INSM1

Chr 20

INSM transcriptional repressor 1

Also known as: IA-1, IA1

NCBI Gene: 3642ENSG00000173404UniProt: Q01101

INSM1 encodes a zinc finger transcriptional repressor that regulates neurogenesis and neuroendocrine cell differentiation during embryonic and fetal development, promoting neuronal progenitor cell generation and differentiation of endocrine cells in the pituitary, pancreas, intestine, and sympathoadrenal system. Mutations cause neurodevelopmental disorders with intellectual disability and neuroendocrine dysfunction, following an autosomal dominant inheritance pattern. The gene shows moderate constraint against loss-of-function variants, consistent with its essential role in early nervous system and endocrine development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
73
Pubs (1 yr)
25
P/LP submissions
0%
P/LP missense
0.81
LOEUF
LOF
Mechanism· predicted
Clinical Summary— INSM1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 74 VUS of 102 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.269
Z-score 1.92
OE 0.26 (0.10–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.12Z-score
OE missense 0.77 (0.67–0.89)
146 obs / 189.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.10–0.81)
0≤0.351.4
Missense OE0.77 (0.67–0.89)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 2 / 7.8Missense obs/exp: 146 / 189.3Syn Z: -0.33
DN
0.4289th %ile
GOF
0.5071th %ile
LOF
0.68top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic3
VUS74
Likely Benign2
Benign1
22
Pathogenic
3
Likely Pathogenic
74
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
3
0
3
VUS
0
72
2
0
74
Likely Benign
0
2
0
0
2
Benign
0
0
0
1
1
Total074271102

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

INSM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Prognostic utility of baseline ASCL1/INSM1 expression and neutrophil-lymphocyte ratio in unresectable SCLC treated with first-line chemoimmunotherapy with or without radiotherapy.
Zhu Y et al.·Front Med
2025
Regulation of INSM1 Gene Expression and Neuroendocrine Differentiation in High-Risk Neuroblastoma.
Chen C et al.·Biology (Basel)
2025Open Access
Sinonasal Lymphoepithelial Carcinoma With Insulinoma-Associated Protein 1 (INSM1) Expression: A Potential Pitfall.
Elsafy H et al.·Int J Surg Pathol
2025
INSM1 governs a neuronal progenitor state that drives glioblastoma in a human stem cell model.
DeSouza PA et al.·Nat Commun
2025Open AccessFunctional
Immunohistochemical expression of Ki-67, INSM1, and SSTR2A in medullary thyroid carcinoma: correlation with tumour size, vascular invasion, and biochemical outcome.
Rossi ED et al.·Virchows Arch
2025
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients