KLC2

Summary

KLC2 (kinesin light chain 2, HGNC:20716) is a protein-coding gene on chromosome 11q13.2, encoding Kinesin light chain 2 (Q9H0B6). Kinesin is a microtubule-associated force-producing protein that plays a role in organelle transport. It is a selective cancer dependency (DepMap: 50.9% of cell lines).

The protein encoded by this gene is a light chain of kinesin, a molecular motor responsible for moving vesicles and organelles along microtubules. Defects in this gene are a cause of spastic paraplegia, optic atrophy, and neuropathy (SPOAN) syndrome.

Source: NCBI Gene 64837 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spastic paraplegia, optic atropy, and neuropathy (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 206 total — 2 pathogenic
• Phenotypes (HPO): 34
• Cancer dependency (DepMap): dependent in 50.9% of screened cell lines
• MANE Select transcript: NM_001318734

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20716
Approved symbol	KLC2
Name	kinesin light chain 2
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12387
Ensembl gene	ENSG00000174996
Ensembl biotype	protein_coding
OMIM	611729
Entrez	64837

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 29 protein_coding, 2 retained_intron

ENST00000316924, ENST00000394065, ENST00000394066, ENST00000394067, ENST00000394078, ENST00000417856, ENST00000421552, ENST00000440228, ENST00000461611, ENST00000475757, ENST00000483152, ENST00000526758, ENST00000531240, ENST00000534023, ENST00000852032, ENST00000852033, ENST00000852034, ENST00000852035, ENST00000852036, ENST00000917338, ENST00000917339, ENST00000917340, ENST00000917341, ENST00000917342, ENST00000917343, ENST00000917344, ENST00000917345, ENST00000942284, ENST00000942285, ENST00000942286, ENST00000942287

RefSeq mRNA: 5 — MANE Select: NM_001318734 NM_001134774, NM_001134775, NM_001134776, NM_001318734, NM_022822

CCDS: CCDS44653, CCDS8130

Canonical transcript exons

ENST00000394067 — 16 exons

Exon	Start	End
ENSE00001189471	66266433	66266490
ENSE00001189478	66266093	66266217
ENSE00001189491	66265854	66266012
ENSE00001189502	66265655	66265763
ENSE00001189512	66265168	66265235
ENSE00001189517	66265023	66265072
ENSE00001189523	66264345	66264444
ENSE00001189529	66264046	66264219
ENSE00001189540	66263660	66263747
ENSE00001189548	66262814	66263036
ENSE00001189579	66257703	66257871
ENSE00001517426	66266873	66267860
ENSE00001770804	66261742	66261972
ENSE00002180680	66258584	66258822
ENSE00002456733	66263851	66263952
ENSE00003526529	66262123	66262192

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 98.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2151 / max 113.2409, expressed in 1709 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115299	7.2425	1639
115297	1.5360	955
115298	1.5123	718
115300	1.4766	772
115295	0.2131	119
115296	0.1388	47
115301	0.0958	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.67	gold quality
cerebellar hemisphere	UBERON:0002245	98.55	gold quality
cerebellar cortex	UBERON:0002129	98.47	gold quality
cerebellum	UBERON:0002037	97.73	gold quality
right frontal lobe	UBERON:0002810	97.21	gold quality
prefrontal cortex	UBERON:0000451	96.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.69	gold quality
anterior cingulate cortex	UBERON:0009835	95.49	gold quality
cingulate cortex	UBERON:0003027	95.48	gold quality
right testis	UBERON:0004534	95.39	gold quality
endothelial cell	CL:0000115	95.38	silver quality
left testis	UBERON:0004533	95.09	gold quality
frontal cortex	UBERON:0001870	95.08	gold quality
neocortex	UBERON:0001950	94.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.73	gold quality
adenohypophysis	UBERON:0002196	94.64	gold quality
pituitary gland	UBERON:0000007	94.47	gold quality
primary visual cortex	UBERON:0002436	93.46	gold quality
cerebral cortex	UBERON:0000956	93.45	gold quality
nucleus accumbens	UBERON:0001882	93.22	gold quality
brain	UBERON:0000955	93.05	gold quality
amygdala	UBERON:0001876	92.98	gold quality
forebrain	UBERON:0001890	92.85	gold quality
telencephalon	UBERON:0001893	92.85	gold quality
putamen	UBERON:0001874	92.79	gold quality
gastrocnemius	UBERON:0001388	92.72	gold quality
occipital lobe	UBERON:0002021	92.50	gold quality
caudate nucleus	UBERON:0001873	92.48	gold quality
hypothalamus	UBERON:0001898	92.46	gold quality
cortical plate	UBERON:0005343	92.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting KLC2, 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-4533	100.00	69.48	2758
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 50.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• Na,K-ATPase traffic toward the plasma membrane in alveolar epithelial cells is driven by kinesin-1, where KLC2 is the isoform regulating this process. (PMID:19773350)
• For the binding of cargos shared by KLC2, we propose a different site located within the groove but not involving N343. (PMID:22470497)
• Results identified KLC2 as a novel target and of miR-125b in non-small-cell lung cancer (NSCLC) and show the oncogenic potential of KLC2 in the progression of NSCLC. (PMID:25668010)
• a homozygous 216-bp deletion located at the non-coding upstream region of the KLC2 gene in patients with SPOAN syndrome causes overexpression of the gene (PMID:26385635)
• The kinesin light chain-2, a target of mRNA stabilizing protein HuR, inhibits p53 protein phosphorylation to promote radioresistance in NSCLC. (PMID:37055376)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Klc2	ENSMUSG00000024862
rattus_norvegicus	Klc2	ENSRNOG00000020299

Paralogs (5): APPBP2 (ENSG00000062725), KLC3 (ENSG00000104892), NPHP3 (ENSG00000113971), KLC1 (ENSG00000126214), KLC4 (ENSG00000137171)

Protein

Protein identifiers

Kinesin light chain 2 — Q9H0B6 (reviewed: Q9H0B6)

All UniProt accessions (8): A8MX29, A8MZ87, C9JHT2, Q9H0B6, E9PI24, E9PM83, E9PP09, E9PQ02

UniProt curated annotations — full annotation on UniProt →

Function. Kinesin is a microtubule-associated force-producing protein that plays a role in organelle transport. The light chain functions in coupling of cargo to the heavy chain or in the modulation of its ATPase activity. Through binding with PLEKHM2 and ARL8B, recruits kinesin-1 to lysosomes and hence direct lysosomes movement toward microtubule plus ends.

Subunit / interactions. Oligomeric complex composed of two heavy chains and two light chains. Interacts (via TPR repeats) with PLEKHM2.

Subcellular location. Cytoplasm. Cytoskeleton. Lysosome membrane.

Disease relevance. Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) [MIM:609541] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPOAN is characterized by spastic paraplegia with progressive joint contractures and spine deformities, loss of independent ambulation by age 10 years, sub-normal vision secondary to congenital optic atrophy, and neuropathy. Inheritance is autosomal recessive. The gene represented in this entry is involved in disease pathogenesis. The disease is caused by a homozygous deletion in the non-coding region of the KLC2 gene.

Similarity. Belongs to the kinesin light chain family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H0B6-1	1	yes
Q9H0B6-2	2

RefSeq proteins (5): NP_001128246, NP_001128247, NP_001128248, NP_001305663, NP_073733 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002151	Kinesin_light	Family
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR015792	Kinesin_light_repeat	Repeat
IPR019734	TPR_rpt	Repeat

Pfam: PF13374, PF13424

UniProt features (50 total): modified residue 12, helix 12, repeat 6, compositionally biased region 5, strand 4, region of interest 3, sequence conflict 2, turn 2, chain 1, coiled-coil region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3EDT	X-RAY DIFFRACTION	2.7
3CEQ	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0B6-F1	72.79	0.50

Functional residue map

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

Post-translational modifications (12): 151, 175, 179, 445, 508, 521, 581, 582, 589, 608, 610, 615

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-5625970	RHO GTPases activate KTN1
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-983189	Kinesins
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 199 (showing top): ELVIDGE_HYPOXIA_DN, WWTAAGGC_UNKNOWN, PAX4_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_VACUOLAR_MEMBRANE, GOCC_KINESIN_COMPLEX, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, REACTOME_MEMBRANE_TRAFFICKING, chr11q13, CAGCAGG_MIR370, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, GOBP_ORGANELLE_LOCALIZATION, TAANNYSGCG_UNKNOWN, GCCNNNWTAAR_UNKNOWN

GO Biological Process (2): microtubule-based movement (GO:0007018), lysosome localization (GO:0032418)

GO Molecular Function (3): kinesin binding (GO:0019894), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (13): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), lysosomal membrane (GO:0005765), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), plasma membrane (GO:0005886), membrane (GO:0016020), kinesin I complex (GO:0016938), protein-containing complex (GO:0032991), lysosome (GO:0005764), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Adaptive Immune System	1
RHO GTPase Effectors	1
Golgi-to-ER retrograde transport	1
Factors involved in megakaryocyte development and platelet production	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Vesicle-mediated transport	1
Membrane Trafficking	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Signal Transduction	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
microtubule-based process	1
vacuolar localization	1
cytoskeletal protein binding	1
cell adhesion molecule binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
lysosome	1
lytic vacuole membrane	1
microtubule associated complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
kinesin complex	1
cellular_component	1
lytic vacuole	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2833 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLC2	KIF5B	P33176	982
KLC2	KIF5A	Q12840	972
KLC2	MAPK8IP3	Q9UPT6	943
KLC2	KIF5C	O60282	940
KLC2	HAP1	P54257	909
KLC2	MAPK8IP1	Q9UQF2	903
KLC2	APP	P05067	896
KLC2	MAPK8IP2	Q13387	883
KLC2	CLSTN1	O94985	826
KLC2	PLEKHM2	Q8IWE5	761
KLC2	ARL5B	Q96KC2	699
KLC2	KIF1A	Q12756	694
KLC2	HTT	P42858	679
KLC2	TRAK2	O60296	638
KLC2	DPYSL2	Q16555	621

IntAct

207 interactions, top by confidence:

A	B	Type	Score
KLC2	YWHAQ	psi-mi:“MI:0915”(physical association)	0.900
YWHAZ	KLC2	psi-mi:“MI:0915”(physical association)	0.870
YWHAG	KLC2	psi-mi:“MI:0915”(physical association)	0.870
KLC2	YWHAZ	psi-mi:“MI:0915”(physical association)	0.870
YWHAH	TSC2	psi-mi:“MI:0914”(association)	0.850
MOB1B	LATS1	psi-mi:“MI:0914”(association)	0.840
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
EXOC3	EXOC5	psi-mi:“MI:0914”(association)	0.790
KIF5B	KLC1	psi-mi:“MI:0914”(association)	0.730
KLC1	KIF5B	psi-mi:“MI:0914”(association)	0.730
DOP1A	MON2	psi-mi:“MI:0914”(association)	0.680
AZIN1	OAZ2	psi-mi:“MI:0914”(association)	0.670
KLC2	YWHAE	psi-mi:“MI:0915”(physical association)	0.650
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
SFN	KLC2	psi-mi:“MI:0915”(physical association)	0.630
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
N	KLC2	psi-mi:“MI:0915”(physical association)	0.600
KLC2	DOP1A	psi-mi:“MI:0915”(physical association)	0.590
KLC2	DOP1A	psi-mi:“MI:0914”(association)	0.590
KLC2	DOP1A	psi-mi:“MI:0407”(direct interaction)	0.590

BioGRID (286): KLC2 (Affinity Capture-MS), KLC2 (Affinity Capture-MS), KLC2 (Affinity Capture-MS), KLC2 (Affinity Capture-MS), KLC2 (Affinity Capture-MS), KLC2 (Affinity Capture-MS), KLC2 (Affinity Capture-MS), KLC2 (Affinity Capture-MS), KLC2 (Affinity Capture-MS), KIF5B (Co-fractionation), KIF5C (Co-fractionation), KLC2 (Co-fractionation), KLC2 (Co-fractionation), LSM3 (Co-fractionation), LSM7 (Co-fractionation)

ESM2 similar proteins: A0A8I6A2H6, A2VEI2, A4IG32, A4IHK8, A5D7A0, D2HZB0, D4A1F2, E9Q4Z2, F1MF74, O00763, O08874, O14795, O94851, P23092, Q05AA6, Q08BI9, Q13474, Q17QM6, Q3TWN3, Q4FZY0, Q4KUS2, Q4V8B2, Q5E9V1, Q5R9G1, Q5RDI4, Q5U2P1, Q5ZJT0, Q62768, Q62769, Q69ZT9, Q6DFA1, Q86XE3, Q8BHD4, Q8BML1, Q8IWE4, Q8K0V2, Q8WN03, Q96C19, Q9BQI0, Q9BUP0

Diamond homologs: O88447, O88448, P37285, P46822, P46824, P46825, Q05090, Q07866, Q2HJJ0, Q2TBQ9, Q5PQM2, Q5R581, Q5R8E2, Q68G30, Q6P597, Q91W40, Q9DBS5, Q9H0B6, Q9NSK0

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKAA1	up-regulates	KLC2	phosphorylation
AMPK	up-regulates	KLC2	phosphorylation
KLC2	“up-regulates activity”	FYCO1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 181 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	45.2×	4e-10
Activation of BAD and translocation to mitochondria	7	44.8×	7e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	39.5×	2e-08
Activation of BH3-only proteins	7	29.2×	2e-07
RHO GTPases activate PKNs	8	21.3×	2e-07
Parasite infection	6	17.4×	3e-05
Leishmania phagocytosis	6	17.4×	3e-05
Intrinsic Pathway for Apoptosis	7	17.2×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	7	16.2×	2e-04
intracellular protein localization	11	7.3×	2e-04
protein transport	15	4.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	122
Likely benign	47
Benign	14

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1684657	NC_000011.10:g.66257087_66257300del	Pathogenic
222029	NM_001134775.1(KLC2):c.-451_-235del	Pathogenic

SpliceAI

2389 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66258790:G:GT	donor_gain	1.0000
11:66258820:CAG:C	donor_loss	1.0000
11:66258821:AG:A	donor_loss	1.0000
11:66258822:GG:G	donor_loss	1.0000
11:66258823:G:GA	donor_loss	1.0000
11:66261973:G:GG	donor_gain	1.0000
11:66262117:TCCCA:T	acceptor_loss	1.0000
11:66262121:A:AG	acceptor_gain	1.0000
11:66262122:G:GG	acceptor_gain	1.0000
11:66262177:GA:G	donor_gain	1.0000
11:66262190:CAG:C	donor_loss	1.0000
11:66262191:AGG:A	donor_loss	1.0000
11:66262193:GTGC:G	donor_loss	1.0000
11:66263033:ATCGG:A	donor_loss	1.0000
11:66263034:TCGGT:T	donor_loss	1.0000
11:66263035:CGGTG:C	donor_loss	1.0000
11:66263037:G:GA	donor_loss	1.0000
11:66263037:G:GG	donor_gain	1.0000
11:66263656:CCAG:C	acceptor_loss	1.0000
11:66263658:A:AG	acceptor_gain	1.0000
11:66263658:AG:A	acceptor_gain	1.0000
11:66263658:AGG:A	acceptor_gain	1.0000
11:66263659:G:GC	acceptor_loss	1.0000
11:66263659:G:GG	acceptor_gain	1.0000
11:66263659:GG:G	acceptor_gain	1.0000
11:66263659:GGG:G	acceptor_gain	1.0000
11:66263743:CAGCC:C	donor_gain	1.0000
11:66263744:AGCC:A	donor_gain	1.0000
11:66263745:GCC:G	donor_gain	1.0000
11:66263745:GCCG:G	donor_gain	1.0000

AlphaMissense

4037 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66261818:T:C	L102P	1.000
11:66261839:T:C	L109P	1.000
11:66261851:T:C	L113P	1.000
11:66262886:T:C	L201P	1.000
11:66262895:T:C	L204P	1.000
11:66262934:C:A	A217D	1.000
11:66262943:T:A	L220H	1.000
11:66262943:T:C	L220P	1.000
11:66262945:T:C	C221R	1.000
11:66262946:G:A	C221Y	1.000
11:66262947:C:G	C221W	1.000
11:66262958:T:C	L225P	1.000
11:66262967:T:C	L228P	1.000
11:66263003:C:A	A240D	1.000
11:66263009:T:G	M242R	1.000
11:66263012:T:C	L243P	1.000
11:66263016:C:A	N244K	1.000
11:66263016:C:G	N244K	1.000
11:66263021:T:C	L246P	1.000
11:66263024:C:A	A247E	1.000
11:66263027:T:C	L248P	1.000
11:66263692:T:C	L262P	1.000
11:66263695:T:C	L263P	1.000
11:66263707:T:C	L267P	1.000
11:66263864:T:C	L285P	1.000
11:66263868:C:A	N286K	1.000
11:66263868:C:G	N286K	1.000
11:66263871:C:A	N287K	1.000
11:66263871:C:G	N287K	1.000
11:66263873:T:C	L288P	1.000

dbSNP variants (sampled 300 via entrez): RS1000013085 (11:66255230 G>T), RS1000035003 (11:66248230 A>C), RS1000106649 (11:66247919 G>C), RS1000423122 (11:66267715 T>C,G), RS1000452740 (11:66254903 C>T), RS1000752780 (11:66266578 T>G), RS1000795096 (11:66266292 C>T), RS1000839733 (11:66249475 G>A,C), RS1000870744 (11:66249011 A>G), RS1001143410 (11:66260614 T>C), RS1001205236 (11:66255599 C>G,T), RS1001343690 (11:66249632 A>G), RS1001403730 (11:66242840 A>G), RS1001448336 (11:66267563 A>G), RS1001599826 (11:66268004 C>A)

Disease associations

OMIM: gene MIM:611729 | disease phenotypes: MIM:609541

GenCC curated gene-disease

Disease	Classification	Inheritance
spastic paraplegia, optic atropy, and neuropathy	Strong	Autosomal recessive

Mondo (1): spastic paraplegia, optic atropy, and neuropathy (MONDO:0012297)

Orphanet (1): Spastic paraplegia-optic atrophy-neuropathy syndrome (Orphanet:320406)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000543	Optic disc pallor
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000975	Hyperhidrosis
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001371	Flexion contracture
HP:0001761	Pes cavus
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002194	Delayed gross motor development
HP:0002267	Exaggerated startle response
HP:0002540	Inability to walk
HP:0002600	Hyporeflexia of lower limbs
HP:0002650	Scoliosis
HP:0002808	Kyphosis
HP:0002828	Multiple joint contractures
HP:0003380	Decreased number of peripheral myelinated nerve fibers
HP:0003390	Sensory axonal neuropathy
HP:0003438	Absent Achilles reflex
HP:0003477	Peripheral axonal neuropathy
HP:0003487	Babinski sign
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0003693	Distal amyotrophy
HP:0007002	Motor axonal neuropathy
HP:0007020	Progressive spastic paraplegia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001241_12	Bipolar disorder	2.000000e-07
GCST008103_21	Bipolar disorder	2.000000e-08
GCST009391_727	Metabolite levels	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009774	serine measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563702	Spastic Paraplegia, Optic Atrophy, and Neuropathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
bisphenol A	decreases expression, affects expression, affects cotreatment	2
Acetaminophen	increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	increases methylation, decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
lead acetate	increases expression	1
beta-lapachone	increases expression	1
cupric chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Quercetin	decreases phosphorylation	1
Silicon Dioxide	decreases methylation	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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