RAB23

Summary

RAB23 (RAB23, member RAS oncogene family, HGNC:14263) is a protein-coding gene on chromosome 6p12.1-p11.2, encoding Ras-related protein Rab-23 (Q9ULC3). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

This gene encodes a small GTPase of the Ras superfamily. Rab proteins are involved in the regulation of diverse cellular functions associated with intracellular membrane trafficking, including autophagy and immune response to bacterial infection. The encoded protein may play a role in central nervous system development by antagonizing sonic hedgehog signaling. Disruption of this gene has been implicated in Carpenter syndrome as well as cancer. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51715 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RAB23-related Carpenter syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 310 total — 19 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 94
• MANE Select transcript: NM_016277

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14263
Approved symbol	RAB23
Name	RAB23, member RAS oncogene family
Location	6p12.1-p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000112210
Ensembl biotype	protein_coding
OMIM	606144
Entrez	51715

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 20 protein_coding

ENST00000317483, ENST00000468148, ENST00000875526, ENST00000875527, ENST00000875528, ENST00000875529, ENST00000875530, ENST00000875531, ENST00000875532, ENST00000875533, ENST00000875534, ENST00000938835, ENST00000938836, ENST00000938837, ENST00000938838, ENST00000938839, ENST00000964673, ENST00000964674, ENST00000964675, ENST00000964676

RefSeq mRNA: 5 — MANE Select: NM_016277 NM_001278666, NM_001278667, NM_001278668, NM_016277, NM_183227

CCDS: CCDS4962

Canonical transcript exons

ENST00000468148 — 7 exons

Exon	Start	End
ENSE00001360629	57221726	57222307
ENSE00001860416	57186992	57190600
ENSE00003890262	57193842	57193934
ENSE00003892754	57196450	57196606
ENSE00003893502	57194770	57194852
ENSE00003893898	57207628	57207713
ENSE00003894439	57210226	57210445

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 98.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6796 / max 443.1959, expressed in 1636 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74184	10.0177	1628
74180	0.6949	253
74179	0.3264	127
74185	0.2415	91
74183	0.1609	73
74182	0.1374	52
74181	0.0518	14
74186	0.0490	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	98.53	gold quality
saphenous vein	UBERON:0007318	97.45	gold quality
secondary oocyte	CL:0000655	96.28	gold quality
seminal vesicle	UBERON:0000998	95.86	gold quality
calcaneal tendon	UBERON:0003701	95.57	gold quality
urethra	UBERON:0000057	94.88	gold quality
myometrium	UBERON:0001296	94.57	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.29	gold quality
visceral pleura	UBERON:0002401	93.91	gold quality
body of uterus	UBERON:0009853	93.22	gold quality
popliteal artery	UBERON:0002250	93.07	gold quality
tibial artery	UBERON:0007610	93.05	gold quality
stromal cell of endometrium	CL:0002255	92.95	gold quality
skin of hip	UBERON:0001554	92.91	gold quality
aorta	UBERON:0000947	92.71	gold quality
urinary bladder	UBERON:0001255	92.43	gold quality
ascending aorta	UBERON:0001496	92.22	gold quality
thoracic aorta	UBERON:0001515	92.21	gold quality
smooth muscle tissue	UBERON:0001135	91.74	gold quality
descending thoracic aorta	UBERON:0002345	91.19	gold quality
gall bladder	UBERON:0002110	91.07	gold quality
right coronary artery	UBERON:0001625	90.99	gold quality
uterus	UBERON:0000995	89.89	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.87	gold quality
lower esophagus	UBERON:0013473	89.82	gold quality
endocervix	UBERON:0000458	89.65	gold quality
vena cava	UBERON:0004087	89.60	gold quality
endometrium	UBERON:0001295	89.46	gold quality
superficial temporal artery	UBERON:0001614	89.21	gold quality
colonic epithelium	UBERON:0000397	88.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

209 targeting RAB23, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548P	99.98	72.25	3784

