTS	P30990	461
IGSF9	FN1	P02751	453
IGSF9	VSIG2	Q96IQ7	451
IGSF9	PRR15	Q8IV56	409
IGSF9	NMRK1	Q9NWW6	396
IGSF9	ZNF710	Q8N1W2	382
IGSF9	NOC2L	Q9Y3T9	374
IGSF9	ANXA9	O76027	372
IGSF9	COBL	O75128	364
IGSF9	FAM241B	Q96D05	364
IGSF9	PLLP	Q9Y342	363
IGSF9	BICDL1	Q6ZP65	355
IGSF9	NRSN1	Q8IZ57	355
IGSF9	GLUL	P15104	348

IntAct

7 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
IGSF9	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
MAGI1	CIT	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CBLN4	AGRN	psi-mi:“MI:0914”(association)	0.350
ASCC2	IGSF9	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): IGSF9 (Affinity Capture-RNA), IGSF9 (Two-hybrid), CYB5B (Two-hybrid), PAQR5 (Two-hybrid), TMEM65 (Two-hybrid), IGSF9 (Two-hybrid), IGSF9 (Affinity Capture-MS), IGSF9 (Affinity Capture-MS), IGSF9 (Affinity Capture-MS), IGSF9 (Co-fractionation), IGSF9 (Co-fractionation)

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

Diamond homologs: A1KZ92, A2A8L5, A2AJ76, A2VEC9, A4IGL7, A7MBJ4, B3EWY9, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, F1NWE3, G5EBF1, G5ECS8, O08721, O08722, O08747, O14514, O15146, O15394, O55005, O60241, O60242, O95185, O95428, P07996, P10586, P11680, P11834, P13590, P22648, P27918, P32736, P35440, P35441, P35442, P35446

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	200
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3559 predictions. Top by Δscore:

Variant	Effect	Δscore
1:159927755:CACA:C	donor_gain	1.0000
1:159927756:ACACC:A	donor_loss	1.0000
1:159927757:CACCT:C	donor_loss	1.0000
1:159927759:CCTAG:C	donor_gain	1.0000
1:159927763:G:C	donor_gain	1.0000
1:159927774:G:C	donor_gain	1.0000
1:159927883:TCCTC:T	acceptor_gain	1.0000
1:159927884:CCTCC:C	acceptor_gain	1.0000
1:159927885:CTC:C	acceptor_gain	1.0000
1:159927886:TC:T	acceptor_gain	1.0000
1:159927887:CCTG:C	acceptor_gain	1.0000
1:159927888:C:CC	acceptor_gain	1.0000
1:159929349:A:AC	donor_gain	1.0000
1:159929350:C:CC	donor_gain	1.0000
1:159929393:TCT:T	acceptor_loss	1.0000
1:159929394:C:CC	acceptor_gain	1.0000
1:159929404:A:C	acceptor_gain	1.0000
1:159929633:CTTA:C	donor_loss	1.0000
1:159929634:TTACC:T	donor_loss	1.0000
1:159929635:TA:T	donor_loss	1.0000
1:159929636:A:AC	donor_gain	1.0000
1:159929636:AC:A	donor_gain	1.0000
1:159929637:C:A	donor_loss	1.0000
1:159929637:C:CC	donor_gain	1.0000
1:159929637:CC:C	donor_gain	1.0000
1:159929637:CCT:C	donor_gain	1.0000
1:159929637:CCTTG:C	donor_gain	1.0000
1:159929814:CCTAG:C	acceptor_loss	1.0000
1:159929885:GCTCA:G	donor_loss	1.0000
1:159929886:CTCAC:C	donor_loss	1.0000

AlphaMissense

7483 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:159943039:C:A	W57C	0.999
1:159943039:C:G	W57C	0.999
1:159943041:A:G	W57R	0.999
1:159943041:A:T	W57R	0.999
1:159931196:A:G	W527R	0.998
1:159931196:A:T	W527R	0.998
1:159934225:A:G	W357R	0.998
1:159934225:A:T	W357R	0.998
1:159934715:A:G	W261R	0.998
1:159934715:A:T	W261R	0.998
1:159936799:C:A	W170C	0.998
1:159936799:C:G	W170C	0.998
1:159936801:A:G	W170R	0.998
1:159936801:A:T	W170R	0.998
1:159937697:A:G	L130P	0.998
1:159937763:C:G	C108S	0.998
1:159937764:A:T	C108S	0.998
1:159930760:A:G	F582S	0.997
1:159931201:A:T	V525D	0.997
1:159931820:A:G	W452R	0.997
1:159931820:A:T	W452R	0.997
1:159932560:G:C	N399K	0.997
1:159932560:G:T	N399K	0.997
1:159934223:C:A	W357C	0.997
1:159934223:C:G	W357C	0.997
1:159937762:G:C	C108W	0.997
1:159937764:A:G	C108R	0.997
1:159931514:C:A	W484C	0.996
1:159931514:C:G	W484C	0.996
1:159931818:C:A	W452C	0.996

dbSNP variants (sampled 300 via entrez): RS1000208933 (1:159947588 T>C), RS1000215251 (1:159944970 G>A), RS1000247109 (1:159938312 C>A,G,T), RS1000583083 (1:159939887 C>T), RS1000658078 (1:159940184 G>A,T), RS1000880411 (1:159944600 G>A), RS1000944519 (1:159931514 C>G), RS1000998542 (1:159931257 A>C,G), RS1001592392 (1:159943306 C>T), RS1001596692 (1:159934506 C>T), RS1001687850 (1:159937675 C>G,T), RS1001721377 (1:159940424 T>C), RS1001769959 (1:159930718 C>T), RS1001806061 (1:159940773 GATTTTTAT>G), RS1001932351 (1:159933010 C>A,T)

Disease associations

OMIM: gene MIM:609738 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST008103_100	Bipolar disorder	3.000000e-06
GCST010697_46	Cortical surface area (min-P)	1.000000e-14
GCST010698_86	Subcortical volume (min-P)	6.000000e-19
GCST010699_11	Brain morphology (min-P)	2.000000e-10
GCST010700_45	Cortical thickness (MOSTest)	5.000000e-08
GCST010701_14	Cortical surface area (MOSTest)	3.000000e-08
GCST010702_133	Subcortical volume (MOSTest)	9.000000e-15
GCST010703_148	Brain morphology (MOSTest)	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Calcitriol	decreases expression, increases expression, affects cotreatment	2
Estradiol	affects binding, decreases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Aflatoxin B1	decreases methylation	2
methyleugenol	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
ferrous chloride	decreases expression	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
enniatins	increases expression	1
monomethylarsonous acid	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Vehicle Emissions	decreases expression, increases abundance	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1

Clinical trials (associated diseases)

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