LIAT1

Chr 17

ligand of ATE1

Also known as: C17orf97, CK20

NCBI Gene: 400566 ENSG00000187624 UniProt: Q6ZQX7

The LIAT1 protein participates in nucleolar liquid-liquid phase separation and may be involved in protein arginylation. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly. The gene shows low constraint to loss-of-function variation, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, UniProt

Predicted to enable molecular condensate scaffold activity. Predicted to be involved in membraneless organelle assembly and protein arginylation. Predicted to be located in cytoplasm and nucleus. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.97

Clinical Summary— LIAT1

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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

7 VUS of 33 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.97LOEUF

pLI 0.000

Z-score -2.25

OE 2.59 (0.99–1.97)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.02Z-score

OE missense 1.00 (0.90–1.11)

252 obs / 251.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?2.59 (0.99–1.97)

0≤0.351.4

Missense OE?1.00 (0.90–1.11)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 6 / 2.3Missense obs/exp: 252 / 251.3Syn Z: -0.27

This gene — mechanism propensity

0.7131th %ile

GOF

0.87top 5%

LOF

0.4726th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

33 submitted variants in ClinVar

ClinVar

Classification Summary

VUS7

Likely Benign22

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	7	0	7
Likely Benign	4	18	22
Benign	0	0	0
Total	11	18	29

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

View in ClinVar →

56 pathogenic / likely-pathogenic (of 106) ClinVar copy-number / structural variants overlap LIAT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →