KIF4A

kinesin family member 4A, the group of Kinesins

Basic information

Region (hg38): X:70290104-70420886

Links

ENSG00000090889 ∙ NCBI:24137 ∙ OMIM:300521 ∙ HGNC:13339 ∙ Uniprot:O95239 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Limited), mode of inheritance: XLR
• intellectual disability, X-linked 100 (Moderate), mode of inheritance: XL
• intellectual disability, autosomal dominant 40 (Limited), mode of inheritance: XL
• intellectual disability, X-linked 100 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 100; Taurodontism, microdontia, and dens invaginatus	XL	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	Dental; Neurologic	24812067; 31616463

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KIF4A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIF4A 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				9	6	15
missense			77	7	3	87
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			6	6	2	14
non coding					1	1
Total	0	0	78	16	10

Variants in KIF4A

This is a list of pathogenic ClinVar variants found in the KIF4A region.

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

Position	Type	Phenotype	Significance	ClinVar
X-70290433-C-T			Likely benign (-)
X-70290485-C-T		Intellectual disability, X-linked 100	Benign (Aug 19, 2021)
X-70290485-C-C			Benign (Dec 31, 2019)
X-70297011-G-A			Likely benign (Sep 19, 2018)
X-70297015-C-T			Likely benign (Jun 15, 2018)
X-70297135-G-C			Uncertain significance (Dec 15, 2023)
X-70297148-A-G			Uncertain significance (Sep 19, 2016)
X-70297150-A-G			Uncertain significance (Nov 19, 2023)
X-70297157-T-C			Uncertain significance (Aug 01, 2022)
X-70299139-T-C			Likely benign (Apr 07, 2018)
X-70299148-A-G		KIF4A-related disorder	Benign (May 08, 2018)
X-70301895-A-G			Uncertain significance (Oct 14, 2022)
X-70301928-T-C			Uncertain significance (Sep 01, 2022)
X-70301961-A-T		not specified	Uncertain significance (Dec 20, 2023)
X-70302053-A-C		not specified	Uncertain significance (Apr 03, 2023)
X-70302383-G-A		Intellectual disability, X-linked 100	Pathogenic (Aug 11, 2023)
X-70302403-G-A			Uncertain significance (May 30, 2024)
X-70329420-G-T		Ventriculomegaly;Multicystic kidney dysplasia;Corpus callosum, agenesis of;Intellectual disability, X-linked 100;Hydrocephalus • Congenital cerebellar hypoplasia	Likely pathogenic (Feb 18, 2019)
X-70329449-A-G		not specified	Uncertain significance (Apr 16, 2024)
X-70329450-G-A			Uncertain significance (Dec 01, 2022)
X-70329485-C-T		not specified	Uncertain significance (Jan 25, 2023)
X-70329501-A-G		not specified	Uncertain significance (Dec 14, 2023)
X-70330168-G-A			Uncertain significance (Jul 13, 2022)
X-70330172-A-G		Intellectual disability, X-linked 100	Uncertain significance (Sep 23, 2022)
X-70330186-A-T		KIF4A-related disorder • not specified	Uncertain significance (Oct 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KIF4A	protein_coding	protein_coding	ENST00000374403	30	130804

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000200	125736	1	7	125744	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.56	300	453	0.662	0.0000353	8131
Missense in Polyphen		51	122.98	0.41469		2353
Synonymous	0.740	150	162	0.926	0.0000121	2268
Loss of Function	6.08	5	52.5	0.0952	0.00000422	871

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000134	0.0000992
East Asian	0.0000722	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000742	0.0000527
Middle Eastern	0.0000722	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Motor protein that translocates PRC1 to the plus ends of interdigitating spindle microtubules during the metaphase to anaphase transition, an essential step for the formation of an organized central spindle midzone and midbody and for successful cytokinesis. May play a role in mitotic chromosomal positioning and bipolar spindle stabilization. {ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105}.
• Pathway: Retinoblastoma (RB) in Cancer;Developmental Biology;Recycling pathway of L1;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;L1CAM interactions;Axon guidance;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.119

Intolerance Scores

• loftool: 0.241
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.58

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.656
• ghis: 0.667

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.737

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kif4
• Phenotype: normal phenotype

Gene ontology

• Biological process: mitotic cytokinesis;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;organelle organization;microtubule-based movement;mitotic spindle organization;anterograde axonal transport;antigen processing and presentation of exogenous peptide antigen via MHC class II;mitotic spindle midzone assembly
• Cellular component: nucleoplasm;chromosome;cytoplasm;cytosol;kinesin complex;microtubule;spindle microtubule;membrane;nuclear matrix;midbody;intercellular bridge;axon cytoplasm
• Molecular function: DNA binding;microtubule motor activity;protein binding;ATP binding;microtubule binding;ATPase activity