CDKN1C

cyclin dependent kinase inhibitor 1C

Basic information

Region (hg38): 11:2883212-2885775

Previous symbols: [ "BWCR", "BWS" ]

Links

ENSG00000129757 ∙ NCBI:1028 ∙ OMIM:600856 ∙ HGNC:1786 ∙ Uniprot:P49918 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Beckwith-Wiedemann syndrome (Definitive), mode of inheritance: Autosomal dominant inheritance with paternal imprinting
• IMAGe syndrome (Definitive), mode of inheritance: Autosomal dominant inheritance with paternal imprinting
• rhabdomyosarcoma (Moderate), mode of inheritance: AD
• Beckwith-Wiedemann syndrome (Definitive), mode of inheritance: AD
• IMAGe syndrome (Moderate), mode of inheritance: AD
• IMAGe syndrome (Supportive), mode of inheritance: AD
• Beckwith-Wiedemann syndrome due to CDKN1C mutation (Supportive), mode of inheritance: AD
• intrauterine growth restriction-short stature-early adult-onset diabetes syndrome (Supportive), mode of inheritance: AD
• Silver-Russell syndrome (Limited), mode of inheritance: AD
• Beckwith-Wiedemann syndrome (Strong), mode of inheritance: AD
• IMAGe syndrome (Moderate), mode of inheritance: AD
• Beckwith-Wiedemann syndrome (Definitive), mode of inheritance: AD
• IMAGe syndrome (Definitive), mode of inheritance: AD
• IMAGe syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
IMAGE syndrome; Beckwith-Wiedemann syndrome	AD	Endocrine; Oncologic	While IMAGe syndrome may have a number of recognizable features, recognition may allow preventive/treatment measures related to adrenal insufficiency; In Beckwith-Wiedemann syndrome, surveillance and early detection of and treatment for malignancy may decrease morbidity and mortality; Recognition and surveillance for and treatment of neonatal hypoglycemia can be beneficial	Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Renal	8841187; 10424811; 11181570; 11751681; 12439823; 15769992; 15999116; 15887271; 16835919; 18668518; 19302842; 20503313; 20301568; 22585446; 22634751; 24065356
The conditions may involve imprinting mechanisms

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDKN1C gene.

• Beckwith-Wiedemann syndrome (1029 variants)
• not provided (79 variants)
• Beckwith-Wiedemann syndrome;IMAGe syndrome (43 variants)
• Inborn genetic diseases (30 variants)
• not specified (25 variants)
• IMAGe syndrome (13 variants)
• IMAGe syndrome;Beckwith-Wiedemann syndrome (10 variants)
• CDKN1C-related condition (9 variants)
• IMAGe syndrome;Beckwith-Wiedemann syndrome due to CDKN1C mutation (1 variants)
• Silver-Russell syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDKN1C 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			8	282	1	291
missense	4	3	422	7	1	437
nonsense	21	1	1			23
start loss			5			5
frameshift	50	10	2	3		65
inframe indel	1		26	134	1	162
splice donor/acceptor (+/-2bp)		2	4			6
splice region			6	11		17
non coding			3	26	2	31
Total	76	16	471	452	5

Highest pathogenic variant AF is 0.00000694

Variants in CDKN1C

This is a list of pathogenic ClinVar variants found in the CDKN1C region.

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

Position	Type	Phenotype	Significance	ClinVar
11-2883776-A-G			Uncertain significance (-)
11-2883810-G-A			Likely benign (Jul 01, 2022)
11-2883919-C-T		CDKN1C-related disorder	Likely benign (Sep 26, 2019)
11-2883920-G-A		CDKN1C-related disorder	Likely benign (Aug 29, 2019)
11-2883974-G-GC		Beckwith-Wiedemann syndrome • IMAGe syndrome • CDKN1C-related disorder	Benign (Jul 22, 2021)
11-2883974-G-GCC			Likely benign (Dec 01, 2023)
11-2883979-C-A		Beckwith-Wiedemann syndrome • Beckwith-Wiedemann syndrome;IMAGe syndrome	Uncertain significance (Jan 24, 2022)
11-2883979-C-G		Beckwith-Wiedemann syndrome	Uncertain significance (Dec 27, 2023)
11-2883979-C-CT		Beckwith-Wiedemann syndrome	Likely benign (Feb 23, 2021)
11-2883984-G-A		CDKN1C-related disorder	Likely benign (Sep 15, 2022)
11-2883986-G-A		CDKN1C-related disorder	Likely benign (May 06, 2022)
11-2883997-A-G		Beckwith-Wiedemann syndrome	Pathogenic (-)
11-2883998-C-T		Beckwith-Wiedemann syndrome • IMAGe syndrome	Uncertain significance (Feb 27, 2023)
11-2884005-C-T		Beckwith-Wiedemann syndrome	Likely benign (Dec 29, 2023)
11-2884009-G-A		Beckwith-Wiedemann syndrome	Uncertain significance (Oct 19, 2023)
11-2884010-C-A		Beckwith-Wiedemann syndrome	Likely benign (Jan 12, 2022)
11-2884014-C-T		Beckwith-Wiedemann syndrome	Uncertain significance (Apr 05, 2023)
11-2884019-G-A		Beckwith-Wiedemann syndrome	Likely benign (Jul 26, 2022)
11-2884019-G-C		Beckwith-Wiedemann syndrome	Likely benign (Nov 10, 2021)
11-2884020-C-T		Beckwith-Wiedemann syndrome	Uncertain significance (Sep 30, 2020)
11-2884021-G-A		Beckwith-Wiedemann syndrome	Uncertain significance (May 02, 2023)
11-2884022-C-A		Beckwith-Wiedemann syndrome	Likely benign (Aug 16, 2023)
11-2884022-C-T		Beckwith-Wiedemann syndrome	Likely benign (Aug 17, 2023)
11-2884025-G-C		Beckwith-Wiedemann syndrome	Likely benign (Nov 17, 2023)
11-2884025-G-T		Beckwith-Wiedemann syndrome	Likely benign (Jun 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDKN1C	protein_coding	protein_coding	ENST00000414822	2	2669

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.820	0.177	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.93	64	125	0.513	0.00000575	1912
Missense in Polyphen		14	36.694	0.38154		342
Synonymous	-0.339	60	56.7	1.06	0.00000278	738
Loss of Function	2.20	0	5.65	0.00	2.43e-7	70

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Potent tight-binding inhibitor of several G1 cyclin/CDK complexes (cyclin E-CDK2, cyclin D2-CDK4, and cyclin A-CDK2) and, to lesser extent, of the mitotic cyclin B-CDC2. Negative regulator of cell proliferation. May play a role in maintenance of the non- proliferative state throughout life.
• Disease: DISEASE: Beckwith-Wiedemann syndrome (BWS) [MIM:130650]: A disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors. {ECO:0000269|PubMed:10424811, ECO:0000269|PubMed:26077438}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies (IMAGE) [MIM:614732]: A rare condition characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and commenced on steroid replacement therapy. Other reported features in this condition include, hypercalciuria and/or hypercalcemia, craniosynostosis, cleft palate, and scoliosis. {ECO:0000269|PubMed:22634751}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell cycle - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;Primary Focal Segmental Glomerulosclerosis FSGS;Dopaminergic Neurogenesis;Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway;Oxidative Damage;G1 to S cell cycle control;Endochondral Ossification;Hedgehog;Cyclin D associated events in G1;G1 Phase;Mitotic G1-G1/S phases;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Haploinsufficiency Scores

• pHI: 0.750
• hipred: Y
• hipred_score: 0.628
• ghis: 0.617

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdkn1c
• Phenotype: hematopoietic system 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); reproductive system phenotype; 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); normal phenotype; embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary 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); limbs/digits/tail phenotype; craniofacial phenotype; vision/eye phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: cdkn1ca
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;skeletal system development;kidney development;cell cycle arrest;regulation of exit from mitosis;aging;myeloid cell differentiation;adrenal gland development;positive regulation of transforming growth factor beta receptor signaling pathway;negative regulation of kinase activity;multicellular organism growth;negative regulation of phosphorylation;neuron maturation;camera-type eye development;negative regulation of cyclin-dependent protein serine/threonine kinase activity;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;negative regulation of epithelial cell proliferation;digestive system development;uterus development;embryonic placenta morphogenesis;genetic imprinting;regulation of lens fiber cell differentiation;negative regulation of cyclin-dependent protein kinase activity
• Cellular component: nucleus;cytoplasm
• Molecular function: protein kinase inhibitor activity;cyclin-dependent protein serine/threonine kinase inhibitor activity;protein binding;protein-containing complex binding