RAB9B

Summary

RAB9B (RAB9B, member RAS oncogene family, HGNC:14090) is a protein-coding gene on chromosome Xq22.2, encoding Ras-related protein Rab-9B (Q9NP90). 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 member of a subfamily of RAS small guanosine triphosphate (GTP)-binding proteins that regulate membrane trafficking. The encoded protein may be involved in endosome-to-Golgi transport.

Source: NCBI Gene 51209 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 122 total — 18 pathogenic, 5 likely-pathogenic
• MANE Select transcript: NM_016370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14090
Approved symbol	RAB9B
Name	RAB9B, member RAS oncogene family
Location	Xq22.2
Locus type	gene with protein product
Status	Approved
Aliases	RAB9L
Ensembl gene	ENSG00000123570
Ensembl biotype	protein_coding
OMIM	300285
Entrez	51209

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000243298, ENST00000873736, ENST00000963274, ENST00000963275

RefSeq mRNA: 1 — MANE Select: NM_016370 NM_016370

CCDS: CCDS14515

Canonical transcript exons

ENST00000243298 — 3 exons

Exon	Start	End
ENSE00000840323	103822327	103825826
ENSE00001105684	103832060	103832257
ENSE00001105686	103827005	103827078

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 95.93.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0091 / max 96.1379, expressed in 479 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200027	1.6688	429
200026	0.3403	141

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	95.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.03	gold quality
endothelial cell	CL:0000115	92.99	gold quality
myocardium	UBERON:0002349	92.32	gold quality
middle temporal gyrus	UBERON:0002771	91.90	gold quality
heart right ventricle	UBERON:0002080	91.27	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.95	silver quality
cerebellar vermis	UBERON:0004720	85.93	gold quality
cerebellar cortex	UBERON:0002129	85.02	gold quality
cerebellar hemisphere	UBERON:0002245	84.96	gold quality
primary visual cortex	UBERON:0002436	84.85	gold quality
deltoid	UBERON:0001476	84.83	silver quality
cerebellum	UBERON:0002037	84.83	gold quality
quadriceps femoris	UBERON:0001377	84.67	silver quality
vastus lateralis	UBERON:0001379	84.18	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.81	gold quality
cortical plate	UBERON:0005343	83.79	gold quality
biceps brachii	UBERON:0001507	83.70	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.44	silver quality
tibialis anterior	UBERON:0001385	83.19	silver quality
cardiac ventricle	UBERON:0002082	82.85	gold quality
heart left ventricle	UBERON:0002084	82.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.54	gold quality
heart	UBERON:0000948	82.12	gold quality
prefrontal cortex	UBERON:0000451	81.98	gold quality
superior frontal gyrus	UBERON:0002661	81.62	gold quality
right coronary artery	UBERON:0001625	81.60	gold quality
occipital lobe	UBERON:0002021	81.11	gold quality
muscle tissue	UBERON:0002385	81.11	gold quality
cardiac atrium	UBERON:0002081	80.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	517.84
E-ANND-3	no	3.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

222 targeting RAB9B, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab9b	ENSDARG00000103391
mus_musculus	Rab9b	ENSMUSG00000043463
rattus_norvegicus	Rab9b	ENSRNOG00000047960

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), 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-9B — Q9NP90 (reviewed: Q9NP90)

Alternative names: Rab-9-like protein

All UniProt accessions (1): Q9NP90

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. RAB9B is involved in the transport of proteins between the endosomes and the trans Golgi network. May use NDE1/NDEL1 as an effector to interact with the dynein motor complex in order to control retrograde trafficking of RAB9-associated late endosomes to the TGN.

Subunit / interactions. Interacts (GTP-bound form) with SGSM1; the GDP-bound form has much lower affinity for SGSM1. The GTP-bound form but not the GDP-bound form interacts with HPS4 and the BLOC-3 complex (heterodimer of HPS1 and HPS4) but does not interact with HPS1 alone. Interacts (GTP-bound form) with NDE1.

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

Tissue specificity. Ubiquitous.

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 (1): NP_057454* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041824	Rab9	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (40 total): binding site 18, helix 8, strand 6, short sequence motif 2, lipid moiety-binding region 2, turn 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2OCB	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP90-F1	92.54	0.84

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 (18): 34; 36; 38; 39; 39; 62; 65; 124; 125; 155; 156; 18 …

Post-translational modifications (3): 34, 200, 201

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-9706019	RHOBTB3 ATPase cycle

MSigDB gene sets: 128 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE45365_NK_CELL_VS_CD8_TCELL_UP, REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_RETROGRADE_TRANSPORT_ENDOSOME_TO_GOLGI, VECCHI_GASTRIC_CANCER_EARLY_DN, GOBP_IMPORT_INTO_CELL, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_ENDOCYTOSIS, GOBP_CYTOSOLIC_TRANSPORT, GOCC_PHAGOCYTIC_VESICLE

GO Biological Process (4): receptor-mediated endocytosis (GO:0006898), protein transport (GO:0015031), Rab protein signal transduction (GO:0032482), retrograde transport, endosome to Golgi (GO:0042147)

GO Molecular Function (8): G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), GTPase activity (GO:0003924), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (10): lysosome (GO:0005764), late endosome (GO:0005770), cytosol (GO:0005829), plasma membrane (GO:0005886), secretory granule membrane (GO:0030667), phagocytic vesicle membrane (GO:0030670), phagocytic vesicle (GO:0045335), membrane (GO:0016020), organelle membrane (GO:0031090), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Innate Immune System	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Post-translational protein modification	1
Rab regulation of trafficking	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
guanyl ribonucleotide binding	2
cytoplasm	2
cellular anatomical structure	2
membrane	2
endocytosis	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
small GTPase-mediated signal transduction	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ribonucleoside triphosphate phosphatase activity	1
binding	1
catalytic activity	1
lytic vacuole	1
endosome	1
cell periphery	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
endocytic vesicle membrane	1
phagocytic vesicle	1
endocytic vesicle	1
membrane-bounded organelle	1
intracellular vesicle	1

Protein interactions and networks

STRING

1260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB9B	TCEAL1	Q15170	591
RAB9B	RHOBTB3	O94955	539
RAB9B	DENND2A	Q9ULE3	539
RAB9B	ADAMTS18	Q8TE60	474
RAB9B	MORF4L2	Q15014	430
RAB9B	WT1	P19544	429
RAB9B	BTG2	P78543	423
RAB9B	CCZ1B	P86790	417
RAB9B	DENND2C	Q68D51	407
RAB9B	DENND2D	Q9H6A0	397
RAB9B	PPM1D	O15297	392
RAB9B	RABIF	P47224	382
RAB9B	VPS35	Q96QK1	382
RAB9B	RABGEF1	Q9UJ41	381
RAB9B	PAK5	Q9P286	366

IntAct

14 interactions, top by confidence:

A	B	Type	Score
RAB9B	CHM	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
HPS4	RAB9B	psi-mi:“MI:0915”(physical association)	0.370
RHOBTB3	RAB9B	psi-mi:“MI:0915”(physical association)	0.370
PACC1	DEGS1	psi-mi:“MI:0914”(association)	0.350
RUSF1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
PRPH2	TOR1A	psi-mi:“MI:0914”(association)	0.350
PACC1	TNPO2	psi-mi:“MI:0914”(association)	0.350
RAB9B	VSIG8	psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SLC1A1	SCD	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): CHML (Affinity Capture-MS), CHM (Affinity Capture-MS), ASPRV1 (Affinity Capture-MS), RABGGTA (Affinity Capture-MS), CPA4 (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS), HAL (Affinity Capture-MS), RABGGTB (Affinity Capture-MS), PHACTR4 (Affinity Capture-MS), PHACTR4 (Affinity Capture-MS), CHM (Affinity Capture-MS), CHML (Affinity Capture-MS), RABGGTA (Affinity Capture-MS), RAB9B (Affinity Capture-MS), CPA4 (Affinity Capture-MS)

ESM2 similar proteins: C8VQY7, G4MYS1, H9BW96, I1RMF2, O01803, O04157, O24461, O76742, O94655, O97572, P09527, P11023, P18067, P19892, P20336, P24408, P28187, P31022, P32939, P36411, P36864, P51149, P51150, P51151, P63011, P63012, P93267, Q06AU3, Q39573, Q3T0F5, Q40787, Q41640, Q43463, Q4R4R9, Q5R4W9, Q5R9Y4, Q8BHH2, Q948K8, Q99P75, Q9C2L8

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	5
Uncertain significance	37
Likely benign	35
Benign	6

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
11073	NM_000533.5(PLP1):c.646C>T (p.Pro216Ser)	Pathogenic
11081	NM_000533.5(PLP1):c.607G>C (p.Asp203His)	Pathogenic
11087	NM_000533.5(PLP1):c.3G>A (p.Met1Ile)	Pathogenic
1345557	NM_000533.5(PLP1):c.4+1G>A	Pathogenic
1387745	NM_000533.5(PLP1):c.428del (p.Gly143fs)	Pathogenic
1388919	NM_000533.5(PLP1):c.416_417del (p.Cys139fs)	Pathogenic
1686084	NM_000533.5(PLP1):c.665C>G (p.Ser222Cys)	Pathogenic
2053904	NM_000533.5(PLP1):c.180T>G (p.Tyr60Ter)	Pathogenic
2080617	NM_000533.5(PLP1):c.588dup (p.Ile197fs)	Pathogenic
2138677	NM_000533.5(PLP1):c.670C>T (p.Leu224Phe)	Pathogenic
219649	NM_000533.5(PLP1):c.2T>C (p.Met1Thr)	Pathogenic
265416	NM_000533.5(PLP1):c.191+1G>A	Pathogenic
280441	NM_000533.5(PLP1):c.673del (p.Leu225fs)	Pathogenic
3660851	NM_000533.5(PLP1):c.220G>T (p.Gly74Ter)	Pathogenic
3723230	NM_000533.5(PLP1):c.1_2del (p.Met1fs)	Pathogenic
816705	NM_000533.5(PLP1):c.453+159G>A	Pathogenic
832054	NC_000023.10:g.(?102831398)(103220942_?)dup	Pathogenic
952824	NM_000533.5(PLP1):c.454-314T>G	Pathogenic
11092	NM_000533.5(PLP1):c.509C>T (p.Ser170Phe)	Likely pathogenic
1184577	NM_000533.5(PLP1):c.423_426del (p.Cys141fs)	Likely pathogenic
1483024	NM_000533.5(PLP1):c.453+1G>T	Likely pathogenic
191252	NM_000533.5(PLP1):c.650G>A (p.Gly217Asp)	Likely pathogenic
817275	NM_000533.5(PLP1):c.739del (p.Ala247fs)	Likely pathogenic

SpliceAI

295 predictions. Top by Δscore:

Variant	Effect	Δscore
X:103827074:GGGTG:G	acceptor_gain	0.9900
X:103827075:GGTG:G	acceptor_gain	0.9900
X:103827077:TG:T	acceptor_gain	0.9900
X:103827079:C:CC	acceptor_gain	0.9900
X:103832054:CCTTA:C	donor_loss	0.9900
X:103832056:TTAC:T	donor_loss	0.9900
X:103832058:A:AC	donor_gain	0.9900
X:103832058:A:T	donor_loss	0.9900
X:103832058:AC:A	donor_gain	0.9900
X:103832059:C:CC	donor_gain	0.9900
X:103832059:C:CG	donor_loss	0.9900
X:103832059:CC:C	donor_gain	0.9900
X:103832059:CCCAA:C	donor_gain	0.9900
X:103827003:AC:A	donor_gain	0.9800
X:103827004:CC:C	donor_gain	0.9800
X:103827075:GGTGC:G	acceptor_loss	0.9800
X:103827077:TGC:T	acceptor_loss	0.9800
X:103827078:GC:G	acceptor_loss	0.9800
X:103827079:C:CG	acceptor_loss	0.9800
X:103827080:T:A	acceptor_loss	0.9800
X:103827087:CAGAA:C	acceptor_loss	0.9800
X:103825826:CCT:C	acceptor_loss	0.9700
X:103825827:C:CA	acceptor_loss	0.9700
X:103825828:T:A	acceptor_loss	0.9700
X:103826999:ACCT:A	donor_loss	0.9700
X:103827000:CCT:C	donor_loss	0.9700
X:103827001:CTACC:C	donor_loss	0.9700
X:103827002:T:TA	donor_loss	0.9700
X:103827036:T:A	donor_gain	0.9700
X:103827076:GTG:G	acceptor_gain	0.9700

AlphaMissense

1343 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:103825578:G:C	F69L	1.000
X:103825578:G:T	F69L	1.000
X:103825580:A:G	F69L	1.000
X:103825600:T:A	D62V	1.000
X:103825600:T:G	D62A	1.000
X:103825536:G:C	C83W	0.999
X:103825557:G:C	F76L	0.999
X:103825557:G:T	F76L	0.999
X:103825559:A:G	F76L	0.999
X:103825599:G:C	D62E	0.999
X:103825599:G:T	D62E	0.999
X:103825600:T:C	D62G	0.999
X:103825601:C:G	D62H	0.999
X:103825602:C:A	W61C	0.999
X:103825602:C:G	W61C	0.999
X:103825604:A:G	W61R	0.999
X:103825604:A:T	W61R	0.999
X:103825653:G:C	F44L	0.999
X:103825653:G:T	F44L	0.999
X:103825655:A:G	F44L	0.999
X:103825663:C:T	G41E	0.999
X:103825689:A:C	F32L	0.999
X:103825689:A:T	F32L	0.999
X:103825691:A:G	F32L	0.999
X:103825708:C:G	R26P	0.999
X:103825725:T:A	K20N	0.999
X:103825725:T:G	K20N	0.999
X:103825726:T:A	K20I	0.999
X:103825727:T:G	K20Q	0.999
X:103825729:C:T	G19E	0.999

dbSNP variants (sampled 300 via entrez): RS1000071136 (X:103776956 C>A,G), RS1000084555 (X:103795143 G>T), RS1000131576 (X:103804191 G>A), RS1000150149 (X:103796962 G>A,C,T), RS1000280564 (X:103808639 A>G), RS1000294911 (X:103819854 C>T), RS1000323304 (X:103828370 A>C), RS1000328400 (X:103831463 T>C), RS1000359645 (X:103811904 T>C), RS1000488168 (X:103819899 C>G,T), RS1000561231 (X:103777790 G>A), RS1000605455 (X:103826799 T>C), RS1000629759 (X:103780053 T>G), RS1000630920 (X:103817794 C>A,T), RS1000675261 (X:103828861 C>T)

Disease associations

OMIM: gene MIM:300285 | disease phenotypes: MIM:312080, MIM:312920, MIM:303350

GenCC curated gene-disease

Mondo (3): Pelizaeus-Merzbacher spectrum disorder (MONDO:0010714), hereditary spastic paraplegia 2 (MONDO:0010733), hereditary spastic paraplegia (MONDO:0019064)

Orphanet (3): Pelizaeus-Merzbacher disease (Orphanet:702), Spastic paraplegia type 2 (Orphanet:99015), Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D020371	Pelizaeus-Merzbacher Disease	C10.228.140.163.100.362.775; C10.228.140.695.625.775; C10.314.400.775; C16.320.322.906; C16.320.565.189.362.775; C18.452.132.100.362.775; C18.452.648.189.362.775
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
CGP 52608	increases reaction, affects binding	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	affects expression	1
Folic Acid	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression, increases abundance	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT07382739	PHASE2	RECRUITING	A Phase 2 Study of Radiotherapy-induced Immune Priming to Enhance Elranatamab (Elra) in Relapsed Refractory Multiple Myeloma (RRMM) With Extramedullary Disease (EMD) and Paramedullary Disease (PMD) PRIME-EMD-PMD
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT01005004	PHASE1	COMPLETED	Study of Human Central Nervous System (CNS) Stem Cells Transplantation in Pelizaeus-Merzbacher Disease (PMD) Subjects
NCT02254863	PHASE1	RECRUITING	UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells
NCT06150716	PHASE1	RECRUITING	Orbit Study: A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered ION356 in Participants With Pelizaeus Merzbacher Disease (PMD)
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT01391637	Not specified	COMPLETED	Long-Term Follow-Up Study of Human Stem Cells Transplanted in Subjects With Connatal Pelizaeus-Merzbacher Disease (PMD)
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT05659901	Not specified	RECRUITING	Rocket Study: A Study to Characterize Biomarkers and Disease Progression in Participants With Pelizaeus-Merzbacher Disease
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia
NCT05411627	Not specified	WITHDRAWN	A Pilot Study of Shockwave Therapy in HSP
NCT05432999	Not specified	COMPLETED	Extracorporeal Shockwave Therapy for Spasticity in People With Spinal Cord Injury
NCT05613114	Not specified	COMPLETED	Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia