KIF7

Summary

KIF7 (kinesin family member 7, HGNC:30497) is a protein-coding gene on chromosome 15q26.1, encoding Kinesin-like protein KIF7 (Q2M1P5). Essential for hedgehog signaling regulation: acts both as 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.

This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies.

Source: NCBI Gene 374654 — RefSeq curated summary.

At a glance

• Gene–disease (curated): acrocallosal syndrome (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,899 total — 58 pathogenic, 35 likely-pathogenic
• Phenotypes (HPO): 172
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_198525

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30497
Approved symbol	KIF7
Name	kinesin family member 7
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	JBTS12
Ensembl gene	ENSG00000166813
Ensembl biotype	protein_coding
OMIM	611254
Entrez	374654

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 24 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000394412, ENST00000445906, ENST00000558928, ENST00000677187, ENST00000696512, ENST00000896344, ENST00000896345, ENST00000896346, ENST00000896347, ENST00000896348, ENST00000896349, ENST00000896350, ENST00000929691, ENST00000929692, ENST00000929693, ENST00000929694, ENST00000929695, ENST00000929696, ENST00000929697, ENST00000946199, ENST00000946200, ENST00000946201, ENST00000946202, ENST00000946203, ENST00000946204, ENST00000946205, ENST00000946206

RefSeq mRNA: 1 — MANE Select: NM_198525 NM_198525

CCDS: CCDS32325

Canonical transcript exons

ENST00000394412 — 19 exons

Exon	Start	End
ENSE00001106880	89630287	89630493
ENSE00001106898	89629375	89629573
ENSE00001106909	89631495	89631710
ENSE00001183532	89628976	89629122
ENSE00001243168	89633141	89633266
ENSE00001316652	89632820	89632996
ENSE00001367400	89646830	89647057
ENSE00001370338	89645336	89645451
ENSE00001372202	89645013	89645165
ENSE00001375524	89633686	89633883
ENSE00001382537	89642203	89642405
ENSE00001387055	89645893	89646026
ENSE00001611207	89648255	89648774
ENSE00001667882	89647596	89647712
ENSE00001732604	89649741	89649941
ENSE00001955717	89627977	89628786
ENSE00002254819	89652603	89652954
ENSE00003542216	89648974	89649367
ENSE00003848928	89655399	89655467

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 87.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.7270 / max 32.0846, expressed in 1156 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151446	2.7270	1156

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	87.14	gold quality
cardiac muscle of right atrium	UBERON:0003379	85.57	gold quality
left ventricle myocardium	UBERON:0006566	85.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.48	gold quality
ascending aorta	UBERON:0001496	83.89	gold quality
nasal cavity epithelium	UBERON:0005384	83.82	gold quality
thoracic aorta	UBERON:0001515	83.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.48	gold quality
lower esophagus	UBERON:0013473	83.41	gold quality
right ovary	UBERON:0002118	83.10	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.87	gold quality
ventricular zone	UBERON:0003053	82.78	gold quality
mucosa of stomach	UBERON:0001199	82.38	gold quality
stromal cell of endometrium	CL:0002255	82.29	gold quality
left ovary	UBERON:0002119	81.78	gold quality
upper arm skin	UBERON:0004263	81.75	gold quality
descending thoracic aorta	UBERON:0002345	81.53	gold quality
left uterine tube	UBERON:0001303	81.26	gold quality
myocardium	UBERON:0002349	81.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.79	gold quality
body of uterus	UBERON:0009853	80.68	gold quality
aorta	UBERON:0000947	79.95	gold quality
endocervix	UBERON:0000458	79.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	79.04	gold quality
left coronary artery	UBERON:0001626	78.79	gold quality
sural nerve	UBERON:0015488	78.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	78.60	gold quality
ganglionic eminence	UBERON:0004023	78.55	gold quality
cardiac atrium	UBERON:0002081	78.27	gold quality
ectocervix	UBERON:0012249	78.27	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting KIF7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-6841-5P	97.19	67.29	409
HSA-MIR-6886-3P	96.96	66.36	844
HSA-MIR-2355-3P	96.84	68.54	909
HSA-MIR-6078	75.68	58.05	34

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 17)

• Our data show the role of KIF7 in human primary cilia, especially in the Hedgehog pathway through the regulation of GLI targets, and expand the clinical spectrum of ciliopathies. (PMID:21552264)
• Data report mutations in the KIF7 gene, a known regulator of sonic hedgehog signaling and a putative ciliary motor protein, in Joubert syndrome patients. (PMID:21633164)
• The high-resolution structure of the human KIF7 motor domain is reported and is compared with that of conventional kinesin, the founding member of the kinesin superfamily. (PMID:22281744)
• report the first missense homozygous disease-causing mutation in KIF7 and expand the clinical spectrum associated with mutations in this gene to include multiple epiphyseal dysplasia (PMID:22587682)
• six novel mutations were identified at the KIF7 locus in five suspected Acrocallosal syndrome cases (PMID:23125460)
• This study confirms that KIF7 mutations can cause acrocallosal syndrome. (PMID:23142271)
• Studied the ExoS to identify unknown cellular targets associated with ExoS-induced cytotoxicity in a P. aeruginosa infection model.A pull-down assay revealed that ExoS bound the truncated KIF7 gene encoding the N-terminal domain (residues 1-109) of KIF7. (PMID:24462444)
• Kif7 may contribute to pathogenesis of gestational trophoblastic disease through enhancing survival and promoting dissemination of trophoblasts. (PMID:25265279)
• results suggested that PPFIA1 functioned with PP2A to promote the dephosphorylation of Kif7, triggering Kif7 localization to the tips of primary cilia and promoting Gli transcriptional activity. (PMID:25492966)
• We identified a Turkish family who had a novel homozygous sequence change, c.2593-2A>C, located at the acceptor splice site of intron 12 of KIF7 (IVS12-2A>C). (PMID:25714560)
• two children who both had two missense mutations in the Kinesin Family Member 7 (KIF7) gene, are reported. (PMID:26174511)
• The expression of KIF7 was lower in cancer tissues than in paratumor tissues, and KIF7 expression was associated with recurrence-free survival and overall survival in epithelial ovarian cancer patients. (PMID:31658044)
• Co-occurrence of mutations in KIF7 and KIAA0556 in Joubert syndrome with ocular coloboma, pituitary malformation and growth hormone deficiency: a case report and literature review. (PMID:32164589)
• Identification of novel candidate genes in heterotaxy syndrome patients with congenital heart diseases by whole exome sequencing. (PMID:32738303)
• Human papillomavirus 16 (HPV 16) E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by downregulating the expression of KIF7. (PMID:32945133)
• Mutations in KIF7 implicated in idiopathic scoliosis in humans and axial curvatures in zebrafish. (PMID:33382518)
• Sequences in the stalk domain regulate auto-inhibition and ciliary tip localization of the immotile kinesin-4 KIF7. (PMID:34114033)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif7	ENSDARG00000033099
mus_musculus	Kif7	ENSMUSG00000050382
rattus_norvegicus	Kif7	ENSRNOG00000026857

Paralogs (41): KIF1B (ENSG00000054523), KIF26A (ENSG00000066735), KIF2A (ENSG00000068796), KIF22 (ENSG00000079616), KIF3C (ENSG00000084731), KIF9 (ENSG00000088727), KIF16B (ENSG00000089177), KIF4A (ENSG00000090889), KIF3B (ENSG00000101350), KIF20A (ENSG00000112984), KIF21B (ENSG00000116852), KIF17 (ENSG00000117245), KIF14 (ENSG00000118193), KIF18A (ENSG00000121621), KIF25 (ENSG00000125337), KIF1C (ENSG00000129250), KIF1A (ENSG00000130294), KIF3A (ENSG00000131437), KIF12 (ENSG00000136883), KIF13A (ENSG00000137177), KIF23 (ENSG00000137807), KIF11 (ENSG00000138160), CENPE (ENSG00000138778), KIF21A (ENSG00000139116), KIFC3 (ENSG00000140859), KIF2B (ENSG00000141200), KIF2C (ENSG00000142945), KIF5A (ENSG00000155980), KIF26B (ENSG00000162849), KIF15 (ENSG00000163808), KIF6 (ENSG00000164627), KIF27 (ENSG00000165115), KIFC2 (ENSG00000167702), KIF5C (ENSG00000168280), KIF5B (ENSG00000170759), KIF18B (ENSG00000186185), KIF24 (ENSG00000186638), KIF19 (ENSG00000196169), KIF13B (ENSG00000197892), KIF4B (ENSG00000226650)

Protein

Protein identifiers

Kinesin-like protein KIF7 — Q2M1P5 (reviewed: Q2M1P5)

All UniProt accessions (4): Q2M1P5, A0A7I2V527, A0A8Q3SIQ8, F8WD21

UniProt curated annotations — full annotation on UniProt →

Function. Essential for hedgehog signaling regulation: acts both as 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. Involved in the regulation of microtubular dynamics. Required for proper organization of the ciliary tip and control of ciliary localization of SUFU-GLI2 complexes. 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. Involved in the regulation of epidermal differentiation and chondrocyte development.

Subunit / interactions. Can form homodimers and interacts with microtubules. Interacts with GLI1, GLI2, GLI3, SMO and SUFU. Interacts with NPHP1. Interacts with SMO and DLG5 (via PDZ4 or guanylate kinase-like domain).

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Cilium basal body.

Tissue specificity. Embryonic stem cells, melanotic melanoma and Jurkat T-cells. Expressed in heart, lung, liver, kidney, testis, retina, placenta, pancreas, colon, small intestin, prostate and thymus.

Post-translational modifications. Polyubiquitinated by UBR3.

Disease relevance. 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. Bardet-Biedl syndrome (BBS) [MIM:209900] A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. 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. 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. 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. The disease is caused by variants affecting the gene represented in this entry. 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 intellectual disability. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. Al-Gazali-Bakalinova syndrome (AGBK) [MIM:607131] An autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KIF27 subfamily.

RefSeq proteins (1): NP_940927* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001752	Kinesin_motor_dom	Domain
IPR019821	Kinesin_motor_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR027640	Kinesin-like_fam	Family
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00225, PF25764

UniProt features (64 total): sequence variant 17, strand 14, helix 14, region of interest 8, coiled-coil region 3, turn 3, chain 1, domain 1, binding site 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4A14	X-RAY DIFFRACTION	1.6
2XT3	X-RAY DIFFRACTION	1.88
7RX0	ELECTRON MICROSCOPY	3.89
6MLQ	ELECTRON MICROSCOPY	4.2
6MLR	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2M1P5-F1	68.07	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 94–101

Post-translational modifications (1): 898

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-5632684	Hedgehog ‘on’ state
R-HSA-162582	Signal Transduction
R-HSA-5358351	Signaling by Hedgehog

MSigDB gene sets: 419 (showing top): GGGNRMNNYCAT_UNKNOWN, GCANCTGNY_MYOD_Q6, GOCC_KINESIN_COMPLEX, CAGCTG_AP4_Q5, GOCC_MICROTUBULE_ORGANIZING_CENTER, CREB_Q4, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, ATF4_Q2, GOBP_SMOOTHENED_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, MYB_Q5_01, BOYLAN_MULTIPLE_MYELOMA_C_D_UP, GOCC_CILIARY_TIP

GO Biological Process (3): microtubule-based movement (GO:0007018), negative regulation of smoothened signaling pathway (GO:0045879), positive regulation of smoothened signaling pathway (GO:0045880)

GO Molecular Function (7): microtubule motor activity (GO:0003777), ATP binding (GO:0005524), microtubule binding (GO:0008017), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), protein binding (GO:0005515)

GO Cellular Component (10): fibrillar center (GO:0001650), cytoplasm (GO:0005737), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), cilium (GO:0005929), ciliary basal body (GO:0036064), ciliary tip (GO:0097542), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Hedgehog	2
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
smoothened signaling pathway	2
regulation of smoothened signaling pathway	2
ATP-dependent activity	2
cilium	2
microtubule-based process	1
negative regulation of signal transduction	1
positive regulation of signal transduction	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
nucleolus	1
intracellular anatomical structure	1
cytoplasm	1
microtubule associated complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
microtubule organizing center	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF7	SUFU	Q9UMX1	998
KIF7	GLI1	P08151	966
KIF7	GLI2	P10070	936
KIF7	GLI3	P10071	919
KIF7	SMO	Q99835	869
KIF7	PTCH1	Q13635	783
KIF7	PRKACA	P17612	770
KIF7	PRKACB	P22694	770
KIF7	PRKACG	P22612	770
KIF7	GSK3B	P49841	753
KIF7	SHH	Q15465	750
KIF7	IHH	Q14623	691
KIF7	KIF3A	Q9Y496	658
KIF7	ARRB2	P32121	647
KIF7	HHIP	Q96QV1	642

IntAct

119 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
NEFM	NEFL	psi-mi:“MI:0914”(association)	0.800
KIF7	P4HA2	psi-mi:“MI:0915”(physical association)	0.670
CINP	KIF7	psi-mi:“MI:0914”(association)	0.640
RALBP1	JUN	psi-mi:“MI:0914”(association)	0.640
INAVA	CYTH3	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
GLI2	KIF7	psi-mi:“MI:0914”(association)	0.570
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
LGALS3BP	RGPD8	psi-mi:“MI:0914”(association)	0.530
ZNF331	USP9Y	psi-mi:“MI:0914”(association)	0.530
FGL2	PCNT	psi-mi:“MI:0914”(association)	0.530
DISC1	AP4M1	psi-mi:“MI:0914”(association)	0.530
STX11	EXOC5	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
CINP	CHMP2A	psi-mi:“MI:0914”(association)	0.530
NEFM	EVI5	psi-mi:“MI:0914”(association)	0.530
KIF7	YWHAH	psi-mi:“MI:0914”(association)	0.530
USP15	PRPF3	psi-mi:“MI:0914”(association)	0.530
ZNF263	AHCYL1	psi-mi:“MI:0914”(association)	0.530
NEFM	VWA8	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ZNF785	TRIO	psi-mi:“MI:0914”(association)	0.530
DYNLRB2	PAFAH1B1	psi-mi:“MI:0914”(association)	0.510
KIAA0753	OFD1	psi-mi:“MI:2364”(proximity)	0.480
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (184): KIF7 (Affinity Capture-MS), KIF7 (Affinity Capture-MS), KIF7 (Proximity Label-MS), KIF7 (Proximity Label-MS), KIF7 (Proximity Label-MS), KIF7 (Affinity Capture-MS), KIF7 (Affinity Capture-MS), KIF7 (Proximity Label-MS), KIF7 (Proximity Label-MS), KIF7 (Proximity Label-MS), KIF7 (Proximity Label-MS), KIF7 (Proximity Label-MS), KIF7 (Proximity Label-MS), KIF7 (Proximity Label-MS), KIF7 (Proximity Label-MS)

ESM2 similar proteins: A0JNT9, A0JPP8, A1X157, O15169, O75145, O75335, P39880, P60469, Q07DZ5, Q08CF3, Q08E13, Q09YM8, Q2M1P5, Q2QLG9, Q2VUH7, Q32PN7, Q3TMW1, Q3UHC7, Q3UIL6, Q3UIW5, Q3UJV1, Q5DU25, Q5FWS6, Q5JU85, Q5PRF9, Q5XI59, Q5ZJ07, Q674X7, Q68UI8, Q69ZS8, Q6IPM2, Q6NZT2, Q6P402, Q6P730, Q6ZP65, Q80XS6, Q80Y83, Q8JZP9, Q8K1S6, Q8R4R9

Diamond homologs: A0A068FIK2, A0JN40, A1ZAJ2, A8BB91, A8BKD1, B1AVY7, B7EJ91, B7ZNG0, B9F2Y7, B9GE13, F1M4A4, F1M5N7, F1QN54, F4IIS5, F4J1U4, F4K0J3, G5EGS3, O14343, O14782, O15066, O23826, O35066, O35071, O35787, O43896, O45935, O55165, O60282, O60333, O75037, O88658, O95239, P17210, P21613, P23678, P28738, P28741, P33173, P33174, P33175

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
KIF7	“up-regulates quantity by stabilization”	GLI2	binding
SMO	“up-regulates activity”	KIF7	relocalization
KIF7	“up-regulates quantity by stabilization”	GLI1	binding
KIF7	“up-regulates quantity by stabilization”	GLI3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 137 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Loss of Nlp from mitotic centrosomes	11	19.0×	2e-09
Loss of proteins required for interphase microtubule organization from the centrosome	11	19.0×	2e-09
AURKA Activation by TPX2	11	18.2×	2e-09
RHO GTPases activate PKNs	5	17.2×	4e-04
Regulation of PLK1 Activity at G2/M Transition	12	16.6×	2e-09
Recruitment of mitotic centrosome proteins and complexes	11	16.3×	5e-09
Anchoring of the basal body to the plasma membrane	12	14.8×	2e-09
Recruitment of NuMA to mitotic centrosomes	11	13.9×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
non-motile cilium assembly	6	13.6×	1e-03
cilium assembly	13	7.5×	2e-05
intracellular protein localization	9	7.4×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1899 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	35
Uncertain significance	1031
Likely benign	586
Benign	61

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1324624	NM_198525.3(KIF7):c.1212_1222del (p.Leu405fs)	Pathogenic
1349038	NC_000015.9:g.(?90171650)(90177134_?)del	Pathogenic
1387829	NM_198525.3(KIF7):c.3248dup (p.Asn1083fs)	Pathogenic
1422094	NM_198525.3(KIF7):c.1702dup (p.Leu568fs)	Pathogenic
1426103	NM_198525.3(KIF7):c.1404_1411del (p.Val469fs)	Pathogenic
1453752	NM_198525.3(KIF7):c.1546C>T (p.Gln516Ter)	Pathogenic
1456011	NM_198525.3(KIF7):c.283C>T (p.Gln95Ter)	Pathogenic
1458781	NC_000015.9:g.(?90176897)(90196161_?)del	Pathogenic
1895830	NM_198525.3(KIF7):c.877dup (p.Gln293fs)	Pathogenic
1899253	NM_198525.3(KIF7):c.2446C>T (p.Gln816Ter)	Pathogenic
1956764	NM_198525.3(KIF7):c.3514C>T (p.Arg1172Ter)	Pathogenic
1966171	NM_198525.3(KIF7):c.1269dup (p.Arg424fs)	Pathogenic
2013484	NM_198525.3(KIF7):c.2497C>T (p.Gln833Ter)	Pathogenic
2018067	NM_198525.3(KIF7):c.1108_1114dup (p.Ala372fs)	Pathogenic
2018195	NM_198525.3(KIF7):c.895del (p.Ile299fs)	Pathogenic
208593	NM_198525.3(KIF7):c.2944G>T (p.Glu982Ter)	Pathogenic
2110237	NM_198525.3(KIF7):c.2287C>T (p.Gln763Ter)	Pathogenic
2116256	NM_198525.3(KIF7):c.2227C>T (p.Gln743Ter)	Pathogenic
2124781	NM_198525.3(KIF7):c.3312dup (p.Asp1105Ter)	Pathogenic
217670	NM_198525.3(KIF7):c.3331C>T (p.Arg1111Ter)	Pathogenic
217671	NM_198525.3(KIF7):c.2917C>T (p.Arg973Ter)	Pathogenic
2202020	NM_198525.3(KIF7):c.2770C>T (p.Gln924Ter)	Pathogenic
2275645	NM_198525.3(KIF7):c.2530G>T (p.Glu844Ter)	Pathogenic
2628789	NM_198525.3(KIF7):c.1640dup (p.Arg549fs)	Pathogenic
264771	NM_198525.3(KIF7):c.3179A>G (p.Asn1060Ser)	Pathogenic
2702087	NM_198525.3(KIF7):c.1823del (p.Leu608fs)	Pathogenic
280302	NM_198525.3(KIF7):c.1106del (p.Ala369fs)	Pathogenic
2812476	NM_198525.3(KIF7):c.1462C>T (p.Gln488Ter)	Pathogenic
2827463	NM_198525.3(KIF7):c.1329G>A (p.Trp443Ter)	Pathogenic
30895	NM_198525.3(KIF7):c.2896_2897del (p.Ala966fs)	Pathogenic

