ARRDC5

Summary

ARRDC5 (arrestin domain containing 5, HGNC:31407) is a protein-coding gene on chromosome 19p13.3, encoding Arrestin domain-containing protein 5 (A6NEK1). Plays an essential role in spermatogenesis.

Predicted to be involved in protein transport and spermatogenesis. Predicted to be located in membrane. Predicted to be active in endosome and plasma membrane.

Source: NCBI Gene 645432 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_001080523

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31407
Approved symbol	ARRDC5
Name	arrestin domain containing 5
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205784
Ensembl biotype	protein_coding
OMIM	620944
Entrez	645432

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000650722, ENST00000718248, ENST00000718249

RefSeq mRNA: 2 — MANE Select: NM_001080523 NM_001080523, NM_001367189

CCDS: CCDS45929

Canonical transcript exons

ENST00000650722 — 3 exons

Exon	Start	End
ENSE00001489815	4890437	4891573
ENSE00001489817	4896671	4896876
ENSE00003850414	4902573	4902896

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 81.02.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4830 / max 133.8733, expressed in 271 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178506	1.3078	266
178507	0.1409	49
178505	0.0197	3
178503	0.0078	3
178504	0.0067	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	81.02	gold quality
testis	UBERON:0000473	80.64	gold quality
right testis	UBERON:0004534	80.28	gold quality
blood	UBERON:0000178	73.04	gold quality
monocyte	CL:0000576	70.87	gold quality
leukocyte	CL:0000738	70.64	gold quality
bone marrow cell	CL:0002092	69.47	silver quality
granulocyte	CL:0000094	66.99	gold quality
bone marrow	UBERON:0002371	66.25	gold quality
spleen	UBERON:0002106	65.60	gold quality
lymph node	UBERON:0000029	63.85	gold quality
vermiform appendix	UBERON:0001154	56.87	gold quality
colonic epithelium	UBERON:0000397	56.28	gold quality
tonsil	UBERON:0002372	55.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	52.83	gold quality
small intestine	UBERON:0002108	51.96	gold quality
gall bladder	UBERON:0002110	50.47	gold quality
upper lobe of left lung	UBERON:0008952	49.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	49.01	gold quality
duodenum	UBERON:0002114	48.46	gold quality
right lung	UBERON:0002167	48.35	gold quality
lung	UBERON:0002048	47.67	gold quality
substantia nigra	UBERON:0002038	46.37	gold quality
right coronary artery	UBERON:0001625	46.36	gold quality
sural nerve	UBERON:0015488	45.61	gold quality
lower esophagus mucosa	UBERON:0035834	45.54	silver quality
left uterine tube	UBERON:0001303	44.48	gold quality
intestine	UBERON:0000160	44.21	gold quality
urinary bladder	UBERON:0001255	44.20	gold quality
multicellular organism	UBERON:0000468	43.03	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting ARRDC5, 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-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-3690	96.44	65.18	737

Cross-species orthologs

33 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:110353	ENSDARG00000039443
danio_rerio	zgc:110626	ENSDARG00000053159
danio_rerio	si:dkey-172m14.2	ENSDARG00000067664
danio_rerio	arrdc1a	ENSDARG00000068148
danio_rerio	si:ch211-130m23.2	ENSDARG00000095136
mus_musculus	Arrdc5	ENSMUSG00000073380
rattus_norvegicus	Arrdc5	ENSRNOG00000047223
drosophila_melanogaster	CG1105	FBGN0037465
drosophila_melanogaster	CG10086	FBGN0037517
drosophila_melanogaster	CG2641	FBGN0037518
drosophila_melanogaster	CG3014	FBGN0037519
drosophila_melanogaster	CG2993	FBGN0037521
drosophila_melanogaster	CG14696	FBGN0037853
drosophila_melanogaster	Leash	FBGN0037856
drosophila_melanogaster	CG18744	FBGN0042101
drosophila_melanogaster	CG18745	FBGN0042102
drosophila_melanogaster	CG18746	FBGN0042103
drosophila_melanogaster	CG18747	FBGN0042104
drosophila_melanogaster	CG18748	FBGN0042105
caenorhabditis_elegans		WBGENE00006429
caenorhabditis_elegans		WBGENE00008843
caenorhabditis_elegans		WBGENE00009852
caenorhabditis_elegans		WBGENE00011052
caenorhabditis_elegans		WBGENE00011053
caenorhabditis_elegans		WBGENE00011054
caenorhabditis_elegans		WBGENE00012464
caenorhabditis_elegans		WBGENE00012467
caenorhabditis_elegans		WBGENE00013043
caenorhabditis_elegans		WBGENE00014159
caenorhabditis_elegans		WBGENE00014161
caenorhabditis_elegans		WBGENE00018060
caenorhabditis_elegans		WBGENE00018061
caenorhabditis_elegans		WBGENE00020612

