RAB38

Summary

RAB38 (RAB38, member RAS oncogene family, HGNC:9776) is a protein-coding gene on chromosome 11q14.2, encoding Ras-related protein Rab-38 (P57729). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

Enables several functions, including AP-1 adaptor complex binding activity; AP-3 adaptor complex binding activity; and BLOC-2 complex binding activity. Involved in several processes, including endosome to melanosome transport; melanosome assembly; and phagosome acidification. Located in several cellular components, including cytoplasmic vesicle; lysosome; and mitochondria-associated endoplasmic reticulum membrane contact site.

Source: NCBI Gene 23682 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_022337

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9776
Approved symbol	RAB38
Name	RAB38, member RAS oncogene family
Location	11q14.2
Locus type	gene with protein product
Status	Approved
Aliases	NY-MEL-1
Ensembl gene	ENSG00000123892
Ensembl biotype	protein_coding
OMIM	606281
Entrez	23682

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000243662, ENST00000526372, ENST00000531138, ENST00000916357

RefSeq mRNA: 1 — MANE Select: NM_022337 NM_022337

CCDS: CCDS8281

Canonical transcript exons

ENST00000243662 — 3 exons

Exon	Start	End
ENSE00000989347	88175183	88175443
ENSE00000989348	88149675	88149955
ENSE00001222090	88113251	88114140

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 96.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5111 / max 406.6094, expressed in 1039 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121764	11.5111	1039

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	96.43	gold quality
lower esophagus mucosa	UBERON:0035834	95.45	gold quality
palpebral conjunctiva	UBERON:0001812	95.35	gold quality
upper leg skin	UBERON:0004262	94.84	gold quality
gingiva	UBERON:0001828	94.69	gold quality
mammalian vulva	UBERON:0000997	94.11	gold quality
squamous epithelium	UBERON:0006914	94.08	gold quality
esophagus squamous epithelium	UBERON:0006920	93.98	gold quality
adrenal tissue	UBERON:0018303	93.55	gold quality
tongue squamous epithelium	UBERON:0006919	93.25	gold quality
penis	UBERON:0000989	93.06	gold quality
epithelium of esophagus	UBERON:0001976	92.83	gold quality
esophagus mucosa	UBERON:0002469	92.62	gold quality
cervix squamous epithelium	UBERON:0006922	91.60	silver quality
skin of abdomen	UBERON:0001416	91.54	gold quality
hair follicle	UBERON:0002073	91.10	silver quality
zone of skin	UBERON:0000014	90.96	gold quality
skin of leg	UBERON:0001511	90.62	gold quality
cervix epithelium	UBERON:0004801	90.29	gold quality
germinal epithelium of ovary	UBERON:0001304	90.17	gold quality
oral cavity	UBERON:0000167	89.97	gold quality
right adrenal gland cortex	UBERON:0035827	89.17	gold quality
upper arm skin	UBERON:0004263	88.72	silver quality
pigmented layer of retina	UBERON:0001782	88.71	gold quality
right adrenal gland	UBERON:0001233	88.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.58	gold quality
skin of hip	UBERON:0001554	87.17	gold quality
left adrenal gland	UBERON:0001234	87.00	gold quality
adrenal cortex	UBERON:0001235	86.85	gold quality
left adrenal gland cortex	UBERON:0035825	86.80	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	15.62
E-ANND-3	yes	8.57
E-MTAB-6524	no	150.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting RAB38, 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-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
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-7110-3P	100.00	73.18	2486
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057

Literature-anchored findings (GeneRIF, showing 13)

• Not a new major locus for Japanese oculocutaneous albinisms. (PMID:12850305)
• Varp physically interacts with Rab38, and preferentially binds to the active GTP-bound form of Rab38 both in vitro and in vivo. (PMID:18477474)
• Studies confirmed elevated expression of three target antigens RAB38, TBCE, and DUSP12 in CML. (PMID:20103624)
• that Rab38 and Rab32 are the specific factors that direct the ubiquitous machinery to mediate transport from early endosomes to maturing LROs. (PMID:22511774)
• BLOC-3 is a Rab32 and Rab38 guanine nucleotide exchange factor, with a specific function in the biogenesis of lysosome-related organelles. (PMID:23084991)
• The expression levels of RAB38 were significantly associated with grade progression as well as prognosis in gliomas. RAB38 is an important prognostic biomarker and potential therapeutic target in gliomas. (PMID:24026199)
• MiR-124 significantly decreases the H2O2-induced apoptosis of human hepatic L02 cells by targeting the Rab38 gene and activating the AKT pathway. (PMID:24875359)
• Rab38 and its close homolog Rab32 bind to Myosin Vc but not to Myosin Va or Myosin Vb. Binding depends on residues in the switch II region of Rab32 and Rab38 and regions of the Myosin Vc coiled-coil tail domain. (PMID:25324551)
• Rab38 was associated with albuminuria in type 2 diabetes patients. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. (PMID:26631737)
• RAB38 silencing also inhibited the development of pancreatic cancer in vivo. A high level of RAB38 was significantly associated with the malignant phenotypes of pancreatic cancer. (PMID:30569114)
• RAB38 Facilitates Energy Metabolism and Counteracts Cell Death in Glioblastoma Cells. (PMID:34209035)
• Evaluation of CRISPR/Cas9 exon-skipping vector for choroideremia using human induced pluripotent stem cell-derived RPE. (PMID:36413603)
• Endogenous Rab38 regulates LRRK2’s membrane recruitment and substrate Rab phosphorylation in melanocytes. (PMID:37625589)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab38b	ENSDARG00000112889
mus_musculus	Rab38	ENSMUSG00000030559
rattus_norvegicus	Rab38	ENSRNOG00000016769

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), RAB23 (ENSG00000112210), DNAJC27 (ENSG00000115137), RAB29 (ENSG00000117280), RAB32 (ENSG00000118508), RAB14 (ENSG00000119396), RAB9B (ENSG00000123570), RAB9A (ENSG00000123595), 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-38 — P57729 (reviewed: P57729)

Alternative names: Melanoma antigen NY-MEL-1

All UniProt accessions (3): P57729, H0YDB7, H0YEA4

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 sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB38 may be involved in melanosomal transport and docking. Involved in the proper sorting of TYRP1. Involved in peripheral melanosomal distribution of TYRP1 in melanocytes; the function, which probably is implicating vesicle-trafficking, includes cooperation with ANKRD27 and VAMP7. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays an important role in the control of melanin production and melanosome biogenesis. In concert with RAB32, regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes.

Subunit / interactions. Interacts with ANKRD27.

Subcellular location. Cell membrane. Melanosome. Cytoplasmic vesicle. Phagosome. Phagosome membrane. Melanosome membrane.

Tissue specificity. Expressed in melanocytes.

Post-translational modifications. Although at least one in vitro system can process and methylate the prenylated C-terminal, in an in vitro system that normally express Rab-38 and in vivo the prenylated C-terminal is not proteolytically processed and not methylated.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) including the BLOC-3 complex composed of HPS1 and HPS4 which promote the exchange of bound GDP for free GTP. Regulated by GTPase activating proteins (GAPs) including SGSM2 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 drive 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 (1): NP_071732* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030697	Rab29/Rab38/Rab32	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (38 total): binding site 18, strand 6, helix 6, short sequence motif 2, lipid moiety-binding region 2, chain 1, site 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6HDU	X-RAY DIFFRACTION	1.79
6S5H	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57729-F1	86.73	0.68

Functional residue map

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

Catalytic / active sites (1): 208 (not methylated)

Ligand- & substrate-binding residues (18): 35; 36; 38; 41; 41; 65; 68; 128; 130; 160; 161; 19 …

Post-translational modifications (2): 205, 208

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 257 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, TATTATA_MIR374, GOBP_CELLULAR_PIGMENTATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (14): intracellular protein transport (GO:0006886), mitochondrion organization (GO:0007005), small GTPase-mediated signal transduction (GO:0007264), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), melanosome organization (GO:0032438), endosome to melanosome transport (GO:0035646), positive regulation of melanin biosynthetic process (GO:0048023), platelet dense granule organization (GO:0060155), protein localization to membrane (GO:0072657), phagosome acidification (GO:0090383), melanosome assembly (GO:1903232), positive regulation of protein localization to cell periphery (GO:1904377), positive regulation of phosphatidylcholine biosynthetic process (GO:2001247)

GO Molecular Function (11): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GTP-dependent protein binding (GO:0030742), AP-1 adaptor complex binding (GO:0035650), AP-3 adaptor complex binding (GO:0035651), BLOC-2 complex binding (GO:0036461), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (19): mitochondrion (GO:0005739), lysosome (GO:0005764), early endosome (GO:0005769), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020), phagocytic vesicle membrane (GO:0030670), melanosome membrane (GO:0033162), melanosome (GO:0042470), mitochondria-associated endoplasmic reticulum membrane contact site (GO:0044233), cell body (GO:0044297), phagocytic vesicle (GO:0045335), perinuclear region of cytoplasm (GO:0048471), Golgi apparatus (GO:0005794), organelle membrane (GO:0031090), cytoplasmic vesicle (GO:0031410), vesicle (GO:0031982)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
cellular anatomical structure	5
intracellular protein localization	3
protein-containing complex binding	3
transport	2
intracellular membrane-bounded organelle	2
membrane	2
membrane-bounded organelle	2
protein transport	1
intracellular transport	1
organelle organization	1
intracellular signaling cassette	1
establishment of protein localization	1
cellular process	1
pigment granule organization	1
endosome to pigment granule transport	1
melanin biosynthetic process	1
regulation of melanin biosynthetic process	1
positive regulation of secondary metabolite biosynthetic process	1
secretory granule organization	1
localization within membrane	1
intracellular pH reduction	1
phagosome maturation	1
melanosome organization	1
organelle assembly	1
positive regulation of protein localization	1
regulation of protein localization to cell periphery	1
protein localization to cell periphery	1
phosphatidylcholine biosynthetic process	1
positive regulation of phospholipid biosynthetic process	1
regulation of phosphatidylcholine biosynthetic process	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB38	NCAPG	Q9BPX3	927
RAB38	ANKRD27	Q96NW4	889
RAB38	TYRP1	P17643	823
RAB38	TYR	P14679	741
RAB38	MYO7A	P78427	702
RAB38	HPS4	Q9NQG7	629
RAB38	LRRK2	Q5S007	584
RAB38	C9orf72	Q96LT7	555
RAB38	HPS3	Q969F9	548
RAB38	SMCR8	Q8TEV9	539
RAB38	VAMP7	P51809	526
RAB38	WDR41	Q9HAD4	525
RAB38	HPS1	Q92902	521
RAB38	RABIF	P47224	489
RAB38	CTSC	P53634	479

IntAct

70 interactions, top by confidence:

A	B	Type	Score
	RAB38	psi-mi:“MI:0407”(direct interaction)	0.680
	RAB38	psi-mi:“MI:0883”(gtpase reaction)	0.680
RAB32	RAB38	psi-mi:“MI:0915”(physical association)	0.670
RAB32	CHM	psi-mi:“MI:0914”(association)	0.640
RAB38	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.560
	RAB38	psi-mi:“MI:0407”(direct interaction)	0.560
LRRK2	RAB38	psi-mi:“MI:0407”(direct interaction)	0.560
RAB38	A2M	psi-mi:“MI:0915”(physical association)	0.560
RAB38	DNM2	psi-mi:“MI:0915”(physical association)	0.560
RAB38	TOR1A	psi-mi:“MI:0915”(physical association)	0.560
RAB38	GFAP	psi-mi:“MI:0915”(physical association)	0.560
RAB38	MECP2	psi-mi:“MI:0915”(physical association)	0.560
RAB38	NDUFV2	psi-mi:“MI:0915”(physical association)	0.560
RAB38	SMN1	psi-mi:“MI:0915”(physical association)	0.560
RAB38	JPH3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (37): RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-Western), RAB38 (Affinity Capture-RNA), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RAB38 (Affinity Capture-MS)

ESM2 similar proteins: A1DZY4, A6QP66, O35626, P0C0E4, P51157, P51158, P55040, P55041, P57729, P63032, P63033, P70425, Q06AU5, Q0VCJ7, Q12829, Q13637, Q19143, Q3SWY9, Q5BJQ5, Q5E9J3, Q5FVY2, Q5R541, Q5RFI2, Q6DGN0, Q6IMA3, Q6IMA7, Q6IMB1, Q6P0U3, Q6T310, Q7TNZ5, Q7YS69, Q8AVS6, Q8QZZ8, Q8R367, Q8TAI7, Q8VHP8, Q8VHQ4, Q8WXH6, Q922H7, Q92730

Diamond homologs: A4FV54, C8VQY7, F1PTE3, G4MYS1, H9BW96, I1RMF2, O04157, O04486, O24461, O24466, O76173, O76742, O94655, O97572, P09527, P10536, P18067, P22125, P22128, P24408, P28186, P28187, P31022, P32939, P35280, P35286, P35288, P36411, P36586, P36861, P36864, P51149, P51150, P51151, P51153, P55258, P57729, P61006, P61007, P61028

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
BLOC-3	“up-regulates activity”	RAB38	“guanine nucleotide exchange factor”
RAB38	“up-regulates activity”	BLOC-2	relocalization
RAB38	“up-regulates activity”	“AP-3 complex”	relocalization
RAB38	“up-regulates activity”	“AP-1 complex”	relocalization
RAB38	“up-regulates activity”	“Neuronal AP-3”	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

595 predictions. Top by Δscore:

Variant	Effect	Δscore
11:88149670:ATTAC:A	donor_loss	1.0000
11:88149671:TTACC:T	donor_loss	1.0000
11:88149672:TACCT:T	donor_loss	1.0000
11:88149673:A:AT	donor_loss	1.0000
11:88149674:C:G	donor_loss	1.0000
11:88149956:C:CC	acceptor_gain	1.0000
11:88149960:C:CT	acceptor_gain	1.0000
11:88149963:C:CT	acceptor_gain	1.0000
11:88149963:C:T	acceptor_gain	1.0000
11:88149964:A:T	acceptor_gain	1.0000
11:88175179:TCA:T	donor_loss	1.0000
11:88175182:C:CA	donor_loss	1.0000
11:88117686:T:C	donor_gain	0.9900
11:88149673:A:AC	donor_gain	0.9900
11:88149674:C:CC	donor_gain	0.9900
11:88149824:A:C	donor_gain	0.9900
11:88149951:TTGAC:T	acceptor_gain	0.9900
11:88149952:TGAC:T	acceptor_gain	0.9900
11:88149953:GAC:G	acceptor_gain	0.9900
11:88149954:AC:A	acceptor_gain	0.9900
11:88149955:CC:C	acceptor_gain	0.9900
11:88175181:A:AC	donor_gain	0.9900
11:88175182:C:CC	donor_gain	0.9900
11:88175182:CCTG:C	donor_gain	0.9900
11:88114136:TTTTC:T	acceptor_gain	0.9800
11:88114138:TTCC:T	acceptor_loss	0.9800
11:88114139:TCC:T	acceptor_loss	0.9800
11:88114140:CC:C	acceptor_loss	0.9800
11:88114140:CCTA:C	acceptor_gain	0.9800
11:88114141:C:CC	acceptor_gain	0.9800

AlphaMissense

1400 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:88175191:T:A	D65V	1.000
11:88175191:T:G	D65A	1.000
11:88175195:A:G	W64R	1.000
11:88175195:A:T	W64R	1.000
11:88175247:G:C	F46L	1.000
11:88175247:G:T	F46L	1.000
11:88175249:A:G	F46L	1.000
11:88149774:T:A	K128N	0.999
11:88149774:T:G	K128N	0.999
11:88149775:T:A	K128I	0.999
11:88149790:A:T	V123D	0.999
11:88149846:C:A	W104C	0.999
11:88149846:C:G	W104C	0.999
11:88149848:A:G	W104R	0.999
11:88149848:A:T	W104R	0.999
11:88149955:C:T	G68D	0.999
11:88175183:C:A	G68C	0.999
11:88175183:C:G	G68R	0.999
11:88175190:A:C	D65E	0.999
11:88175190:A:T	D65E	0.999
11:88175191:T:C	D65G	0.999
11:88175192:C:A	D65Y	0.999
11:88175192:C:G	D65H	0.999
11:88175193:C:A	W64C	0.999
11:88175193:C:G	W64C	0.999
11:88175248:A:G	F46S	0.999
11:88175257:C:T	G43D	0.999
11:88175258:C:G	G43R	0.999
11:88175263:G:A	T41I	0.999
11:88175283:G:C	F34L	0.999

dbSNP variants (sampled 300 via entrez): RS1000002309 (11:88099771 T>C), RS1000008245 (11:87941275 A>G), RS1000022514 (11:88015374 C>A), RS1000023238 (11:87831394 TA>T,TAA), RS1000025897 (11:88083302 G>A), RS1000026941 (11:88040018 T>C), RS1000047293 (11:87960737 A>G), RS1000052827 (11:88144387 G>C), RS1000059892 (11:88039755 G>A,C), RS1000076886 (11:88058538 T>A), RS1000082516 (11:87975925 A>G,T), RS1000088721 (11:87823569 A>T), RS1000120006 (11:87823810 G>T), RS1000124857 (11:87825692 C>T), RS1000135976 (11:87946564 C>A,T)

Disease associations

OMIM: gene MIM:606281 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000267_6	Multiple sclerosis (age of onset)	2.000000e-06
GCST002516_1	Frontotemporal dementia	2.000000e-07
GCST003250_2	Urinary albumin-to-creatinine ratio in diabetes	6.000000e-07
GCST003855_6	Gut microbiota (bacterial taxa)	2.000000e-09
GCST006030_7	Chloride levels	4.000000e-08
GCST006032_6	Sodium levels	6.000000e-12
GCST007426_2	Triiodothyronine levels	6.000000e-08
GCST011741_57	LDL cholesterol levels in HIV infection	4.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0007778	urinary albumin to creatinine ratio
EFO:0007874	gut microbiome measurement
EFO:0009282	sodium measurement
EFO:0008392	triiodothyronine measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
sodium arsenite	affects expression, decreases expression, increases expression	4
Benzo(a)pyrene	decreases methylation, increases expression	3
Silicon Dioxide	decreases expression	2
Tetrachlorodibenzodioxin	increases expression, affects expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
sotorasib	decreases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
trametinib	decreases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Estradiol	decreases expression, affects cotreatment	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Smoke	increases expression	1

Clinical trials (associated diseases)

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