KIF7

kinesin family member 7, the group of Kinesins

Basic information

Region (hg38): 15:89608788-89663086

Links

ENSG00000166813 ∙ NCBI:374654 ∙ OMIM:611254 ∙ HGNC:30497 ∙ Uniprot:Q2M1P5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acrocallosal syndrome (Definitive), mode of inheritance: AR
• hydrolethalus syndrome 2 (Moderate), mode of inheritance: AR
• acrocallosal syndrome (Moderate), mode of inheritance: AR
• acrocallosal syndrome (Supportive), mode of inheritance: AR
• hydrolethalus syndrome (Supportive), mode of inheritance: AR
• orofaciodigital syndrome type 6 (Supportive), mode of inheritance: AR
• multiple epiphyseal dysplasia, Al-Gazali type (Supportive), mode of inheritance: AR
• acrocallosal syndrome (Strong), mode of inheritance: AR
• hydrolethalus syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hydrolethalus syndrome 2; Acrocallosal syndrome; Joubert syndrome 12; Al-Gazali-Bakalinova syndrome	AR/Digenic	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	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal; Ophthalmologic	457430; 7424976; 7102724; 7166318; 3802558; 3366141; 2658584; 2729349; 2729348; 2658583; 2308155; 2051463; 1659985; 1887856; 1499582; 8092201; 8723075; 11857542; 18618999; 20301500; 21633164; 21552264; 22246503; 22587682; 23142271
The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Digenic inheritance (with CEP41) has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KIF7 gene.

• Acrocallosal syndrome (1121 variants)
• not provided (308 variants)
• Inborn genetic diseases (97 variants)
• not specified (84 variants)
• Multiple epiphyseal dysplasia, Al-Gazali type (25 variants)
• Hydrolethalus syndrome 2 (21 variants)
• KIF7-related condition (9 variants)
• Acrocallosal syndrome;Hydrolethalus syndrome 2;Multiple epiphyseal dysplasia, Al-Gazali type (7 variants)
• Acrocallosal syndrome;Multiple epiphyseal dysplasia, Al-Gazali type;Hydrolethalus syndrome 2 (6 variants)
• Intellectual disability (5 variants)
• Multiple epiphyseal dysplasia, Al-Gazali type;Acrocallosal syndrome;Hydrolethalus syndrome 2 (3 variants)
• Hydrolethalus syndrome 2;Acrocallosal syndrome;Multiple epiphyseal dysplasia, Al-Gazali type (2 variants)
• KIF7-related ciliopathy spectrum disorder (2 variants)
• Short-limb skeletal dysplasia with severe combined immunodeficiency (1 variants)
• Nephronophthisis (1 variants)
• 7 conditions (1 variants)
• Hydrolethalus syndrome;Acrocallosal syndrome (1 variants)
• Hydrolethalus syndrome 2;Multiple epiphyseal dysplasia, Al-Gazali type;Acrocallosal syndrome (1 variants)
• Multiple epiphyseal dysplasia, Al-Gazali type;Hydrolethalus syndrome 2;Acrocallosal syndrome (1 variants)
• Familial aplasia of the vermis (1 variants)
• Joubert syndrome 12 (1 variants)
• Scoliosis, isolated, susceptibility to, 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIF7 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			10	265	9	284
missense		1	612	13	8	634
nonsense	21	5	2			28
start loss			1			1
frameshift	19	2	4			25
inframe indel		1	18	1		20
splice donor/acceptor (+/-2bp)		7	2			9
splice region	1		11	22	3	37
non coding		1	19	138	38	196
Total	40	17	668	417	55

Highest pathogenic variant AF is 0.0000591

Variants in KIF7

This is a list of pathogenic ClinVar variants found in the KIF7 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-89608818-G-A		not specified	Uncertain significance (Jun 23, 2023)
15-89608848-C-G			Benign (Mar 29, 2018)
15-89608850-C-T		not specified	Uncertain significance (Feb 01, 2023)
15-89608862-T-C		not specified	Uncertain significance (Oct 17, 2023)
15-89608865-C-G		not specified	Uncertain significance (Apr 04, 2023)
15-89608888-C-A		not specified	Uncertain significance (Dec 08, 2021)
15-89608905-T-C		not specified	Uncertain significance (Feb 06, 2023)
15-89616422-A-T		not specified	Uncertain significance (Jun 29, 2023)
15-89618175-T-C		not specified	Uncertain significance (Nov 19, 2022)
15-89619710-A-G		not specified	Likely benign (Dec 13, 2021)
15-89619723-G-A		not specified	Uncertain significance (Dec 12, 2022)
15-89619801-G-A		not specified	Uncertain significance (Oct 10, 2023)
15-89621417-A-G		not specified	Uncertain significance (Apr 07, 2023)
15-89621426-G-T		not specified	Uncertain significance (Nov 15, 2021)
15-89621465-T-C		not specified	Uncertain significance (Feb 01, 2023)
15-89621528-C-T		not specified	Uncertain significance (Nov 23, 2022)
15-89623630-A-C		not specified	Uncertain significance (Dec 14, 2023)
15-89623750-C-G		not specified	Uncertain significance (Feb 02, 2022)
15-89623800-G-A		not specified	Uncertain significance (Aug 09, 2021)
15-89623827-A-G		not specified	Likely benign (Sep 26, 2023)
15-89623908-G-A			Benign (Jun 10, 2018)
15-89623921-C-T		not specified	Uncertain significance (Dec 15, 2022)
15-89623926-T-A		not specified	Uncertain significance (Apr 08, 2023)
15-89623937-C-A		not specified	Uncertain significance (May 18, 2022)
15-89623990-C-A		not specified	Uncertain significance (Sep 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KIF7	protein_coding	protein_coding	ENST00000394412	18	46663

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.27e-22	0.471	125651	0	97	125748	0.000386

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.689	876	820	1.07	0.0000604	8495
Missense in Polyphen		319	336.62	0.94767		3430
Synonymous	-1.07	388	362	1.07	0.0000256	2826
Loss of Function	2.02	43	59.9	0.718	0.00000336	634

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000450	0.000447
Ashkenazi Jewish	0.000500	0.000496
East Asian	0.000655	0.000653
Finnish	0.000280	0.000277
European (Non-Finnish)	0.000444	0.000440
Middle Eastern	0.000655	0.000653
South Asian	0.000280	0.000261
Other	0.000660	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for hedgehog signaling regulation: acts as both a negative and positive regulator of sonic hedgehog (Shh) and Indian hedgehog (Ihh) pathways, acting downstream of SMO, through both SUFU-dependent and -independent mechanisms (PubMed:21633164). Involved in the regulation of microtubular dynamics. Required for proper organization of the ciliary tip and control of ciliary localization of SUFU-GLI2 complexes (By similarity). Required for localization of GLI3 to cilia in response to Shh. Negatively regulates Shh signaling by preventing inappropriate activation of the transcriptional activator GLI2 in the absence of ligand. Positively regulates Shh signaling by preventing the processing of the transcription factor GLI3 into its repressor form. In keratinocytes, promotes the dissociation of SUFU-GLI2 complexes, GLI2 nuclear translocation and Shh signaling activation (By similarity). Involved in the regulation of epidermal differentiation and chondrocyte development (By similarity). {ECO:0000250|UniProtKB:B7ZNG0, ECO:0000269|PubMed:21633164}.
• Disease: DISEASE: Note=Ciliary dysfunction leads to a broad spectrum of disorders, collectively termed ciliopathies. The ciliopathy range of diseases includes Meckel-Gruber syndrome, Bardet-Biedl syndrome, Joubert syndrome, and hydrolethalus syndrome among others. Single-locus allelism is insufficient to explain the variable penetrance and expressivity of such disorders, leading to the suggestion that variations across multiple sites of the ciliary proteome influence the clinical outcome. Primary ciliopathy loci can be modulated by pathogenic lesions in other ciliary genes to either exacerbate overall severity or induce specific endophenotypes. KIF7 may be causally associated with diverse ciliopathies, and also acts as a modifier gene across the ciliopathy spectrum.; DISEASE: Bardet-Biedl syndrome (BBS) [MIM:209900]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:21552264}. Note=The gene represented in this entry may act as a disease modifier. Heterozygous missense mutations in KIF7 may genetically interact with other BBS genes and contribute to disease manifestation and severity.; DISEASE: Hydrolethalus syndrome 2 (HLS2) [MIM:614120]: An embryonic lethal disorder characterized by hydrocephaly or anencephaly, postaxial polydactyly of the upper limbs, and pre- or postaxial polydactyly of the lower limbs. Duplication of the hallux is a common finding. {ECO:0000269|PubMed:21552264}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Acrocallosal syndrome (ACLS) [MIM:200990]: An autosomal recessive syndrome characterized by hypogenesis or agenesis of the corpus callosum. Clinical features include postaxial polydactyly, hallux duplication, macrocephaly, craniofacial abnormalities, severe developmental delay and mental retardation. {ECO:0000269|PubMed:21552264, ECO:0000269|PubMed:23125460, ECO:0000269|PubMed:26174511}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Joubert syndrome 12 (JBTS12) [MIM:200990]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. {ECO:0000269|PubMed:21633164}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Al-Gazali-Bakalinova syndrome (AGBK) [MIM:607131]: An autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance. {ECO:0000269|PubMed:22587682}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Basal cell carcinoma - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);Hedgehog Signaling Pathway;Hedgehog Signaling Pathway;Signal Transduction;Hedgehog;Hedgehog ,off, state;Signaling by Hedgehog (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.786
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.98

Haploinsufficiency Scores

• pHI: 0.157
• hipred: Y
• hipred_score: 0.514
• ghis: 0.532

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.672

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Kif7
• Phenotype: respiratory system phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system 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); reproductive system phenotype; vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail 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); skeleton phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: kif7
• Affected structure: slow muscle cell
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: microtubule-based movement;negative regulation of smoothened signaling pathway;positive regulation of smoothened signaling pathway
• Cellular component: cytoplasm;kinesin complex;microtubule;cilium;ciliary basal body;ciliary tip
• Molecular function: microtubule motor activity;protein binding;ATP binding;microtubule binding;ATPase activity