ARL5C

Summary

ARL5C (ARF like GTPase 5C, HGNC:31111) is a protein-coding gene on chromosome 17q12, encoding Putative ADP-ribosylation factor-like protein 5C (A6NH57). Binds and exchanges GTP and GDP.

Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport; protein localization to Golgi membrane; and vesicle-mediated transport. Predicted to be active in trans-Golgi network.

Source: NCBI Gene 390790 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_001143968

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31111
Approved symbol	ARL5C
Name	ARF like GTPase 5C
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000141748
Ensembl biotype	protein_coding
Entrez	390790

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 retained_intron, 1 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000269586, ENST00000578912, ENST00000581255, ENST00000581554, ENST00000583123

RefSeq mRNA: 1 — MANE Select: NM_001143968 NM_001143968

CCDS: CCDS45664

Canonical transcript exons

ENST00000269586 — 6 exons

Exon	Start	End
ENSE00000950711	39162711	39162858
ENSE00001157802	39160591	39160742
ENSE00002710050	39165715	39166161
ENSE00002831274	39161268	39161351
ENSE00003589380	39165079	39165139
ENSE00003632375	39156894	39156942

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 68.42.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0283 / max 11.1345, expressed in 10 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165580	0.0162	9
165581	0.0120	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.42	gold quality
body of pancreas	UBERON:0001150	62.55	gold quality
monocyte	CL:0000576	59.42	gold quality
leukocyte	CL:0000738	59.19	gold quality
granulocyte	CL:0000094	58.55	gold quality
putamen	UBERON:0001874	54.36	gold quality
caudate nucleus	UBERON:0001873	53.79	gold quality
skin of hip	UBERON:0001554	53.41	silver quality
nucleus accumbens	UBERON:0001882	53.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	51.89	gold quality
pancreas	UBERON:0001264	51.55	gold quality
lymph node	UBERON:0000029	50.78	gold quality
right frontal lobe	UBERON:0002810	50.38	gold quality
anterior cingulate cortex	UBERON:0009835	50.34	gold quality
prefrontal cortex	UBERON:0000451	50.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	48.87	gold quality
mucosa of stomach	UBERON:0001199	48.80	gold quality
right coronary artery	UBERON:0001625	48.68	gold quality
amygdala	UBERON:0001876	48.39	gold quality
Ammon’s horn	UBERON:0001954	48.24	gold quality
gastrocnemius	UBERON:0001388	48.20	gold quality
frontal cortex	UBERON:0001870	48.14	gold quality
neocortex	UBERON:0001950	47.94	gold quality
descending thoracic aorta	UBERON:0002345	47.94	gold quality
middle temporal gyrus	UBERON:0002771	47.76	gold quality
cerebral cortex	UBERON:0000956	47.53	gold quality
muscle of leg	UBERON:0001383	47.45	gold quality
popliteal artery	UBERON:0002250	46.84	gold quality
forebrain	UBERON:0001890	46.72	gold quality
tibial artery	UBERON:0007610	46.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.78

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arl5c	ENSMUSG00000038352
rattus_norvegicus	Arl5c	ENSRNOG00000036880

Paralogs (30): ARF5 (ENSG00000004059), SAR1A (ENSG00000079332), ARFRP1 (ENSG00000101246), TRIM23 (ENSG00000113595), ARL6 (ENSG00000113966), ARL1 (ENSG00000120805), ARL4A (ENSG00000122644), ARL8B (ENSG00000134108), ARF3 (ENSG00000134287), ARL3 (ENSG00000138175), ARF1 (ENSG00000143761), ARL8A (ENSG00000143862), ARL11 (ENSG00000152213), SAR1B (ENSG00000152700), ARL5A (ENSG00000162980), ARF6 (ENSG00000165527), ARL5B (ENSG00000165997), ARF4 (ENSG00000168374), ARL13B (ENSG00000169379), ARL13A (ENSG00000174225), ARL10 (ENSG00000175414), ARL4D (ENSG00000175906), ARL14 (ENSG00000179674), ARL15 (ENSG00000185305), ARL17A (ENSG00000185829), ARL4C (ENSG00000188042), ARL9 (ENSG00000196503), ARL2 (ENSG00000213465), ARL16 (ENSG00000214087), ARL17B (ENSG00000228696)

Protein

Protein identifiers

Putative ADP-ribosylation factor-like protein 5C — A6NH57 (reviewed: A6NH57)

Alternative names: ADP-ribosylation factor-like protein 12

All UniProt accessions (2): A6NH57, K7EM39

UniProt curated annotations — full annotation on UniProt →

Function. Binds and exchanges GTP and GDP.

Similarity. Belongs to the small GTPase superfamily. Arf family.

RefSeq proteins (1): NP_001137440* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005225	Small_GTP-bd	Domain
IPR006689	Small_GTPase_ARF/SAR	Family
IPR024156	Small_GTPase_ARF	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00025

UniProt features (6 total): binding site 3, initiator methionine 1, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NH57-F1	85.33	0.59

Functional residue map

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

Ligand- & substrate-binding residues (3): 23–30; 66–70; 125–128

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, GOCC_TRANS_GOLGI_NETWORK, GOBP_PROTEIN_LOCALIZATION_TO_GOLGI_APPARATUS, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, CHEN_METABOLIC_SYNDROM_NETWORK, GOBP_INTRACELLULAR_TRANSPORT, GSE14415_FOXP3_KO_NATURAL_TREG_VS_TCONV_DN, ZNF16_TARGET_GENES

GO Biological Process (3): intracellular protein transport (GO:0006886), vesicle-mediated transport (GO:0016192), protein localization to Golgi membrane (GO:1903292)

GO Molecular Function (3): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166)

GO Cellular Component (2): cytoplasm (GO:0005737), trans-Golgi network (GO:0005802)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	1
protein transport	1
intracellular transport	1
transport	1
cellular process	1
protein localization to Golgi apparatus	1
protein localization to membrane	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
Golgi apparatus subcompartment	1

Protein interactions and networks

STRING

1507 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARL5C	VWA5B1	Q5TIE3	482
ARL5C	OR5D13	Q8NGL4	445
ARL5C	WDR89	Q96FK6	430
ARL5C	VPS54	Q9P1Q0	407
ARL5C	OR4M2	Q8NGB6	398
ARL5C	GTF3C5	Q9Y5Q8	397
ARL5C	TSKU	Q8WUA8	338
ARL5C	NSUN6	Q8TEA1	337
ARL5C	ARL16	Q0P5N6	327
ARL5C	WRAP73	Q9P2S5	322
ARL5C	KRT33B	Q14525	316
ARL5C	FOXO3B	A0A2Z4LIS9	314
ARL5C	SLC39A12	Q504Y0	310
ARL5C	HNRNPM	P52272	299
ARL5C	KRT40	Q6A162	299

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A4D1S5, A6NH57, O45379, O59781, O88848, P25160, P25378, P34212, P38116, P40994, P51152, P51646, Q02804, Q0IIM2, Q13795, Q18510, Q2KJ96, Q32LJ2, Q3SXC5, Q54E92, Q54HK2, Q54I24, Q54JJ3, Q54V41, Q54V47, Q54Y14, Q54YV7, Q55AD9, Q5JT25, Q5M9P8, Q5R4G5, Q5R579, Q5RCQ6, Q60Z38, Q61DE0, Q63055, Q6P068, Q6P3A9, Q80ZU0, Q8BXL7

Diamond homologs: A6NH57, B5FYQ0, O00909, O23778, O48649, O48920, P0CM16, P0CM17, P0DH91, P11076, P18085, P19146, P22274, P25160, P26990, P26991, P34212, P34727, P36397, P36405, P36406, P36407, P36579, P37996, P38116, P40616, P40940, P40945, P40946, P40994, P49076, P49702, P51643, P51644, P51645, P51646, P51821, P51822, P51823, P51824

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1226 predictions. Top by Δscore:

Variant	Effect	Δscore
17:39157468:C:CT	acceptor_gain	1.0000
17:39160595:C:A	donor_gain	1.0000
17:39161352:C:CC	acceptor_gain	1.0000
17:39162705:CCTCA:C	donor_loss	1.0000
17:39162706:CTCA:C	donor_loss	1.0000
17:39162707:TCA:T	donor_loss	1.0000
17:39162708:CA:C	donor_loss	1.0000
17:39162709:A:AT	donor_loss	1.0000
17:39162710:CCTC:C	donor_loss	1.0000
17:39162859:C:CC	acceptor_gain	1.0000
17:39165077:A:AC	donor_gain	1.0000
17:39165077:ACAAC:A	donor_gain	1.0000
17:39165078:C:CC	donor_gain	1.0000
17:39165078:CAA:C	donor_gain	1.0000
17:39165078:CAACC:C	donor_gain	1.0000
17:39165147:C:CT	acceptor_gain	1.0000
17:39161261:GGCTT:G	donor_loss	0.9900
17:39161262:GCTT:G	donor_loss	0.9900
17:39161263:CTTAC:C	donor_loss	0.9900
17:39161264:TTA:T	donor_loss	0.9900
17:39161265:TA:T	donor_loss	0.9900
17:39161266:ACC:A	donor_loss	0.9900
17:39161267:C:T	donor_loss	0.9900
17:39161348:TAAA:T	acceptor_gain	0.9900
17:39162748:AGAG:A	donor_gain	0.9900
17:39162821:CAA:C	acceptor_gain	0.9900
17:39162854:TCAAG:T	acceptor_gain	0.9900
17:39162855:CAAG:C	acceptor_gain	0.9900
17:39162855:CAAGC:C	acceptor_gain	0.9900
17:39162856:AAGC:A	acceptor_loss	0.9900

AlphaMissense

1194 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:39161349:A:C	F86L	0.775
17:39161349:A:T	F86L	0.775
17:39161351:A:G	F86L	0.775
17:39160704:C:A	K126N	0.735
17:39160704:C:G	K126N	0.735
17:39160717:A:T	I122K	0.707
17:39162780:G:C	F62L	0.688
17:39162780:G:T	F62L	0.688
17:39162782:A:G	F62L	0.688
17:39161328:G:C	S93R	0.638
17:39161328:G:T	S93R	0.638
17:39161330:T:G	S93R	0.638
17:39160713:A:C	F123L	0.625
17:39160713:A:T	F123L	0.625
17:39160715:A:G	F123L	0.625
17:39162858:G:C	F36L	0.625
17:39162858:G:T	F36L	0.625
17:39165080:A:G	F36L	0.625
17:39161331:G:C	D92E	0.617
17:39161331:G:T	D92E	0.617
17:39160705:T:G	K126T	0.599
17:39160723:A:T	V120D	0.588

dbSNP variants (sampled 300 via entrez): RS1000005266 (17:39163048 G>A,T), RS1000029943 (17:39159533 G>A), RS1000860254 (17:39165845 C>G,T), RS1000956016 (17:39164191 T>C), RS1001008466 (17:39164597 A>G), RS1001333427 (17:39165623 G>A), RS1002020818 (17:39156293 C>A), RS1002045058 (17:39161703 G>A), RS1002054849 (17:39165803 T>A,C), RS1002107312 (17:39165600 C>G,T), RS1002264825 (17:39167316 C>G), RS1002589443 (17:39157580 G>A), RS1002978055 (17:39163086 G>T), RS1003056194 (17:39167012 A>G), RS1003064596 (17:39157473 A>G)

Disease associations

OMIM: gene `` | 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
GCST008916_86	Asthma	2.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	1
Testosterone	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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