KLC2

protein-coding

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

Gene summary

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. [provided by RefSeq, Mar 2016]

MANE transcript

NM_001318734.2

Inheritance

ClinVar variants

U:132B:42

Top phenotype

Spastic paraplegia, optic atrophy, and neuropathy

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr11:66,257,294-66,267,860

External References & Databases

Ensembl (ENSG00000174996)

Transcript & Mutation Effects

hg38 • Region Span ~10.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spastic paraplegia, optic atropy, and neuropathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0012297

Submitter: Labcorp Genetics (formerly Invitae)

spastic paraplegia, optic atropy, and neuropathySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012297

Submitter: Orphanet

spastic paraplegia, optic atropy, and neuropathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0012297

Submitter: Ambry Genetics

spastic paraplegia, optic atropy, and neuropathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012297

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spastic paraplegia, optic atrophy, and neuropathyAR

Manifestation: Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 26385635

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KLC2 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 119

not specifiedTotal: 88

KLC2-related disorderTotal: 12

Spastic paraplegia, optic atropy, and neuropathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001318734.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	32 clinvar	4 clinvar	37
missense			120 clinvar	6 clinvar		126
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	132	38	4	174

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 73 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001318734.2	RefSeq	NP_001305663.1	15	MANE Select
ENST00000394067.7	Ensembl	ENSP00000377631.2	15	MANE Select
NM_001134774.2	RefSeq	NP_001128246.1	14	Standard
NM_001134775.2	RefSeq	NP_001128247.1	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
klc2	Danio rerio	Structure: post-vent region Quality: kinked abnormal

Gene / Model

Organism

Observed Phenotype

klc2

Danio rerio

Structure: post-vent region

Quality: kinked

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Salmonella infection - Homo sapiens (human)
Signal Transduction
Vesicle-mediated transport
Membrane Trafficking
RHO GTPases activate KTN1

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

Molecular Function

microtubule motor activity
protein binding
kinesin binding
cadherin binding

Cellular Component

nucleoplasm
mitochondrion
cytosol
kinesin complex
microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000417856
Coding exons: 15
Length: 10567
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125742
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.02	285	398	0.715	0.0000257	4001
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000091	0.000088	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.380
RVIS EVS: -0.93
RVIS percentile EVS: 9.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.589

Gene Damage Prediction

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