Literature-anchored findings (GeneRIF, showing 30)

• Rab23 is overexpressed and/or activated in hepatocellular carcinoma (HCC). Rab23 may be both a HCC predictor and a target for treating HCC. (PMID:17373734)
• RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development. (PMID:17503333)
• Data show that RAB23 participates in central nervous system development. (PMID:18485483)
• RAB23 amplifications are associated with gastric cancer (PMID:18559507)
• A RAB23 mutation (c.86dupA) present in the homozygote state in four relatives of Comorian origin with Carpenter syndrome, is reported. (PMID:20358613)
• Carpenter syndrome: extended RAB23 mutation spectrum and analysis of nonsense-mediated mRNA decay (PMID:21412941)
• association of the 6p12.1 locus with sarcoidosis implicates this locus as a further susceptibility factor and RAB23 as a potential signalling component (PMID:21540310)
• Rab23 directly associates with Su(Fu) and inhibits Gli1 function in a Su(Fu)-dependent manner. (PMID:22365972)
• Rab9A and Rab23 GTPases play crucial roles in autophagy of Group A Streptococcus. (PMID:22452336)
• The inhibition of the Rab23 cycle decreases the expression and nuclear localization of Gli1. (PMID:23007279)
• Rab23 expression level was the highest in Bcap-37 cells. (PMID:23948406)
• Rab23 was a target gene of miR-367, and ectopic expression of Rab23 could reverse the invasion and migration inhibitory activity of miR-367. (PMID:25489984)
• Data indicate the essential role of GTP binding protein RAB 23 (Rab23) in pancreatic ductal adenocarcinoma (PDAC) inva-sion, motility and metastasis. (PMID:25867419)
• Rab23 is expressed in breast cancer cells, and ectopic expression of Rab23 inhibits the growth and proliferation as well as induces cell apoptosis in breast cancer cells These effects may be due to the inhibition by Rab23 of Gli1 and Gli2 mRNA expression (PMID:26238143)
• Rab23 enhance squamous cell carcinoma cell invasion via up-regulating Rac1. (PMID:26648292)
• High Rab23 expression is associated with bladder cancer. (PMID:26715272)
• Rab23 serves as an important oncoprotein in human astrocytoma by regulating cell invasion and migration through Rac1 activity (PMID:26897750)
• Forced expression of MiR-92b decreased the mRNA and protein level of RAB23, and RAB23 rescued the biological functions of miR-92b. Taken together, this study revealed the oncogenic roles and the regulation of RAB23 in esophageal squamous cell carcinoma, suggesting RAB23 might be a therapeutic target (PMID:27659550)
• Down-regulation of Rab23 suppressed the proliferation, migration and invasion of prostate cancer cells. (PMID:28277196)
• miR-429 was down-regulated in hepatocellular carcinoma (HCC) tissues and cells. Up regulation of miR-429 decreased the migratory capacity and reversed the EMT to MET in HCC cells. RAB23 was confirmed as a target of miR-429. (PMID:29191386)
• Genetic variants in RAB23 and ANXA11 genes were associated with an increased risk of sarcoidosis-associated uveitis. (PMID:29416296)
• miR-16 acts as a tumor repressor in osteosarcoma cells by reducing epithelial mesenchymal transition, migration and invasion by targeting RAB23 expression. (PMID:29771408)
• Rab23 Promotes Hepatocellular Carcinoma Cell Migration Via Rac1/TGF-beta Signaling. (PMID:30191377)
• RAB family small GTP binding protein RAB 23 (Rab23) and ADP-ribosylation factor-like 13B (Arl13b) have been implicated in ciliopathy-associated human diseases and could regulate hedgehog proteins (Hh) signalling cascade in multifaceted manners [Review]. (PMID:31465935)
• OSER1-AS1 acted as a ceRNA to sponge miR-372-3p, thereby positively regulating the Rab23 expression and ultimately acting as a tumor suppressor gene in hepatocellular carcinoma progression (PMID:31635804)
• miR-597-3p inhibits invasion and migration of thyroid carcinoma SW579 cells by targeting RAB23. (PMID:32856288)
• miR3673p downregulates Rab23 expression and inhibits Hedgehog signaling resulting in the inhibition of the proliferation, migration, and invasion of prostate cancer cells. (PMID:34278506)
• Expansion of the phenotypic and mutational spectrum of Carpenter syndrome. (PMID:34748996)
• Downregulation of Rab23 inhibits hepatocellular carcinoma by repressing SHH signaling pathway. (PMID:37884351)
• Biomarker of Pulmonary Inflammatory Response in LUAD: miR-584-5p Targets RAB23 to Suppress Inflammation Induced by LPS in A549 Cells. (PMID:38093594)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab23	ENSDARG00000004151
mus_musculus	Rab23	ENSMUSG00000004768
rattus_norvegicus	Rab23	ENSRNOG00000012629
drosophila_melanogaster	Rab23	FBGN0037364

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), RAB36 (ENSG00000100228), IFT27 (ENSG00000100360), RAB40AL (ENSG00000102128), RAB11A (ENSG00000103769), RAB2A (ENSG00000104388), RAB3D (ENSG00000105514), RAB3A (ENSG00000105649), RAB5C (ENSG00000108774), RAB34 (ENSG00000109113), RAB5B (ENSG00000111540), RAB35 (ENSG00000111737), DNAJC27 (ENSG00000115137), RAB29 (ENSG00000117280), RAB32 (ENSG00000118508), RAB14 (ENSG00000119396), RAB9B (ENSG00000123570), RAB9A (ENSG00000123595), RAB38 (ENSG00000123892), RAB22A (ENSG00000124209), RAB17 (ENSG00000124839), RAB2B (ENSG00000129472), RAB25 (ENSG00000132698), RAB33A (ENSG00000134594), RAB30 (ENSG00000137502), RAB1A (ENSG00000138069), RAB20 (ENSG00000139832), RAB15 (ENSG00000139998), RAB40B (ENSG00000141542), RAB13 (ENSG00000143545), RABL2A (ENSG00000144134), RAB5A (ENSG00000144566), RAB19 (ENSG00000146955), RAB41 (ENSG00000147127)

Protein

Protein identifiers

Ras-related protein Rab-23 — Q9ULC3 (reviewed: Q9ULC3)

All UniProt accessions (1): Q9ULC3

UniProt curated annotations — full annotation on UniProt →

Function. The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. In conjunction with IFT57 and KIF17, it drives the localization of specific G protein-coupled receptors, such as the dopamime receptor DRD1, to primary cilia. Has a critical role in the formation and elongation of neuronal primary cilia, thereby impacting the activation of sonic hedgehog (Shh) signaling. Additionally, it is involved in the down-regulation of Shh signaling by cooperating with SUFU to prevent the nuclear import of GLI1 transcription factor, thus suppressing its transcriptional activity. Regulates GLI1 in differentiating chondrocytes. Likewise, regulates GLI3 proteolytic processing and modulates GLI2 and GLI3 transcription factor activity. Plays a role in autophagic vacuole assembly, and mediates defense against pathogens, such as S.aureus, by promoting their capture by autophagosomes that then merge with lysosomes.

Subunit / interactions. Interacts with SUFU. Interacts with KIF17.

Subcellular location. Cell membrane. Cytoplasm. Cytoplasmic vesicle. Autophagosome. Endosome membrane. Phagosome. Phagosome membrane.

Disease relevance. Carpenter syndrome 1 (CRPT1) [MIM:201000] A rare autosomal recessive disorder characterized by acrocephaly with variable synostosis of the sagittal, lambdoid, and coronal sutures; peculiar facies; brachydactyly of the hands with syndactyly; preaxial polydactyly and syndactyly of the feet; congenital heart defects; growth retardation; intellectual disability; hypogenitalism; and obesity. In addition, cerebral malformations, oral and dental abnormalities, coxa valga, genu valgum, hydronephrosis, precocious puberty, and hearing loss may be observed. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. Regulated by GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity. Inhibited by GDP dissociation inhibitors (GDIs).

Domain organisation. Switch 1, switch 2 and the interswitch regions are characteristic of Rab GTPases and mediate the interactions with Rab downstream effectors. The switch regions undergo conformational changes upon nucleotide binding which drives interaction with specific sets of effector proteins, with most effectors only binding to GTP-bound Rab.

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

RefSeq proteins (5): NP_001265595, NP_001265596, NP_001265597, NP_057361, NP_899050 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR034114	Rab23	Family
IPR050227	Rab	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (65 total): binding site 28, sequence variant 8, helix 8, strand 7, modified residue 3, sequence conflict 3, short sequence motif 2, chain 1, propeptide 1, region of interest 1, lipid moiety-binding region 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8YL3	X-RAY DIFFRACTION	1.2
8YO0	X-RAY DIFFRACTION	1.3
8YIM	X-RAY DIFFRACTION	1.35
8YNR	X-RAY DIFFRACTION	1.8
8YP0	X-RAY DIFFRACTION	1.88
9RS9	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULC3-F1	80.39	0.60

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 (28): 22; 23; 23; 23; 24; 24; 35; 36; 37; 38; 40; 41 …

Post-translational modifications (4): 186, 187, 234, 234

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8873719	RAB geranylgeranylation

MSigDB gene sets: 461 (showing top): TGCGCANK_UNKNOWN, KEGG_HEDGEHOG_SIGNALING_PATHWAY, GOBP_VACUOLE_ORGANIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, CHANDRAN_METASTASIS_DN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MACROAUTOPHAGY, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_NUCLEAR_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT

GO Biological Process (10): autophagosome assembly (GO:0000045), intracellular protein transport (GO:0006886), cellular defense response (GO:0006968), negative regulation of protein import into nucleus (GO:0042308), GTP metabolic process (GO:0046039), cilium assembly (GO:0060271), craniofacial suture morphogenesis (GO:0097094), anatomical structure morphogenesis (GO:0009653), protein transport (GO:0015031), system development (GO:0048731)

GO Molecular Function (7): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (15): cytoplasm (GO:0005737), autophagosome (GO:0005776), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), endosome membrane (GO:0010008), endomembrane system (GO:0012505), cell junction (GO:0030054), phagocytic vesicle membrane (GO:0030670), ciliary basal body (GO:0036064), phagocytic vesicle (GO:0045335), endosome (GO:0005768), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
organelle assembly	2
intracellular protein localization	2
anatomical structure development	2
vacuole	2
microtubule organizing center	2
cytoplasm	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
protein transport	1
intracellular transport	1
defense response	1
protein import into nucleus	1
regulation of protein import into nucleus	1
negative regulation of nucleocytoplasmic transport	1
negative regulation of intracellular protein transport	1
negative regulation of protein localization to nucleus	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
anatomical structure morphogenesis	1
bone morphogenesis	1
cranial skeletal system development	1
developmental process	1
transport	1
establishment of protein localization	1
multicellular organism development	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1

Protein interactions and networks

STRING

1106 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB23	GLI3	P10071	881
RAB23	SMO	Q99835	871
RAB23	GLI2	P10070	853
RAB23	SUFU	Q9UMX1	838
RAB23	RSPH14	Q9UHP6	810
RAB23	TTC21B	Q7Z4L5	803
RAB23	TULP3	O75386	790
RAB23	TCTN1	Q2MV58	784
RAB23	SHH	Q15465	745
RAB23	EVI5L	Q96CN4	700
RAB23	ARL13B	Q3SXY8	644
RAB23	FKBP8	Q14318	631
RAB23	IFT22	Q9H7X7	625
RAB23	CPLANE2	Q9BU20	608
RAB23	KIF17	Q9P2E2	607

IntAct

36 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PLPPR1	STXBP3	psi-mi:“MI:0914”(association)	0.530
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
RAB23	POTEKP	psi-mi:“MI:0915”(physical association)	0.400
RAB23	ZER1	psi-mi:“MI:0915”(physical association)	0.400
RAB23	NT5C	psi-mi:“MI:0915”(physical association)	0.400
RAB23	ARFGAP1	psi-mi:“MI:0915”(physical association)	0.370
RAB23	CREB3	psi-mi:“MI:0915”(physical association)	0.370
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.350
TREX1	ACTA2	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
GDI1	U2SURP	psi-mi:“MI:0914”(association)	0.350
GDI2	SGTA	psi-mi:“MI:0914”(association)	0.350
RAB23	GDI1	psi-mi:“MI:0914”(association)	0.350
TREX1	ITGB8	psi-mi:“MI:0914”(association)	0.350
CREB1	STK25	psi-mi:“MI:0914”(association)	0.350
CTNNA1	EFCAB5	psi-mi:“MI:0914”(association)	0.350
PTBP3		psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
KCNK3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (81): RAB23 (Affinity Capture-MS), RAB23 (Proximity Label-MS), RAB23 (Two-hybrid), POTEKP (Affinity Capture-MS), RAB23 (Affinity Capture-MS), RAB23 (Affinity Capture-MS), RAB23 (Affinity Capture-MS), RAB23 (Affinity Capture-MS), RAB23 (Affinity Capture-MS), RAB23 (Proximity Label-MS), RAB23 (Proximity Label-MS), RAB23 (Proximity Label-MS), RAB23 (Proximity Label-MS), RAB23 (Proximity Label-MS), RAB23 (Proximity Label-MS)

ESM2 similar proteins: A1DZY4, A7MBL8, O08874, O35626, O54785, O94806, P0C0E4, P35288, P35295, P51157, P51158, P53666, P53670, P53671, P55040, P55041, P62205, P63032, P63033, P70032, Q06AU5, Q07139, Q09930, Q12829, Q16513, Q32L23, Q3SWY9, Q5E9J3, Q5FVY2, Q5R541, Q5RFI2, Q6IMB1, Q6P0U3, Q6T310, Q8AVS6, Q8BPM2, Q8BWW9, Q8K1Y2, Q8VHP8, Q8VHQ4

Diamond homologs: A2WSI7, A2Y7R5, A2YEQ6, H9BW96, O17915, O76742, O97572, P09527, P18067, P22127, P24408, P24409, P28748, P32835, P32836, P33519, P34139, P35288, P36411, P36864, P38542, P38543, P38544, P38545, P38546, P38547, P38548, P41914, P41915, P41916, P41917, P41918, P41919, P42558, P51149, P51150, P51151, P52301, P54765, P54766

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RAB23	down-regulates	GLI3
RAB23	down-regulates	GLIS2

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	18
Uncertain significance	93
Likely benign	144
Benign	12

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070344	NM_016277.5(RAB23):c.82del (p.Arg28fs)	Pathogenic
1071136	NM_016277.5(RAB23):c.421A>T (p.Lys141Ter)	Pathogenic
1210114	NM_016277.5(RAB23):c.398+1G>A	Pathogenic
1366841	NM_016277.5(RAB23):c.526C>T (p.Gln176Ter)	Pathogenic
18426	NM_016277.5(RAB23):c.86dup (p.Tyr29Ter)	Pathogenic
2017670	NM_016277.5(RAB23):c.426del (p.Arg142fs)	Pathogenic
2691650	NM_016277.5(RAB23):c.467del (p.Leu156fs)	Pathogenic
2827988	NM_016277.5(RAB23):c.430_431del (p.Lys144fs)	Pathogenic
3008390	NM_016277.5(RAB23):c.313_316del (p.Glu105fs)	Pathogenic
3245987	NC_000006.11:g.(?57075004)(57075178_?)del	Pathogenic
3245988	NC_000006.11:g.(?57061071)(57061424_?)del	Pathogenic
3764578	NM_016277.5(RAB23):c.208del (p.Glu70fs)	Pathogenic
4060661	NM_016277.5(RAB23):c.362_363insG (p.Asn121fs)	Pathogenic
417740	NM_016277.5(RAB23):c.481G>C (p.Val161Leu)	Pathogenic
4591	NM_016277.5(RAB23):c.434T>A (p.Leu145Ter)	Pathogenic
4592	NM_016277.5(RAB23):c.408dup (p.Glu137Ter)	Pathogenic
832125	NC_000006.12:g.(?57186982)(57222324_?)del	Pathogenic
954806	NM_016277.5(RAB23):c.17del (p.Met6fs)	Pathogenic
963114	NM_016277.5(RAB23):c.142G>T (p.Glu48Ter)	Pathogenic
1210462	NM_016277.5(RAB23):c.559del (p.Ser187fs)	Likely pathogenic
1347492	NM_016277.5(RAB23):c.156-1G>C	Likely pathogenic
1476916	NM_016277.5(RAB23):c.358_398+177delinsGGTGTACAGTTG	Likely pathogenic
1498654	NM_016277.5(RAB23):c.482-1_486del	Likely pathogenic
2120775	NM_016277.5(RAB23):c.481+1G>A	Likely pathogenic
2813651	NM_016277.5(RAB23):c.174_241+587delinsTTATCATTAA	Likely pathogenic
3384105	NM_016277.5(RAB23):c.482-1G>A	Likely pathogenic
3594052	NM_016277.5(RAB23):c.399-2A>G	Likely pathogenic
3594053	NM_016277.5(RAB23):c.394A>T (p.Lys132Ter)	Likely pathogenic
3594054	NM_016277.5(RAB23):c.315_316del (p.Lys106fs)	Likely pathogenic
4077457	NM_016277.5(RAB23):c.155+1G>T	Likely pathogenic

SpliceAI

1085 predictions. Top by Δscore:

Variant	Effect	Δscore
6:57193837:CTT:C	donor_loss	1.0000
6:57193840:A:AC	donor_gain	1.0000
6:57193840:AC:A	donor_gain	1.0000
6:57193840:ACC:A	donor_loss	1.0000
6:57193841:C:CA	donor_gain	1.0000
6:57193841:CC:C	donor_gain	1.0000
6:57193841:CCA:C	donor_gain	1.0000
6:57193841:CCAA:C	donor_gain	1.0000
6:57193841:CCAAT:C	donor_gain	1.0000
6:57193853:C:CT	donor_gain	1.0000
6:57193854:T:TT	donor_gain	1.0000
6:57193930:AAAAA:A	acceptor_gain	1.0000
6:57193931:AAAA:A	acceptor_gain	1.0000
6:57193933:AA:A	acceptor_gain	1.0000
6:57193935:C:CC	acceptor_gain	1.0000
6:57193940:A:AC	acceptor_gain	1.0000
6:57193940:A:C	acceptor_gain	1.0000
6:57194851:CA:C	acceptor_gain	1.0000
6:57196448:A:AC	donor_gain	1.0000
6:57196449:C:CC	donor_gain	1.0000
6:57196449:CTT:C	donor_gain	1.0000
6:57196451:T:TA	donor_gain	1.0000
6:57207615:T:TA	donor_gain	1.0000
6:57207709:TAACT:T	acceptor_gain	1.0000
6:57207712:CT:C	acceptor_gain	1.0000
6:57207714:C:CC	acceptor_gain	1.0000
6:57210221:CTTA:C	donor_gain	1.0000
6:57210222:TTACT:T	donor_loss	1.0000
6:57210223:TACTG:T	donor_loss	1.0000
6:57210224:A:AC	donor_gain	1.0000

AlphaMissense

1568 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:57196482:C:A	K122N	1.000
6:57196482:C:G	K122N	1.000
6:57196484:T:C	K122E	1.000
6:57196485:G:C	N121K	1.000
6:57196485:G:T	N121K	1.000
6:57196541:A:G	W103R	1.000
6:57196541:A:T	W103R	1.000
6:57196561:G:A	S96F	1.000
6:57207656:A:C	F71L	1.000
6:57207656:A:T	F71L	1.000
6:57207657:A:C	F71C	1.000
6:57207657:A:G	F71S	1.000
6:57207658:A:G	F71L	1.000
6:57207658:A:T	F71I	1.000
6:57207669:C:T	G67D	1.000
6:57207670:C:A	G67C	1.000
6:57207670:C:G	G67R	1.000
6:57207672:G:T	A66E	1.000
6:57207677:G:C	D64E	1.000
6:57207677:G:T	D64E	1.000
6:57207678:T:A	D64V	1.000
6:57207678:T:C	D64G	1.000
6:57207678:T:G	D64A	1.000
6:57207679:C:A	D64Y	1.000
6:57207679:C:G	D64H	1.000
6:57207680:C:A	W63C	1.000
6:57207680:C:G	W63C	1.000
6:57207682:A:G	W63R	1.000
6:57207682:A:T	W63R	1.000
6:57210243:A:C	F46L	1.000

dbSNP variants (sampled 300 via entrez): RS1000006515 (6:57221885 C>G), RS1000093833 (6:57221724 A>C,G), RS1000198931 (6:57195035 T>C), RS1000214951 (6:57201151 T>C), RS1000343202 (6:57215440 C>T), RS1000365062 (6:57223031 T>C), RS1000467222 (6:57223340 A>G), RS1000519579 (6:57215779 ATGTT>A), RS1000571921 (6:57216060 C>T), RS1000639304 (6:57217223 A>C), RS1000759647 (6:57200851 A>G), RS1000810921 (6:57189866 T>A), RS1000889527 (6:57206384 A>C), RS1000944085 (6:57213740 T>A,C), RS1001037551 (6:57213468 A>G)

Disease associations

OMIM: gene MIM:606144 | disease phenotypes: MIM:201000, MIM:600057

GenCC curated gene-disease

Disease	Classification	Inheritance
RAB23-related Carpenter syndrome	Definitive	Autosomal recessive
Carpenter syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
RAB23-related Carpenter syndrome	Definitive	AR

Mondo (3): RAB23-related Carpenter syndrome (MONDO:0008710), Carpenter syndrome (MONDO:0019012), bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039)

Orphanet (2): Carpenter syndrome (Orphanet:65759), Classic bladder exstrophy (Orphanet:93930)

HPO phenotypes

94 total (30 of 94 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000072	Hydroureter
HP:0000098	Tall stature
HP:0000126	Hydronephrosis
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000256	Macrocephaly
HP:0000262	Turricephaly
HP:0000263	Oxycephaly
HP:0000272	Malar flattening
HP:0000275	Narrow face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000445	Wide nose
HP:0000457	Depressed nasal ridge
HP:0000470	Short neck
HP:0000481	Abnormal cornea morphology
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000506	Telecanthus
HP:0000648	Optic atrophy
HP:0000826	Precocious puberty
HP:0000929	Abnormal skull morphology

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005752_153	Systemic lupus erythematosus	6.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	increases expression, affects expression, affects cotreatment, decreases expression	3
manganese chloride	decreases expression, affects cotreatment, increases abundance	2
Calcitriol	decreases expression, affects cotreatment	2
Manganese	decreases expression, affects cotreatment, increases abundance	2
Valproic Acid	increases expression	2
Aflatoxin B1	increases expression	2
Particulate Matter	decreases expression, decreases reaction, increases abundance	2
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
salinomycin	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	increases expression	1
3,4,5,4’-tetramethoxystilbene	affects expression	1
bisphenol B	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
jinfukang	decreases expression, affects cotreatment	1
NSC 689534	affects binding, increases expression	1
bisphenol AF	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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