RAB43

Summary

RAB43 (RAB43, member RAS oncogene family, HGNC:19983) is a protein-coding gene on chromosome 3q21.3, encoding Ras-related protein Rab-43 (Q86YS6). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

Enables GTPase activity. Involved in Golgi organization; phagosome maturation; and retrograde transport, plasma membrane to Golgi. Located in Golgi apparatus and phagocytic vesicle.

Source: NCBI Gene 339122 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (Strong, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 269 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 43
• MANE Select transcript: NM_198490

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19983
Approved symbol	RAB43
Name	RAB43, member RAS oncogene family
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	RAB41, RAB11B, ISY1
Ensembl gene	ENSG00000172780
Ensembl biotype	protein_coding
Entrez	339122

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 17 protein_coding

ENST00000315150, ENST00000393304, ENST00000393305, ENST00000393307, ENST00000393308, ENST00000457077, ENST00000476465, ENST00000615093, ENST00000870644, ENST00000870645, ENST00000870646, ENST00000870647, ENST00000870648, ENST00000870649, ENST00000870650, ENST00000915978, ENST00000915979

RefSeq mRNA: 7 — MANE Select: NM_198490 NM_001204883, NM_001204884, NM_001204885, NM_001204886, NM_001204887, NM_001204888, NM_198490

CCDS: CCDS33850, CCDS56275

Canonical transcript exons

ENST00000315150 — 3 exons

Exon	Start	End
ENSE00000000192	129087572	129091346
ENSE00003513122	129094986	129095169
ENSE00003901349	129121286	129121804

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 93.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4047 / max 171.2075, expressed in 1741 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44484	5.0146	1651
44483	3.9043	1342
44482	0.4858	288

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	93.23	gold quality
granulocyte	CL:0000094	90.14	gold quality
right lobe of liver	UBERON:0001114	89.09	gold quality
liver	UBERON:0002107	88.12	gold quality
leukocyte	CL:0000738	86.89	gold quality
monocyte	CL:0000576	86.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.72	gold quality
lymph node	UBERON:0000029	83.84	gold quality
bone marrow	UBERON:0002371	83.62	gold quality
bone marrow cell	CL:0002092	83.33	gold quality
metanephros cortex	UBERON:0010533	82.26	gold quality
upper lobe of left lung	UBERON:0008952	81.94	gold quality
right lung	UBERON:0002167	81.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.20	gold quality
adult mammalian kidney	UBERON:0000082	80.94	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.84	gold quality
ascending aorta	UBERON:0001496	80.72	gold quality
cortex of kidney	UBERON:0001225	80.70	gold quality
thoracic aorta	UBERON:0001515	80.69	gold quality
thyroid gland	UBERON:0002046	80.49	gold quality
left lobe of thyroid gland	UBERON:0001120	80.46	gold quality
spleen	UBERON:0002106	80.34	gold quality
right lobe of thyroid gland	UBERON:0001119	80.18	gold quality
vermiform appendix	UBERON:0001154	79.87	gold quality
descending thoracic aorta	UBERON:0002345	79.77	gold quality
stromal cell of endometrium	CL:0002255	79.43	gold quality
left ovary	UBERON:0002119	79.30	gold quality
lung	UBERON:0002048	79.26	gold quality
right ovary	UBERON:0002118	79.22	gold quality
tibial artery	UBERON:0007610	79.22	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	113.96
E-GEOD-110499	no	280.07
E-ANND-3	no	1.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

159 targeting RAB43, 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-190A-3P	100.00	80.35	5520
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-4319	99.76	69.83	2586

Literature-anchored findings (GeneRIF, showing 14)

• The results of PCR amplification indicated that human RAB41 is widely expressed in brain, testis, lung, heart, ovary, colon, kidney, uterus and spleen but not in liver. (PMID:15018353)
• Rab43 is the target of RN-tre and is required for Shiga toxin uptake. (PMID:17562788)
• Results indicate that Rab1 and Rab43 are key Rabs required for the biogenesis and maintenance of a functional Golgi structure, and suggest that other Rabs acting at the Golgi complex are likely to be functionally redundant. (PMID:17684057)
• Rab18 and Rab43 have key roles in ER-Golgi trafficking. (PMID:18664496)
• Rab1a/b and Rab43, are important for herpes simplex virus 1 virion assembly (PMID:21680502)
• SGK1,3 enhances the expression level of mature hERG channels by inhibiting Nedd4-2 as well as by promoting Rab11-mediated hERG recycling. (PMID:23589291)
• Data indicate taht the parasitophorous vacuole (PV), marked with Rab14, Rab30, or Rab43, colocalize with host-derived sphingolipids in the vacuolar space. (PMID:23615442)
• several crystal structures of the myosin Va or the myosin Vb globular tail domain that gives insights into how the motor is linked to the recycling membrane compartments via Rab11 or the melanophilin adaptor that binds to Rab27a. (PMID:24248336)
• High RAB43 expression is associated with epithelial-mesenchymal transition in gliomas. (PMID:28075478)
• Rab43 directly interacts with GPCRs and controls the forward ER-to-Golgi traffic of nascent GPCRs. (PMID:29069590)
• vesicle-associated RhoB is a regulator of the Rab11-mediated recycling of LFA-1 to the cell surface, an event that is necessary for T lymphocyte motility. (PMID:29233918)
• A germline mutation of Rab43 gene is identified to be associated with the onset of a familial liver-colon cancer syndrome. (PMID:31226964)
• Downregulation of TNFRSF19 and RAB43 by a novel miRNA, miR-HCC3, promotes proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma cells. (PMID:32102752)
• miR-4742-5p promotes invasiveness of gastric cancer via targeting Rab43: An in vitro study. (PMID:35597125)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab43	ENSDARG00000059404
mus_musculus	Rab43	ENSMUSG00000030055

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), 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)

Protein

Protein identifiers

Ras-related protein Rab-43 — Q86YS6 (reviewed: Q86YS6)

Alternative names: Ras-related protein Rab-41

All UniProt accessions (2): C9JFM7, Q86YS6

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. Involved in retrograde transport from the endocytic pathway to the Golgi apparatus. Required for the structural integrity of the Golgi complex. Also controls the anterograde ER-to-Golgi transport of nascent G-protein-coupled receptors (including ADRA2A, ADRA2B, ADRA2C, ADRA1B, ADRB2 and AGTR1) and regulates the ER sorting of GPCR members by virtue of its ability to interact directly. Involved in the transport of Shiga toxin from early and recycling endosomes to the trans-Golgi network. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis.

Subunit / interactions. Interacts with GDI1, GDI2, CHM and CHML; phosphorylation at Thr-82 disrupts these interactions. Interacts (GTP-bound) with USP6NL; USP6NL acts as a GAP. Interacts with ADRA2B (GTP-bound); mediates ADRA2B ER-to-Golgi cell transport.

Subcellular location. Golgi apparatus. cis-Golgi network membrane. trans-Golgi network membrane. Endoplasmic reticulum membrane. Endoplasmic reticulum-Golgi intermediate compartment membrane. Cytoplasmic vesicle. Phagosome membrane.

Tissue specificity. Widely expressed in brain, testis, lung, heart, ovary, colon, kidney, uterus and spleen but not in liver.

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) including USP6NL, which increase the GTP hydrolysis activity. Inhibited by GDP dissociation inhibitors (GDIs).

Domain organisation. Switch I, switch II 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.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86YS6-1	1	yes
Q9ULR0-1	2, ISY1-RAB43
Q86YS6-2	3

RefSeq proteins (7): NP_001191812, NP_001191813, NP_001191814, NP_001191815, NP_001191816, NP_001191817, NP_940892* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR048040	Rab19/43	Family
IPR050209	Rab_GTPases_membrane_traffic	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (57 total): binding site 26, helix 8, strand 6, mutagenesis site 5, modified residue 4, region of interest 2, lipid moiety-binding region 2, splice variant 2, chain 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9LTQ	X-RAY DIFFRACTION	1.6
2HUP	X-RAY DIFFRACTION	2.05
9LTP	X-RAY DIFFRACTION	2.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YS6-F1	85.53	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.

Ligand- & substrate-binding residues (26): 32; 32; 33; 33; 45; 50; 50; 73; 76; 131; 131; 132 …

Post-translational modifications (6): 49, 82, 193, 212, 210, 212

Mutagenesis-validated functional residues (5):

Position	Phenotype
32	constitutively inactive (gdp-bound) mutant. disruption of golgi structure. localized to the cytoplasm. loss of interacti
77	constitutively active (gtp-bound) mutant. decreased cell-surface transport and signaling of adernergic receptor adra2b.
82	loss of phosphorylation. no effect on binding of gdi1 and gdi2.
82	phosphomimetic mutant. loss of binding to gdi1, gdi2, chm and chml.
131	disruption of golgi structure. localized to the cytoplasm. loss of interaction with adra2b. decreased cell-surface trans

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-8873719	RAB geranylgeranylation

MSigDB gene sets: 644 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_GOLGI_ORGANIZATION, E2F_Q4, E2F_Q4_01, GOBP_PIGMENT_GRANULE_LOCALIZATION, PAX4_01, GOBP_VACUOLE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_PEPTIDE, GOBP_TRANSITION_METAL_ION_TRANSPORT, SP3_Q3, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS

GO Biological Process (9): autophagosome assembly (GO:0000045), intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi organization (GO:0007030), virion assembly (GO:0019068), retrograde transport, plasma membrane to Golgi (GO:0035526), cellular response to type II interferon (GO:0071346), phagosome maturation (GO:0090382), regulation of Golgi organization (GO:1903358)

GO Molecular Function (5): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (12): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505), phagocytic vesicle membrane (GO:0030670), trans-Golgi network membrane (GO:0032588), cis-Golgi network membrane (GO:0033106), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
bounding membrane of organelle	3
intracellular transport	2
organelle organization	2
organelle membrane	2
cellular anatomical structure	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
intracellular protein localization	1
protein transport	1
intercellular transport	1
Golgi vesicle transport	1
endomembrane system organization	1
viral process	1
viral life cycle	1
vesicle-mediated transport	1
response to type II interferon	1
cellular response to cytokine stimulus	1
phagolysosome assembly	1
exocytosis	1
Golgi organization	1
regulation of organelle organization	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
Golgi apparatus	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1467 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB43	USP6NL	Q92738	736
RAB43	ISY1	Q9ULR0	613
RAB43	D6RC18	D6RC18	582
RAB43	TBC1D20	Q96BZ9	490
RAB43	HDHD5	Q9BXW7	463
RAB43	EFCC1	Q9HA90	448
RAB43	RILPL1	Q5EBL4	444
RAB43	RILPL2	Q969X0	443
RAB43	TBC1D8B	Q0IIM8	419
RAB43	TBC1D22A	Q8WUA7	389
RAB43	GRTP1	Q5TC63	384
RAB43	ZSCAN2	Q7Z7L9	348
RAB43	ADRA2B	P18089	342
RAB43	PRAF2	O60831	337
RAB43	TBC1D3B	A6NDS4	319

IntAct

14 interactions, top by confidence:

A	B	Type	Score
HSPB1	RAB43	psi-mi:“MI:0915”(physical association)	0.510
Snw1	AKR7A2	psi-mi:“MI:0914”(association)	0.350
Rab5c		psi-mi:“MI:0914”(association)	0.350
RAB5C	GCA	psi-mi:“MI:0914”(association)	0.350
Crnkl1	PLRG1	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
RAB43	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
LHFPL2	SRC	psi-mi:“MI:0914”(association)	0.350
RAB43	TRAPPC3	psi-mi:“MI:0914”(association)	0.350

BioGRID (47): RAB43 (Affinity Capture-MS), RAB43 (Affinity Capture-MS), RAB43 (Affinity Capture-RNA), RAB43 (Affinity Capture-RNA), RAB43 (Affinity Capture-MS), WHAMM (Affinity Capture-MS), NBN (Affinity Capture-MS), C7orf43 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), TRAPPC11 (Affinity Capture-MS), GDI1 (Affinity Capture-MS), GDI2 (Affinity Capture-MS), CLEC16A (Affinity Capture-MS), RAB33B (Affinity Capture-MS), TRAPPC12 (Affinity Capture-MS)

ESM2 similar proteins: A8NU18, D3Z8L7, G4N1S3, O08989, O14807, O42785, O93856, O95716, P01114, P08647, P0CQ42, P0CQ43, P10301, P10833, P22126, P28775, P35276, P46629, P51146, P51156, P56371, P59190, P61017, P61018, P62070, P62071, P70425, P70426, P97538, Q01387, Q05058, Q12526, Q1RMR4, Q29RR0, Q3SZA1, Q4X241, Q53B90, Q5BJQ5, Q63942, Q86YS6

Diamond homologs: A4D1S5, A4FV54, F1PTE3, O04486, O24466, O76173, P01123, P10536, P11620, P16976, P17609, P20790, P20791, P22125, P22128, P28186, P28188, P31584, P33723, P34139, P34140, P35280, P35286, P35294, P36410, P36863, P40392, P51153, P51156, P53994, P55258, P59279, P61006, P61007, P61019, P61028, P61105, P62820, P62821, P62822

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	83
Likely benign	131
Benign	33

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
4813460	NM_004218.4(RAB11B):c.64G>T (p.Val22Leu)	Pathogenic
2770910	NM_004218.4(RAB11B):c.220C>G (p.Arg74Gly)	Likely pathogenic
3235921	NM_004218.4(RAB11B):c.85T>C (p.Ser29Pro)	Likely pathogenic
3337505	NM_004218.4(RAB11B):c.196G>T (p.Asp66Tyr)	Likely pathogenic

SpliceAI

4355 predictions. Top by Δscore:

Variant	Effect	Δscore
19:8390437:G:GG	donor_gain	1.0000
19:8399861:A:AG	acceptor_gain	1.0000
19:8399861:AGT:A	acceptor_gain	1.0000
19:8399862:G:GA	acceptor_gain	1.0000
19:8399862:GTG:G	acceptor_gain	1.0000
19:8399862:GTGGT:G	acceptor_gain	1.0000
19:8400033:G:GT	donor_gain	1.0000
19:8400034:A:T	donor_gain	1.0000
19:8400054:TCCGC:T	donor_gain	1.0000
19:8400057:GC:G	donor_gain	1.0000
19:8400059:G:GG	donor_gain	1.0000
19:8400083:G:T	donor_gain	1.0000
19:8402081:TGCA:T	acceptor_loss	1.0000
19:8402082:GCAG:G	acceptor_loss	1.0000
19:8402083:CAGGT:C	acceptor_loss	1.0000
19:8402084:A:T	acceptor_loss	1.0000
19:8402276:GCAG:G	donor_gain	1.0000
19:8402277:CAG:C	donor_loss	1.0000
19:8402278:AGGTG:A	donor_loss	1.0000
19:8402279:GG:G	donor_loss	1.0000
19:8402280:G:C	donor_loss	1.0000
19:8402479:TTCCA:T	acceptor_loss	1.0000
19:8402480:TCCAG:T	acceptor_loss	1.0000
19:8402482:CA:C	acceptor_loss	1.0000
19:8402483:A:AG	acceptor_gain	1.0000
19:8402483:AG:A	acceptor_loss	1.0000
19:8402484:G:GG	acceptor_gain	1.0000
19:8402484:GAAAA:G	acceptor_gain	1.0000
19:8402541:G:GT	donor_gain	1.0000
19:8402581:A:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000087837 (3:129095236 C>T), RS1000121834 (3:129120132 G>A), RS1000124666 (3:129112145 C>T), RS1000164774 (3:129093902 G>A), RS1000191151 (3:129118741 C>T), RS1000266175 (3:129092945 G>A,C), RS1000268835 (3:129111608 C>G), RS1000492609 (3:129120484 C>A,T), RS1000504354 (3:129102282 G>C), RS1000604764 (3:129113128 T>C), RS1000886774 (3:129107211 G>A), RS1000920026 (3:129101750 C>A,G,T), RS1000970396 (3:129101511 G>A), RS1001002274 (3:129094565 A>AG), RS1001070248 (3:129120181 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:617807

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (MONDO:0060624)

Orphanet (0):

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000297	Facial hypotonia
HP:0000395	Prominent antihelix
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000540	Hypermetropia
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000733	Motor stereotypy
HP:0000817	Reduced eye contact
HP:0000954	Single transverse palmar crease
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001320	Cerebellar vermis hypoplasia
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001385	Hip dysplasia
HP:0001761	Pes cavus
HP:0001776	Bilateral talipes equinovarus
HP:0001845	Overlapping toe
HP:0002066	Gait ataxia
HP:0002119	Ventriculomegaly
HP:0002136	Broad-based gait
HP:0002188	Delayed CNS myelination

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005956_82	Waist-to-hip ratio adjusted for BMI	2.000000e-07
GCST005958_5	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-10
GCST005962_16	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-11
GCST90002385_310	High light scatter reticulocyte count	3.000000e-14
GCST90002386_59	High light scatter reticulocyte percentage of red cells	5.000000e-15
GCST90002387_38	Immature fraction of reticulocytes	1.000000e-16
GCST90020025_588	Waist-to-hip ratio adjusted for BMI	7.000000e-09
GCST90020027_365	Waist-hip index	7.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Air Pollutants	affects cotreatment, affects expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Ozone	affects expression, increases abundance, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, affects expression, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, affects expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	increases expression	1
abrine	decreases expression	1
MT19c compound	decreases expression	1
Acrolein	affects cotreatment, affects expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cisplatin	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	increases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Methotrexate	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

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