LINS1

Chr 15AR

lines homolog 1

Also known as: LINS, MRT27, WINS1

NCBI Gene: 55180ENSG00000140471UniProt: Q8NG48

The Drosophila segment polarity gene lin encodes a protein, lines, which plays important roles in development of the epidermis and hindgut. This gene encodes a protein containing a lines-like domain. This gene is located on chromosome 15 and clustered with the gene encoding ankyrin repeat and SOCS box-containing protein 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 27MIM #614340
AR
308
ClinVar variants
114
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LINS1
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
114 Pathogenic / Likely Pathogenic· 96 VUS of 308 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.96LOEUF
pLI 0.000
Z-score 1.70
OE 0.62 (0.41–0.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.68Z-score
OE missense 1.10 (1.01–1.19)
427 obs / 389.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.62 (0.41–0.96)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (1.01–1.19)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 14 / 22.8Missense obs/exp: 427 / 389.0Syn Z: 0.03

ClinVar Variant Classifications

308 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic85
Likely Pathogenic29
VUS96
Likely Benign47
Benign38
Conflicting13
85
Pathogenic
29
Likely Pathogenic
96
VUS
47
Likely Benign
38
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
79
0
85
Likely Pathogenic
14
1
14
0
29
VUS
3
64
29
0
96
Likely Benign
0
7
5
35
47
Benign
0
6
27
5
38
Conflicting
—13
Total237815440308

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

View in ClinVar →

Protein Context — Lollipop Plot

LINS1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

LINS1-related intellectual developmental disorder

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
LINES HOMOLOG 1; LINS1
MIM #610350 · *

Intellectual developmental disorder, autosomal recessive 27

MIM #614340

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Domain-specific phenotypes in LINS1-related disorder-A Chinese family with the Q92X variant and literature review.
Li XY et al.·Am J Med Genet C Semin Med Genet
2024Review
Novel LINS1 missense mutation in a family with non-syndromic intellectual disability.
Sheth J et al.·Am J Med Genet A
2017Case report
Identification of a novel nonsense homozygous mutation of LINS1 gene in two sisters with intellectual disability, schizophrenia, and anxiety.
Chen CH et al.·Biomed J
2021
Prenatal exome sequencing, a powerful tool for improving the description of prenatal features associated with genetic disorders.
Thauvin-Robinet C et al.·Prenat Diagn
2024
Identification of a Novel Missense Homozygous Variant in LINS1 in Two Distinct Iranian Families With Consanguineous Marriage.
Alimoradi E et al.·Mol Genet Genomic Med
2026Case report
[Identification of LINS1 gene variant in a patient with severe mental retardation].
Zhang X et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2020Case report
Novel chemosensitive single-nucleotide polymorphism markers to targeted regimens in metastatic colorectal cancer.
Kim JC et al.·Clin Cancer Res
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools