LINS1

Chr 15

lines homolog 1

Also known as: LINS, MRT27, WINS1

NCBI Gene: 55180 ENSG00000140471 UniProt: Q8NG48

LINS1 encodes a protein containing a lines-like domain that plays important roles in epidermal and hindgut development. Mutations cause autosomal recessive intellectual developmental disorder. The gene shows minimal constraint against loss-of-function variants (pLI near 0, LOEUF 0.96), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, OMIM

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.96

Clinical Summary— LINS1

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

34 unique Pathogenic / Likely Pathogenic· 78 VUS of 210 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.000

Z-score 1.70

OE 0.62 (0.41–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.68Z-score

OE missense 1.10 (1.01–1.19)

427 obs / 389.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.62 (0.41–0.96)

0≤0.351.4

Missense OE?1.10 (1.01–1.19)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 14 / 22.8Missense obs/exp: 427 / 389.0Syn Z: 0.03

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongLINS1-related intellectual developmental disorderLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6358th %ile

GOF

0.5268th %ile

LOF

0.4037th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

210 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic24

VUS78

Likely Benign45

Benign37

Conflicting11

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	0	0	0	10
Likely Pathogenic	23	1	0	0	24
VUS	4	70	4	0	78
Likely Benign	0	7	3	35	45
Benign	0	6	26	5	37
Conflicting	—				11
Total	37	84	33	40	205

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

View in ClinVar →

83 pathogenic / likely-pathogenic (of 108) ClinVar copy-number / structural variants overlap LINS1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →