GON4L

Chr 1AR

gon-4 like

Also known as: GON-4, GON4, LTMS, YARP

NCBI Gene: 54856 ENSG00000116580 UniProt: Q3T8J9 OMIM: 610393

GON4L encodes a transcription regulator that activates histone gene transcription and is required for B-cell development. Mutations cause Li-Takada-Miyake syndrome with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.95, LOEUF 0.30), indicating intolerance to disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of DNA-templated transcription. Predicted to act upstream of or within B cell differentiation. Located in nuclear body. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.301 OMIM phenotype

Clinical Summary— GON4L

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 4 VUS of 88 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.951

Z-score 7.13

OE 0.20 (0.14–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.65Z-score

OE missense 0.86 (0.82–0.91)

984 obs / 1140.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.14–0.30)

0≤0.351.4

Missense OE?0.86 (0.82–0.91)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 19 / 93.3Missense obs/exp: 984 / 1140.5Syn Z: -0.51

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedGON4L-related intellectual developmental disorderLOFAR

This gene — mechanism propensity

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

0.2599th %ile

GOF

0.2398th %ile

LOF

0.80top 5%

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

88 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic1

VUS4

Likely Benign24

Benign2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	1	0	0	0	1
VUS	0	4	0	0	4
Likely Benign	0	6	2	16	24
Benign	0	0	1	1	2
Total	3	10	3	17	33

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap GON4L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →