KIF14

kinesin family member 14, the group of Kinesins

Basic information

Region (hg38): 1:200551497-200620751

Links

ENSG00000118193 ∙ NCBI:9928 ∙ OMIM:611279 ∙ HGNC:19181 ∙ Uniprot:Q15058 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome (Moderate), mode of inheritance: AR
• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
• lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome (Supportive), mode of inheritance: AR
• autosomal recessive primary microcephaly (Definitive), mode of inheritance: AR
• lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome (Strong), mode of inheritance: AR
• microcephaly 20, primary, autosomal recessive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Meckel syndrome 12; Microcephaly 20, primary, autosomal recessive	AR	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	Genitourinary; Neurologic; Ophthalmologic; Renal	24128419; 28892560; 29343805

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KIF14 gene.

• not provided (2 variants)
• Microcephaly 20, primary, autosomal recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIF14 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			1	31	9	41
missense			130	22	6	158
nonsense	1	1	2			4
start loss						0
frameshift	2	3	1			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3	3			6
splice region		1	4	4	2	11
non coding				13	44	57
Total	3	7	138	66	59

Highest pathogenic variant AF is 0.00000657

Variants in KIF14

This is a list of pathogenic ClinVar variants found in the KIF14 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-200553141-G-A			Benign (Nov 12, 2018)
1-200553157-C-T			Benign (Nov 12, 2018)
1-200553223-A-T			Benign (Nov 12, 2018)
1-200553391-C-A			Likely benign (Nov 27, 2023)
1-200553391-C-T			Likely benign (Jan 10, 2024)
1-200553393-C-T		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
1-200553413-G-A		Inborn genetic diseases	Uncertain significance (Nov 07, 2022)
1-200553438-G-C		Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome • Microcephaly 20, primary, autosomal recessive	Benign (Jan 29, 2024)
1-200553438-GG-CA			Likely benign (Sep 19, 2022)
1-200553451-G-A		KIF14-related disorder	Likely benign (Sep 17, 2019)
1-200553458-T-C		Inborn genetic diseases	Uncertain significance (Nov 09, 2022)
1-200553464-C-T		Inborn genetic diseases • KIF14-related disorder	Uncertain significance (Jul 12, 2022)
1-200553465-G-A		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
1-200553473-A-G		Inborn genetic diseases	Uncertain significance (Jun 29, 2021)
1-200553491-C-T		Inborn genetic diseases	Uncertain significance (May 05, 2023)
1-200553492-C-T		Microcephaly 20, primary, autosomal recessive • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 24, 2024)
1-200553493-G-A		Microcephaly 20, primary, autosomal recessive;Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome	Benign/Likely benign (Jan 09, 2024)
1-200553531-T-G		Inborn genetic diseases	Uncertain significance (Jan 27, 2022)
1-200553545-T-C			Uncertain significance (Apr 10, 2023)
1-200553553-C-G		not specified • KIF14-related disorder	Uncertain significance (Oct 04, 2016)
1-200553593-C-A		Inborn genetic diseases	Uncertain significance (Oct 14, 2021)
1-200553593-CA-C			Uncertain significance (Mar 11, 2022)
1-200553645-T-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
1-200553658-A-G			Uncertain significance (Aug 01, 2022)
1-200553663-T-C			Uncertain significance (Jul 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KIF14	protein_coding	protein_coding	ENST00000367350	29	69235

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000411	1.00	125654	0	93	125747	0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.769	762	824	0.925	0.0000407	10913
Missense in Polyphen		175	229	0.76418		3076
Synonymous	1.01	258	280	0.923	0.0000138	2973
Loss of Function	5.63	23	76.0	0.303	0.00000386	1008

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000916	0.000790
Ashkenazi Jewish	0.00	0.00
East Asian	0.000726	0.000707
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000390	0.000387
Middle Eastern	0.000726	0.000707
South Asian	0.000369	0.000359
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (By similarity). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (PubMed:24784001, PubMed:16648480). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (PubMed:16431929). Regulates cell growth through regulation of cell cycle progression and cytokinesis (PubMed:24854087). During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (PubMed:24854087). During late neurogenesis, regulates the cerebellar, cerebral cortex and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (By similarity). Also is required for chromosome congression and alignment during mitotic cell cycle process (PubMed:15843429). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (PubMed:23209302). {ECO:0000250|UniProtKB:L0N7N1, ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:16648480, ECO:0000269|PubMed:23209302, ECO:0000269|PubMed:24784001, ECO:0000269|PubMed:24854087}.
• Disease: DISEASE: Meckel syndrome 12 (MKS12) [MIM:616258]: A form of Meckel syndrome, a disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:24128419}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Microcephaly 20, primary, autosomal recessive (MCPH20) [MIM:617914]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH20 features include mild to moderate intellectual disability, autistic features, poor speech. Disease severity is highly variable. {ECO:0000269|PubMed:28892560, ECO:0000269|PubMed:29343805}. Note=The disease is caused by mutations affecting the gene represented in this entry. The disease-causing variant NM_014875.2:c.263T>A, which produces a premature truncation of the protein at Leu-88 (p.Leu88Ter), may also partly result in the deletion of 372 bp of exon 2 of KIF14 by activation of a cryptic splice site. This in-frame deletion predicts a protein that lacks 124 aa (p.Gly58-Leu181del). The disease-causing mutation NM_014875.2:c.3662G>T, resulting in the missence variant p.Gly1221Val, may also induce the skipping of exon 24, resulting in a protein that misses 76 aa (p.Gly1221_ Lys1296delinsVal). {ECO:0000269|PubMed:28892560}.
• Pathway: Signal Transduction;RHO GTPases activate CIT;RHO GTPase Effectors;Signaling by Rho GTPases (Consensus)

Recessive Scores

• pRec: 0.117

Intolerance Scores

• loftool: 0.785
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.42

Haploinsufficiency Scores

• pHI: 0.0682
• hipred: N
• hipred_score: 0.389
• ghis: 0.446

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.440

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kif14
• Phenotype: craniofacial phenotype; cellular phenotype; growth/size/body region 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); vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: regulation of cell growth;microtubule-based movement;microtubule depolymerization;mitotic metaphase plate congression;positive regulation of cell population proliferation;regulation of G2/M transition of mitotic cell cycle;cerebellar granular layer structural organization;cerebellar Purkinje cell layer structural organization;cerebellar cortex development;hippocampus development;olfactory bulb development;cell proliferation in forebrain;cerebral cortex development;regulation of cell adhesion;regulation of cell migration;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;regulation of myelination;activation of protein kinase activity;positive regulation of cytokinesis;regulation of Rap protein signal transduction;negative regulation of integrin activation;substrate adhesion-dependent cell spreading;negative regulation of apoptotic process;proteasome-mediated ubiquitin-dependent protein catabolic process;regulation of neuron apoptotic process;negative regulation of neuron apoptotic process;establishment of protein localization;cell division;regulation of cell maturation;regulation of G1/S transition of mitotic cell cycle
• Cellular component: nucleus;cytosol;kinesin complex;microtubule;plasma membrane;membrane;midbody;spindle midzone;Flemming body
• Molecular function: microtubule motor activity;protein binding;ATP binding;microtubule binding;ATP-dependent microtubule motor activity, plus-end-directed;tubulin binding;ATPase activity;protein kinase binding;PDZ domain binding