• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
ARCN1 (HGNC:649) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
archain 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
COPD
Alias symbols
No aliases found
%HI
9.21(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.1(Read more about gnomAD LOEUF score)
Cytoband
11q23.3
Genomic Coordinates
GRCh37/hg19: chr11:118443124-118473748 NCBI Ensembl UCSC
GRCh38/hg38: chr11:118572409-118603033 NCBI Ensembl UCSC
MANE Select Transcript
NM_001655.5 ENST00000264028.5 (Read more about MANE Select)
Function
Component of the coatomer, a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non- clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribo... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-22011
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
05/10/2022

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay Monarch
HI Evidence:
  • PUBMED: 27476655
    Izumi 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 additional de novo missense in a different gene SYT1 which is speculated to be the cause of this proband's seizures. Subject 3 is the father of subject 4, both have frameshift c.157_158del, leading to p.Ser53Cysfs*39; both are affected with short stature, rhizomelic shortening and developmental delay. Functional studies on truncations confirmed reduced mRNA expression, and Western blot demonstrated reduced protein expression.
  • PUBMED: 33154040
    Tidwell et al. (2020) describe a single proband with microcephaly, severe global developmental delay, and multiple congenital abnormalities. At birth he was documented to have a small ventricular septal defect (which was closed by 3 wk), a patent foramen ovale, rhizomelic shortening of extremities on clinical examination, pectus carinatum, and underdeveloped genitalia including severe penoscrotal hypospadias and cryptorchidism. His distinctive facial features recorded then included bulbous nasal tip, microretrognathia, and downturned corners of the mouth. A previous genomic microarray identified a 95-kb loss at 12q23.2 including exons 1–4 of the NUP37 gene and exons 1–9 of the PARPBP gene. This is not seen in either parents, but authors speculate on coverage from NGS that it may be maternally inherited. Trio Exome sequencing reveals a de novo intronic variant in ARCN1 in intron 3 of 8 Chr 11(GRCh37):g.118455180A > G, (NM_001655.5:c.654-15A > G). cDNA analysis shows insertion of 14 nucleotides that creates a premature stop codon p.Pro219Phefs*13, i.e loss of function.
  • PUBMED: 31075182
    Reunert et al. (2019) report a single proband with microcephaly, retrognathia, and cleft uvula. At first glycosylation studies pointed toward PGM1 related glycosylation abnormalities, but PGM1 sequencing was negative. Exome sequencing revealed a de novo c.380dupT (p.L127Ffs*14) in ARCN1.
  • PUBMED: 35300924
    Ritter et al. (2022) in a collaboration via Gene Matcher describe 14 new cases, making a total of 20 cases. Intrauterine growth restriction, micrognathia, and short stature were present in all patients. Seven unrelated probands have de novo truncating variants, 2 additional unrelated probands have truncations but inheritance unknown. The other five are family members of the above 9 unrelated probands. The phenotype has resemblance with Stickler syndrome.
HI Evidence Comments:
Truncating variants in ARCN1 have been described in approximately 20 individuals with ARCN1-related rhizomelic short stature, microcephaly, micrognathia, and developmental delay. In most of these individuals, the variants are de novo, and functional analyses for some of them have confirmed reduced expression and loss of protein.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000011.9) (NC_000011.10)