KIF1B

kinesin family member 1B, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes|Kinesins

Basic information

Region (hg38): 1:10210569-10381603

Previous symbols: [ "CMT2A", "CMT2" ]

Links

ENSG00000054523 ∙ NCBI:23095 ∙ OMIM:605995 ∙ HGNC:16636 ∙ Uniprot:O60333 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuroblastoma, susceptibility to, 1 (Limited), mode of inheritance: AD
• pheochromocytoma (Moderate), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 2A1 (Limited), mode of inheritance: AD
• hereditary pheochromocytoma-paraganglioma (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 2A1 (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 2A1 (Limited), mode of inheritance: AD
• pheochromocytoma (Limited), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 2A1 (No Known Disease Relationship), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuroblastoma, susceptibility to 1; Pheochromocytoma	AD	Oncologic	Surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality	Neurologic; Oncologic	9409358; 11389829; 18334619; 24102379

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KIF1B gene.

• Hereditary cancer-predisposing syndrome (1886 variants)
• Charcot-Marie-Tooth disease type 2 (984 variants)
• Neuroblastoma (225 variants)
• not provided (207 variants)
• Charcot-Marie-Tooth disease (113 variants)
• Pheochromocytoma (47 variants)
• not specified (34 variants)
• Charcot-Marie-Tooth disease type 2A1 (23 variants)
• KIF1B-related condition (13 variants)
• Inborn genetic diseases (5 variants)
• Neuroblastoma, susceptibility to, 1 (5 variants)
• Ovarian cancer (2 variants)
• Malignant tumor of breast (2 variants)
• Intellectual disability (2 variants)
• Pheochromocytoma;Charcot-Marie-Tooth disease type 2A1;Neuroblastoma, susceptibility to, 1 (2 variants)
• Adult-onset proximal spinal muscular atrophy, autosomal dominant (1 variants)
• 7 conditions (1 variants)
• EMG: axonal abnormality;Vitiligo;Distal muscle weakness;EMG abnormality (1 variants)
• EEG abnormality;Exaggerated startle response;Global developmental delay (1 variants)
• Pain;EMG abnormality;EMG: myopathic abnormalities;Joint laxity (1 variants)
• Adrenal pheochromocytoma;Palpitations;Recurrent paroxysmal headache (1 variants)
• Multiple endocrine neoplasia, type 2a (1 variants)
• NEUROBLASTOMA, SUSCEPTIBILITY TO, 1, INCLUDED (1 variants)
• Neuroblastoma, susceptibility to, 1;Charcot-Marie-Tooth disease type 2A1;Pheochromocytoma (1 variants)
• Pheochromocytoma;Charcot-Marie-Tooth disease type 2A1;Neuroblastoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIF1B gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			24	672	10	706
missense			1146	25	6	1177
nonsense			17			17
start loss						0
frameshift			17			17
inframe indel			14			14
splice donor/acceptor (+/-2bp)			13	1	1	15
splice region			65	65	4	134
non coding			83	182	118	383
Total	0	0	1314	880	135

Variants in KIF1B

This is a list of pathogenic ClinVar variants found in the KIF1B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-10210657-GCC-G			Benign (Jun 22, 2018)
1-10210698-C-T		Neuroblastoma • Pheochromocytoma • Charcot-Marie-Tooth disease type 2	Likely benign (Jun 14, 2016)
1-10210750-G-C		Neuroblastoma	Benign (Jun 23, 2018)
1-10210812-C-T		Neuroblastoma	Uncertain significance (Jan 13, 2018)
1-10210822-C-T		Neuroblastoma	Benign (Jun 23, 2018)
1-10210831-G-A		Neuroblastoma	Likely benign (Jan 12, 2018)
1-10210861-G-A		Neuroblastoma	Uncertain significance (Jan 12, 2018)
1-10210879-G-T		Neuroblastoma	Benign (Jan 13, 2018)
1-10210891-G-A		Neuroblastoma	Uncertain significance (Jan 13, 2018)
1-10232246-A-G		Neuroblastoma	Uncertain significance (Jan 13, 2018)
1-10232261-G-A		Neuroblastoma	Uncertain significance (Jan 12, 2018)
1-10232301-CAT-C			Benign (Mar 03, 2015)
1-10232301-C-CAT		Neuroblastoma • Charcot-Marie-Tooth disease type 2 • Pheochromocytoma	Likely benign (Jun 14, 2016)
1-10232324-T-C		KIF1B-related disorder • not specified	Conflicting classifications of pathogenicity (Jun 13, 2022)
1-10232328-A-C		not specified	Uncertain significance (Jan 06, 2022)
1-10232333-C-T		Charcot-Marie-Tooth disease type 2 • KIF1B-related disorder • not specified	Uncertain significance (Dec 06, 2023)
1-10232334-G-A		Charcot-Marie-Tooth disease type 2 • not specified	Likely benign (Oct 19, 2022)
1-10232336-G-T		not specified	Uncertain significance (Jul 11, 2022)
1-10232346-G-A		not specified	Likely benign (May 11, 2020)
1-10232348-A-T		not specified	Uncertain significance (Aug 02, 2021)
1-10232351-T-C		Charcot-Marie-Tooth disease type 2	Uncertain significance (Jul 08, 2023)
1-10232359-C-A		not specified	Likely benign (Dec 10, 2023)
1-10232362-G-T		not specified	Uncertain significance (Sep 23, 2020)
1-10232364-A-G		not specified	Likely benign (Aug 29, 2022)
1-10232367-G-A		Charcot-Marie-Tooth disease type 2	Likely benign (Dec 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KIF1B	protein_coding	protein_coding	ENST00000263934	46	170799

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.88e-10	125727	0	20	125747	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.60	663	980	0.676	0.0000595	11646
Missense in Polyphen		310	550.14	0.5635		6395
Synonymous	0.169	348	352	0.989	0.0000211	3361
Loss of Function	8.57	11	106	0.103	0.00000647	1209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000883	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Motor for anterograde transport of mitochondria. Has a microtubule plus end-directed motility. Isoform 2 is required for induction of neuronal apoptosis. {ECO:0000269|PubMed:18334619}.
• Disease: DISEASE: Neuroblastoma 1 (NBLST1) [MIM:256700]: A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine- producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. {ECO:0000269|PubMed:18334619}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Kinesins;Factors involved in megakaryocyte development and platelet production;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: 0.274

Intolerance Scores

• loftool: 0.206
• rvis_EVS: -1.45
• rvis_percentile_EVS: 3.93

Haploinsufficiency Scores

• pHI: 0.201
• hipred: Y
• hipred_score: 0.613
• ghis: 0.561

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.958

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kif1b
• Phenotype: homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); embryo phenotype; skeleton 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); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: kif1b
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: apoptotic process;microtubule-based movement;neuron-neuron synaptic transmission;neuromuscular synaptic transmission;anterograde axonal transport;positive regulation of gene expression;vesicle-mediated transport;cytoskeleton-dependent intracellular transport;lysosome localization;mitochondrion transport along microtubule;response to rotenone;anterograde neuronal dense core vesicle transport;retrograde neuronal dense core vesicle transport;cellular response to nerve growth factor stimulus;protein localization to cell periphery
• Cellular component: mitochondrion;kinesin complex;microtubule;microtubule associated complex;axon;dendrite;cytoplasmic vesicle membrane;cytoplasmic vesicle;neuron projection;axon cytoplasm
• Molecular function: microtubule motor activity;protein binding;ATP binding;microtubule binding;ATP-dependent microtubule motor activity, plus-end-directed;ATPase activity;kinesin binding;kinase binding;scaffold protein binding