KIF21A

kinesin family member 21A, the group of Kinesins|WD repeat domain containing

Basic information

Region (hg38): 12:39293227-39443390

Previous symbols: [ "FEOM1" ]

Links

ENSG00000139116 ∙ NCBI:55605 ∙ OMIM:608283 ∙ HGNC:19349 ∙ Uniprot:Q7Z4S6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital fibrosis of extraocular muscles type 1 (Strong), mode of inheritance: AD
• congenital fibrosis of extraocular muscles (Supportive), mode of inheritance: AD
• congenital fibrosis of extraocular muscles type 1 (Strong), mode of inheritance: AD
• congenital fibrosis of extraocular muscles type 1 (Definitive), mode of inheritance: AD
• congenital fibrosis of extraocular muscles type 1 (Strong), mode of inheritance: AD
• congenital fibrosis of extraocular muscles (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fibrosis of extraocular muscles, congenital 1	AD	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	Musculoskeletal	10922204; 14595441; 15621877; 15621876; 15223798; 15671279; 15827546; 18332320; 19896199; 20301522; 21042561; 21805025

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KIF21A gene.

• Congenital fibrosis of extraocular muscles type 1 (120 variants)
• not provided (58 variants)
• Inborn genetic diseases (47 variants)
• Congenital fibrosis of extraocular muscles (5 variants)
• KIF21A-related condition (4 variants)
• not specified (3 variants)
• Fibrosis of extraocular muscles, congenital, 3b (2 variants)
• Congenital aniridia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIF21A 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			5	9	16	30
missense	2	2	75	13	17	109
nonsense		1				1
start loss						0
frameshift			4			4
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)			2			2
splice region			1	3	4	8
non coding			26	2	22	50
Total	2	3	113	25	55

Variants in KIF21A

This is a list of pathogenic ClinVar variants found in the KIF21A region.

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

Position	Type	Phenotype	Significance	ClinVar
12-39293267-T-A		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 13, 2018)
12-39293402-T-A		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 13, 2018)
12-39293414-A-G		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 12, 2018)
12-39293489-T-C		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 13, 2018)
12-39293578-T-TA		Congenital fibrosis of extraocular muscles	Uncertain significance (Jun 14, 2016)
12-39293612-A-G		Congenital fibrosis of extraocular muscles type 1	Benign (Jan 13, 2018)
12-39293717-T-C		Congenital fibrosis of extraocular muscles type 1	Benign (Jan 12, 2018)
12-39293733-GA-G		Congenital fibrosis of extraocular muscles	Benign (Jun 14, 2016)
12-39293733-G-GA		Congenital fibrosis of extraocular muscles	Uncertain significance (Jun 14, 2016)
12-39293734-A-G		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 13, 2018)
12-39293779-A-C		Congenital fibrosis of extraocular muscles type 1	Benign (Jan 13, 2018)
12-39293842-C-T		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 13, 2018)
12-39293893-A-G		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 12, 2018)
12-39293952-T-C		Congenital fibrosis of extraocular muscles type 1	Benign (Jan 13, 2018)
12-39293973-T-C		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 13, 2018)
12-39293977-T-C		Congenital fibrosis of extraocular muscles type 1	Benign (Jan 12, 2018)
12-39294006-T-C		Congenital fibrosis of extraocular muscles type 1	Benign (Jan 13, 2018)
12-39294058-G-A		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 13, 2018)
12-39294098-A-T		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 12, 2018)
12-39294187-T-C		Congenital fibrosis of extraocular muscles type 1	Benign (Jan 13, 2018)
12-39294213-G-C		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 12, 2018)
12-39294353-G-C		Congenital fibrosis of extraocular muscles type 1	Likely benign (Jan 13, 2018)
12-39294359-C-T		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 12, 2018)
12-39294488-C-A		Congenital fibrosis of extraocular muscles type 1	Uncertain significance (Jan 13, 2018)
12-39294488-C-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KIF21A	protein_coding	protein_coding	ENST00000361418	38	150163

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.86e-8	1.00	125660	0	88	125748	0.000350

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.65	650	870	0.747	0.0000444	11019
Missense in Polyphen		219	345.29	0.63425		4302
Synonymous	0.261	293	299	0.981	0.0000150	3132
Loss of Function	5.88	31	91.8	0.338	0.00000497	1130

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000326	0.000326
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000327	0.000326
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000303	0.000299
Middle Eastern	0.000327	0.000326
South Asian	0.00111	0.00108
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Microtubule-binding motor protein probably involved in neuronal axonal transport. In vitro, has a plus-end directed motor activity (By similarity). {ECO:0000250}.
• Disease: DISEASE: Fibrosis of extraocular muscles, congenital, 1 (CFEOM1) [MIM:135700]: A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Patients affected by congenital fibrosis of extraocular muscles type 1 show an absence of the superior division of the oculomotor nerve (cranial nerve III) and corresponding oculomotor subnuclei. {ECO:0000269|PubMed:14595441, ECO:0000269|PubMed:16157808, ECO:0000269|PubMed:17511870, ECO:0000269|PubMed:24715754}. Note=The disease is caused by mutations 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: 0.139

Intolerance Scores

• loftool: 0.856
• rvis_EVS: -0.15
• rvis_percentile_EVS: 42.34

Haploinsufficiency Scores

• pHI: 0.209
• hipred: Y
• hipred_score: 0.578
• ghis: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.466

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kif21a
• Phenotype: cellular phenotype; muscle phenotype; vision/eye phenotype; 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); normal 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)

Gene ontology

• Biological process: microtubule-based movement
• Cellular component: cytosol;kinesin complex;microtubule;plasma membrane
• Molecular function: microtubule motor activity;protein binding;ATP binding;microtubule binding;ATPase activity