ERGIC2

Chr 12

ERGIC and golgi 2

Also known as: CDA14, Erv41, PTX1, cd002

NCBI Gene: 51290 ENSG00000087502 UniProt: Q96RQ1 OMIM: 612236

ERGIC2 encodes a protein involved in transport between the endoplasmic reticulum and Golgi apparatus. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and thin corpus callosum. The gene shows moderate constraint against loss-of-function variants, suggesting some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

ERGIC2, or PTX1, is a ubiquitously expressed nuclear protein that is downregulated in prostate carcinoma (Kwok et al., 2001 [PubMed 11445006]).[supplied by OMIM, Aug 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.63

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.013

Z-score 2.82

OE 0.33 (0.19–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.07Z-score

OE missense 0.78 (0.69–0.90)

152 obs / 193.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.19–0.63)

0≤0.351.4

Missense OE?0.78 (0.69–0.90)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 7 / 20.9Missense obs/exp: 152 / 193.7Syn Z: 0.69

Background carrier burden — how many people carry a rare variant somewhere in ERGIC2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

427 rare PASS variants

Rare truncating (LoF)

1 in 3,000

80 rare PASS variants

Rare synonymous (reference)

1 in 870

124 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ERGIC2. 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 260	1 in 4,300
South Asian	~43k	1 in 160	1 in 6,000
Remaining (unassigned)	~30k	1 in 260	≈ 1 in 7,400
European (Finnish)	~27k	1 in 2,000	1 in 5,300
Admixed American	~22k	1 in 150	1 in 1,700
African / African American	~21k	1 in 210	1 in 2,000
East Asian	~20k	1 in 190	1 in 1,700
Ashkenazi Jewish	~13k	1 in 370	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 400	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 13 coding exons well covered in gnomAD exomes; exons 3, 4, 5, 6, 7 and 5 more marginal. Genomes: all 13.? see exons ↓