ARCN1

Summary

ARCN1 (archain 1 coat protein complex I subunit delta, HGNC:649) is a protein-coding gene on chromosome 11q23.3, encoding Coatomer subunit delta (P48444). 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. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 372 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 324 total — 21 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 46
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001655

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:649
Approved symbol	ARCN1
Name	archain 1 coat protein complex I subunit delta
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	delta-COP
Ensembl gene	ENSG00000095139
Ensembl biotype	protein_coding
OMIM	600820
Entrez	372

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000264028, ENST00000359415, ENST00000392859, ENST00000534182, ENST00000935080, ENST00000935081, ENST00000935082, ENST00000954507

RefSeq mRNA: 11 — MANE Select: NM_001655 NM_001142281, NM_001425073, NM_001425074, NM_001425075, NM_001425076, NM_001425077, NM_001425078, NM_001425079, NM_001425080, NM_001425081, NM_001655

CCDS: CCDS44749, CCDS8400

Canonical transcript exons

ENST00000264028 — 10 exons

Exon	Start	End
ENSE00000611294	118590341	118590506
ENSE00000748272	118583809	118584014
ENSE00000748273	118584480	118584644
ENSE00000748281	118592709	118592856
ENSE00000748282	118593590	118593698
ENSE00000796035	118597707	118597911
ENSE00002163320	118572409	118572550
ENSE00003555948	118581246	118581509
ENSE00003580071	118583179	118583358
ENSE00003846316	118600625	118603033

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 93.4668 / max 997.1908, expressed in 1824 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117015	93.3333	1824
206467	0.1335	39

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.25	gold quality
islet of Langerhans	UBERON:0000006	98.25	gold quality
body of pancreas	UBERON:0001150	97.83	gold quality
pancreas	UBERON:0001264	97.57	gold quality
calcaneal tendon	UBERON:0003701	97.55	gold quality
cardia of stomach	UBERON:0001162	97.53	gold quality
jejunal mucosa	UBERON:0000399	97.46	gold quality
type B pancreatic cell	CL:0000169	97.44	gold quality
adenohypophysis	UBERON:0002196	97.40	gold quality
corpus epididymis	UBERON:0004359	97.40	gold quality
urethra	UBERON:0000057	97.37	gold quality
tibia	UBERON:0000979	97.36	gold quality
pituitary gland	UBERON:0000007	97.30	gold quality
synovial joint	UBERON:0002217	97.26	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.23	gold quality
pylorus	UBERON:0001166	97.22	gold quality
saphenous vein	UBERON:0007318	97.03	gold quality
colonic mucosa	UBERON:0000317	97.01	gold quality
decidua	UBERON:0002450	97.01	gold quality
smooth muscle tissue	UBERON:0001135	96.98	gold quality
ascending aorta	UBERON:0001496	96.97	gold quality
thoracic aorta	UBERON:0001515	96.96	gold quality
cartilage tissue	UBERON:0002418	96.94	gold quality
ventricular zone	UBERON:0003053	96.85	gold quality
lower lobe of lung	UBERON:0008949	96.79	gold quality
aorta	UBERON:0000947	96.62	gold quality
trachea	UBERON:0003126	96.61	gold quality
penis	UBERON:0000989	96.60	gold quality
pericardium	UBERON:0002407	96.56	gold quality
descending thoracic aorta	UBERON:0002345	96.54	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-112	no	2.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

161 targeting ARCN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3919	99.87	69.45	2489

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• native crystals of delta-COP had unit-cell parameters a = 100.23, b = 136.77, c = 44.39 A (PMID:22750876)
• Single nucleotide polymorphisms in the PHLDB1 and ARCN1 genes are associated with increased risk of Glioma. (PMID:23300798)
• The authors demonstrated that miR-33a could impede influenza A virus replication at the stage of virus internalization by suppressing ARCN1 expression. (PMID:26498766)
• report of a clinically recognizable craniofacial disorder characterized by facial dysmorphisms, severe micrognathia, rhizomelic shortening, microcephalic dwarfism, and mild developmental delay due to loss-of-function heterozygous mutations in ARCN1, which encodes the coatomer subunit delta of COPI (PMID:27476655)
• Novel de novo ARCN1 intronic variant causes rhizomelic short stature with microretrognathia and developmental delay. (PMID:33154040)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arcn1a	ENSDARG00000002792
danio_rerio	arcn1b	ENSDARG00000031214
mus_musculus	Arcn1	ENSMUSG00000032096
rattus_norvegicus	Arcn1	ENSRNOG00000061108
drosophila_melanogaster	deltaCOP	FBGN0028969
caenorhabditis_elegans		WBGENE00015734

Protein

Protein identifiers

Coatomer subunit delta — P48444 (reviewed: P48444)

Alternative names: Archain, Delta-coat protein

All UniProt accessions (4): P48444, B0YIW5, B0YIW6, E9PK34

UniProt curated annotations — full annotation on UniProt →

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-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors.

Subunit / interactions. Oligomeric complex that consists of at least the alpha, beta, beta’, gamma, delta, epsilon and zeta subunits.

Subcellular location. Cytoplasm. Golgi apparatus membrane. Cytoplasmic vesicle. COPI-coated vesicle membrane.

Tissue specificity. Ubiquitously expressed.

Disease relevance. Short stature-micrognathia syndrome (SSMG) [MIM:617164] An autosomal dominant disorder characterized by facial dysmorphism, severe micrognathia, microcephaly, rhizomelic short stature, and mild developmental delay. The disease is caused by variants affecting the gene represented in this entry. the skeletal phenotype, that characterizes this disorder, may be due to defective type I collagen transport and reduction of collagen secretion.

Similarity. Belongs to the adaptor complexes medium subunit family. Delta-COP subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P48444-1	1	yes
P48444-2	2

RefSeq proteins (11): NP_001135753, NP_001412002, NP_001412003, NP_001412004, NP_001412005, NP_001412006, NP_001412007, NP_001412008, NP_001412009, NP_001412010, NP_001646* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011012	Longin-like_dom_sf	Homologous_superfamily
IPR022775	AP_mu_sigma_su	Domain
IPR027059	Coatomer_dsu	Family
IPR028565	MHD	Domain
IPR036168	AP2_Mu_C_sf	Homologous_superfamily

Pfam: PF00928, PF01217

UniProt features (16 total): modified residue 7, sequence variant 2, initiator methionine 1, chain 1, splice variant 1, sequence conflict 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48444-F1	84.25	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 351, 493, 223, 233, 241, 244, 309

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic

MSigDB gene sets: 316 (showing top): GOBP_HINDBRAIN_DEVELOPMENT, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_ADULT_BEHAVIOR, KENNY_CTNNB1_TARGETS_UP, MORF_RAD21, GCAAGGA_MIR502, MODULE_264, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ADULT_LOCOMOTORY_BEHAVIOR, MORF_PSMC2

GO Biological Process (11): intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), adult locomotory behavior (GO:0008344), cerebellar Purkinje cell layer maturation (GO:0021691), pigmentation (GO:0043473), Golgi localization (GO:0051645), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), Golgi vesicle transport (GO:0048193), establishment of localization in cell (GO:0051649)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (12): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), COPI vesicle coat (GO:0030126), transport vesicle (GO:0030133), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), COPI-coated vesicle (GO:0030137), COPI-coated vesicle membrane (GO:0030663), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
cellular anatomical structure	3
endomembrane system	3
intracellular protein localization	2
intracellular transport	2
Golgi vesicle transport	2
transport	2
Golgi apparatus	2
intracellular membrane-bounded organelle	2
protein transport	1
intercellular transport	1
locomotory behavior	1
adult behavior	1
cerebellar Purkinje cell layer development	1
cerebellar cortex maturation	1
anatomical structure maturation	1
biological_process	1
organelle localization	1
establishment of protein localization	1
cellular process	1
vesicle-mediated transport	1
establishment of localization	1
cellular localization	1
nucleic acid binding	1
binding	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vesicle coat	1
COPI-coated vesicle membrane	1
cytoplasmic vesicle	1
intracellular anatomical structure	1
Golgi-associated vesicle	1
coated vesicle	1
COPI-coated vesicle	1
Golgi-associated vesicle membrane	1
coated vesicle membrane	1
intracellular vesicle	1

Protein interactions and networks

STRING

2564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARCN1	COPB2	P35606	999
ARCN1	COPA	P53621	999
ARCN1	COPZ1	P61923	999
ARCN1	COPB1	P53618	998
ARCN1	COPE	O14579	998
ARCN1	COPG1	Q9Y678	984
ARCN1	COPG2	Q9UBF2	818
ARCN1	GOLPH3	Q9H4A6	796
ARCN1	AP2B1	P21851	720
ARCN1	SEC13	P55735	625
ARCN1	AP4E1	Q9UPM8	617
ARCN1	COPZ2	Q9P299	572
ARCN1	ARF1	P10947	571
ARCN1	SEC31A	O94979	557
ARCN1	ATP6AP1	Q15904	557