SpliceAI

4220 predictions. Top by Δscore:

Variant	Effect	Δscore
15:89608791:T:A	acceptor_gain	1.0000
15:89608794:T:A	acceptor_gain	1.0000
15:89608802:GAA:G	acceptor_gain	1.0000
15:89616491:GGCAG:G	donor_gain	1.0000
15:89616492:GCAGG:G	donor_gain	1.0000
15:89616494:AGGT:A	donor_loss	1.0000
15:89616495:GGT:G	donor_loss	1.0000
15:89616496:G:GC	donor_loss	1.0000
15:89616497:T:G	donor_loss	1.0000
15:89619706:A:AG	acceptor_gain	1.0000
15:89619707:G:GG	acceptor_gain	1.0000
15:89619834:A:G	donor_gain	1.0000
15:89621388:TGCA:T	acceptor_loss	1.0000
15:89621389:GCAG:G	acceptor_loss	1.0000
15:89621390:CA:C	acceptor_loss	1.0000
15:89621391:A:AG	acceptor_gain	1.0000
15:89621391:AG:A	acceptor_loss	1.0000
15:89621392:G:GA	acceptor_gain	1.0000
15:89621392:GA:G	acceptor_gain	1.0000
15:89621392:GAC:G	acceptor_gain	1.0000
15:89621392:GACC:G	acceptor_gain	1.0000
15:89621392:GACCA:G	acceptor_gain	1.0000
15:89621530:G:GT	donor_gain	1.0000
15:89621550:GGTA:G	donor_loss	1.0000
15:89621551:G:GC	donor_loss	1.0000
15:89621552:T:A	donor_loss	1.0000
15:89623621:A:AG	acceptor_gain	1.0000
15:89623622:G:GG	acceptor_gain	1.0000
15:89628951:A:AC	donor_gain	1.0000
15:89628952:C:CC	donor_gain	1.0000

AlphaMissense

8639 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:89630442:C:G	A1055P	0.999
15:89630445:C:G	A1054P	0.999
15:89647619:C:G	A513P	0.999
15:89630298:A:G	Y1103H	0.998
15:89630309:A:G	L1099P	0.998
15:89630450:A:G	L1052P	0.998
15:89630454:C:G	A1051P	0.998
15:89630463:C:G	A1048P	0.998
15:89652662:A:T	V90D	0.998
15:89630298:A:C	Y1103D	0.997
15:89630342:A:G	L1088P	0.997
15:89631544:C:G	R1021P	0.997
15:89631556:A:G	L1017P	0.997
15:89645066:A:G	L713P	0.997
15:89647627:A:G	L510P	0.997
15:89648769:A:G	L310P	0.997
15:89629563:A:G	L1110P	0.996
15:89630294:A:G	F1104S	0.996
15:89630333:A:G	L1091P	0.996
15:89630421:C:G	A1062P	0.996
15:89630438:A:T	I1056N	0.996
15:89631577:A:G	L1010P	0.996
15:89631652:A:G	L985P	0.996
15:89648769:A:T	L310H	0.996
15:89648996:A:C	Y301D	0.996
15:89649154:A:G	F248S	0.996
15:89649840:A:G	S144P	0.996
15:89629560:C:G	R1111P	0.995
15:89630306:A:G	L1100P	0.995
15:89630354:A:G	L1084P	0.995

dbSNP variants (sampled 300 via entrez): RS1000135015 (15:89652318 C>T), RS1000252998 (15:89655350 T>A), RS1000331763 (15:89641294 CAG>C), RS1000402274 (15:89630560 T>C,G), RS1000506156 (15:89628257 C>G), RS1000527701 (15:89647793 C>T), RS1000639693 (15:89654389 A>G), RS1000641843 (15:89632374 A>G), RS1000671791 (15:89636287 C>T), RS1000704300 (15:89636010 T>C), RS1000746966 (15:89648173 G>A,T), RS1000806980 (15:89643671 G>A), RS1000810977 (15:89618521 T>G), RS1000843512 (15:89618186 GAA>G), RS1000942720 (15:89625865 C>A,T)

Disease associations

OMIM: gene MIM:611254 | disease phenotypes: MIM:200990, MIM:607131, MIM:614120, MIM:181800, MIM:200900, MIM:256100, MIM:236680, MIM:213300, MIM:119530

GenCC curated gene-disease

Disease	Classification	Inheritance
acrocallosal syndrome	Definitive	Autosomal recessive
hydrolethalus syndrome 2	Strong	Autosomal recessive
multiple epiphyseal dysplasia, Al-Gazali type	Supportive	Autosomal recessive
hydrolethalus syndrome	Supportive	Autosomal recessive
orofaciodigital syndrome type 6	Supportive	Autosomal recessive

Mondo (15): acrocallosal syndrome (MONDO:0008708), multiple epiphyseal dysplasia, Al-Gazali type (MONDO:0011778), hydrolethalus syndrome 2 (MONDO:0013585), scoliosis, isolated, susceptibility to, 1 (MONDO:0008419), short-limb skeletal dysplasia with severe combined immunodeficiency (MONDO:0008704), intellectual disability (MONDO:0001071), nephronophthisis (MONDO:0019005), hydrolethalus syndrome (MONDO:0006037), Joubert syndrome (MONDO:0018772), cerebellar ataxia (MONDO:0000437), strabismus (MONDO:0003432), pathologic nystagmus (MONDO:0004843), postaxial polydactyly of fingers (MONDO:0017426), orofacial cleft 1 (MONDO:0007335), orofaciodigital syndrome type 6 (MONDO:0010176)

Orphanet (11): Multiple epiphyseal dysplasia-macrocephaly-facial dysmorphism syndrome (Orphanet:166024), Hydrolethalus (Orphanet:2189), Acrocallosal syndrome (Orphanet:36), Short-limb skeletal dysplasia with severe combined immunodeficiency (Orphanet:935), Nephronophthisis (Orphanet:655), Isolated Joubert syndrome (Orphanet:475), Rare ataxia (Orphanet:102002), Male infertility due to gonadal dysgenesis or sperm disorder (Orphanet:399764), Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), OBSOLETE: Postaxial polydactyly of fingers (Orphanet:294942)

HPO phenotypes

172 total (30 of 172 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000098	Tall stature
HP:0000104	Renal agenesis
HP:0000143	Rectovaginal fistula
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000180	Lobulated tongue
HP:0000190	Abnormal oral frenulum morphology
HP:0000193	Bifid uvula
HP:0000194	Open mouth
HP:0000199	Tongue nodules
HP:0000204	Cleft upper lip
HP:0000207	Triangular mouth
HP:0000212	Gingival overgrowth
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000269	Prominent occiput
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000286	Epicanthus

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002930_10	Cobalt levels	3.000000e-06

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D055673	Acrocallosal Syndrome	C10.500.034.500; C16.131.666.034.500
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D013285	Strabismus	C10.292.562.887; C11.590.810
C536079	Hydrolethalus syndrome (supp.)
C564621	Macrocephaly with Multiple Epiphyseal Dysplasia and Distinctive Facies (supp.)
C566121	Orofacial Cleft 1 (supp.)
C536531	Orofaciodigital syndrome 6 (supp.)
C565984	Short-Limb Skeletal Dysplasia with Severe Combined Immunodeficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2021751 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1052700	KIF7, PLIN1		0.00	0

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, decreases methylation, decreases expression	3
sodium arsenite	increases expression	2
FR900359	increases phosphorylation	1
propionaldehyde	increases methylation	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases methylation	1
manganese chloride	decreases expression, increases abundance	1
caprylic aldehyde	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
pentanal	increases methylation	1
heptanal	increases methylation	1
clothianidin	increases expression	1
bisphenol S	decreases methylation	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Folic Acid	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Manganese	decreases expression, increases abundance	1
Smoke	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2024749	Binding	Inhibition of Kif7 ATPase activity	Triphenylbutanamines: kinesin spindle protein inhibitors with in vivo antitumor activity. — J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1V8	Abcam HeLa KIF7 KO	Cancer cell line	Female
CVCL_D7T6	Ubigene A-549 KIF7 KO	Cancer cell line	Male
CVCL_SU85	HAP1 KIF7 (-) 1	Cancer cell line	Male
CVCL_SU86	HAP1 KIF7 (-) 2	Cancer cell line	Male
CVCL_SU87	HAP1 KIF7 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

220 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06759272	PHASE4	NOT_YET_RECRUITING	Impact of CYP2C19 Genotype-guided Approach in Antiplatelet Therapy on Platelet Reactivity Index Among Coronary Artery Disease (CAD) Patients
NCT07351643	PHASE4	NOT_YET_RECRUITING	CCTA Evaluation of SGLT2i-related Pericoronary Fat Changes in Non-diabetic ACS Patients Without HF
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT07174986	PHASE2/PHASE3	RECRUITING	Early Double Sequential Defibrillation in Out of Hospital Cardiac Arrest
NCT01171404	Not specified	COMPLETED	Study Evaluating How Patients With Acute Coronary Syndrome Are Managed During 2 Years After Discharge
NCT03444012	Not specified	COMPLETED	ADHERE-S (NIS Brilique)
NCT04220619	Not specified	WITHDRAWN	RescueTEE for In-hospital Cardiac Arrest (ReTEECA Trial)
NCT04580706	Not specified	UNKNOWN	The Effect of Frailty and Other Geriatric Syndromes on the Prognosis of Elderly Patients With Acute Coronary Syndrome
NCT04937803	Not specified	COMPLETED	Safety and Efficacy of Drug-Coated Balloon for De-novo Lesions in Patients With Acute Coronary Syndromes (DCB-ACS)
NCT04987268	Not specified	COMPLETED	CHIP and Residual Cardiovascular Event Tendency After Smoking Cessation
NCT05243485	Not specified	COMPLETED	Prehospital Triage of Patients With Suspected Non-ST-segment Elevation Acute Coronary Syndrome: the TRIAGE-ACS Study
NCT05857735	Not specified	COMPLETED	Kuwait Heart Foundation Registry of Acute Coronary Events
NCT06757777	Not specified	NOT_YET_RECRUITING	Evaluation of Remnant Cholesterol Levels and Monocyte-to-HDL-cholesterol Ratio as Predictors of Coronary Artery Disease Severity in Patients With Acute Coronary Syndrome
NCT06899776	Not specified	ACTIVE_NOT_RECRUITING	Assessing Chest Pain Using Point-of-Care High-Sensitivity Troponin I in the Emergency Department
NCT07026708	Not specified	RECRUITING	TIRANA-ACS: A Prospective Registry Study for the Targeted Investigation of Residual Inflammation After Non-ST/ ST Elevation Acute Coronary Syndrome
NCT07096973	Not specified	RECRUITING	Cardiac REhabilitation COhort at the Medicine Campus DaVos to invEstigate Recovery
NCT07128667	Not specified	NOT_YET_RECRUITING	Clinical Features and Long-Term Prognosis in Young Patients With Acute Myocardial Infarction
NCT07190274	Not specified	NOT_YET_RECRUITING	Prospective Observational Cohort Study on Impact of Frailty on Risk Prediction, Treatment Strategies, and Short-Term Outcomes in Patients With Acute Coronary Syndrome
NCT07231835	Not specified	RECRUITING	Registry of Coronary Disease Outcomes Revascularizing With Drug-Coated Balloons
NCT07258823	Not specified	NOT_YET_RECRUITING	the Effectiveness of Continuous Compression-synchronous Ventilation (Bio-CPR)
NCT07264881	Not specified	NOT_YET_RECRUITING	For Patients With Myocardial Infarction and Multiple Vessel: Testing if Ultrasound (UFR) Can Guide All Needed Treatment in One Procedure, Avoiding a Return Hospital Visit for a Second Operation.
NCT07422688	Not specified	ENROLLING_BY_INVITATION	Optical Coherence Tomography in Acute Vessel Evaluation
NCT07474441	Not specified	COMPLETED	Early Coronary Angiography in Advanced Chronic Kidney Disease With Acute Coronary Syndrome
NCT07486791	Not specified	RECRUITING	A Clinical Study on the Effect of Cardiopulmonary Function and Quality of Life in Patients With Acute Coronary Syndrome Complicated by Heart Failure by Lying-Sitting-Standing Sequential Baduanjin
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation