ICA1

Chr 7

islet cell autoantigen 1

Also known as: ICA69, ICAp69

NCBI Gene: 3382ENSG00000003147UniProt: Q05084

This gene encodes a protein with an arfaptin homology domain that is found both in the cytosol and as membrane-bound form on the Golgi complex and immature secretory granules. This protein is believed to be an autoantigen in insulin-dependent diabetes mellitus and primary Sjogren's syndrome. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

126
ClinVar variants
27
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ICA1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 85 VUS of 126 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.58LOEUF
pLI 0.001
Z-score 3.39
OE 0.35 (0.22–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.49Z-score
OE missense 0.91 (0.82–1.02)
236 obs / 258.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.35 (0.22–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.82–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 11 / 31.6Missense obs/exp: 236 / 258.3Syn Z: -0.47

ClinVar Variant Classifications

126 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
VUS85
Likely Benign10
Benign4
27
Pathogenic
85
VUS
10
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
0
0
0
VUS
0
80
5
0
85
Likely Benign
0
2
8
0
10
Benign
0
0
2
2
4
Total082422126

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

View in ClinVar →

Protein Context — Lollipop Plot

ICA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Novel and rare functional genomic variants in multiple autoimmune syndrome and Sjögren's syndrome.
Johar AS et al.·J Transl Med
2015Functional
Measurement of ionized calcium in serum with ion-selective electrodes: a mature technology that can meet the daily service needs.
Bowers GN Jr et al.·Clin Chem
1986Review
An evaluation of the ICA1 ionized calcium analyzer in a clinical chemistry laboratory.
Smith SC et al.·Scand J Clin Lab Invest Suppl
1983
Additive effects of genetic variants associated with intraocular pressure in primary open-angle glaucoma.
Mabuchi F et al.·PLoS One
2017
Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus.
Blue Mountains Eye Study (BMES) et al.·Hum Mol Genet
2013
Molecular phenotype of inflammatory bowel disease-associated neoplasms with microsatellite instability.
Schulmann K et al.·Gastroenterology
2005
Clinical studies on ionized calcium using the radiometer ICA1 analyzer.
Buckley BM et al.·Scand J Clin Lab Invest Suppl
1983
Comparison of two commercial ionised calcium analysers, and values in South African blacks.
Moodley GP et al.·S Afr Med J
1987
Attention-related potentials allow for a highly accurate discrimination of mild cognitive impairment subtypes.
Missonnier P et al.·Neurodegener Dis
2013
In vitro vascular toxicity of tariquidar, a potential tool for in vivo PET studies.
Durante M et al.·Toxicol In Vitro
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools