INSM1

Summary

INSM1 (INSM transcriptional repressor 1, HGNC:6090) is a protein-coding gene on chromosome 20p11.23, encoding Insulinoma-associated protein 1 (Q01101). Sequence-specific DNA-binding transcriptional regulator that plays a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and/or fetal development.

Insulinoma-associated 1 (INSM1) gene is intronless and encodes a protein containing both a zinc finger DNA-binding domain and a putative prohormone domain. This gene is a sensitive marker for neuroendocrine differentiation of human lung tumors.

Source: NCBI Gene 3642 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_002196

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6090
Approved symbol	INSM1
Name	INSM transcriptional repressor 1
Location	20p11.23
Locus type	gene with protein product
Status	Approved
Aliases	IA-1, IA1
Ensembl gene	ENSG00000173404
Ensembl biotype	protein_coding
OMIM	600010
Entrez	3642

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000310227

RefSeq mRNA: 1 — MANE Select: NM_002196 NM_002196

CCDS: CCDS13143

Canonical transcript exons

ENST00000310227 — 1 exons

Exon	Start	End
ENSE00001205563	20368104	20370949

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 97.57.

FANTOM5 (CAGE): breadth broad, TPM avg 5.4589 / max 855.9551, expressed in 394 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183775	5.4589	394

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	97.57	gold quality
ganglionic eminence	UBERON:0004023	97.51	gold quality
ventricular zone	UBERON:0003053	89.62	gold quality
islet of Langerhans	UBERON:0000006	88.63	gold quality
pituitary gland	UBERON:0000007	86.70	gold quality
adenohypophysis	UBERON:0002196	85.79	gold quality
cerebellar vermis	UBERON:0004720	82.11	gold quality
embryo	UBERON:0000922	81.28	gold quality
cerebellum	UBERON:0002037	80.92	gold quality
cerebellar cortex	UBERON:0002129	80.26	gold quality
cerebellar hemisphere	UBERON:0002245	80.20	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.93	gold quality
paraflocculus	UBERON:0005351	76.80	gold quality
cortical plate	UBERON:0005343	74.26	gold quality
putamen	UBERON:0001874	71.91	gold quality
caudate nucleus	UBERON:0001873	70.87	gold quality
nucleus accumbens	UBERON:0001882	70.72	gold quality
pancreas	UBERON:0001264	69.58	gold quality
hypothalamus	UBERON:0001898	68.42	gold quality
pylorus	UBERON:0001166	68.36	gold quality
brain	UBERON:0000955	67.92	gold quality
central nervous system	UBERON:0001017	67.26	gold quality
prefrontal cortex	UBERON:0000451	66.59	gold quality
forebrain	UBERON:0001890	66.46	gold quality
substantia nigra pars reticulata	UBERON:0001966	66.38	gold quality
substantia nigra pars compacta	UBERON:0001965	66.36	silver quality
rectum	UBERON:0001052	66.23	gold quality
epithelial cell of pancreas	CL:0000083	65.51	silver quality
Brodmann (1909) area 9	UBERON:0013540	65.20	gold quality
Brodmann (1909) area 46	UBERON:0006483	64.82	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	473.57
E-MTAB-5061	yes	5.71
E-ANND-3	yes	5.22

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
CREBBP
INS	Unknown
INSM1	Repression
NEUROD1	Activation
NEUROG3	Unknown
PAX6	Unknown
RGN
TRIB3

JASPAR motifs

Motif	Name	Family
MA0155.1	INSM1	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:17916232

Upstream regulators (CollecTRI, top): AHR, ASCL1, CREBBP, FOXN1, INSM1, MYC, NEUROD1, NEUROG3, POU1F1, TCF3

miRNA regulators (miRDB)

91 targeting INSM1, 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-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-6759-5P	99.99	66.54	785
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-LET-7A-2-3P	99.87	70.53	1921

Literature-anchored findings (GeneRIF, showing 40)

