ARCN1

Chr 11AD

archain 1 coat protein complex I subunit delta

Also known as: COPD, SRMMD, SSMG

NCBI Gene: 372ENSG00000095139UniProt: P48444OMIM: 600820

ARCN1 encodes a component of the coatomer complex that is essential for protein transport between the endoplasmic reticulum and Golgi apparatus and maintains Golgi structural integrity. Mutations cause autosomal dominant short stature-micrognathia syndrome. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.10), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.101 OMIM phenotype
Clinical Summary— ARCN1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
57 unique Pathogenic / Likely Pathogenic· 144 VUS of 359 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 5.05
OE 0.00 (0.00–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.08Z-score
OE missense 0.65 (0.58–0.74)
186 obs / 284.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.10)
0≤0.351.4
Missense OE0.65 (0.58–0.74)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 0 / 29.6Missense obs/exp: 186 / 284.9Syn Z: -0.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongARCN1-related microcephalic dwarfismLOFAD
DN
0.2798th %ile
GOF
0.2796th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 49% of P/LP variants are LoF · LOEUF 0.10

Literature Evidence

LOFIzumi et al. (2016) report 4 individuals with 3 different ARCN1 variants: one nonsense and two frameshifts, all predicted to undergo nonsense mediated decay. Subject 1 has c. 260C>A [p.Ser87*], inheritance unknown. Subject 2 has a de novo ARCN1 frameshift: (c.633del [p.Val212Trpfs*15], and an additiPMID:27476655

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

359 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic11
VUS144
Likely Benign104
Benign25
Conflicting15
46
Pathogenic
11
Likely Pathogenic
144
VUS
104
Likely Benign
25
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
0
25
0
46
Likely Pathogenic
7
1
3
0
11
VUS
1
131
12
0
144
Likely Benign
0
11
36
57
104
Benign
0
3
15
7
25
Conflicting
—15
Total291469164345

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

View in ClinVar →

Protein Context — Lollipop Plot

ARCN1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients