KIF13A

protein-coding

kinesin family member 13A, the group of Kinesins

Gene summary

This gene encodes a member of the kinesin family of microtubule-based motor proteins that function in the positioning of endosomes. This family member can direct mannose-6-phosphate receptor-containing vesicles from the trans-Golgi network to the plasma membrane, and it is necessary for the steady-state distribution of late endosomes/lysosomes. It is also required for the translocation of FYVE-CENT and TTC19 from the centrosome to the midbody during cytokinesis, and it plays a role in melanosome maturation. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

MANE transcript

NM_022113.6

Inheritance

—

ClinVar variants

U:246B:14

Top phenotype

Moderate intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr6:17,759,183-17,987,635

External References & Databases

Ensembl (ENSG00000137177)

Transcript & Mutation Effects

hg38 • Region Span ~228.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KIF13A variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 218

not providedTotal: 18

Moderate intellectual disabilityTotal: 1

Speech apraxiaTotal: 1

SeizureTotal: 1

ApraxiaTotal: 1

Chiari malformationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022113.6. 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			9 clinvar	4 clinvar	4 clinvar	17
missense			227 clinvar	3 clinvar	3 clinvar	233
nonsense			2 clinvar			2
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	246	7	7	260

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022113.6	RefSeq	NP_071396.4	39	MANE Select
ENST00000259711.11	Ensembl	ENSP00000259711.6	39	MANE Select
NM_001105566.3	RefSeq	NP_001099036.1	38	Standard
NM_001105567.3	RefSeq	NP_001099037.1	37	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of proteins
Chaperonin-mediated protein folding
Association of TriC/CCT with target proteins during biosynthesis
Protein folding

Biological Process

intracellular protein transport
microtubule-based movement
cell cycle
endosome to lysosome transport
melanosome organization

Molecular Function

microtubule motor activity
protein binding
ATP binding
microtubule binding
ATPase activity

Cellular Component

centrosome
kinesin complex
microtubule
endosome membrane
midbody

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000259711
Coding exons: 39
Length: 228441
Individuals with no LoFs: 124604
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 124654
p: 0.000201

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.05	774	952	0.813	0.0000509	11809
Missense (PolyPhen)		301	428.87	0.70185		5305
Synonymous	0.308	354	361	0.979	0.0000202	3426
Loss of Function	7.86	15	99.7	0.150	0.00000592	1131

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00033	0.00032	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00039	0.00039	rare
Finnish	0.000095	0.000093	rare
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.00024	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plus end-directed microtubule-dependent motor protein involved in intracellular transport and regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome biogenesis and cytokinesis. Mediates the transport of M6PR- containing vesicles from trans-Golgi network to the plasma membrane via direct interaction with the AP-1 complex. During melanosome maturation, required for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes by creating peripheral recycling endosomal subdomains in melanocytes. Also required for the abcission step in cytokinesis: mediates translocation of ZFYVE26, and possibly TTC19, to the midbody during cytokinesis. {ECO:0000269|PubMed:19841138, ECO:0000269|PubMed:20208530}.;

Recessive Scores

pRec: 0.133

Intolerance Scores

LoFtool: 0.554
RVIS EVS: -0.09
RVIS percentile EVS: 46.5

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.681

Gene Damage Prediction

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