KIF1C

protein-coding

kinesin family member 1C, the group of Kinesins

Gene summary

The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. Mutations in this gene are a cause of spastic ataxia 2, autosomal recessive. [provided by RefSeq, May 2014]

Previous symbols:

SAX2

MANE transcript

NM_006612.6

Inheritance

AR, AD

ClinVar variants

P:40U:343B:225

Top phenotype

Spastic ataxia 2, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr17:4,997,950-5,028,401

External References & Databases

Ensembl (ENSG00000129250)

Transcript & Mutation Effects

hg38 • Region Span ~30.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spastic ataxia 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012651

Submitter: Ambry Genetics

spastic ataxia 2SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012651

Submitter: Orphanet

spastic ataxia 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012651

Submitter: Labcorp Genetics (formerly Invitae)

spastic ataxia 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012651

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spastic ataxia 2, autosomal recessiveAR

Manifestation: 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: 24319291; 24482476

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KIF1C variants in ClinVar

11 Conditions Cataloged

Spastic ataxia 2Total: 525

not providedTotal: 189

Inborn genetic diseasesTotal: 182

not specifiedTotal: 71

Hereditary spastic paraplegiaTotal: 59

KIF1C-related disorderTotal: 17

Cerebellar ataxiaTotal: 1

Abnormal central motor functionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006612.6. 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	4 clinvar	174 clinvar	10 clinvar	189
missense	1 clinvar	6 clinvar	327 clinvar	37 clinvar	4 clinvar	375
nonsense	5 clinvar	3 clinvar	3 clinvar			11
start loss		1 clinvar				1
frameshift	8 clinvar	6 clinvar	4 clinvar			18
splice donor/acceptor (+/-2bp)	1 clinvar	8 clinvar	5 clinvar			14
Total	15	25	343	211	14	608

Highest pathogenic variant AF is 0.0000074351283

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 78 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006612.6	RefSeq	NP_006603.2	21	MANE Select
ENST00000320785.10	Ensembl	ENSP00000320821.5	21	MANE Select
ENST00000574165.1	Ensembl	ENSP00000458697.1	4	Standard
ENST00000894736.1	Ensembl	ENSP00000564795.1	21	Standard

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

retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
microtubule-based movement
vesicle-mediated transport
cytoskeleton-dependent intracellular transport
anterograde neuronal dense core vesicle transport

Molecular Function

RNA binding
motor activity
microtubule motor activity
protein binding
ATP binding

Cellular Component

endoplasmic reticulum
Golgi apparatus
kinesin complex
microtubule
axon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000320785
Coding exons: 21
Length: 30454
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.40	585	688	0.850	0.0000449	7021
Missense (PolyPhen)		64	97.634	0.65551		998
Synonymous	-1.29	295	268	1.10	0.0000165	2266
Loss of Function	5.52	12	57.0	0.211	0.00000323	605

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00020	0.00018	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Motor required for the retrograde transport of Golgi vesicles to the endoplasmic reticulum. Has a microtubule plus end- directed motility. {ECO:0000269|PubMed:9685376}.;
Disease: DISEASE: Spastic ataxia 2, autosomal recessive (SPAX2) [MIM:611302]: A neurologic disorder characterized by cerebellar ataxia, dysarthria, and variable spasticity of the lower limbs. Cognition is not affected. {ECO:0000269|PubMed:24319291, ECO:0000269|PubMed:24482476}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.163

Intolerance Scores

LoFtool: 0.237
RVIS EVS: -0.65
RVIS percentile EVS: 16.14

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.719

Gene Damage Prediction

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