KIF1B

protein-coding

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

Gene summary

Enables plus-end-directed microtubule motor activity. Involved in apoptotic process involved in development and mitochondrion transport along microtubule. Is active in mitochondrion. Implicated in Charcot-Marie-Tooth disease type 2A1; hepatocellular carcinoma; multiple sclerosis; neuroblastoma; and ovary epithelial cancer. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

CMT2A
CMT2

MANE transcript

NM_001365951.3

Inheritance

AD, AR

ClinVar variants

P:5U:2210B:1213

Top phenotype

Neuroblastoma, susceptibility to 1; Pheochromocytoma

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr1:10,210,570-10,381,603

External References & Databases

Ensembl (ENSG00000054523)

Transcript & Mutation Effects

hg38 • Region Span ~171.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Charcot-Marie-Tooth disease type 2A1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007308

Submitter: Labcorp Genetics (formerly Invitae)

neuroblastoma, susceptibility to, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0009741

Submitter: Ambry Genetics

Charcot-Marie-Tooth disease type 2A1NO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0007308

Submitter: ClinGen

KIF1B was first described in 2001 in a Japanese family with an autosomal dominant axonal Charcot-Marie-Tooth (CMT) phenotype (Zhao et al., PMID: 11389829). The reported variant is considered likely pathogenic and supported by functional evidence. In the same family, a previous linkage analysis had matched the 1p36.2 locus (Saito et al., PMID: 9409358) also containing MFN2, the most frequent gene responsible for axonal CMT (Züchner et al., PMID: 15064763). Other families with an according linkage pattern had no mutations in KIF1B, but in MFN2. MFN2 variants were not excluded in the aforementioned family. Due to high allele frequencies, other reported variants (PMIDs: 30126838, 25802885) did not further support the gene-disease relationship. KIF1B is a kinesin motor protein involved in axonal transport. There are two isoforms, KIF1Bα and KIF1Bβ with the same N-terminal motor domain and different cargo-carrying tails. In an immunofluorescence assay of probed mouse brain cells, KIF1Bβ colocalized with axonal synaptic proteins (Zhao et al., PMID: 11389829). In a morpholino knockout model, zebrafish had truncated posterior lateral line nerves (Lyons et al., PMID: 19503091). Sciatic nerves of KIF1+/- mice had a decreased synaptic protein content and a reduced rate of axonal transport. At the age of 12 months, KIF1B +/- mice had an axonal neuropathy phenotype confirmed by clinical and nerve conduction studies (Zhao et al., PMID: 11389829). Based on this functional evidence, KIF1B is associated with axonal transport, which is a common disease mechanism in CMT2. With one affected family only, the overall evidence to establish a clear gene-disease relationship has, however, not been upheld over time. The panel therefore classifies KIF1B in the category “Disputed”.

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: PanelApp Australia

hereditary pheochromocytoma-paragangliomaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0017366

Submitter: Orphanet

Charcot-Marie-Tooth disease type 2A1SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007308

Submitter: Orphanet

pheochromocytomaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0008233

Submitter: Labcorp Genetics (formerly Invitae)

Charcot-Marie-Tooth disease type 2A1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007308

Submitter: PanelApp Australia

Charcot-Marie-Tooth disease type 2A1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007308

Submitter: Ambry Genetics

pheochromocytomaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0008233

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neuroblastoma, susceptibility to 1; PheochromocytomaAD

Manifestation: Neurologic; Oncologic

Intervention: Oncologic

Rationale: Surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality

Refs: 9409358; 11389829; 18334619; 24102379

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KIF1B variants in ClinVar

42 Conditions Cataloged

not specifiedTotal: 3344

Charcot-Marie-Tooth disease type 2Total: 1435

not providedTotal: 245

KIF1B-related disorderTotal: 112

Charcot-Marie-Tooth diseaseTotal: 107

Charcot-Marie-Tooth disease type 2A1Total: 102

Neuroblastoma, susceptibility to, 1Total: 99

NeuroblastomaTotal: 82

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001365951.3. 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			31 clinvar	1086 clinvar	4 clinvar	1121
missense	1 clinvar	2 clinvar	2088 clinvar	119 clinvar	4 clinvar	2214
nonsense	1 clinvar	1 clinvar	27 clinvar			29
start loss						0
frameshift			32 clinvar			32
splice donor/acceptor (+/-2bp)			32 clinvar			32
Total	2	3	2210	1205	8	3428

Highest pathogenic variant AF is 0.0000099138115

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001365951.3	RefSeq	NP_001352880.1	48	MANE Select
ENST00000676179.1	Ensembl	ENSP00000502065.1	48	MANE Select
NM_001365952.1	RefSeq	NP_001352881.1	48	Standard
NM_001365953.1	RefSeq	NP_001352882.1	20	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
kif1b	Danio rerio	Structure: thrombocyte Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

kif1b

Danio rerio

Structure: thrombocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Kinesins
Factors involved in megakaryocyte development and platelet production
Hemostasis

Biological Process

apoptotic process
microtubule-based movement
neuron-neuron synaptic transmission
neuromuscular synaptic transmission
anterograde axonal transport

Molecular Function

microtubule motor activity
protein binding
ATP binding
microtubule binding
ATP-dependent microtubule motor activity, plus-end-directed

Cellular Component

mitochondrion
kinesin complex
microtubule
microtubule associated complex
axon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263934
Coding exons: 46
Length: 170799
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125747
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.60	663	980	0.676	0.0000595	11646
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.274

Intolerance Scores

LoFtool: 0.206
RVIS EVS: -1.45
RVIS percentile EVS: 3.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.958

Gene Damage Prediction

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