• IA-1 gene was shown to be developmentally regulated in fetal pancreatic cells, and its expression pattern is consistent with parallel changes in islet-specific transcription factors during the endocrine differentiation of AR42J cells. (PMID:11854618)
• IA-1 gene is developmentally expressed in the nervous system and the NeuroD1/E47 transcription factors up-regulate IA-1 gene expression through the proximal E-box element of the IA-1 promoter (PMID:12890672)
• results presented in this study define INSM1 as a transcriptional repressor of the neuroD/b2 gene. The molecular mechanism of INSM1 transcriptional repression is attributed to the recruitment of cyclin D1 and HDAC-1 and -3 (PMID:16569215)
• in mice and humans, INSM1 is likewise expressed transiently during terminal neurogenic divisions, from late progenitors to nascent neurons, and particularly during symmetric neuronogenic divisions. (PMID:18205207)
• INSM1 is a new zinc-finger transcription factor that modulates insulin gene transcription during early pancreas development. (PMID:18417529)
• INSM1 role as an important regulator during neuroendocrine differentiation [review] (PMID:19246490)
• The INSM1 promoter can direct herpes simplex virus thymidine kinase gene expression in a nude mouse model of neuroendocrine cancer and effectively repress tumor growth in response to ganciclovir treatment. (PMID:19604042)
• Data show that the consistent functional effect of INSM1, either with or without other ITFs, promotes pancreatic duct cell differentiation as well as induces Panc-1 cell cycle arrest. (PMID:20215568)
• The results suggest that INSM1 up-regulation plays a positive role in HSV-1 replication, probably by binding to the ICP0 promoter. (PMID:21609490)
• Both the AR42J cell line and the primary cultured mouse acinar cells support role for INSM1 in pancreatic acinar cell trans-differentiation model. (PMID:21830214)
• INSM1 autoantibodies were associated with risk of developing type 1 diabetes. (PMID:25523979)
• INSM1 expression was significantly increased in Neuroendocrine neoplastic vs nonneoplastic tissue. (PMID:26386079)
• Data supports our hypothesis that a positive-feedback loop of sonic hedgehog signaling induced INSM1 through N-myc and INSM1 enhanced N-myc stability contributing to the transformation of human neuroblastoma. (PMID:26456864)
• Insulinoma-Associated Protein 1 is a crucial regulator of neuroendocrine differentiation in lung cancer. (PMID:26482608)
• the INSM1-promoter specific conditional replicating adenovirus represents a sensitive diagnostic tool to aid clinicians in the detection of NE tumors. (PMID:26530405)
• Small cell lung cancer tissues were strongly positive for INSM1. INSM1 signal was not detected on normal adjacent tissues from lung cancer patients or normal lung tissues (PMID:27072116)
• INSM1 is closely related to the development of high-grade neuroendocrine carcinoma of uterine cervix, and a useful new neuroendocrine marker in conducting its correct and rapid diagnosis (PMID:27908529)
• Solution NMR structure of zinc finger 4 and 5 from human INSM1 has been presented. (PMID:28160313)
• Our data suggest that children with the INSM1 binding site within the CLDN14 risk haplotype have a higher likelihood of hypercalciuria and kidney stones. Enhanced CLDN14 expression may play a role in the pathophysiology of their hypercalciuria. (PMID:28229505)
• High INSM1 expression is associated with small-cell lung cancer. (PMID:28667074)
• Suggest that INSM1 is valuable for identification of the high-grade thoracic neuroendocrine carcinomas that are sometimes negative for synaptophysin, chromogranin, and CD56. (PMID:28719469)
• Our results suggest that INSM1 is a useful immunohistochemical marker for diagnosing pancreatic neuroendocrine tumor. (PMID:28849340)
• INSM1 is a sensitive marker for Merkel cell carcinoma (PMID:29148079)
• Insulinoma-associated 1 (INSM1) gene is intronless and encodes a protein containing both a zinc finger DNA-binding domain and a putative prohormone domain. This gene is a sensitive marker for neuroendocrine differentiation of human lung tumors. (PMID:29327709)
• specificity of INSM1 for neuroendocrine neoplasms as a group was 100%. INSM1 staining was concordant with surgical pathology specimens in all 20 paired cases (PMID:29360191)
• INSM1 may be used as a standalone first-line marker of neuroendocrine differentiation for tumors of the head and neck. (PMID:29438167)
• nuclear INSM1 immunostaining may serve as a strong nuclear marker in the brain for neoplasms of neuroendocrine or immature neuronal differentiation, when used in concert with other immunostains (PMID:29490065)
• INSM1 functions as a key player in neuroendocrine lung cancer via sonic hedgehog (Shh) signaling that crosstalk with PI3K/AKT and MEK/ERK(1/2) pathway to enhance N-myc stability in neuroendocrine lung cancer. (PMID:29501727)
• INSM1 is a novel sensitive and specific marker for detection of small cell carcinoma of the prostate. (PMID:29885405)
• INSM1 is highly expressed in small-cell lung carcinomas. (PMID:29936498)
• INSM1 holds promise as a neuroendocrine marker that can distinguish Merkel cell carcinoma from its mimickers in the skin. (PMID:30080705)
• INSM1 is a reliable marker of neuroendocrine differentiation in primary lung neoplasms (PMID:30154579)
• NSM1 immunocytochemistry of cytological specimens obtained from endoscopic ultrasound-guided fine needle aspiration cytology can accurately diagnose pancreatic neuroendocrine tumours; therefore, INSM1 could be an important diagnostic tool in assessing therapeutic strategies, including molecular-targeted therapy. (PMID:30290028)
• INSM1 is a sensitive and specific marker for detection of neuroendocrine tumors in cytology samples independent of primary site. (PMID:30502379)
• INSM1 is expressed in most of the tumors with neuroendocrine and neuroepithelial differentiation in this study, confirming the diagnostic utility of INSM1 as a novel and sensitive marker of NE/neuroepithelial differentiation. (PMID:30523500)
• 5’-Iodotubercidin treatment and INSM1 inhibition suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) activity and the AKT signaling pathways required for neuroblastoma cell proliferation. (PMID:30755485)
• we find that the expression of INSM1 is variable among peripheral neuroblastic tumors, with absence of expression in a subset of undifferentiated and poorly differentiated neuroblastomas, as well as in mature ganglioneuromas (PMID:30975032)
• Insulinoma-associated protein 1 controls nasopharyngeal carcinoma to radiotherapy by modulating cyclin D1-dependent DNA repair machinery. (PMID:31155641)
• The sensitivity of INSM1 immunohistochemistry (IHC) was 97% (36 of 37 cases) whereas the sensitivity of INSM1 immunocytochemistry (ICC) was 91% (30 of 33 cases) for the diagnosis of small cell lung carcinoma (SCLC). All cases of non-small cell lung carcinoma were negative for INSM1 (100% specificity). INSM1 appears to be a robust and reliable ICC marker for the confirmation of SCLC diagnosis on cytology smears. (PMID:31343851)
• The results from this study have further established the high sensitivity and specificity of INSM1 in the largest pulmonary cytologic and surgical cohorts to date. (PMID:31345782)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	insm1b	ENSDARG00000053301
danio_rerio	insm1a	ENSDARG00000091756
mus_musculus	Insm1	ENSMUSG00000068154
rattus_norvegicus	Insm1	ENSRNOG00000068937
drosophila_melanogaster	nerfin-1	FBGN0028999
caenorhabditis_elegans		WBGENE00001210

Paralogs (1): INSM2 (ENSG00000168348)

Protein

Protein identifiers

Insulinoma-associated protein 1 — Q01101 (reviewed: Q01101)

Alternative names: Zinc finger protein IA-1

All UniProt accessions (1): Q01101

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific DNA-binding transcriptional regulator that plays a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and/or fetal development. Binds to the consensus sequence 5’-[TG][TC][TC][TT][GA]GGG[CG]A-3’ in target promoters. Acts as a transcriptional repressor of NEUROD1 and INS expression via its interaction with cyclin CCND1 in a cell cycle-independent manner. Negatively regulates skeletal muscle-specific gene expression in endocrine cells of the pituitary by inhibiting the Notch signaling pathway. Represses target gene transcription by recruiting chromatin-modifying factors, such as HDAC1, HDAC2, HDAC3, KDM1A and RCOR1 histone deacetylases. Binds to its own promoter, suggesting autoregulation as a self-control feedback mechanism. Competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at ‘Lys-4’. Promotes the generation and expansion of neuronal basal progenitor cells in the developing neocortex. Involved in the differentiation of endocrine cells of the developing anterior pituitary gland, of the pancreas and intestine, and of sympatho-adrenal cells in the peripheral nervous system. Promotes cell cycle signaling arrest and inhibition of cellular proliferation.

