KIF5C

kinesin family member 5C, the group of Kinesins

Basic information

Region (hg38): 2:148875227-149026759

Links

ENSG00000168280 ∙ NCBI:3800 ∙ OMIM:604593 ∙ HGNC:6325 ∙ Uniprot:O60282 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex cortical dysplasia with other brain malformations 2 (Strong), mode of inheritance: AD
• complex cortical dysplasia with other brain malformations 2 (Strong), mode of inheritance: AD
• complex cortical dysplasia with other brain malformations 2 (Strong), mode of inheritance: AD
• complex cortical dysplasia with other brain malformations 2 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cortical dysplasia, complex, with other brain malformations 2	AD	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	23033978; 23603762; 24812067

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KIF5C gene.

• not_provided (140 variants)
• Complex_cortical_dysplasia_with_other_brain_malformations_2 (38 variants)
• not_specified (36 variants)
• KIF5C-related_disorder (27 variants)
• Inborn_genetic_diseases (6 variants)
• Duane_retraction_syndrome (2 variants)
• Jaw-winking_syndrome (1 variants)
• Cortical_dysplasia (1 variants)
• Craniosynostosis_syndrome (1 variants)
• Intellectual_disability (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIF5C gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004522.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	30	8	40
missense	1	6	72	15	1	95
nonsense		1	3			4
start loss			1			1
frameshift		2	1			3
splice donor/acceptor (+/-2bp)			2			2
Total	1	9	81	45	9

Highest pathogenic variant AF is 0.0000065716

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KIF5C	protein_coding	protein_coding	ENST00000435030	25	250455

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	9.21e-8	124682	0	12	124694	0.0000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.05	253	511	0.495	0.0000285	6320
Missense in Polyphen		44	168.59	0.26098		1955
Synonymous	0.426	183	190	0.961	0.0000107	1686
Loss of Function	6.54	2	53.7	0.0373	0.00000279	680

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000187	0.000187
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000111
Finnish	0.00	0.00
European (Non-Finnish)	0.0000446	0.0000442
Middle Eastern	0.000111	0.000111
South Asian	0.0000368	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in synaptic transmission (PubMed:24812067). Mediates dendritic trafficking of mRNAs (By similarity). Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport. Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). {ECO:0000250|UniProtKB:P28738, ECO:0000250|UniProtKB:P56536, ECO:0000269|PubMed:24812067}.
• Disease: DISEASE: Cortical dysplasia, complex, with other brain malformations 2 (CDCBM2) [MIM:615282]: A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include intrauterine growth retardation, fetal akinesia, seizures, microcephaly, lack of psychomotor development, and arthrogryposis. Brain imaging shows malformations of cortical development, including polymicrogyria, gyral simplification, and thin corpus callosum. {ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23603762, ECO:0000269|PubMed:24812067, ECO:0000269|PubMed:29048727}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Dopaminergic synapse - Homo sapiens (human);Endocytosis - Homo sapiens (human) (Consensus)

Haploinsufficiency Scores

• pHI: 0.755
• hipred: Y
• hipred_score: 0.792
• ghis: 0.581

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kif5c
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; cellular phenotype

Gene ontology

• Biological process: organelle organization;microtubule-based movement;axon guidance;motor neuron axon guidance;synaptic vesicle transport;mRNA transport;anterograde dendritic transport of neurotransmitter receptor complex;anterograde axonal protein transport
• Cellular component: kinesin complex;microtubule;dendrite cytoplasm;ciliary rootlet;neuronal cell body;axonal growth cone;synapse;distal axon;axon cytoplasm
• Molecular function: microtubule motor activity;protein binding;ATP binding;microtubule binding;ATP-dependent microtubule motor activity, plus-end-directed;ATPase activity