KIF22

kinesin family member 22, the group of Kinesins

Basic information

Region (hg38): 16:29790727-29805385

Previous symbols: [ "KNSL4" ]

Links

ENSG00000079616 ∙ NCBI:3835 ∙ OMIM:603213 ∙ HGNC:6391 ∙ Uniprot:Q14807 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepimetaphyseal dysplasia with multiple dislocations (Definitive), mode of inheritance: AD
• spondyloepimetaphyseal dysplasia with multiple dislocations (Strong), mode of inheritance: AD
• spondyloepimetaphyseal dysplasia with multiple dislocations (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloepimetaphyseal dysplasia with joint laxity, type 2	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	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	19277648; 22152677

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KIF22 gene.

• Spondyloepimetaphyseal dysplasia with multiple dislocations (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIF22 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			2	51	4	57
missense	1	6	124	24	16	171
nonsense			2	1		3
start loss						0
frameshift			3			3
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)			3			3
splice region			5	13	3	21
non coding			3	28	14	45
Total	1	6	140	105	34

Highest pathogenic variant AF is 0.00000657

Variants in KIF22

This is a list of pathogenic ClinVar variants found in the KIF22 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-29790757-G-A		not specified	Benign (May 04, 2021)
16-29790764-C-G			Uncertain significance (Nov 06, 2022)
16-29790767-C-T		Spondyloepimetaphyseal dysplasia with multiple dislocations	Uncertain significance (Nov 02, 2021)
16-29790771-C-T		not specified	Benign/Likely benign (Jan 25, 2024)
16-29790776-C-T		not specified	Uncertain significance (Aug 24, 2023)
16-29790783-G-C			Uncertain significance (Jun 05, 2022)
16-29790787-A-T			Uncertain significance (Dec 09, 2022)
16-29790790-C-G			Uncertain significance (Nov 28, 2023)
16-29790790-C-T			Likely benign (Nov 15, 2022)
16-29790794-G-T			Uncertain significance (Oct 13, 2023)
16-29790796-G-A			Uncertain significance (Jul 03, 2023)
16-29790798-G-T			Benign (Jun 13, 2022)
16-29790807-AGCTTCAGCGGCG-A			Uncertain significance (Nov 04, 2023)
16-29790821-C-T			Uncertain significance (Aug 04, 2023)
16-29790822-G-C			Likely benign (Sep 27, 2023)
16-29790828-A-G			Uncertain significance (Nov 16, 2023)
16-29790833-C-T			Benign (Nov 27, 2023)
16-29791094-T-C			Benign (Feb 13, 2020)
16-29796877-A-T			Likely benign (Apr 20, 2023)
16-29796877-ATCT-A		not specified	Benign (Jan 31, 2024)
16-29796883-T-G			Likely benign (May 27, 2021)
16-29796901-C-T			Uncertain significance (Dec 28, 2020)
16-29796902-G-A			Uncertain significance (Jul 11, 2023)
16-29796902-G-T			Likely benign (Nov 27, 2023)
16-29796920-T-C		not specified	Benign (Jan 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KIF22	protein_coding	protein_coding	ENST00000160827	14	14667

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.17e-10	0.977	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.141	398	406	0.980	0.0000249	4254
Missense in Polyphen		145	198.99	0.72867		2090
Synonymous	-1.82	185	156	1.18	0.00000807	1418
Loss of Function	2.24	20	34.2	0.586	0.00000200	355

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000240	0.000239
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000218	0.000217
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000184	0.000176
Middle Eastern	0.000218	0.000217
South Asian	0.000329	0.000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Kinesin family member that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis. Binds to microtubules and to DNA (By similarity). Plays a role in congression of laterally attached chromosomes in NDC80- depleted cells (PubMed:25743205). {ECO:0000250|UniProtKB:Q9I869, ECO:0000269|PubMed:25743205}.
• Disease: DISEASE: Spondyloepimetaphyseal dysplasia with joint laxity, 2 (SEMDJL2) [MIM:603546]: A bone disease characterized by short stature, distinctive midface retrusion, progressive knee malalignment (genu valgum and/or varum), generalized ligamentous laxity, and mild spinal deformity. Intellectual development is not impaired. Radiographic characteristics include significantly retarded epiphyseal ossification that evolves into epiphyseal dysplasia and precocious osteoarthritis, metaphyseal irregularities and vertical striations, constricted femoral neck, slender metacarpals and metatarsals, and mild thoracolumbar kyphosis or scoliosis with normal or mild platyspondyly. The most distinctive features for differential diagnosis of SEMDJL2 are the slender metacarpals and phalanges and the progressive degeneration of carpal bones; however, these 2 features are evident only in older children and young adults. The soft consistency of cartilage in the airways leads to laryngotracheomalacia with proneness to respiratory obstruction and inspiratory stridor in infancy and childhood. {ECO:0000269|PubMed:22152677, ECO:0000269|PubMed:22152678}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Progesterone-mediated oocyte maturation - Homo sapiens (human);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: 0.191

Intolerance Scores

• loftool: 0.800
• rvis_EVS: -0.26
• rvis_percentile_EVS: 34.88

Haploinsufficiency Scores

• pHI: 0.141
• hipred: Y
• hipred_score: 0.678
• ghis: 0.624

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.864

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kif22
• Phenotype: cellular phenotype; embryo 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)

Zebrafish Information Network

• Gene name: kif22
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: mitotic cell cycle;DNA repair;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;microtubule-based movement;sister chromatid cohesion;mitotic metaphase plate congression;antigen processing and presentation of exogenous peptide antigen via MHC class II;metaphase plate congression
• Cellular component: kinetochore;chromatin;nucleus;cytosol;kinesin complex;microtubule;nuclear speck;mitotic spindle
• Molecular function: DNA binding;microtubule motor activity;protein binding;ATP binding;microtubule binding;ATPase activity