CDC14A

cell division cycle 14A, the group of CDC14 phosphatases

Basic information

Region (hg38): 1:100345000-100520277

Previous symbols: [ "DFNB32" ]

Links

ENSG00000079335 ∙ NCBI:8556 ∙ OMIM:603504 ∙ HGNC:1718 ∙ Uniprot:Q9UNH5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• hearing impairment and infertile male syndrome (Strong), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 32 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 32 (Limited), mode of inheritance: AR
• autosomal recessive nonsyndromic deafness 105 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 32, with or without immotile sperm	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Genitourinary	27259055; 29293958

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDC14A gene.

• not provided (158 variants)
• not specified (22 variants)
• Inborn genetic diseases (18 variants)
• Autosomal recessive nonsyndromic hearing loss 32 (14 variants)
• Ear malformation (2 variants)
• Sensorineural hearing loss disorder (1 variants)
• Rare genetic deafness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDC14A 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	20	6	28
missense		4	50	10	4	68
nonsense	4	3	1			8
start loss						0
frameshift	3		2			5
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region			1	3	2	6
non coding				27	38	65
Total	7	8	56	57	48

Highest pathogenic variant AF is 0.0000132

Variants in CDC14A

This is a list of pathogenic ClinVar variants found in the CDC14A region.

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

Position	Type	Phenotype	Significance	ClinVar
1-100351784-A-G			Likely benign (Feb 01, 2024)
1-100352197-G-A			Likely benign (Mar 28, 2019)
1-100352198-C-G			Likely benign (Mar 28, 2019)
1-100352485-A-G			Likely benign (Mar 03, 2019)
1-100352622-G-C			Benign (Nov 10, 2018)
1-100352730-A-T			Benign (Nov 10, 2018)
1-100352908-T-C		Autosomal recessive nonsyndromic hearing loss 32	Benign (Jul 14, 2021)
1-100352908-T-T		not specified	Likely benign (Nov 10, 2017)
1-100352940-CG-C		not specified	Likely benign (Dec 04, 2017)
1-100352982-G-C		not specified	Conflicting classifications of pathogenicity (Mar 11, 2019)
1-100352985-G-A		not specified	Conflicting classifications of pathogenicity (Aug 19, 2022)
1-100352989-G-A			Uncertain significance (Aug 28, 2023)
1-100353013-A-T		CDC14A-related disorder	Likely benign (Jan 10, 2020)
1-100353138-A-G			Likely benign (Feb 14, 2019)
1-100353172-T-G			Benign (Nov 10, 2018)
1-100353717-T-C			Benign (Jun 14, 2018)
1-100353751-T-G			Likely benign (Jun 23, 2023)
1-100353761-G-T		Autosomal recessive nonsyndromic hearing loss 32	Likely pathogenic (Aug 01, 2020)
1-100353772-T-C			Likely benign (Jul 06, 2022)
1-100353810-A-G			Uncertain significance (Aug 22, 2022)
1-100354133-C-G			Likely benign (Jan 02, 2019)
1-100377253-T-C			Likely benign (Jan 25, 2019)
1-100377317-G-T			Benign (Dec 23, 2018)
1-100377597-C-T		not specified • CDC14A-related disorder	Likely benign (Feb 01, 2024)
1-100377608-A-G		Inborn genetic diseases	Uncertain significance (Dec 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDC14A	protein_coding	protein_coding	ENST00000361544	15	175250

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.64e-8	0.996	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.494	309	334	0.924	0.0000172	4066
Missense in Polyphen		58	85.365	0.67944		1077
Synonymous	-1.26	147	129	1.14	0.00000693	1194
Loss of Function	2.62	17	33.3	0.510	0.00000188	413

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000782	0.000720
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.0000578	0.0000544
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000168	0.000167
Middle Eastern	0.0000578	0.0000544
South Asian	0.000238	0.000229
Other	0.000507	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dual-specificity phosphatase. Required for centrosome separation and productive cytokinesis during cell division. Dephosphorylates SIRT2 around early anaphase. May dephosphorylate the APC subunit FZR1/CDH1, thereby promoting APC-FZR1 dependent degradation of mitotic cyclins and subsequent exit from mitosis. {ECO:0000269|PubMed:11901424, ECO:0000269|PubMed:12134069, ECO:0000269|PubMed:17488717, ECO:0000269|PubMed:9367992}.
• Disease: DISEASE: Deafness, autosomal recessive, 105 (DFNB105) [MIM:616958]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:27259055}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell cycle - Homo sapiens (human);Cell Cycle;Signal Transduction;MAPK6/MAPK4 signaling;MAPK family signaling cascades;Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase;APC/C-mediated degradation of cell cycle proteins;Regulation of mitotic cell cycle;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.708
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.93

Haploinsufficiency Scores

• pHI: 0.855
• hipred: Y
• hipred_score: 0.666
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.443

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdc14a

Zebrafish Information Network

• Gene name: cdc14aa
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: increased curvature

Gene ontology

• Biological process: microtubule cytoskeleton organization;mitotic cell cycle;regulation of exit from mitosis;sensory perception of sound;cell population proliferation;positive regulation of cytokinesis;peptidyl-tyrosine dephosphorylation;cell division;mitotic cell cycle arrest
• Cellular component: spindle pole;nucleoplasm;nucleolus;cytoplasm;centrosome;cytosol;nuclear body;stereocilium tip;kinocilium;mitotic spindle;kinociliary basal body
• Molecular function: phosphoprotein phosphatase activity;protein serine/threonine phosphatase activity;protein tyrosine phosphatase activity;protein binding;protein tyrosine/serine/threonine phosphatase activity