ARCN1

Chr 11AD

archain 1 coat protein complex I subunit delta

Also known as: COPD, SRMMD, SSMG

NCBI Gene: 372ENSG00000095139UniProt: P48444

This gene maps in a region, which include the mixed lineage leukemia and Friend leukemia virus integration 1 genes, where multiple disease-associated chromosome translocations occur. It is an intracellular protein. Archain sequences are well conserved among eukaryotes and this protein may play a fundamental role in eukaryotic cell biology. It has similarities to heat shock proteins and clathrin-associated proteins, and may be involved in vesicle structure or trafficking. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Short stature-micrognathia syndromeMIM #617164
AD
0
Active trials
55
Pathogenic / LP
341
ClinVar variants
4
Pubs (1 yr)
2.1
Missense Z
0.10
LOEUF· LoF intolerant
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
55 Pathogenic / Likely Pathogenic· 143 VUS of 341 total submissions

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
LOF
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 · 20% 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

341 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic9
VUS143
Likely Benign104
Benign25
Conflicting14
46
Pathogenic
9
Likely Pathogenic
143
VUS
104
Likely Benign
25
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
36
0
46
Likely Pathogenic
1
0
8
0
9
VUS
1
130
12
0
143
Likely Benign
0
11
36
57
104
Benign
0
3
15
7
25
Conflicting
—14
Total1214410764341

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

View in ClinVar →

ARCN1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ARCN1-related microcephalic dwarfism

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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