Paralogs (5): ARRDC2 (ENSG00000105643), ARRDC3 (ENSG00000113369), ARRDC4 (ENSG00000140450), ARRDC1 (ENSG00000197070), TXNIP (ENSG00000265972)

Protein

Protein identifiers

Arrestin domain-containing protein 5 — A6NEK1 (reviewed: A6NEK1)

All UniProt accessions (1): A0A494BZV3

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in spermatogenesis. May be involved in the anchoring of the sperm head to the tail during spermatogenesis by affecting SEC22A-mediated SUN5 and NDC1 transport and localization.

Subcellular location. Membrane.

Tissue specificity. Testis-enriched.

Similarity. Belongs to the arrestin family.

RefSeq proteins (2): NP_001073992, NP_001354118 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011021	Arrestin-like_N	Domain
IPR011022	Arrestin-like_C	Domain
IPR014752	Arrestin-like_C_sf	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR050357	Arrestin_domain-protein	Family

Pfam: PF00339, PF02752

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NEK1-F1	85.19	0.66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): GOBP_MALE_GAMETE_GENERATION, MARTIN_VIRAL_GPCR_SIGNALING_UP, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, chr19p13, GSE13887_HEALTHY_VS_LUPUS_RESTING_CD4_TCELL_UP, MIR208B_5P, MIR208A_5P, MIR4451, MIR6810_3P, GSE13493_DP_VS_CD4INTCD8POS_THYMOCYTE_DN, GSE13493_DP_VS_CD8POS_THYMOCYTE_DN, GOMF_MOLECULAR_ADAPTOR_ACTIVITY, DESCARTES_FETAL_CEREBELLUM_MICROGLIA, DESCARTES_FETAL_CEREBRUM_MICROGLIA, THAKAR_PBMC_INACTIVATED_INFLUENZA_AGE_21_30YO_RESPONDERS_28DY_DN

GO Biological Process (3): spermatogenesis (GO:0007283), protein transport (GO:0015031), cell differentiation (GO:0030154)

GO Molecular Function (0):

GO Cellular Component (4): cytoplasm (GO:0005737), endosome (GO:0005768), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
developmental process involved in reproduction	1
male gamete generation	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cellular developmental process	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARRDC5	TXNIP	Q9H3M7	584
ARRDC5	LKAAEAR1	Q8TD35	580
ARRDC5	NEDD4	P46934	570
ARRDC5	C4orf17	Q53FE4	507
ARRDC5	WWP2	O00308	497
ARRDC5	VPS26C	O14972	494
ARRDC5	TEX38	Q6PEX7	489
ARRDC5	FREY1	C9JXX5	475
ARRDC5	CXorf65	A6NEN9	474
ARRDC5	OR7D2	Q96RA2	461
ARRDC5	NEDD4L	Q96PU5	449
ARRDC5	FAM194C	Q8ND61	448
ARRDC5	SAG	P10523	446
ARRDC5	VPS26A	O75436	440
ARRDC5	SMCO2	A6NFE2	435

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ARRDC5		psi-mi:“MI:0915”(physical association)	0.370
HSPB1	ARRDC5	psi-mi:“MI:0915”(physical association)	0.370
ARRDC5	PLPP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): ARRDC5 (Two-hybrid), ARRDC5 (Two-hybrid), ARRDC5 (Affinity Capture-Western), ABCD3 (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), DSG2 (Affinity Capture-MS), ABCG2 (Affinity Capture-MS), ATP6V1B2 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), SLC2A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), ATP6V1C1 (Affinity Capture-MS), MYADM (Affinity Capture-MS), BTBD10 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1F4, A6NEK1, G3X9X1, O14972, O15344, O15519, O35075, O70263, O70583, O94955, P82457, P82458, Q2HY40, Q2TBA3, Q32KX1, Q32NJ2, Q497K5, Q4VX76, Q54DI8, Q568M3, Q5M7W1, Q5R5L7, Q5R811, Q5R8Q5, Q5RD56, Q5RDY3, Q5RF33, Q60584, Q62807, Q6TXF1, Q6ZWE6, Q7TP90, Q7TPQ9, Q7ZX59, Q80WG7, Q8BG60, Q8BM47, Q8IY47, Q8NCT1, Q8W4D4

Diamond homologs: A6NEK1, Q32KX1, Q497K5, O45782

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

698 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4891571:GTTC:G	acceptor_loss	1.0000
19:4891572:TTC:T	acceptor_loss	1.0000
19:4891573:TCTA:T	acceptor_loss	1.0000
19:4891574:C:CC	acceptor_gain	1.0000
19:4891582:A:AC	acceptor_gain	1.0000
19:4891582:A:C	acceptor_gain	1.0000
19:4891569:GGGTT:G	acceptor_gain	0.9900
19:4891570:GGTT:G	acceptor_gain	0.9900
19:4891571:GTT:G	acceptor_gain	0.9900
19:4891572:TT:T	acceptor_gain	0.9900
19:4891584:G:C	acceptor_gain	0.9900
19:4891584:G:GC	acceptor_gain	0.9900
19:4899047:CA:C	donor_gain	0.9700
19:4902571:AC:A	donor_gain	0.9700
19:4902572:CC:C	donor_gain	0.9700
19:4902643:A:C	donor_gain	0.9700
19:4902342:TTGA:T	donor_gain	0.9600
19:4902750:G:A	donor_gain	0.9400
19:4902743:A:AC	donor_gain	0.9100
19:4902267:T:C	donor_gain	0.9000
19:4902341:TTTG:T	donor_gain	0.9000
19:4902698:TC:T	donor_gain	0.9000
19:4902699:C:CT	donor_gain	0.9000
19:4902700:C:CT	donor_gain	0.9000
19:4896665:CGGTA:C	donor_loss	0.8900
19:4896666:GGTAC:G	donor_loss	0.8900
19:4896667:GTA:G	donor_loss	0.8900
19:4896668:TACC:T	donor_loss	0.8900
19:4896669:ACC:A	donor_loss	0.8900
19:4896670:C:T	donor_loss	0.8900

AlphaMissense

2168 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4902740:A:G	L43S	0.988
19:4902695:A:G	L58P	0.987
19:4896760:A:G	C138R	0.985
19:4896839:G:C	F111L	0.985
19:4896839:G:T	F111L	0.985
19:4896841:A:G	F111L	0.985
19:4902672:A:G	W66R	0.984
19:4902672:A:T	W66R	0.984
19:4902753:C:G	G39R	0.984
19:4902753:C:T	G39R	0.984
19:4896711:A:T	V154D	0.982
19:4896765:G:T	A136D	0.982
19:4902752:C:T	G39E	0.981
19:4896845:A:C	F109L	0.979
19:4896845:A:T	F109L	0.979
19:4896847:A:G	F109L	0.979
19:4896867:A:G	L102S	0.979
19:4896778:A:C	Y132D	0.978
19:4896828:A:G	L115S	0.978
19:4902689:C:T	G60E	0.978
19:4902753:C:A	G39W	0.978
19:4902746:A:T	V41E	0.977
19:4896758:G:C	C138W	0.976
19:4902583:G:C	F95L	0.976
19:4902583:G:T	F95L	0.976
19:4902584:A:G	F95S	0.976
19:4902585:A:G	F95L	0.976
19:4902701:A:T	V56E	0.976
19:4896840:A:G	F111S	0.974
19:4902722:A:G	L49P	0.974

dbSNP variants (sampled 300 via entrez): RS1000199938 (19:4912238 G>A,C), RS1000322379 (19:4907334 A>T), RS1000393418 (19:4916903 G>A), RS1000438138 (19:4906904 G>A,C), RS1000498571 (19:4911405 C>T), RS1000549901 (19:4912919 C>G), RS1000695457 (19:4916431 C>T), RS1000766184 (19:4917378 G>A), RS1000896579 (19:4901670 A>G), RS1001156157 (19:4917100 C>A,T), RS1001316746 (19:4898668 T>G), RS1001527066 (19:4891885 G>A), RS1001556407 (19:4895629 G>C), RS1001659815 (19:4900257 T>C), RS1001712685 (19:4905587 G>A)

Disease associations

OMIM: gene MIM:620944 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011117_2	Pancreatic cancer	1.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2261988	ARRDC5, UHRF1		0.00	0

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	affects cotreatment, decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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