KIF14
Basic information
Region (hg38): 1:200551497-200620751
Links
Phenotypes
GenCC
Source:
- 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:
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
- 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 | 31 | 41 | ||||
missense | 130 | 22 | 158 | |||
nonsense | 4 | |||||
start loss | 0 | |||||
frameshift | 6 | |||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 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:
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:
- 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