GOLGA6L10

Chr 15

golgin A6 family like 10

Also known as: GOLGA6L18

NCBI Gene: 647042 ENSG00000278662 UniProt: A6NI86

This gene encodes a golgi autoantigen family protein involved in Golgi apparatus structure and function. Mutations cause autosomal recessive intellectual disability with macrocephaly, seizures, and dysmorphic features, typically presenting in early childhood. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

Research

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.88

Clinical Summary— GOLGA6L10

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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

72 VUS of 90 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?

1.88LOEUF

pLI 0.001

Z-score -0.23

OE 1.13 (0.53–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.77Z-score

OE missense 1.68 (1.41–1.93)

90 obs / 53.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.13 (0.53–1.88)

0≤0.351.4

Missense OE?1.68 (1.41–1.93)

0≤0.61.4

Synonymous OE?1.32

0≤1.21.6

LoF obs/exp: 4 / 3.5Missense obs/exp: 90 / 53.5Syn Z: -1.23

This gene — mechanism propensity

0.7325th %ile

GOF

0.79top 25%

LOF

0.2386th %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

90 submitted variants in ClinVar

ClinVar

Classification Summary

VUS72

Likely Benign14

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	66	4	2	72
Likely Benign	11	2	1	14
Benign	2	0	0	2
Total	79	6	3	88

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

View in ClinVar →

5 pathogenic / likely-pathogenic (of 5) ClinVar copy-number / structural variants overlap GOLGA6L10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →