GOLGA4

Chr 3

golgin A4

Also known as: CRPF46, GCP2, GOLG, MU-RMS-40.18, p230

NCBI Gene: 2803 ENSG00000144674 UniProt: Q13439

The protein functions in vesicular trafficking at the Golgi apparatus and is involved in endosome-to-Golgi transport and delivery of transport vesicles containing GPI-linked proteins. Mutations cause autosomal recessive progressive myoclonic epilepsy. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

ResearchSummary from RefSeq, UniProt

The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked cisternae (flattened membrane sacs). Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. This gene encodes one of the golgins, a family of proteins localized to the Golgi. This protein has been postulated to play a role in Rab6-regulated membrane-tethering events in the Golgi apparatus. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2010]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.52

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.000

Z-score 5.95

OE 0.40 (0.32–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.10Z-score

OE missense 1.01 (0.96–1.06)

1081 obs / 1071.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.40 (0.32–0.52)

0≤0.351.4

Missense OE?1.01 (0.96–1.06)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 47 / 116.3Missense obs/exp: 1081 / 1071.5Syn Z: -0.59

Background carrier burden — how many people carry a rare variant somewhere in GOLGA4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 22

2,744 rare PASS variants

Rare truncating (LoF)

1 in 550

378 rare PASS variants

Rare synonymous (reference)

1 in 56

989 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GOLGA4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 34	1 in 620
South Asian	~43k	1 in 24	1 in 700
Remaining (unassigned)	~30k	1 in 18	1 in 500
European (Finnish)	~27k	1 in 91	1 in 2,100
Admixed American	~22k	1 in 25	1 in 900
African / African American	~21k	1 in 22	1 in 620
East Asian	~20k	1 in 31	1 in 610
Ashkenazi Jewish	~13k	1 in 68	1 in 1,300
Middle Eastern	~2,884	1 in 29	1 in 470

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 23 coding exons well covered in gnomAD exomes; exons 18, 20 poorly covered; exons 2, 4, 5, 6, 9 and 4 more marginal. Genomes: all 23.? see exons ↓