INSM2

Summary

INSM2 (INSM transcriptional repressor 2, HGNC:17539) is a protein-coding gene on chromosome 14q13.2, encoding Insulinoma-associated protein 2 (Q96T92). May function as a growth suppressor or tumor suppressor in liver cells and in certain neurons.

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II; neuron differentiation; and regulation of cell cycle process. Predicted to be located in cytoplasm. Predicted to be part of transcription repressor complex. Predicted to be active in nucleus.

Source: NCBI Gene 84684 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 108 total
• MANE Select transcript: NM_032594

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17539
Approved symbol	INSM2
Name	INSM transcriptional repressor 2
Location	14q13.2
Locus type	gene with protein product
Status	Approved
Aliases	IA-6, Mlt1
Ensembl gene	ENSG00000168348
Ensembl biotype	protein_coding
OMIM	614027
Entrez	84684

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000307169

RefSeq mRNA: 1 — MANE Select: NM_032594 NM_032594

CCDS: CCDS9657

Canonical transcript exons

ENST00000307169 — 1 exons

Exon	Start	End
ENSE00001177204	35534164	35537054

Expression profiles

Bgee: expression breadth broad, 76 present calls, max score 86.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3157 / max 156.9076, expressed in 92 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139257	0.3104	90
139258	0.0053	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.63	gold quality
buccal mucosa cell	CL:0002336	72.49	silver quality
Brodmann (1909) area 23	UBERON:0013554	72.00	gold quality
middle temporal gyrus	UBERON:0002771	71.88	silver quality
primary visual cortex	UBERON:0002436	71.09	gold quality
postcentral gyrus	UBERON:0002581	69.24	gold quality
colonic epithelium	UBERON:0000397	69.10	gold quality
superior frontal gyrus	UBERON:0002661	68.13	gold quality
entorhinal cortex	UBERON:0002728	67.32	silver quality
endothelial cell	CL:0000115	66.49	gold quality
parietal lobe	UBERON:0001872	64.88	gold quality
occipital lobe	UBERON:0002021	64.51	gold quality
prefrontal cortex	UBERON:0000451	64.11	gold quality
heart right ventricle	UBERON:0002080	63.91	gold quality
lateral nuclear group of thalamus	UBERON:0002736	63.25	silver quality
nasal cavity epithelium	UBERON:0005384	62.80	gold quality
Brodmann (1909) area 9	UBERON:0013540	62.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	61.75	gold quality
frontal cortex	UBERON:0001870	61.71	gold quality
bone marrow cell	CL:0002092	61.68	gold quality
neocortex	UBERON:0001950	60.85	gold quality
cerebral cortex	UBERON:0000956	59.63	gold quality
anterior cingulate cortex	UBERON:0009835	58.74	gold quality
hypothalamus	UBERON:0001898	58.02	gold quality
colonic mucosa	UBERON:0000317	57.42	gold quality
mucosa of sigmoid colon	UBERON:0004993	56.96	gold quality
superficial temporal artery	UBERON:0001614	56.81	gold quality
right frontal lobe	UBERON:0002810	56.80	gold quality
pons	UBERON:0000988	56.10	silver quality
substantia nigra pars compacta	UBERON:0001965	55.94	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-98556	no	134.34
E-ANND-3	no	1.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NEUROD1, NEUROG3

miRNA regulators (miRDB)

88 targeting INSM2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-548C-3P	99.99	74.01	7587
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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-200A-5P	99.76	69.10	949

Literature-anchored findings (GeneRIF, showing 2)

• insulinoma-associated protein 2 beta (IA-2beta) and zinc transporter-8 may have a role in rapid progression of type 1 diabetes (PMID:20091020)
• Data show that INSM2 is the expressed n fetal pancreas. (PMID:21343251)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	INSM2	ENSDARG00000020655
mus_musculus	Insm2	ENSMUSG00000045440
rattus_norvegicus	Insm2	ENSRNOG00000083293
drosophila_melanogaster	nerfin-1	FBGN0028999
caenorhabditis_elegans		WBGENE00001210

Paralogs (1): INSM1 (ENSG00000173404)

Protein

Protein identifiers

Insulinoma-associated protein 2 — Q96T92 (reviewed: Q96T92)

Alternative names: Zinc finger protein IA-6

All UniProt accessions (1): Q96T92

UniProt curated annotations — full annotation on UniProt →

Function. May function as a growth suppressor or tumor suppressor in liver cells and in certain neurons.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in heart, liver, skeletal muscle, kidney and pancreas, and, to a lesser extent, in brain, lung and spleen. In the pancreas, expressed in islet cells, including insulin- and glucagon-producing alpha- and beta-cells, but not in acinar cells (at protein level). Detected in adrenal glands, particularly in the deeper layer of the cortex (at protein level).

RefSeq proteins (1): NP_115983* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR042972	INSM1/2	Family

Pfam: PF00096

UniProt features (16 total): zinc finger region 5, compositionally biased region 3, sequence conflict 3, region of interest 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96T92-F1	56.48	0.04

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_NEUROGENESIS, WANG_RESPONSE_TO_BEXAROTENE_DN, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, chr14q13, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GOCC_TRANSCRIPTION_REPRESSOR_COMPLEX, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOBP_CELL_CYCLE_PROCESS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_BRAIN_HCP_WITH_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3, CDPCR1_01, MIKKELSEN_NPC_HCP_WITH_H3K4ME3_AND_H3K27ME3

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cell cycle process (GO:0010564), neuron differentiation (GO:0030182), cell differentiation (GO:0030154)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), transcription repressor complex (GO:0017053)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cell cycle process	1
regulation of cell cycle	1
cell differentiation	1
generation of neurons	1
cellular developmental process	1
cis-regulatory region sequence-specific DNA binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transition metal ion binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
transcription regulator complex	1

Protein interactions and networks

STRING

598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INSM2	PTPRN	Q16849	775
INSM2	SLC30A10	Q6XR72	773
INSM2	CD27	P26842	770
INSM2	SLC30A8	Q8IWU4	763
INSM2	CD38	P28907	719
INSM2	CD19	P15391	700
INSM2	NAALADL1	Q9UQQ1	694
INSM2	INS	P01308	687
INSM2	GAD2	Q05329	638
INSM2	CR2	P20023	609
INSM2	CD24	P25063	571
INSM2	KCNN3	Q9UGI6	571
INSM2	AMBP	P00977	507
INSM2	CXCR5	P32302	507
INSM2	CD4	P01730	505

IntAct

2 interactions, top by confidence:

A	B	Type	Score
INSM2	ZSCAN1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (4): INSM2 (Reconstituted Complex), INSM2 (Affinity Capture-MS), INSM2 (Proximity Label-MS), ZSCAN1 (Two-hybrid)

ESM2 similar proteins: A0JNJ4, A4IHR5, A6H7J1, A7UKY7, D4AE48, E9Q9M8, O15209, O35615, O75081, O95785, P03966, P04198, P39881, P49796, P52746, Q01101, Q1LY51, Q29RS4, Q32KV8, Q4KLY2, Q505G8, Q5T6C5, Q5TJE2, Q61976, Q62511, Q63379, Q63ZV0, Q6AY75, Q6NUJ5, Q6NV74, Q6P0F9, Q7T3H2, Q8BG80, Q8CDC7, Q8CE64, Q8IX07, Q8N554, Q8R4U1, Q96C00, Q96JP5

Diamond homologs: A4IHR5, A6H7J1, A7UKY7, G5EFY4, Q01101, Q63ZV0, Q6P0F9, Q7T3H2, Q96T92, Q9JMC2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	104
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

50 predictions. Top by Δscore:

Variant	Effect	Δscore
14:35534435:A:T	donor_gain	0.7400
14:35534434:G:GT	donor_gain	0.5400
14:35534475:TCGCC:T	donor_gain	0.4000
14:35534272:TG:T	donor_gain	0.3900
14:35534427:G:GT	donor_gain	0.3800
14:35534494:G:A	donor_gain	0.3800
14:35535969:G:GT	donor_gain	0.3500
14:35535856:TTAG:T	acceptor_gain	0.3400
14:35535859:G:T	acceptor_gain	0.3400
14:35535857:TAG:T	acceptor_gain	0.3300
14:35536088:A:AG	acceptor_gain	0.3200
14:35536089:G:GG	acceptor_gain	0.3200
14:35534796:G:GA	acceptor_gain	0.3000
14:35534806:C:A	acceptor_gain	0.3000
14:35534370:G:GT	donor_gain	0.2900
14:35535841:G:GA	acceptor_gain	0.2900
14:35535858:A:T	acceptor_gain	0.2900
14:35534501:C:T	donor_gain	0.2800
14:35534493:GGG:G	donor_gain	0.2700
14:35534494:GGG:G	donor_gain	0.2700
14:35534498:G:A	donor_gain	0.2700
14:35534491:CTGGG:C	donor_loss	0.2600
14:35534492:TGGG:T	donor_loss	0.2600
14:35534494:GG:G	donor_gain	0.2600
14:35534495:GG:G	donor_gain	0.2600
14:35534495:GGTG:G	donor_loss	0.2600
14:35534496:GTGA:G	donor_loss	0.2600
14:35534497:T:TT	donor_loss	0.2600
14:35534498:G:GG	donor_loss	0.2600
14:35534499:A:AC	donor_loss	0.2600

AlphaMissense

3588 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:35535045:T:C	C265R	1.000
14:35535129:T:C	C293R	1.000
14:35535150:T:C	F300L	1.000
14:35535151:T:C	F300S	1.000
14:35535151:T:G	F300C	1.000
14:35535152:C:A	F300L	1.000
14:35535152:C:G	F300L	1.000
14:35535156:T:C	C302R	1.000
14:35535167:C:A	N305K	1.000
14:35535167:C:G	N305K	1.000
14:35535169:T:C	L306P	1.000
14:35535177:C:A	H309N	1.000
14:35535177:C:G	H309D	1.000
14:35535179:T:A	H309Q	1.000
14:35535179:T:G	H309Q	1.000
14:35535186:T:A	W312R	1.000
14:35535186:T:C	W312R	1.000
14:35535188:G:C	W312C	1.000
14:35535188:G:T	W312C	1.000
14:35534265:T:C	F5L	0.999
14:35534267:C:A	F5L	0.999
14:35534267:C:G	F5L	0.999
14:35535039:T:C	F263L	0.999
14:35535041:C:A	F263L	0.999
14:35535041:C:G	F263L	0.999
14:35535045:T:A	C265S	0.999
14:35535046:G:A	C265Y	0.999
14:35535046:G:C	C265S	0.999
14:35535047:C:G	C265W	0.999
14:35535054:T:A	C268S	0.999

dbSNP variants (sampled 300 via entrez): RS1000538412 (14:35536849 C>A,G), RS1000825622 (14:35537009 C>A), RS1001595023 (14:35535696 G>T), RS1001775688 (14:35535410 C>T), RS1003052265 (14:35537355 T>A), RS1003760018 (14:35533373 C>T), RS1003988132 (14:35532921 T>C), RS1004019677 (14:35536320 A>C), RS1004422206 (14:35534731 C>G,T), RS1004723621 (14:35536169 G>A,C), RS1004992747 (14:35535890 G>A,T), RS1005117633 (14:35535745 T>A), RS1005329835 (14:35537332 G>T), RS1007849204 (14:35534106 C>T), RS1007882161 (14:35535793 G>A)

Disease associations

OMIM: gene MIM:614027 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007798_138	Asthma	1.000000e-09
GCST007800_83	Asthma (childhood onset)	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression	1
securinine	decreases expression	1
sodium arsenite	affects methylation	1
tetrabromobisphenol A	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
licochalcone B	increases expression	1
bisphenol S	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	decreases expression, affects cotreatment	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Methotrexate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Thapsigargin	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HC78	HEK293 eGFP-INSM2	Transformed cell line	Female

Clinical trials (associated diseases)

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