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 11, primary, autosomal recessive (Strong), mode of inheritance: AR
• 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

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 (4 variants)
• Microcephaly 17, primary, autosomal recessive (3 variants)
• Inborn genetic diseases (2 variants)
• Autosomal recessive primary microcephaly (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.

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			2	100	19	121
missense		2	179	13	3	197
nonsense	4	1				5
start loss						0
frameshift	2	1				3
inframe indel						0
splice donor/acceptor (+/-2bp)	2	1				3
splice region			7	17	5	29
non coding			3	97	92	192
Total	8	5	184	210	114

Highest pathogenic variant AF is 0.0000197

Variants in CIT

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

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

Position	Type	Phenotype	Significance	ClinVar
12-119686885-GGCT-G			Likely benign (Oct 01, 2023)
12-119688250-C-A			Uncertain significance (Mar 28, 2022)
12-119688253-G-C			Benign/Likely benign (Feb 08, 2023)
12-119688259-G-A		CIT-related disorder	Likely benign (Jul 12, 2019)
12-119688269-A-AAGG			Benign (Feb 01, 2024)
12-119688279-G-A			Likely benign (Jan 05, 2021)
12-119689930-C-T			Likely benign (Jul 26, 2018)
12-119689943-T-C			Likely benign (Aug 25, 2018)
12-119690135-C-T			Benign (Oct 03, 2023)
12-119690151-C-T			Uncertain significance (Jun 30, 2022)
12-119690167-A-G			Uncertain significance (Oct 18, 2022)
12-119690180-C-T		Inborn genetic diseases	Uncertain significance (Aug 20, 2024)
12-119690181-G-A			Likely benign (Mar 24, 2022)
12-119690188-G-T		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
12-119690197-C-T		Inborn genetic diseases	Uncertain significance (Mar 20, 2024)
12-119690200-C-A			Uncertain significance (Aug 15, 2022)
12-119690229-G-C			Likely benign (Aug 01, 2024)
12-119690237-G-A		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
12-119690277-T-C			Benign (Dec 01, 2023)
12-119690286-G-A			Likely benign (Sep 01, 2023)
12-119690312-G-A			Uncertain significance (Sep 06, 2019)
12-119690338-C-T		Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
12-119690350-C-T		Inborn genetic diseases	Uncertain significance (Jun 09, 2022)
12-119690357-C-G		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
12-119690368-C-T		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)

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