Subunit / interactions. Interacts (via the SNAG domain) with HDAC1. Interacts (via the SNAG domain) with HDAC2. Interacts (via the SNAG domain) with KDM1A. Interacts (via the SNAG domain) with RCOR1. Interacts with SORBS1. Interacts (via the N-terminal region) with CCND1 (via cyclin N-terminal domain); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and increases its transcriptional repressor activity. Interacts with HDAC3; the interaction increases its transcriptional repressor activity.

Subcellular location. Nucleus.

Tissue specificity. Expressed in pancreatic duct cells. Expressed in several tumor cell lines of neuroendocrine origin including pheochromocytoma, medullary thyroid carcinoma, insulinoma, medulloblastoma, retinoblastoma, pheochromacytoma, medullary thyroid carcinoma and small cell lung carcinoma.

Domain organisation. The C-terminal region is necessary for NEUROD1 promoter DNA-binding and transcriptional repressor activity.

Induction. Up-regulated by transcription factors, such as MASH1, NEUROD1, NEUROG3, NGN3 and TCF3.

Similarity. Belongs to the INSM1 family.

RefSeq proteins (1): NP_002187* (*=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 (32 total): strand 7, region of interest 6, helix 6, zinc finger region 5, compositionally biased region 5, chain 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3ZMS	X-RAY DIFFRACTION	2.96
2LV2	SOLUTION NMR
8JPY	SOLUTION NMR
8JQ1	SOLUTION NMR
8K81	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01101-F1	59.82	0.03

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
43–58	inhibits weakly translational repression activity. inhibits interaction with ccnd1 and cell cycle arrest.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-210746	Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells
R-HSA-1266738	Developmental Biology
R-HSA-186712	Regulation of beta-cell development

MSigDB gene sets: 286 (showing top): AHRARNT_01, E2F_Q4, FXR_IR1_Q6, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_TYPE_B_PANCREATIC_CELL_DEVELOPMENT, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_PANCREAS_DEVELOPMENT, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, MODULE_66

GO Biological Process (27): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of protein phosphorylation (GO:0001933), type B pancreatic cell differentiation (GO:0003309), pancreatic A cell differentiation (GO:0003310), type B pancreatic cell development (GO:0003323), noradrenergic neuron development (GO:0003358), cell population proliferation (GO:0008283), negative regulation of cell population proliferation (GO:0008285), regulation of gene expression (GO:0010468), regulation of cell cycle process (GO:0010564), cell migration (GO:0016477), neuron differentiation (GO:0030182), positive regulation of cell migration (GO:0030335), norepinephrine biosynthetic process (GO:0042421), regulation of protein-containing complex assembly (GO:0043254), positive regulation of cell differentiation (GO:0045597), regulation of cell cycle (GO:0051726), transdifferentiation (GO:0060290), adrenal chromaffin cell differentiation (GO:0061104), sympathetic ganglion development (GO:0061549), positive regulation of neural precursor cell proliferation (GO:2000179), nervous system development (GO:0007399), positive regulation of cell population proliferation (GO:0008284), cell differentiation (GO:0030154), endocrine pancreas development (GO:0031018), endocrine system development (GO:0035270), regulation of cell population proliferation (GO:0042127)

GO Molecular Function (10): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), cyclin binding (GO:0030332), chromatin DNA binding (GO:0031490), histone deacetylase binding (GO:0042826), molecular adaptor activity (GO:0060090), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription repressor complex (GO:0017053)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Regulation of beta-cell development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	3
endocrine pancreas development	2
enteroendocrine cell differentiation	2
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
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
epithelial cell development	1
type B pancreatic cell differentiation	1
noradrenergic neuron differentiation	1
neuron development	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
cell cycle process	1
regulation of cell cycle	1
cell motility	1
generation of neurons	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
norepinephrine metabolic process	1
catecholamine biosynthetic process	1
regulation of cellular component biogenesis	1
regulation of cellular component organization	1
protein-containing complex assembly	1
regulation of cell differentiation	1
positive regulation of cellular process	1
positive regulation of developmental process	1
cell cycle	1
regulation of cellular process	1
glandular epithelial cell differentiation	1
adrenal gland development	1

Protein interactions and networks

STRING

968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INSM1	NEUROD1	Q13562	929
INSM1	PTPRN	Q16849	910
INSM1	MAPK8IP1	Q9UQF2	884
INSM1	SORBS1	Q9BX66	844
INSM1	NEUROG3	Q9Y4Z2	788
INSM1	CCND1	P24385	757
INSM1	ASCL1	P50553	686
INSM1	RFX6	Q8HWS3	644
INSM1	PAX4	O43316	632
INSM1	CHGA	P10645	629
INSM1	SYP	P08247	623
INSM1	NKX2-2	O95096	593
INSM1	NEUROG1	Q92886	582
INSM1	MYCN	P04198	574
INSM1	NKX6-1	P78426	574

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MYC		psi-mi:“MI:0914”(association)	0.350
INSM1	Hdac3	psi-mi:“MI:0914”(association)	0.350
TUBB4A	INSM1	psi-mi:“MI:0915”(physical association)	0.000
MPP3	INSM1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): INSM1 (Two-hybrid), INSM1 (Affinity Capture-Western), INSM1 (Reconstituted Complex), INSM1 (Co-localization), INSM1 (Two-hybrid), INSM1 (Reconstituted Complex), INSM1 (Affinity Capture-Western), INSM1 (Reconstituted Complex), INSM1 (Affinity Capture-Western), INSM1 (Two-hybrid), CCND1 (Two-hybrid), INSM1 (Cross-Linking-MS (XL-MS)), INSM1 (Affinity Capture-RNA), CCND1 (Reconstituted Complex), CCND1 (Affinity Capture-Western)

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

2 interactions.

A	Effect	B	Mechanism
CREBBP	“up-regulates quantity by expression”	INSM1	“transcriptional regulation”
NEUROG3	“up-regulates quantity by expression”	INSM1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2 predictions. Top by Δscore:

Variant	Effect	Δscore
20:20368300:G:GT	donor_gain	0.4100
20:20368287:TG:T	donor_gain	0.2800

AlphaMissense

3228 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:20368280:T:C	F5L	1.000
20:20368282:C:A	F5L	1.000
20:20368282:C:G	F5L	1.000
20:20368991:G:A	G242R	1.000
20:20368991:G:C	G242R	1.000
20:20368992:G:A	G242E	1.000
20:20368995:T:A	L243H	1.000
20:20368995:T:C	L243P	1.000
20:20369001:T:A	I245N	1.000
20:20369001:T:C	I245T	1.000
20:20369001:T:G	I245S	1.000
20:20369066:T:C	F267L	1.000
20:20369067:T:C	F267S	1.000
20:20369068:C:A	F267L	1.000
20:20369068:C:G	F267L	1.000
20:20369072:T:A	C269S	1.000
20:20369072:T:C	C269R	1.000
20:20369073:G:A	C269Y	1.000
20:20369073:G:C	C269S	1.000
20:20369073:G:T	C269F	1.000
20:20369074:C:G	C269W	1.000
20:20369079:T:A	L271Q	1.000
20:20369079:T:C	L271P	1.000
20:20369081:T:A	C272S	1.000
20:20369081:T:C	C272R	1.000
20:20369082:G:A	C272Y	1.000
20:20369082:G:C	C272S	1.000
20:20369082:G:T	C272F	1.000
20:20369083:C:G	C272W	1.000
20:20369112:T:A	L282Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000329102 (20:20367536 G>A), RS1000489924 (20:20366860 A>G), RS1000784945 (20:20367770 C>A,G,T), RS1000840984 (20:20366527 A>G,T), RS1001196034 (20:20369578 C>A,T), RS1001892651 (20:20371171 T>C), RS1002551422 (20:20368561 G>A,T), RS1002648171 (20:20368839 C>G), RS1002833000 (20:20370743 A>C,G), RS1002850664 (20:20368226 A>G), RS1003574072 (20:20371071 G>T), RS1004246779 (20:20366954 T>A,G), RS1004258174 (20:20367239 C>A,T), RS1004580925 (20:20369648 C>A,G,T), RS1004590876 (20:20369881 C>A,G,T)

Disease associations

OMIM: gene MIM:600010 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
methylmercuric chloride	decreases expression, increases expression	2
Resveratrol	affects cotreatment, decreases expression	2
Lead	affects expression, affects methylation	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
trichostatin A	decreases expression	1
arsenite	increases methylation	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
rofecoxib	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
pyrimidifen	decreases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Antimycin A	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Ibuprofen	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Paraquat	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Tunicamycin	increases expression	1
Zinc	decreases expression	1

Clinical trials (associated diseases)

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