CIT

citron rho-interacting serine/threonine kinase, the group of AGC family kinases|MicroRNA protein coding host genes

Basic information

Region (hg38): 12:119685791-119877320

Links

ENSG00000122966

∙ NCBI:11113 ∙ OMIM:605629 ∙ HGNC:1985 ∙ Uniprot:O14578 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

microcephaly 17, primary, autosomal recessive (Moderate), mode of inheritance: AR
autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
microcephaly 17, primary, autosomal recessive (Strong), mode of inheritance: AR
microcephaly 17, primary, autosomal recessive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly 17, 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	Craniofacial; Musculoskeletal; Neurologic	27453578; 27453579; 27503289; 27519304

ClinVar

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

not_provided (378 variants)
Inborn_genetic_diseases (213 variants)
Microcephaly_17,_primary,_autosomal_recessive (45 variants)
CIT-related_disorder (45 variants)
not_specified (26 variants)
Autosomal_recessive_primary_microcephaly (4 variants)
Long_QT_syndrome (2 variants)
Intellectual_disability (2 variants)
Marfanoid_habitus_and_intellectual_disability (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CIT gene is commonly pathogenic or not. These statistics are base on transcript: NM_001206999.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	114 clinvar	13 clinvar	132
missense	4 clinvar	2 clinvar	267 clinvar	25 clinvar	2 clinvar	300
nonsense	6 clinvar	1 clinvar				7
start loss						0
frameshift	2 clinvar	2 clinvar				4
splice donor/acceptor (+/-2bp)	2 clinvar	3 clinvar	1 clinvar			6
Total	14	8	273	139	15

Highest pathogenic variant AF is 0.000024279158

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CIT	protein_coding	protein_coding	ENST00000392521	47	191501

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000300	125701	0	46	125747	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.82	825	1.20e+3	0.689	0.0000743	13576
Missense in Polyphen		234	381.37	0.61358		4263
Synonymous	1.10	442	472	0.936	0.0000301	3901
Loss of Function	8.44	23	125	0.185	0.00000699	1397

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000270	0.000270
Ashkenazi Jewish	0.00	0.00
East Asian	0.000165	0.000163
Finnish	0.0000930	0.0000924
European (Non-Finnish)	0.000266	0.000246
Middle Eastern	0.000165	0.000163
South Asian	0.000167	0.000163
Other	0.000170	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Plays a role in cytokinesis. Required for KIF14 localization to the central spindle and midbody. Putative RHO/RAC effector that binds to the GTP-bound forms of RHO and RAC1. It probably binds p21 with a tighter specificity in vivo. Displays serine/threonine protein kinase activity. Plays an important role in the regulation of cytokinesis and the development of the central nervous system. Phosphorylates MYL9/MLC2. {ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:27453578}.;
Disease: DISEASE: Microcephaly 17, primary, autosomal recessive (MCPH17) [MIM:617090]: 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. MCPH17 is a severe form characterized by lissencephaly, enlarged ventricles, agenesis of the corpus callosum, cerebellar hypoplasia, and brainstem hypoplasia. Patients manifest delayed psychomotor development, intellectual disability, spasticity, axial hypotonia, and dysmorphic features. {ECO:0000269|PubMed:27453578, ECO:0000269|PubMed:27453579, ECO:0000269|PubMed:27503289, ECO:0000269|PubMed:27519304}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: G13 Signaling Pathway;Signal Transduction;RHO GTPases activate CIT;RHO GTPase Effectors;Signaling by Rho GTPases;RhoA signaling pathway (Consensus)

Recessive Scores

pRec: 0.371

Intolerance Scores

loftool: 0.475
rvis_EVS: -2.35
rvis_percentile_EVS: 1.14

Haploinsufficiency Scores

pHI: 0.380
hipred: Y
hipred_score: 0.706
ghis: 0.623

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.858

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cit
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); reproductive system 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); cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; muscle phenotype;

Gene ontology

Biological process: G2/M transition of mitotic cell cycle;mitotic cell cycle;mitotic cytokinesis;protein phosphorylation;Golgi organization;regulation of actin polymerization or depolymerization;positive regulation of cytokinesis;intracellular signal transduction;generation of neurons;neuron apoptotic process
Cellular component: cytosol;membrane;midbody;Golgi cisterna;cleavage furrow;neuronal cell body
Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;Rho GTPase binding;SH3 domain binding;PDZ domain binding;metal ion binding;scaffold protein binding