IntAct

149 interactions, top by confidence:

A	B	Type	Score
COPG1	COPB2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SCYL1	SEC31A	psi-mi:“MI:0914”(association)	0.710
SPTLC1	SPTLC2	psi-mi:“MI:0914”(association)	0.680
COPG1	COPE	psi-mi:“MI:0914”(association)	0.640
SACM1L	COPE	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
ARCN1	COPB1	psi-mi:“MI:0915”(physical association)	0.560
ARCN1	LBHD1	psi-mi:“MI:0915”(physical association)	0.560
Copa	COPE	psi-mi:“MI:0915”(physical association)	0.560
HTT	ARCN1	psi-mi:“MI:0915”(physical association)	0.560
TMED9	COPB2	psi-mi:“MI:0914”(association)	0.530
COPZ1	COPE	psi-mi:“MI:0914”(association)	0.530
COPE	COPB2	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
TGOLN2	PGRMC1	psi-mi:“MI:0914”(association)	0.420
FLT4	ILVBL	psi-mi:“MI:0914”(association)	0.420
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
HMGB2	ARCN1	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350

BioGRID (351): ARCN1 (Affinity Capture-MS), ARCN1 (Affinity Capture-MS), COPA (Co-fractionation), COPB1 (Co-fractionation), COPB2 (Co-fractionation), COPE (Co-fractionation), COPG1 (Co-fractionation), COPZ1 (Co-fractionation), NOB1 (Co-fractionation), SF3B1 (Co-fractionation), ARCN1 (Affinity Capture-MS), ARCN1 (Proximity Label-MS), ARCN1 (Proximity Label-MS), ARCN1 (Affinity Capture-MS), ARCN1 (Affinity Capture-MS)

ESM2 similar proteins: A0JN27, A0PJN4, A1L167, C1C3R6, O88761, O94973, P17427, P18484, P22234, P38024, P48444, P51583, P97834, Q08211, Q0VCK5, Q13042, Q13098, Q28141, Q28F89, Q2YDL1, Q3MHJ2, Q3TXS7, Q4R9A8, Q4VC33, Q5F398, Q5F418, Q5R532, Q5R5S4, Q5R874, Q5RA77, Q5RB59, Q5RBN9, Q5RDU4, Q5RKJ1, Q6GR10, Q6NRB5, Q6NRT5, Q76EZ2, Q7L5Y9, Q7SXR3

Diamond homologs: O74496, P43621, P48444, P49661, P53619, Q09236, Q0DJ99, Q0DJA0, Q55EZ6, Q5RA77, Q5XJY5, Q5ZL57, Q66H80, Q93Y22, Q0J649

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 170 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
COPI-dependent Golgi-to-ER retrograde traffic	10	9.6×	3e-05
COPI-mediated anterograde transport	10	9.5×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
intra-Golgi vesicle-mediated transport	8	28.9×	2e-07
zinc ion transmembrane transport	6	28.9×	1e-05
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	9	20.8×	2e-07
endoplasmic reticulum to Golgi vesicle-mediated transport	12	11.2×	3e-07
cell surface receptor protein tyrosine kinase signaling pathway	8	9.5×	4e-04
intracellular protein transport	13	5.8×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

324 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	6
Uncertain significance	138
Likely benign	101
Benign	25

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1033438	NM_001655.5(ARCN1):c.934C>T (p.Arg312Ter)	Pathogenic
1048776	NM_001655.5(ARCN1):c.1286del (p.Tyr429fs)	Pathogenic
1454993	NM_001655.5(ARCN1):c.553G>T (p.Gly185Ter)	Pathogenic
1698729	NM_001655.5(ARCN1):c.431dup (p.Arg145fs)	Pathogenic
1698855	NM_001655.5(ARCN1):c.508C>T (p.Arg170Ter)	Pathogenic
1704215	NM_001655.5(ARCN1):c.380dup (p.Leu127fs)	Pathogenic
1704218	NM_001655.5(ARCN1):c.1001dup (p.Asp334fs)	Pathogenic
1711329	NM_001655.5(ARCN1):c.941del (p.Arg314fs)	Pathogenic
2114861	NM_001655.5(ARCN1):c.1099C>T (p.Gln367Ter)	Pathogenic
2229622	NM_001655.5(ARCN1):c.76C>T (p.Arg26Ter)	Pathogenic
2430360	NM_001655.5(ARCN1):c.862C>T (p.Arg288Ter)	Pathogenic
267208	NM_001655.5(ARCN1):c.157_158del (p.Ser53fs)	Pathogenic
267209	NM_001655.5(ARCN1):c.260C>A (p.Ser87Ter)	Pathogenic
267210	NM_001655.5(ARCN1):c.633del (p.Val212fs)	Pathogenic
2750345	NM_001655.5(ARCN1):c.711del (p.Phe238fs)	Pathogenic
3064279	NM_001655.5(ARCN1):c.886dup (p.Glu296fs)	Pathogenic
3234102	NM_001655.5(ARCN1):c.1207G>T (p.Glu403Ter)	Pathogenic
4294302	NM_001655.5(ARCN1):c.1288C>T (p.Arg430Ter)	Pathogenic
4531787	NM_001655.5(ARCN1):c.462del (p.Ala155fs)	Pathogenic
4531795	NM_001655.5(ARCN1):c.1142G>A (p.Trp381Ter)	Pathogenic
4723761	NM_001655.5(ARCN1):c.174C>G (p.Tyr58Ter)	Pathogenic
1033437	NM_001655.5(ARCN1):c.1319G>A (p.Trp440Ter)	Likely pathogenic
1320069	NM_001655.5(ARCN1):c.231AGA[1] (p.Glu78del)	Likely pathogenic
1687551	NM_001655.5(ARCN1):c.522_525del (p.Glu174fs)	Likely pathogenic
2434798	NM_001655.5(ARCN1):c.814G>T (p.Glu272Ter)	Likely pathogenic
3377223	NM_001655.5(ARCN1):c.55C>T (p.Arg19Ter)	Likely pathogenic
4813485	NM_001655.5(ARCN1):c.526C>T (p.Gln176Ter)	Likely pathogenic

SpliceAI

1453 predictions. Top by Δscore:

Variant	Effect	Δscore
11:118581505:GAGTG:G	donor_gain	1.0000
11:118581506:AGTGG:A	donor_loss	1.0000
11:118581507:GTG:G	donor_gain	1.0000
11:118581507:GTGGT:G	donor_loss	1.0000
11:118581511:TAAGA:T	donor_loss	1.0000
11:118583161:A:AG	acceptor_gain	1.0000
11:118583161:ATT:A	acceptor_gain	1.0000
11:118583161:ATTG:A	acceptor_gain	1.0000
11:118583162:T:G	acceptor_gain	1.0000
11:118583163:T:A	acceptor_gain	1.0000
11:118583164:G:A	acceptor_gain	1.0000
11:118583166:T:TA	acceptor_gain	1.0000
11:118583171:A:AG	acceptor_gain	1.0000
11:118583171:AC:A	acceptor_gain	1.0000
11:118583172:C:CA	acceptor_gain	1.0000
11:118583172:C:G	acceptor_gain	1.0000
11:118583175:TTA:T	acceptor_loss	1.0000
11:118583177:A:AG	acceptor_gain	1.0000
11:118583177:A:AT	acceptor_loss	1.0000
11:118583178:G:GG	acceptor_gain	1.0000
11:118583178:GA:G	acceptor_gain	1.0000
11:118583178:GAT:G	acceptor_gain	1.0000
11:118583178:GATC:G	acceptor_gain	1.0000
11:118583178:GATCC:G	acceptor_gain	1.0000
11:118583244:T:TA	acceptor_gain	1.0000
11:118583250:T:TA	acceptor_gain	1.0000
11:118583354:GAGAG:G	donor_gain	1.0000
11:118583356:GAG:G	donor_gain	1.0000
11:118583359:G:GG	donor_gain	1.0000
11:118583360:T:G	donor_loss	1.0000

AlphaMissense

3368 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:118581297:C:G	R19G	1.000
11:118581298:G:C	R19P	1.000
11:118581303:T:C	F21L	1.000
11:118581305:T:A	F21L	1.000
11:118581305:T:G	F21L	1.000
11:118581382:C:A	T47K	1.000
11:118581384:T:C	F48L	1.000
11:118581386:T:A	F48L	1.000
11:118581386:T:G	F48L	1.000
11:118581388:T:A	V49D	1.000
11:118581406:G:C	R55T	1.000
11:118581406:G:T	R55I	1.000
11:118581407:A:C	R55S	1.000
11:118581407:A:T	R55S	1.000
11:118581408:T:G	Y56D	1.000
11:118581412:T:A	V57D	1.000
11:118581414:T:G	Y58D	1.000
11:118581445:T:C	L68P	1.000
11:118581462:A:C	S74R	1.000
11:118581463:G:T	S74I	1.000
11:118581464:C:A	S74R	1.000
11:118581464:C:G	S74R	1.000
11:118581467:C:A	N75K	1.000
11:118581467:C:G	N75K	1.000
11:118581469:T:A	I76N	1.000
11:118581469:T:C	I76T	1.000
11:118581469:T:G	I76S	1.000
11:118581472:T:C	L77S	1.000
11:118581477:G:C	D79H	1.000
11:118581478:A:C	D79A	1.000

dbSNP variants (sampled 300 via entrez): RS1000368786 (11:118599281 C>T), RS1000375857 (11:118570493 C>A,G), RS1000506382 (11:118581826 C>A), RS1000757095 (11:118593470 A>G,T), RS1000758268 (11:118587383 A>G), RS1000993213 (11:118575183 T>A), RS1001162182 (11:118599489 G>A), RS1001339403 (11:118571540 C>T), RS1001564768 (11:118588067 C>G,T), RS1001719629 (11:118599758 T>G), RS1002016720 (11:118582167 C>T), RS1002116434 (11:118588454 G>A), RS1002146799 (11:118593534 T>A), RS1002167974 (11:118598359 T>C), RS1002345026 (11:118582319 G>A)

Disease associations

OMIM: gene MIM:600820 | disease phenotypes: MIM:232220, MIM:232240, MIM:613148, MIM:615607, MIM:615615, MIM:615617, MIM:617164

GenCC curated gene-disease

Disease	Classification	Inheritance
short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay	Strong	Autosomal dominant

Mondo (7): glycogen storage disease Ib (MONDO:0009288), inflammatory bowel disease 28 (MONDO:0013153), combined immunodeficiency due to CD3gamma deficiency (MONDO:0014276), immunodeficiency 18 (MONDO:0014278), immunodeficiency 19 (MONDO:0014280), short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (MONDO:0014948), microcephaly (MONDO:0001149)

Orphanet (5): Combined immunodeficiency due to CD3gamma deficiency (Orphanet:169082), Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome (Orphanet:238569), Glycogen storage disease due to glucose-6-phosphatase deficiency (Orphanet:364), Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib (Orphanet:79259), Intrauterine growth retardation-micrognathia-short stature-facial dysmorphism-rhizomelic shortening syndrome (Orphanet:659702)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000054	Micropenis
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000347	Micrognathia
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000518	Cataract
HP:0000545	Myopia
HP:0000601	Hypotelorism
HP:0000717	Autism
HP:0000808	Penoscrotal hypospadias
HP:0001176	Large hands
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001382	Joint hypermobility
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001629	Ventricular septal defect
HP:0002020	Gastroesophageal reflux
HP:0002066	Gait ataxia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002393_445	Monocyte count	4.000000e-12
GCST90002394_351	Monocyte percentage of white cells	3.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C562594	Glycogen Storage Disease IB (supp.)
C567728	Inflammatory Bowel Disease 28, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066887 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.62	Kd	2376	nM	CHEMBL3752910
5.62	ED50	2376	nM	CHEMBL3752910
5.08	Kd	8379	nM	CHEMBL5653589
5.08	ED50	8379	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147879: Binding affinity to human ARCN1 incubated for 45 mins by Kinobead based pull down assay	kd	2.3763	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147879: Binding affinity to human ARCN1 incubated for 45 mins by Kinobead based pull down assay	kd	8.3787	uM

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	4
Tobacco Smoke Pollution	increases expression, affects expression	3
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	increases oxidation, affects expression, affects cotreatment, increases abundance	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Cyclosporine	increases expression	2
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
epigallocatechin gallate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Caffeine	decreases expression	1
Chloroquine	affects localization	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Furaldehyde	decreases expression, affects cotreatment	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650921	Binding	Binding affinity to human ARCN1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

23 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05960617	PHASE2	UNKNOWN	Efficacy and Safety of Empagliflozin in GSD-Ib Patients
NCT02054832	Not specified	COMPLETED	Sleep and Quality of Life in Patients With Glycogen Storage Disease on Standard Versus Modified Uncooked Cornstarch
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04986735	Not specified	UNKNOWN	Prospective Cohort Study of Children With GSD1b Receiving Empagliflozin
NCT05915910	Not specified	TERMINATED	Prospective Collection of Biospecimen in Pediatric Patients and Adult Guardians Diagnosed With Glycogen Storage Disease Type 1B (GSD1b)
NCT07459582	Not specified	RECRUITING	Accuracy of Home Lactate Meter and Accu-chek Glucometer in Patients With Glycogen Storage Disease
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.