KLC2

kinesin light chain 2, the group of Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 11:66257294-66267860

Links

ENSG00000174996

∙ NCBI:64837 ∙ OMIM:611729 ∙ HGNC:20716 ∙ Uniprot:Q9H0B6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

spastic paraplegia, optic atropy, and neuropathy (Limited), mode of inheritance: AR
spastic paraplegia, optic atropy, and neuropathy (Supportive), mode of inheritance: AR
spastic paraplegia, optic atropy, and neuropathy (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia, optic atrophy, and neuropathy	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	26385635

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLC2 gene.

not_provided (98 variants)
not_specified (72 variants)
KLC2-related_disorder (5 variants)
Spastic_paraplegia,_optic_atropy,_and_neuropathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLC2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001318734.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	26 clinvar	4 clinvar	31
missense			103 clinvar	5 clinvar	1 clinvar	109
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	105	31	5

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLC2	protein_coding	protein_coding	ENST00000417856	15	10567

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.975	0.0249	125724	0	18	125742	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.02	285	398	0.715	0.0000257	4001
Missense in Polyphen		78	132.97	0.58659		1313
Synonymous	0.704	151	162	0.930	0.00000972	1258
Loss of Function	4.55	5	33.4	0.150	0.00000171	375

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000907	0.0000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport. The light chain may function in coupling of cargo to the heavy chain or in the modulation of its ATPase activity (By similarity). {ECO:0000250}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:26385635}. Note=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. {ECO:0000269|PubMed:26385635}.;
Pathway: Salmonella infection - Homo sapiens (human);Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;RHO GTPases activate KTN1;Kinesins;Factors involved in megakaryocyte development and platelet production;RHO GTPase Effectors;Signaling by Rho GTPases;Hemostasis;COPI-dependent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

pRec: 0.118

Intolerance Scores

loftool: 0.380
rvis_EVS: -0.93
rvis_percentile_EVS: 9.55

Haploinsufficiency Scores

pHI: 0.265
hipred: Y
hipred_score: 0.698
ghis: 0.618

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.589

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Klc2
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hearing/vestibular/ear phenotype;

Zebrafish Information Network

Gene name: klc2
Affected structure: post-vent region
Phenotype tag: abnormal
Phenotype quality: kinked

Gene ontology

Biological process: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;microtubule-based movement;antigen processing and presentation of exogenous peptide antigen via MHC class II
Cellular component: nucleoplasm;mitochondrion;cytosol;kinesin complex;microtubule;plasma membrane;membrane;kinesin I complex;protein-containing complex
Molecular function: microtubule motor activity;protein binding;kinesin binding;cadherin binding